SKIN The Journal of Cutaneous Medicine

Retiform Plaques: An Additional Diagnostic Consideration

2023-10-13T17:47:08+00:00

A Case of Hand-Foot Skin Reaction-like Eruption Associated with Pembrolizumab

2023-08-31T17:46:33+00:00

Skeletal Muscle Regeneration – A Rare Malignancy Mimicker Encountered in Mohs Micrographic Surgery

2023-10-02T13:07:39+00:00

Coinciding Erythema Nodosum and Sweet Syndrome

2024-01-18T20:20:10+00:00

Leaping over Leprosy

2023-11-20T15:06:10+00:00

Angiokeratoma Corporis Diffusum in the Absence of Known Metabolic Disease and Systemic Features

2023-12-16T17:47:36+00:00

Angiokeratomas are benign capillary ectasias in the superficial dermis. Angiokeratoma corporis diffusum (ACD) is a clinical variant typically associated with an enzyme deficiency in the metabolism of glycoproteins, most notably Fabry disease. ACD has also been found to occur in a benign form with the absence of metabolic disease and lack of systemic features. We present the case of ACD in a 20-year-old male with normal enzyme function and in the absence of any detectable metabolic disorders.

More Than Meets the Eye: Localized Bullous Eruption After Transfusion

2023-12-12T18:26:50+00:00

Sweet syndrome, also known as acute febrile neutrophilic dermatosis, is a neutrophilic dermatosis characterized by the presence of painful erythematous plaques and nodules with a sterile neutrophilic infiltrate on histology. However, the clinical manifestations of sweet syndrome can vary widely. Additionally, Sweet syndrome is often associated with underlying systemic diseases. In this case report, we present the case of a 72-year-old female who developed bullous sweet syndrome with oral involvement following a blood transfusion. Serology revealed an elevated pANCA level and systemic manifestations consistent with granulomatosis with polyangiitis. There have been approximately 50 reported cases of concurrent neutrophilic dermatoses occurring with ANCA-associated vasculitis. Relapse is common in these patients, with all reported cases involving the ears, nose, and throat (ENT) region. Ultimately, the concomitant presentation of ANCA-associated vasculitis and neutrophilic dermatoses is rare. Dermatologists should be aware that testing for ANCA in cases of neutrophilic dermatoses is appropriate, and if positive, close monitoring for signs of systemic vasculitis is warranted.

Dupilumab-induced Acanthosis Nigricans

2023-08-06T14:36:39+00:00

Dupilumab is a human monoclonal IgG4 antibody to interleukin-4 (IL-4) and IL-13 approved for the treatment of moderate-to-severe atopic dermatitis (AD) in patients six months or older. Several cutaneous adverse reactions to dupilumab have been reported, including facial dermatitis and psoriasis. Herein, we present a unique case of dupilumab-induced acanthosis nigricans (AN) in a patient treated for concomitant AD and contact dermatitis, in the absence of other associated conditions or potential culprit medications. The patient had complete resolution of the lesions with discontinuation of medication, and recurrence upon re-initiation of therapy. This case represents a new cutaneous adverse reaction to dupilumab to which dermatologists should be familiar.

Verrucous Cyst in a 7-year-old Girl

2023-08-07T18:27:25+00:00

Background: Verrucous cyst is an uncommon manifestation of human papilloma virus infection. Diagnosis is histopathological and characterized by verrucous changes in an epidermal cyst. This is a report of verrucous cyst in a seven (7) year old girl who had an asymptomatic nodule on her hand.

Case Report: 7-year old girl who had a nodule on the palmar surface of her left hand. A clinical diagnosis of foreign body granuloma was made. Biopsy and histopathology was consistent with a verrucous cyst

Conclusion: The need for histopathological evaluation of skin growths is highlighted by this case report.

Nevus Lipomatosus Cutaneous Superficialis: A Case Report in Egypt

2023-08-14T20:36:39+00:00

Nevus lipomatosus cutaneous superficialis (NLCS) is a rare hamartomatous condition characterized by ectopic mature adipose tissue. We are reporting a case of a 12-year-old female with soft, non-tender, pedunculated nodules with a cerebriform surface over her right lower back. The lesion fulfilled the criteria of the classic type of NLCS and was surgically removed with no visible recurrence on follow up.

A Case of Atypical Presentation of Morpheaform Verrucous Sarcoidosis

2023-09-26T16:34:47+00:00

Morpheaform verrucous sarcoidosis is a rare variation of cutaneous sarcoidosis that is characterized by prominent, localized keratotic plaques on the skin. The etiology of this condition is unknown, and the current literature is limited. Sarcoidosis is typically a systemic condition with high incidence in the African-American population, and cutaneous presentation without systemic manifestation is exceedingly rare. This report details the challenging identification of this condition given the patient's history of multiple concurrent autoimmune and inflammatory conditions. Only nine cases of morpheaform sarcoidosis have been reported in the literature. This case demonstrates the complexity of diagnosing cutaneous sarcoidosis if the clinical systemic symptoms have not yet fully developed. It is important to take a multi-disciplinary approach with dermatology, rheumatology, and pulmonology to arrive at the correct diagnosis as cutaneous lesions can mimic several different cutaneous dermatoses. Therefore, physicians should consider morpheaform sarcoidosis on the differential in patients who present with indurated and eroded verruciform plaques.

Progression of Atypical Fibroxanthoma to Metastatic Pleomorphic Dermal Sarcoma in a Lung Transplant Recipient

2023-09-26T05:56:07+00:00

Introduction: Atypical fibroxanthoma (AFX) and pleomorphic dermal sarcoma (PDS) are rare cutaneous malignancies often seen in elderly patients with photodamaged skin. Although solid organ transplant recipients (SOTRs) with AFX/PDS appear to have worse outcomes than the general population, the risk of progression from AFX to PDS in this group is not well studied. We present the case of a lung transplant patient with AFX recurring as PDS.

Case Presentation: A 68-year-old male lung transplant patient with an extensive history of skin cancer presented with a 9-millimeter erythematous papule on the right vertex scalp. Biopsy revealed AFX, and the tumor cleared with 1 stage of MMS. Seven months later, the patient developed a rapidly growing, hemorrhagic nodule at the site, which was diagnosed as PDS. Despite initial treatment with doxorubicin, pazopanib, and radiation to the lung, liver, and bone lesions, the patient’s disease progressed. The patient was started on pembrolizumab with prednisone to mitigate the risk of organ rejection but succumbed to pneumonia with septic shock and respiratory failure.

Discussion: Transplant patients have an increased risk of poor outcomes related to PDS. ICIs may be considered in advanced cases in which other treatment options have been exhausted. In conclusion, SOTRs with AFX/PDS should be aggressively treated and monitored as their risk of unfavorable outcomes appears to be increased.

Treatment of Steroid-Resistant Beard-Restricted Alopecia Areata with Baricitinib

2023-08-26T19:37:46+00:00

Alopecia areata is an autoimmune disorder causing localized hair loss due to T-cell attack on hair follicles. Beard involvement holds psychological and cultural significance, and treatment guidance for steroid-resistant cases is limited. We present a case of the successful treatment of steroid-resistant beard alopecia areata (BAA) with baricitinib, a JAK-1/2 inhibitor, in a 37-year-old male. Prior therapies, including topical ruxolitinib and intralesional steroids, had failed. Over 9 months, baricitinib (4 mg daily) and oral minoxidil led to reduced alopecic patches, increased hair density, and resolved inflammation. This case underscores the potential of JAK inhibitors for BAA, emphasizing the importance of establishing clear guidelines to direct treatment of in order to optimize patient outcomes.

Cutaneous Ulcerations as the Presenting Sign of Acute Aortic Occlusion

2023-08-21T04:44:23+00:00

This is a report of a case of acute aortic occlusion (AAO) in a 46-year-old woman who presented with confluent and coalescing punched-out ulcerations on the bilateral medial buttocks and abdominal ulcerations. This case highlights how AAO, although rare, should be considered in patients with cardiovascular risk factors presenting with acute lower extremity pain and new-onset cutaneous ulcerations of the perineum and/or abdomen.

Drug-Induced Erythema Annulare Centrifugum after Dupilumab Therapy: A Case Report.

2023-12-12T18:39:05+00:00

Introduction: Dupilumab is a fully human monoclonal antibody therapy FDA-approved to treat moderate-to-severe atopic dermatitis (AD) by interrupting the pro-inflammatory signaling pathway of interleukins 4 and 13. Common side effects of dupilumab include injection-site reactions, ophthalmic complications, and upper respiratory infections. We discuss the necessity for early recognition and management of dupilumab-induced EAC which has not been previously reported as a potential adverse effect.

Case Report: A 48-year-old woman began treatment with dupilumab for severe AD and subsequently presented with a 3-month history of erythematous annular plaques with trailing scale on the trunk and extremities. She failed treatment with topical corticosteroids as well as topical and oral antifungals prior to being diagnosed with biopsy-confirmed erythema annulare centrifugum (EAC). The condition worsened after replacing dupilumab with tralokinumab but resolved after discontinuation of the drugs and has remained clear since.

Conclusion: EAC is a reactive erythema that typically presents as expanding annular papules and plaques with central clearing and in some cases, trailing scale at the rim of the lesions. There are currently no reports in the literature describing the development of EAC secondary to dupilumab. Clinicians should be aware that EAC may be a potential adverse effect of dupilumab.

Histopathological Granuloma Formation in a Subacute Cutaneous Lupus Erythematosus Patient

2023-12-14T15:37:49+00:00

Introduction: Subacute cutaneous lupus erythematosus (SCLE) is one of the cutaneous lupus erythematous subtypes. Being an autoimmune condition in nature, its diagnosis requires compatible clinical presentation with histopathological findings.

Objective: To present a subacute cutaneous lupus erythematosus with granuloma formation.

Case Report: A 56- year-old woman presented with longstanding red plaques on her face, trunk, and extremities. Two skin biopsies were performed during two different visits. The results showed tuberculoid leprosy and multiple granuloma annulare. She was treated accordingly for years with no improvement in her condition. Later, the third skin biopsy with CD123 immunohistochemical stain was done. The result was most consistent with cutaneous lupus erythematosus. Together with her clinical findings, she was finally diagnosed with SCLE. Her rashes resolved after being treated with hydroxychloroquine and topical steroid.

Conclusion: The diagnosis of SCLE must be made based on both clinical presentations and histopathological findings.

Galli Galli Disease: A Challenging Diagnosis in a Bahraini Female Patient

2023-09-07T13:19:24+00:00

Dowling-Degos Disease (DDD) is an inherited cutaneous disease which presents with classic and atypical cutaneous findings, including macules of hyperpigmentation and hypopigmentation in the flexural creases. A variant, termed Galli-Galli Disease (GGD), presents similarly, with the distinguishing feature of acantholysis on histology. Reports of GGD in the literature are rare, due to the infrequency of the diagnosis. This may contribute to a lack of available information and delayed diagnosis, which can result in a frustrating clinical course for patients. We present a female patient who presented with complaints of a burning sensation and painful rash for the last three years on a background of hypopigmented and hyperpigmented macules on the trunk, upper extremities and flexural creases. Comprehensive dermatopathological evaluation and clinical correlates led to the diagnosis of GGD.

The Association Between Internet Search Patterns and Scabies Incidence Across the United States

2023-11-20T15:26:58+00:00

Background

Scabies, a contagious skin infestation caused by Sarcoptes scabiei, is a significant public health concern [1]. Traditional surveillance methods for scabies suffer from time lag and incomplete data, hindering early detection and response [5]. The widespread use of the internet and search engines, such as Google^TM, offer new opportunities for alternative surveillance approaches.

Objective

This study aimed to explore the association between scabies search volumes on Google Trends^TM (GTs) and scabies incidence at the state level across the United States.

Methods

GTs data for each U.S. state and scabies incidence from 2011 to 2019 were analyzed for summary statistics and association.

Results

The mean Spearman correlation coefficient for the period of 2011-2019 indicated a strong positive correlation between GTs RSVs for “scabies” and the incidence of scabies in the United States. Using an unpaired t-test, this correlation was found to be statistically significant.

Conclusions

In resource-scarce environments where access to care is a common barrier, healthcare providers and departments can leverage this information to effectively target populations and employ resources for scabies prevention and treatment. Analyzing search engine term patterns can enhance our understanding of people's behavior when they suspect a scabies infestation.

Iron Deficiency Anemia Pruritus: A Review with Proposed Mechanisms of Action

2023-12-12T18:29:04+00:00

Chronic generalized pruritus without a primary skin lesion presents a dilemma for clinicians. A minority can be attributed to systemic diseases. Iron deficiency anemia (IDA) presents one such poorly defined cause. We comprehensively review the literature to support IDA pruritus as a valid etiology in the patient with chronic, generalized pruritus. Several studies and case reports describe the association of pruritus and IDA, and more importantly, resolution of the pruritus upon iron supplementation, strongly suggesting IDA as the primary etiology. Thus, we recommend obtaining a CBC and iron studies in all cases of chronic generalized pruritus without a primary lesion.

Based on currently available evidence, we also present novel mechanisms of actions in which iron deficiency may precipitate pruritus that have not been proposed in the literature. Iron deficiency may precipitate pruritus at the level of the skin through decreased skin thickness, elasticity, or barrier function, thereby promoting xerosis. Iron deficiency may also cause neurologic pruritus from damage, compression, or irritation of nerves. The levels of known chemical mediators of itch, such as serotonin, opioids, and neurotrophins, are also affected by iron homeostasis. IDA pruritus likely manifests from a complex interplay of multiple proposed pathways.

Human Leukocyte Antigen DQB1 and its Implication in Scleroderma Pathogenesis: A Systematic Review

2024-01-14T17:53:37+00:00

This systematic review explores the association between HLA-DQB1 genes and scleroderma, a chronic autoimmune disease characterized by collagen synthesis dysregulation and tissue fibrosis. A thorough investigation was conducted by utilizing Google Scholar and PubMed to search for relevant studies in the English language. Two independent reviewers were involved in the process of screening for appropriate studies. A limitation of the exclusion of non-English studies potentially introduces language bias. Inclusion criteria focused on articles investigating the association between HLA genes and scleroderma, providing data on patient and control groups. Risk of bias was conducted using the NIH Quality Assessment Tool for Case-Control Studies. The analyses focused on odds ratios (OR) as a measure of the strength of the association of HLA genes with disease susceptibility. Subgroup analyses were performed for Caucasian and Asian samples, along with a combined analysis. In Caucasian samples, DQB1*02:02 was associated with lower odds of scleroderma (OR=0.51, 95% CI [0.41, 0.63]), while DQB1*03:01 was associated with higher odds (OR=1.55, 95% CI [1.22, 1.97]). In Asian samples, DQB1*04:02 and DQB1*06:01 were associated with higher odds of scleroderma (OR=1.51, 95% CI [1.01, 2.24] and OR=1.33, 95% CI [1.06, 1.67], respectively), while DQB1*06:04 was associated with lower odds (OR=0.55, 95% CI [0.37, 0.82]). Combined samples showed decreased odds of scleroderma in DQB1*06:03 (OR=0.68, 95% CI [0.48, 0.95]) and DQB1*06:04 (OR=0.56, 95% CI [0.39, 0.81]). Future research should explore the interaction between HLA genes and environmental factors to enhance early detection and intervention strategies for individuals at risk of developing scleroderma.

Pitfalls in Laser-Based Device Tattoo Removal: A Literature Review

2024-03-05T08:14:32+00:00

Laser therapy has been popular and widely used for tattoo removal. Basic principles for utilizing lasers in tattoo removal for different types and colors of tattoos are required to minimize and avoid unwanted side effects. Appropriate parameters of lasers are not the only keys to successful laser removal treatment. In this review, common pitfalls in removing tattoos with lasers are discussed. Several factors should be taken into consideration and realistic goals should be discussed at the first encounter with patients. Non-ablative lasers may apply to a simple tattoo without any cutaneous reaction while ablative lasers are better for traumatic tattoos. Laser is not always the best option for tattoo removal in some circumstances and other measures can be considered for the best interest of patients and outcome.

Long-Term Efficacy of Ritlecitinib up to Month 24 From the ALLEGRO Phase 2b/3 and Long-Term Phase 3 Clinical Studies in Alopecia Areata

2024-02-06T09:17:06+00:00

Introduction: Ritlecitinib demonstrated efficacy and safety to Week 48 in patients aged ≥12 years with alopecia areata (AA) in ALLEGRO-2b/3 (NCT03732807). ALLEGRO-LT (NCT04006457) is an ongoing, phase 3, open-label study investigating the long-term safety and efficacy of ritlecitinib in AA. We report updated interim efficacy results of ritlecitinib up to Month 24 from ALLEGRO-2b/3 and ALLEGRO-LT.

Methods: Patients aged ≥12 years with AA and ≥50% scalp hair loss who rolled-over to ALLEGRO-LT from ALLEGRO-2b/3 were included. Data are reported for patients who received: 1) daily ritlecitinib 50-mg with a 4-week 200-mg daily loading dose (“200/50-mg”); 2) daily ritlecitinib 50-mg with no loading dose (“50-mg”). Outcomes include the proportions of patients with response (based on Severity of Alopecia Tool [SALT] score ≤20, SALT ≤10, and Patients’ Global Impression of Change [PGI-C] score of “moderately improved” or “greatly improved”) through Month 24, and the proportions of patients sustaining SALT ≤20 response from Month 12 through Month 24. Observed and imputed (modified last observation carried forward [mLOCF]) data, to account for missing values, are reported (data cutoff: December 9, 2022).

Results: The 200/50-mg and 50-mg groups included 194 and 191 patients; 127 (65.5%) and 111 (58.1%) were ongoing at the data cutoff. SALT ≤20 response rates in the 200/50-mg and 50-mg groups increased from Month 12 (45.9% and 45.1% [observed]; 41.8% and 40.3% [mLOCF]) to Month 24 (63.1% and 60.8% [observed]; 50.8% and 46.1% [mLOCF]). SALT ≤10 response rates increased between Months 12 and 24 for the 200/50-mg group (39.4% to 51.1% [observed]; 35.6% to 40.9% [mLOCF]) and 50-mg group (34.2% to 50.8% [observed]; 30.9% to 37.7% [mLOCF]). Of SALT ≤20 responders at Month 12, 92.8% (200/50-mg) and 79.7% (50-mg) (observed) sustained this response through Month 24. PGI-C response rates were maintained from Month 12 (200/50-mg: 69.4% [observed], 65.3% [mLOCF]; 50-mg: 61.6% [observed], 57.7% [mLOCF]) to Month 24 (200/50-mg: 76.4% [observed], 65.4% [mLOCF]; 50-mg: 70.0% [observed], 56.6% [mLOCF]).

Conclusion: Ritlecitinib 50-mg (with or without a 200-mg loading dose) demonstrated clinically meaningful and sustained clinician- and patient-reported efficacy through Month 24, which supports its long-term use in patients aged ≥12 years with severe AA.

Real-World Assessment of Disease Characteristics and Clinical Outcomes in Alopecia Areata in a Global Noninterventional Observational Cohort (ADAAGIO)

2024-03-06T21:20:01+00:00

Background: A range of medications with varying efficacy are used to treat alopecia areata (AA). There remains limited evidence on prevailing treatments, disease characteristics, and clinical outcomes of patients with AA in routine practice, particularly for those with extensive hair loss. This study sought to address this evidence gap.

Methods: This was a retrospective chart review study spanning the United Kingdom, France, Spain, and Germany. Adult and adolescent patients with ≥50% scalp hair loss were included. The study index date was defined as date of de novo or progression to ≥50% scalp hair loss and patients were required to have ≥6 months of postindex follow-up (i.e., index date to last clinic visit); index dates ranged 2015-2019. Analyses were descriptive and reported patient demographics, baseline clinical characteristics, and Dermatologic Life Quality Index (DLQI) score. The primary clinical endpoint was absolute Severity of Alopecia Tool (SALT) score and was assessed longitudinally based on post-index visits in which SALT was recorded. Sustained SALT ≤20 was also assessed via Kaplan-Meier methods to evaluate time to achieving SALT ≤20 without subsequent regression within 6 months to SALT >30.

Results: A total of 741 patients were included. Median age at AA diagnosis was 27 years and 52.6% were female. Mean (SD) baseline SALT score at index was 63.5 (15.6), with 80.2% having patchy AA and 19.8% having alopecia totalis or universalis. Among patients with DLQI measured at index, mean (SD) DLQI score was 19.2 (7.2) with 84.5% reporting either a large (DLQI 11-20) or extremely large (DLQI 21-30) impact of AA. Topical corticosteroids were the most common treatment observed post-index, with 55.6% receiving ≥1 course with a median cumulative exposure of 4 months. Intralesional corticosteroids (22.5%), systemic immunosuppressants (22.0%), and oral (17.3%) or topical (19.4%) minoxidil were also common. Among patients with SALT measured at 12 months post-index, there was a mean (SD) absolute SALT reduction of -44.6% (37.3%) from baseline. However, at 12 months post-index, most patients (90.1%) failed to achieve SALT ≤20 that was sustained for ≥6 months.

Conclusions: Although patients in this study experienced a substantial absolute SALT score reduction, few patients achieved and subsequentially sustained the more clinically meaningful SALT threshold of ≤20. These findings highlight the potential suboptimal effectiveness of the varied treatments applied in this population.

Early Oligoarticular Psoriatic Arthritis Responds to Treatment With Apremilast: Week 16 Results From FOREMOST - a Phase 4 Randomized Controlled Trial

2024-01-29T18:38:53+00:00

Early Oligoarticular Psoriatic Arthritis Responds to Treatment With Apremilast: Week 16 Results From FOREMOST – a Phase 4 Randomized Controlled Trial

Laure Gossec¹, Dafna Gladman², Laura C. Coates³, Jacob Aelion⁴, Jitendra Vasandani⁵, Jyotsna Reddy⁶, Rebecca Wang⁶, Michele Brunori⁶, Stephen Colgan⁶, Philip Mease⁷

¹Sorbonne Université and Pitié Salpêtrière Hospital, Paris, France; ²Toronto Western Hospital, Toronto, ON, Canada; ³University of Oxford, Oxford, UK; ⁴West Tennessee Research Institute, Jackson, TN, USA; ⁵West Texas Clinical Research, Lubbock, TX, USA; ⁶Amgen Inc., Thousand Oaks, CA, USA; ⁷Swedish Medical Center/Providence St. Joseph Health and University of Washington School of Medicine, Seattle, WA, USA

Introduction & Objectives:

Psoriatic arthritis (PsA) is underdiagnosed in dermatology practice, typically presenting 10 years after skin symptoms. Dermatologists may encounter early PsA since up to 30% of patients with psoriasis have PsA. Oligoarticular PsA affects ≤4 joints, is very common, and is underrepresented in clinical trials as most pivotal studies exclude patients with <3 swollen and tender joints. Here, we report the efficacy and safety of apremilast vs. placebo for the treatment of early oligoarticular PsA.

Materials & Methods:

FOREMOST (NCT03747939) is a phase 4, multicenter, randomized, double-blind, placebo-controlled, parallel-group study. Patients with PsA,based on CAPSAR criteria, duration ≤5 years, swollen joint count (SJC) >1 but ≤4, and tender joint count (TJC) >1 but ≤4 were randomized 2:1 to apremilast 30 mg BID (APR) or placebo for 24 weeks. The primary endpoint was the achievement of minimal disease activity (MDA)-Joints¹ (mandating SJC ≤1 and TJC ≤1, and 3/5 alternate items) at week 16.

Results:

Of 308 patients randomized (APR: n=203; placebo: n=105), mean PsA duration was 9.9 months, mean age was 50.9 years, and 39.9% of patients were using csDMARD. MDA-Joints response was achieved in 33.9% vs. 16.0% for patients treated with APR vs. placebo (primary endpoint, P=0.0008). At week 16, a significantly greater proportion, 70.2%, of patients treated with APR achieved cDAPSA REM/LDA vs. 51.8% with placebo (P=0.0017). A greater proportion of patients achieved a good/moderate response in PASDAS score with APR (59.9%) vs. placebo (42.7%). Greater improvements from baseline in PsA Impact of Disease (PsAID)-12 score (LS mean change, −1.5 vs. −0.4; nominal P<0.0001) and nail psoriasis score (visual analog scale [VAS]; LS mean change, −13.9 vs. −6.8; nominal P=0.0094) were observed with APR vs. placebo at week 16. Patients treated with APR also achieved greater improvement in quality of life measures (Patient Pain [VAS ≤15: 59.6 vs. 13.8; nominal P=0.0022], Patient Global Assessment [PtGA; VAS ≤20: 61.7 vs. 20.1; nominal P=0.0286]) when compared to placebo at week 16. No new safety signals were identified.

Conclusion:

FOREMOST is the first global randomized controlled trial exclusively studying early oligoarticular PsA. We report the first results of FOREMOST, the primary outcome, and show better disease control is achievable with APR, with twice the MDA-Joint response compared with placebo at 16 weeks. These findings show APR treatment of early oligoarticular PsA improves clinical and quality of life outcomes and may inform optimal management of these patients.

Reference: 1. Coates LC, et al. J Rheumatol. 2016;43:371–5.

Impact of Oral, Selective, Allosteric Tyrosine Kinase 2 Inhibitor, Deucravacitinib, on Psoriasis in Patients with Active Psoriatic Arthritis: Results from a Phase 2 Trial

2024-02-26T22:28:25+00:00

Introduction: Deucravacitinib (DEUC), an oral, selective, allosteric tyrosine kinase 2 inhibitor, is approved in the US, EU, and other countries for treatment of adults with moderate-to-severe plaque psoriasis (PsO) who are candidates for systemic therapy. DEUC was superior to apremilast and placebo (PBO) in two phase 3 trials in patients with moderate to severe PsO. DEUC was efficacious on multiple measures of arthritis severity vs PBO in a phase 2 trial in patients with active psoriatic arthritis (PsA) who had ≥1 PsO lesion (≥2 cm). In patients with body surface area (BSA) involvement ≥3% at baseline (80% of patients in this trial), a greater proportion achieved PASI 75 with DEUC (6 mg QD: 42.4%, P=0.01; 12 mg QD: 59.6%, P<0.0001) vs PBO (20.4%) at Week 16. This analysis evaluated the impact of DEUC on PsO in patients with PsA in the phase 2 trial (NCT03881059).

Methods: The phase 2 double-blind PsA trial randomized patients (N=203) 1:1:1 to PBO, DEUC 6 mg once daily (QD), or DEUC 12 mg QD. After Week 16, patients could enroll in an optional, double-blind period until Week 52. DEUC-treated patients achieving minimal disease activity at Week 16 continued DEUC to Week 52. PsO disease activity measurements were assessed.

Results: Baseline PsO characteristics were comparable across groups. At Week 16, significant decreases from baseline in mean PASI were observed with DEUC vs PBO in patients with baseline BSA ≥3%-<10% or PASI ≤12 even with very low baseline PASI scores, and also in those with baseline BSA ≥10% and PASI >12. Significant decreases in PASI from baseline were observed with DEUC vs PBO in patients with background csDMARD use (DEUC 6 mg, -4.0 and 12 mg, -4.9 vs PBO, -2.3; both P<0.05) and those without csDMARD use (-3.7 and -4.0 vs -2.5, respectively; both P<0.001). At Week 16, greater proportions of DEUC vs PBO patients achieved PASI ≤1 with baseline BSA ≥3% (DEUC 6 mg: 32.2%; DEUC 12 mg: 44.2%; PBO: 18.5%) and in patients with baseline BSA ≥10% and PASI >12 (23.1%; 28.6%; 0.0%). In patients with baseline BSA ≥3%, decreases in mean PASI at Week 16 were maintained through Week 52 in patients continuing DEUC 6 mg (absolute PASI score, Week 16: 2.39, Week 52: 1.22) and 12 mg (Week 16: 0.64, Week 52: 0.24).

Conclusion: DEUC significantly improved PsO in patients with PsA, regardless of baseline PsO severity and background csDMARD use. Improvement was comparable to that observed in the phase 3 POETYK PSO-1 trial.

Evaluating the Efficacy and Safety of Bimekizumab for Plaque Psoriasis and Psoriatic Arthritis: An Expert Consensus Panel Report

2024-03-15T20:17:30+00:00

Background: While there are numerous effective therapies for psoriasis, there remains an unmet need as some patients still suffer from inadequate response with available medications. Bimekizumab is a first-in-class monoclonal antibody that inhibits both interleukin (IL)-17A and IL-17F and was recently approved by the Food and Drug Administration. The aim of this study was for a panel of experts in psoriasis management to review the available data on bimekizumab and create consensus statements on its use in clinical practice.

Methods: A comprehensive literature search of PubMed, Scopus, and Google Scholar was conducted for English-language original research articles, systematic reviews, and meta-analyses discussing the safety and efficacy of bimekizumab for moderate to severe plaque psoriasis and psoriatic arthritis. A panel of nine dermatology physician assistants and one dermatology nurse practitioner with significant expertise in the management of psoriasis convened virtually on December 16, 2023, to review the studies and create recommendations for their peers on the use of bimekizumab. A modified Delphi process was implemented to reach a consensus on these statements and the Strength of Recommendation Taxonomy was used to assign each one a strength of recommendation.

Results: The literature search resulted in 92 articles that met search criteria. After a thorough screening of these studies for relevance to the discussion questions, 20 articles remained and were distributed to each panelist prior to the meeting. The panel unanimously voted to adopt 10 consensus recommendations and assigned all 10 statements a strength of recommendation of “A.”

Conclusion: Bimekizumab has a very high efficacy in the treatment of moderate to severe psoriasis and psoriatic arthritis. It also has a favorable safety profile that is consistent with that of other biologics, except for an increased risk of oral candidiasis.

Roflumilast Cream 0.3% in Patients With Chronic Plaque Psoriasis: Individual Patient PASI and PASI-HD Responses: Pooled DERMIS-1 and DERMIS-2 Phase 3 Trials

2024-01-24T19:36:44+00:00

Background: Roflumilast cream 0.3% is a highly potent phosphodiesterase 4 inhibitor approved as a nonsteroidal, once-daily treatment for patients with plaque psoriasis. Pooled efficacy and safety results from two Phase 3 clinical trials (DERMIS-1 and DERMIS-2) have been presented previously. The Psoriasis Area and Severity Index (PASI) is used to assess the severity of plaque psoriasis in clinical trials; however, PASI is not precise when the area of involvement is <10% of a given anatomic region. A modified version of the PASI, the PASI-high discrimination (PASI-HD), allows more precise assessment of psoriasis in body regions where <10% area is affected. We present individual patient responses using PASI and PASI-HD.

Methods: Patients aged ≥2 years with at least mild plaque psoriasis involving 2-20% body surface area were randomized 2:1 to apply roflumilast cream 0.3% or vehicle cream once daily for 8 weeks. The primary efficacy endpoint was Investigator Global Assessment (IGA) Success (score of Clear or Almost Clear plus ≥2-grade improvement from baseline) at Week 8. PASI and PASI-HD were used to measure disease severity; individual patient PASI and PASI-HD responses were plotted graphically. Safety and tolerability were also evaluated and were reported previously.

Results: Roflumilast- and vehicle-treated patients had similar baseline demographic and disease characteristics. At Week 8, statistically significantly more roflumilast- than vehicle-treated patients achieved IGA Success (39.9% vs. 6.5%; P<0.0001). Statistically significant differences favoring roflumilast were observed at Week 8 for percentages of patients achieving a 50% reduction in PASI (72.1% vs. 25.5%; P<0.0001), 75% reduction (40.3% vs. 6.5%, P<0.0001), 90% reduction (19.7% vs 2.3%; P<0.0001), and 100% reduction (12.3% vs 0.8%; P<0.001). Likewise, statistically significant differences favoring roflumilast were observed at Week 8 for percentages of patients achieving 50% reduction in PASI-HD (79.4% vs. 33.1%; P<0.0001), 75% reduction (59.9% vs. 17.9%, P<0.0001), 90% reduction (39.9% vs 9.1%; P<0.0001), and 100% reduction (12.3% vs 0.8%; P<0.0001). Roflumilast cream demonstrated low rates of application-site adverse events (AEs), treatment-related AEs, and discontinuations due to AEs, comparable to vehicle. At the first application of roflumilast cream 0.3% (day 1), 96% of patients reported no or mild sensation, increasing to 99% of patients at Weeks 4 and 8.

Conclusions: Roflumilast cream 0.3% provided greater improvement in IGA Success, PASI, and PASI-HD versus vehicle with favorable safety and tolerability in patients with psoriasis in two Phase 3 trials. PASI-HD provided higher discrimination of effects of treatment in areas with <10% involvement than the traditional PASI.

ClinicalTrials.gov Identifiers: DERMIS-1: NCT04211363; DERMIS-2: NCT04211389

Financial Disclosures: Arcutis Biotherapeutics, Inc.

Apremilast for the Treatment of Psoriasis in Special Areas in Pediatric Patients in the SPROUT Study

2024-01-29T16:27:07+00:00

Introduction & Objective: Psoriasis in special areas is difficult to treat and causes significant disease burden. Approved systemic therapies for moderate to severe plaque psoriasis in pediatric patients are limited and require subcutaneous injection. Apremilast, a unique oral immunomodulator that inhibits phosphodiesterase-4, is approved in multiple countries for use in adults with psoriasis, regardless of severity. In this study, the efficacy of apremilast for psoriasis in special areas in pediatric patients was assessed over 16 weeks.

Materials & Methods: SPROUT (NCT03701763) is a phase 3, randomized, double-blind, placebo-controlled study in patients 6-17 years with moderate to severe plaque psoriasis (Psoriasis Area and Severity Index ≥12, body surface area ≥10%, and static Physician Global Assessment [sPGA] ≥3) inadequately controlled by/inappropriate for topical therapy. Patients were stratified by age and randomized 2:1 to receive apremilast (weight-based 20 mg or 30 mg twice-a-day) or placebo for 16 weeks, then apremilast through week 52. Scalp Physician Global Assessment (ScPGA) response, modified sPGA of genitalia (sPGA-G) response, Whole Body Itch-Numeric Rating Scale (WBI-NRS) response, and change from baseline in Children’s Dermatology Life Quality Index (CDLQI) were assessed through week 16.

Results: Of 245 randomized patients (apremilast: 163; placebo: 82), 101 (41.2%) were 6-11 years and 144 (58.8%) were 12-17 years; 120 (49.0%) patients weighed ≥20 to <50 kg and 125 (51.0%) weighed ≥50 kg. At baseline, 81.0% of the patients treated with apremilast and 84.1% of patients treated with placebo had moderate to severe scalp psoriasis (ScPGA ≥3). Significantly more patients achieved ScPGA response at week 16 with apremilast vs placebo (36.4% vs 18.8%; P=0.0091). At baseline, 110 patients (44.9%; 45.4% apremilast and 43.9% placebo) had moderate to severe genital psoriasis (sPGA-G ≥3). Achievement of sPGA-G response at week 16 was numerically greater with apremilast vs placebo (39.2% vs 25.0%), although not significant, possibly due to small sample size (apremilast: n=74; placebo: n=36). Significantly more patients achieved WBI-NRS response at week 16 with apremilast vs placebo (52.0% vs 32.1%; P=0.0110). Greater improvements in CDLQI were seen at week 16 with apremilast vs placebo (least-squares mean change from baseline −5.1 vs −3.2; P=0.0009). Adverse events were consistent with the known apremilast safety profile. In 21 patients vaccinated during the study (including for COVID-19, influenza, diphtheria, pertussis, tetanus, meningococcus, and hepatitis B), no new safety issues occurred.

Conclusions: Apremilast significantly improved scalp psoriasis, itch, and quality of life in pediatric patients with moderate to severe psoriasis. At week 16, patients with moderate to severe genital psoriasis showed a trend toward improvement, although not significant due partially to the sample size.

Effect of Spesolimab on Achieving Sustained Disease Remission in Patients with Generalized Pustular Psoriasis: Results from the Effisayil 2 Study

2024-02-22T21:34:03+00:00

Introduction: Generalized pustular psoriasis (GPP) is a chronic, rare disease characterized by flares of widespread skin pustulation. Intravenous (IV) spesolimab, an anti-interleukin-36 receptor monoclonal antibody, is approved for GPP flare treatment; however, the optimal dosing and long-term efficacy of subcutaneous (SC) spesolimab treatment in patients with GPP has not yet been reported. We report the effect of SC spesolimab on achieving sustained disease remission in Effisayil 2 (NCT04399837), a 48-week trial that evaluated the efficacy and safety of SC spesolimab in preventing GPP flares.

Methods: Patients with a history of GPP were randomized (1:1:1:1) to receive placebo (n=31), low- (n=31, 300 mg loading dose [LD]; 150 mg every 12 weeks [q12w]), medium- (n=31, 600 mg LD; 300 mg q12w) or high-dose (n=30, 600 mg LD; 300 mg every 4 weeks [q4w]) SC spesolimab over 48 weeks. Sustained remission was defined as GPP Physician Global Assessment (GPPGA) total score of 0 or 1 at all visits up to Week 48, or GPPGA total score of 0 or 1 and all GPPGA subscores ≤2 at all visits up to Week 48. Sustained pustular clearance was defined as GPPGA pustulation subscore of 0 at all visits from Week 4 to Week 48. Any use of IV spesolimab or another standard of care for GPP worsening was considered a failure of remission. Missing data were imputed by a sequential logistic regression multiple imputation method. Adjusted risk differences (RD) were calculated by the Mantel−Haenszel type-weighted average of differences.

Results: 31 patients received placebo, and 30 patients received high-dose spesolimab. Compared to placebo, more patients had sustained remission in the high-dose arm using both GPPGA total score 0 or 1 (63.3% vs 29.0%; RD [95% CI] 0.35 [0.10–0.59]), and GPPGA total score 0 or 1 and all GPPGA subscores ≤2 (60.4% vs 29.0%; RD [95% CI] 0.32 [0.07–0.56]). Compared to placebo, more patients in the high-dose arm had sustained pustular clearance over 48 weeks (63.6% vs 25.8%; RD [95% CI] 0.38 [0.14–0.62]).

Conclusion: Overall, high-dose SC spesolimab q4w is effective for the long-term management of GPP skin symptoms.

Deucravacitinib, an Oral, Selective, Allosteric Tyrosine Kinase 2 Inhibitor, in the Phase 3 Clinical Trials in Psoriasis, POETYK PSO-1 and PSO-2: Time to Meaningful Improvements in Itch as Assessed by the Psoriasis Symptoms and Signs Diary

2024-02-22T21:35:29+00:00

Introduction: In the phase 3 POETYK PSO-1 and PSO-2 trials in psoriasis, patients completed the Psoriasis Symptoms and Signs Diary (PSSD) daily, recording the average severity of psoriasis symptoms and signs, including itch, over the past 24 hours. Patients receiving deucravacitinib experienced greater improvement in PSSD scores than patients receiving placebo or apremilast, as previously reported. In this analysis, we evaluate the time to improvement in itch in patients treated with deucravacitinib vs placebo in both POETYK trials.

Methods: In each trial, adults with moderate to severe plaque psoriasis were randomized 1:2:1 to placebo, deucravacitinib 6 mg once daily, and apremilast 30 mg twice daily; at Week 16, patients receiving placebo crossed over to receive deucravacitinib. Adjusted mean score change from baseline for the PSSD itch item was modeled for deucravacitinib vs placebo using an analysis of covariance model with factors for geographic region, body weight, and prior biologic use, and the baseline value as a covariate. Improvements of ≥2 points on individual PSSD items have been established earlier as meaningful to patients. Time to ≥2-, ≥3-, and ≥4-point improvements from baseline to Week 16 on the PSSD itch item was estimated with Kaplan-Meier methods. Cox models estimated hazard ratios (HRs) for these improvements. Missing data for each analysis were imputed using modified baseline observation carried forward methods.

Results: In each trial, significantly greater improvement from baseline in itch score was observed within 2 weeks with deucravacitinib vs placebo. Across both trials, the median (95% confidence interval [CI]) time to ≥2-point and ≥3-point improvements was 6.0 (5.0– 7.0) and 9.0 (8.0–11.0) weeks, respectively, for patients receiving deucravacitinib and not reached for patients receiving placebo (censored at Week 16). Patients receiving deucravacitinib were 3 times more likely to achieve a ≥2-point meaningful improvement in itch score than patients receiving placebo (HR [95% CI]: 3.0 [2.1–4.1] and 3.4 [2.6–4.5] in POETYK PSO-1 and PSO-2, respectively). HRs in favor of deucravacitinib increased as the threshold for improvement increased: at ≥3 points, HRs (95% CI) were 4.0 (2.6–6.1) and 4.9 (3.4–6.9), and at ≥4 points, HRs (95% CI) were 6.5 (3.4–12.4) and 8.8 (5.1–15.2), in POETYK PSO-1 and PSO-2, respectively.

Conclusion: Patients receiving deucravacitinib vs placebo experienced improvement in their itch within 2 weeks of treatment. About half of patients receiving deucravacitinib experienced meaningful improvement in itch within 6 weeks.

Sponsored by: Bristol Myers Squibb.

Expected Spesolimab Plasma Exposure following Intravenous and Subcutaneous Dosing in Patients with Generalized Pustular Psoriasis

2024-02-22T22:44:01+00:00

Introduction: Generalized pustular psoriasis (GPP) is a chronic, potentially life-threatening inflammatory skin disease characterized by widespread flares of sterile pustules. Spesolimab is a first-in-class anti-interleukin-36 receptor monoclonal antibody approved to treat GPP flares in adults via intravenous (IV) infusion. The aim of this study was to simulate the plasma pharmacokinetics (PK) of IV versus subcutaneous (SC) doses of spesolimab to compare drug exposure profiles and support dosing strategies in patients with GPP.

Methods: A population PK model was developed using individual-level PK, anti-drug antibody, and covariate data from eighteen studies in which subjects were treated with IV or SC spesolimab.¹ The resulting PK model was used to simulate concentration-time profiles following varying doses of IV and SC spesolimab. Peak plasma concentration (C_max), time to peak plasma concentration (T_max), and area under the curve (AUC) were summarized for each dose regimen.

Results: Simulated spesolimab exposures demonstrated that the C_max and AUC of the single dose 900 mg IV infusion consistently exceeded that of various single doses of SC spesolimab tested. A SC dose greater than two-fold higher would be required to attain a C_max comparable to that of spesolimab 900 mg IV. The difference in exposure between the two administration routes was most pronounced in the first 2 weeks after administration. Slow absorption is expected with SC injection, with T_max attained at later time points after SC dosing compared to immediately following the 90-minute infusion for IV dosing. Results were the same when simulating a two-dose regimen administered one week apart.

Conclusions: PK simulations suggest that treatment with IV and SC spesolimab can result in differences in drug exposure in clinical practice. The immediate and high exposure of IV spesolimab compared with the lower exposure of SC spesolimab are supportive of IV dosing with spesolimab in acute GPP flare treatment vs SC dosing.

Spesolimab Use for Generalized Pustular Psoriasis Flare Prevention in Patients with Concomitant Plaque Psoriasis: Results from the Effisayil 2 Trial

2024-02-22T23:35:27+00:00

Introduction & Objectives: Generalized pustular psoriasis (GPP) is a chronic inflammatory, potentially life-threatening skin disease, characterized by flares of sterile pustules. Spesolimab, an anti-interleukin-36 receptor monoclonal antibody, is approved to treat GPP flares in adults. Effisayil 2 (NCT04399837) evaluated the efficacy and safety of subcutaneous spesolimab in preventing GPP flares. Here, we report the effect of spesolimab versus placebo on Target Plaque Severity Score (TPSS) in patients with concomitant plaque psoriasis (PsO) in Effisayil 2.

Materials & Methods: Eligible patients with a history of GPP were randomized (1:1:1:1) to high-dose spesolimab (loading dose 600 mg, maintenance dose 300 mg every 4 weeks), medium-dose spesolimab (loading: 600 mg, maintenance: 300 mg every 12 weeks), low-dose spesolimab (loading: 300 mg, maintenance: 150 mg every 12 weeks), or placebo for 48 weeks. One PsO lesion of ≥9 cm² with TPSS total score ≥5 and induration sub-score ≥2 was selected by the investigator at baseline for each participant. Severity of erythema, scaling, and induration (plaque thickness) of the target lesion was assessed at baseline and subsequent visits on a 5-point scale (0, none to 4, very marked), with the summation of the 3 subscores representing the TPSS total score (0-12).

Results: TPSS was measured in the 33/123 (27%) patients with PsO in the trial (9 placebo, 10 low-dose, 7 medium-dose, 7 high-dose). Mean TPSS total score was 4.2 in placebo and 4.6 in spesolimab-treated patients at baseline. By Week 4, mean TPSS remained similar in both groups (placebo, 4.3; spesolimab, 4.6). By Week 16, mean TPSS in the placebo group increased to 4.4 and decreased to 3.6 in spesolimab-treated patients. Mean TPSS total scores at Week 48 for both groups were below baseline (placebo, 3.3; spesolimab, 3.8). The number of patients with TPSS data declined in both groups over time due to GPP flare and/or early discontinuation.

Conclusion: Low baseline TPSS scores observed in this subpopulation of 33 GPP patients with concomitant PsO suggest that concomitant PsO plaque characteristics in GPP are generally mild to moderate. TPSS scores remained low and consistent throughout the trial in both dosing groups and decreases in TPSS score by Week 16 (spesolimab-treated) and Week 48 (both groups) compared to baseline were observed.

Measuring GPPGA, Pain, Symptom, and Quality of Life Index Scores in Untreated Generalized Pustular Psoriasis: Results from the Placebo Group of the Effisayil-2 Trial

2024-02-23T00:08:06+00:00

Introduction & Objectives: Generalized pustular psoriasis (GPP) is a chronic inflammatory, and potentially life-threatening skin disease, characterized by flares of sterile pustules. Spesolimab is approved to treat GPP flares in adults. Effisayil 2 (NCT04399837) evaluated the efficacy and safety of subcutaneous spesolimab in preventing GPP flares. Here, we report on the underlying disease burden of untreated GPP by longitudinally analyzing patients in the placebo group who did not experience a GPP flare.

Materials & Methods: Eligible patients with a history of GPP were randomized (1:1:1:1) to receive one of three subcutaneous spesolimab regimens or placebo for 48 weeks. Patients were assessed for measures of chronic disease burden through the use of Generalized Pustular Psoriasis Physician Global Assessment (GPPPGA) Total Score, Pain Visual Analog Scale (VAS), and Psoriasis Symptom Scale (PSS) at baseline and at 4-week intervals during the trial, and Dermatology Quality of Life Index (DLQI) at baseline and weeks 4, 8, 12, 24, 36, and 48.

Results: 16/31 placebo-treated patients experienced a GPP flare over the 48-week observational period of the trial, defined as an increase in GPPPGA score by ≥2 from baseline and the pustular component of GPPPGA ≥2. Of the remaining (“non-flaring”) 15 patients, 40% (6/15) had at least one GPPPGA Total Score value of 2 (skin not clear or almost clear); 4/6 reported such score at ≥4 visits. Pain scores ranged from 0 to 92.47, with 47% (7/15) and 20% (3/15) of patients having at least one “moderate” and “severe” VAS score over 48 weeks, respectively. Most of the 7 patients’ pain scores fluctuated with episodic peaks and valleys. 47% (7/15) and 13% (2/15) of patients had at least one “moderate” and “severe” PSS score, respectively. “Moderate” and “very large” effect on quality of life was reported, at least once, in 67% (10/15) and 40% (6/15) of patients, respectively.

Conclusion: Acute flare was reported in more than 50% (16/31) of patients in the placebo group over 48 weeks. Despite not meeting the trial’s definition of GPP flare, most of the 15 “non-flaring” placebo-treated patients showed clear evidence of underlying GPP disease activity – nearly half did not have “clear” or “almost clear” skin and had moderate pain and symptoms; a small subset reported severe pain and symptoms. Majority of patients experienced a moderate to very large impact on quality of life over the 48 weeks. These findings suggest that untreated GPP negatively affects patients even in the absence of acute flare events.

Tapinarof Cream 1% Once Daily is Efficacious in the Treatment of Mild to Severe Plaque Psoriasis in the Head and Neck Region

2024-02-26T21:13:58+00:00

Introduction: Tapinarof cream 1% (VTAMA^®, Dermavant Sciences, Inc.) is a non-steroidal, topical aryl hydrocarbon receptor agonist approved for the treatment of plaque psoriasis in adults, with no restrictions on location, extent, or duration of use. In the phase 3 PSOARING trial program, tapinarof cream 1% once daily (QD) was efficacious and well tolerated for treating psoriasis, including the head and neck region. However, efficacy data specific to scalp treatment were not captured.
Objective: To assess efficacy, safety, and tolerability of tapinarof cream for the treatment of adults with plaque psoriasis affecting the head and neck region, including the scalp.
Methods: In this phase 4, open-label trial, adults received tapinarof for 12 weeks. Patients had plaque psoriasis affecting the head and neck (stable for ≥3 months), and a target lesion Physician Global Assessment (tPGA) score of 2 (mild), 3 (moderate), or 4 (severe). The primary endpoint was the proportion achieving a tPGA response (tPGA score of clear [0], or almost clear [1] and ≥2-grade improvement from baseline at Week 12). Additional endpoints included time to achieve tPGA response; proportion with complete clearance (tPGA score=0); and with ≥75% and ≥90% improvement in Psoriasis Area and Severity Index score (PASI; head and neck region). Safety and tolerability evaluations included adverse events (AEs) and investigator-assessed Local Tolerability Scale (LTS) scores.
Results: 31 patients with mild to severe plaque psoriasis affecting the head and neck region received tapinarof. At baseline, 54.8% had a tPGA score of 3 and 58.1% (18/31) had the target lesion on the scalp. At Week 12, 88.5% (n=23/26) achieved a tPGA response and 80.8% (n=21/26) achieved complete clearance (tPGA=0). There was rapid onset of efficacy, with both tPGA response and complete clearance achieved as early as Week 1, the first assessment, in some patients. Median times to tPGA response and complete clearance were ~4 and 8 weeks, respectively. At Week 12, 96.2% (n=25/26) and 84.6% (n=22/26) achieved a ≥75% and ≥90% improvement in PASI (head and neck region), respectively. Most AEs were mild or moderate, consistent with previous trials; the most frequent were contact dermatitis, folliculitis, and headache. Most patients had no irritation of the head and neck region (LTS score=0) at all visits.
Conclusions: Tapinarof cream 1% QD demonstrated rapid onset of clinically meaningful efficacy as early as Week 1 in patients with plaque psoriasis affecting the head and neck region, including for scalp lesions. Tapinarof cream is a cosmetically elegant, well-tolerated, non-steroidal treatment option in adults with mild to severe plaque psoriasis, including in the head and neck region.
Funding Support: Dermavant Sciences, Inc.

Tapinarof Cream 1% Once Daily Improves Patient-Reported Outcomes in the Treatment of Mild to Severe Plaque Psoriasis in the Head and Neck Region

2024-02-26T21:25:13+00:00

Introduction: Tapinarof cream 1% (VTAMA^®, Dermavant Sciences, Inc.) is a non-steroidal, topical aryl hydrocarbon receptor agonist approved for the treatment of plaque psoriasis in adults with no restrictions on location, extent, or duration of use. In the phase 3 PSOARING trial program, tapinarof cream 1% once daily (QD) for the treatment of plaque psoriasis was efficacious and well tolerated. Plaque psoriasis affecting the head and neck region occurs commonly, with a high impact on patients’ health-related quality of life, through pruritus and psychological distress. Patients may consider topicals unacceptable for scalp/facial use due to poor cosmetic properties (e.g., greasiness), leading to low medication adherence. There is a need for efficacious, cosmetically elegant, non-steroidal topicals that can be used without restrictions.
Objective: To assess patient-reported outcomes (PROs) with tapinarof cream for adults with mild to severe plaque psoriasis in the head and neck region, including the scalp, in a phase 4, open-label trial.
Methods: Adults with head and neck region target lesion Physician Global Assessment (tPGA) score of 2 (mild), 3 (moderate), or 4 (severe) received tapinarof for 12 weeks. PROs included Peak Pruritus Numerical Rating Scale (PP-NRS) score for the head and neck region; achievement of ≥4-point reduction in PP-NRS score; Dermatology Life Quality Index (DLQI) score by visit; and responses to a Patient Satisfaction Questionnaire^© (PSQ) at Week 12.
Results: 31 patients received tapinarof; 58.1% (18/31) had the target lesion on the scalp. Baseline mean PP-NRS (head and neck region) and total DLQI scores were 5.8 and 9.7, respectively, demonstrating significant pruritus and disease impact. Improvement in mean PP-NRS score was demonstrated at Week 1 (–1.6), the earliest assessment, surpassing the minimal clinically important ≥4-point improvement by Week 12 (−4.2). At Week 12, 70.0% (n=14/20) achieved ≥4-point reduction in PP-NRS score. Mean DLQI minimal clinically important difference of −4.0 was demonstrated as early as Week 1 (−4.0), improving to −7.2 at Week 12. Most patients strongly agreed or agreed with PSQ questions assessing satisfaction with cosmetic elegance (93.3%), quick absorption (96.7%), application ease (86.7%), efficacy (83.3%), and confidence in tapinarof (83.3%). Compared with topicals used previously for plaque psoriasis, most strongly agreed or agreed that tapinarof was more effective (76.9%) and easier to use (76.9%).
Conclusions: In patients with plaque psoriasis affecting the head and neck region, tapinarof cream 1% QD demonstrated rapid and clinically meaningful improvements in patient-reported pruritus and disease impact as early as Week 1, the first assessment, with continued improvement through Week 12. Patients reported high rates of satisfaction and positive perceptions of tapinarof.
Funding Support: Dermavant Sciences, Inc.

Deucravacitinib in Moderate Plaque Psoriasis: Efficacy in the Phase 3 POETYK PSO-1 and PSO-2 Trials

2024-02-26T21:53:27+00:00

Introduction: Deucravacitinib, an oral, selective, allosteric TYK2 inhibitor, was efficacious and well tolerated in adults with moderate to severe plaque psoriasis in the global, 52-week, phase 3 POETYK PSO-1 (NCT03624127) and PSO-2 (NCT03611751) trials. We report clinical efficacy of deucravacitinib in the patient subgroup from these trials with baseline plaque psoriasis of moderate severity.

Methods: PSO-1 and PSO-2 randomized patients with moderate to severe plaque psoriasis (PASI ≥12, sPGA ≥3, BSA involvement ≥10% at baseline) 1:2:1 to oral placebo, deucravacitinib 6 mg once daily, or apremilast 30 mg twice daily. Placebo patients crossed over to deucravacitinib at Week 16 in both trials. In PSO-1, deucravacitinib-treated patients received continuous deucravacitinib through Week 52. In PSO-2, PASI 75 responders at Week 24 on deucravacitinib were rerandomized to placebo or deucravacitinib (1:1) through Week 52. In patients meeting criteria for plaque psoriasis of moderate severity, defined as sPGA 3 and BSA 10%-15% at baseline, in the pooled PSO-1/PSO-2 trials, PSO-1 alone, and the PSO-1 placebo crossover population, deucravacitinib efficacy vs placebo was evaluated by PASI 75, PASI 90, and sPGA 0/1 (clear/almost clear) responses (nonresponder imputation) and PASI change from baseline (mBOCF). The Clopper-Pearson method was used to calculate 95% CIs.

Results: PSO-1/PSO-2 moderate psoriasis subgroup PASI 75 response rates were higher with deucravacitinib vs placebo at Week 16 (49.1% [95% CI, 42.5%-55.7%] vs 11.7% [95% CI%, 5.9%-17.4%]) and continued to increase through Week 24 (63.8% [95% CI, 57.5%-70.1%]). PSO-1 PASI 75 response rates were higher with deucravacitinib vs placebo at Week 16 (54.1% [95% CI, 42.1%-65.7%] vs 12.0% [95% CI, 4.5%-24.3%]), Week 24, and were sustained until Week 52. Week 52 PASI 75 response rates for deucravacitinib and placebo crossover groups were comparable (74.3% [95% CI, 62.8%-83.8%] and 67.4% [95% CI, 51.5%-80.9%], respectively). PASI 90 and sPGA 0/1 response rates and change from baseline PASI followed similar patterns, with marked improvement vs placebo at Week 16; peak responses were observed at Week 24 and sustained through Week 52. Efficacy results were comparable to those previously reported for moderate to severe psoriasis.

Conclusion: Deucravacitinib efficacy was confirmed in moderate plaque psoriasis and was consistent with published data in the PSO-1 and PSO-2 overall study population with moderate to severe plaque psoriasis.

Deucravacitinib Long-Term Efficacy in Week 16 Placebo Crossovers: 3-year Results from the POETYK PSO Program

2024-02-26T22:08:29+00:00

Introduction: Deucravacitinib, an oral, selective, allosteric TYK2 inhibitor, is approved in the US, EU, and other countries for treatment of adults with moderate-to-severe plaque psoriasis who are candidates for systemic therapy. Deucravacitinib was efficacious and well-tolerated in the global, 52-week, phase 3 POETYK PSO-1 (NCT03624127) and PSO-2 (NCT03611751) trials and through 2 additional years in the POETYK long-term extension (LTE) (NCT04036435) trial in patients treated with deucravacitinib from Day 1 of PSO-1/PSO-2. Here, long-term efficacy was assessed through 3 years in patients who crossed over from placebo to deucravacitinib at Week 16 in PSO-1 or PSO-2 and entered the LTE trial.

Methods: PSO-1 and PSO-2 randomized patients 1:2:1 to oral placebo, deucravacitinib 6 mg once daily, or apremilast 30 mg twice daily. At Week 16, patients randomized to placebo crossed over to deucravacitinib. At Week 52, patients could enroll in the LTE and receive open-label deucravacitinib. Efficacy was evaluated in patients who crossed over from placebo to deucravacitinib at Week 16 of the parent trial and received continuous deucravacitinib through 3 years (Week 148; cutoff June 15, 2022). Outcomes included ≥75%/≥90% reduction from baseline in Psoriasis Area and Severity Index (PASI 75/90) and static Physician Global Assessment score of 0 (clear) or 1 (almost clear) (sPGA 0/1). Efficacy is reported using modified nonresponder imputation (mNRI) in patients who reached the Week 148 assessment and those who discontinued before Week 148.

Results: Of 421 patients originally randomized to placebo, 348 crossed over to deucravacitinib at Week 16; of these, 298 completed the parent trials and entered the LTE, with 254 meeting mNRI criteria Efficacy response rates improved from Week 16 on placebo (PASI 75, 13.4%; PASI 90, 4.3%; sPGA 0/1, 11.0%) through Week 52 on deucravacitinib (PASI 75, 75.9%; PASI 90, 47.5%; sPGA 0/1, 59.4%), were generally maintained well through Week 112 (PASI 75, 78.4%; PASI 90, 52.0%; sPGA 0/1, 57.8%), with persistent responses overall observed through Week 148 (PASI 75, 74.4%; PASI 90, 48.1%; sPGA 0/1, 51.1%). Conclusion: These findings further confirm earlier results of once-daily oral deucravacitinib as an effective long-term treatment for patients with moderate to severe plaque psoriasis.

Deucravacitinib in Plaque Psoriasis: 3-year Safety and Efficacy Results from the Phase 3 POETYK PSO-1 and PSO-2 Trials

2024-02-26T22:24:08+00:00

Introduction: Deucravacitinib, an oral, selective, allosteric TYK2 inhibitor, is approved in the US, EU, and other countries for treatment of adults with moderate-to-severe plaque psoriasis who are candidates for systemic therapy. Deucravacitinib was superior to placebo and apremilast in the POETYK PSO-1 (NCT03624127) and PSO-2 (NCT03611751) parent trials in moderate to severe plaque psoriasis. The POETYK long-term extension (LTE; NCT04036435) trial enrolled patients completing PSO-1/PSO-2. We report deucravacitinib safety and efficacy for up to 3 years (Week 148; through cutoff 6/15/2022).

Methods: PSO-1/PSO-2 randomized patients 1:2:1 to oral placebo, deucravacitinib 6 mg QD, or apremilast 30 mg twice daily. At Week 52, patients enrolled in the LTE received open-label deucravacitinib 6 mg QD. Safety was evaluated in patients receiving ≥1 deucravacitinib dose using exposure-adjusted incidence rate per 100 person-years (EAIR/PY). Efficacy outcomes (PASI 75/90; sPGA 0/1) were analyzed using modified nonresponder imputation (mNRI) in patients receiving continuous deucravacitinib from Day 1 of the parent trial and treated in the LTE.

Results: Of 1519 patients who received ≥1 deucravacitinib dose (3294.3 PY cumulative exposure), 513 received continuous deucravacitinib from Day 1 in PSO-1/PSO-2 and were treated in the LTE. EAIRs/100 PY were comparable, or decreased, between the 2-year and 3-year cumulative periods, respectively, for AEs (154.4, 144.8), serious AEs (6.1, 5.5), discontinuations due to AEs (2.8, 2.4), herpes zoster (0.7, 0.6), malignancies (0.9, 0.9), major adverse cardiovascular events (0.4, 0.3), venous thromboembolism (0.1, 0.1), and deaths (0.4, 0.3). Response rates were maintained at Week 148 by mNRI (PASI 75, 73.2%; PASI 90, 48.1%; sPGA 0/1, 54.1%).

Conclusion: Deucravacitinib maintained a consistent safety profile and durable efficacy for up to 3 years.

Gene Expression Differences Identified in Skin Samples of Mycosis Fungoides, Atopic Dermatitis, and Psoriasis

2024-02-27T16:49:10+00:00

Background: Recent advances in the understanding of the molecular mechanisms underlying atopic dermatitis (AD) and psoriasis (PSO) have led to the development of multiple targeted therapies. Yet, molecular heterogeneity contributes to inconsistent clinical presentation and therapeutic response. Further, systemic treatment of presumed AD or PSO can lead to delays in both diagnosis and proper treatment of patients with a true diagnosis of mycosis fungoides (MF) – a potentially dangerous clinical mimic of AD and PSO that requires a rigorous histologic and molecular workup to diagnose. Therefore, a non-invasive method to distinguish molecular profiles of MF from AD and PSO could inform accurate diagnoses and avoid inappropriate treatment of MF. We have previously shown transcriptomic differences in AD and PSO samples obtained by a non-invasive scraping technique. However, this technique has not been used to assess differences in gene expression profiles of MF samples.

Objectives: To identify gene expression differences based on diagnosis of MF, AD, or PSO and response to targeted systemic AD or PSO therapies.

Methods: Lesional baseline samples were assessed from 76 patients (AD, n=24; PSO, n=48; and MF, n=4) enrolled in one of two IRB-approved studies (IDENTITY or SIGNAL-MF). Lesional samples were collected by epidermal scraping and preserved in RNA buffer. Library preparation and next generation RNA sequencing was performed using the Ion AmpliSeq Transcriptome Human Gene Expression panel on the S5 Prime sequencer (ThermoFisher). Clinical responses for AD and PSO were further assessed over 3 months using the eczema and psoriasis area and severity index (EASI and PASI, respectively). Genes were considered differentially expressed if there was a log₂fold change >|1.0| and p_adj<.05.

Results: Statistically significant differences in gene expression were observed between AD, PSO, and MF lesions. Further, genes were differentially expressed in baseline skin scrapings obtained from super-responders to dupilumab, which blocks both IL-4 and IL-13 signaling, and PSO therapies including the IL-23 inhibitor risankizumab relative to those who did not achieve ≥90% improvement.

Conclusion: A non-invasive molecular test could be developed to distinguish between AD, PSO, and MF, and further identify super-responders to targeted PSO and AD therapies.

Clinical Characteristics of Generalized Pustular Psoriasis Flares in the Real-World Setting

2024-02-27T21:52:15+00:00

No Abstract Available

Bimekizumab Efficacy through Year 1 in Patients with Moderate to Severe Plaque Psoriasis Who Had Not Achieved a PASI 90 Response by Week 16: A Pooled Analysis from Four Phase 3/3B Trials

2024-03-01T17:05:13+00:00

Introduction: Psoriasis Area and Severity Index (PASI) is a commonly used tool for evaluating skin clearance; patients with ≥90% reduction from baseline PASI (PASI 90) have a level of skin clearance that has been associated with improved quality of life.¹ Bimekizumab (BKZ) is a monoclonal IgG1 antibody that selectively inhibits interleukin (IL)-17F in addition to IL-17A.² High PASI 90 response rates have been observed with BKZ, maintained through three years, across four phase 3/3b trials and an open-label extension (OLE).^3–7 Here, we evaluate PASI response through Year 1 in patients who had not had a PASI 90 response during at least one visit up to and including Week 16, in four phase 3/3b trials of BKZ in moderate to severe plaque psoriasis.

Methods: Data were pooled from the double-blinded 52-week BE VIVID,³ 56-week BE READY,⁴ 56-week BE SURE,⁵ phase 3 trials, and the 48-week double-blind period of the BE RADIANT⁶ phase 3b trial. Included patients were randomized to BKZ 320 mg every 4 weeks (Q4W) to Week 16 and then received either BKZ 320 mg Q4W or Q8W maintenance dosing until end of Year 1 (Week 52 for BE VIVID; Week 48 for other trials). Results are reported as observed case (OC).

Results: Of the 1,362 patients randomized to BKZ across four phase 3/3b trials, 92.6% (n=1,261) had a PASI 90 response during at least one visit up to and including Week 16 while 7.1% (n=97) had not. PASI response was unavailable for 4 patients. The median (minimum, maximum) percent change from baseline PASI among the 97 patients without a PASI 90 response by Week 16 was −77.3 (−89.7, +20.0) at Week 16 (n=78) and −92.9 (−100, +90.7) at Year 1 (n=51).

Overall, 61.9% (60/97) of patients without a PASI 90 response by Week 16 completed their respective phase 3/3b trials and entered an OLE. By Year 1, 55.0% (33/60) achieved PASI 90 during at least one visit.

Conclusion: While the vast majority (92.6%) of patients treated with BKZ had a PASI 90 response during at least one visit up to Week 16, a large proportion of patients without a PASI 90 response by Week 16 who completed the phase 3/3b trials and entered an OLE had a PASI 90 response during at least one visit up to Year 1 (55.0%).

Real-World Efficacy of Spesolimab: Reports from Four Patients with Generalized Pustular Psoriasis

2024-03-05T18:55:49+00:00

Introduction: Generalized pustular psoriasis (GPP) is a rare, chronic, autoinflammatory skin disease characterized by widespread pustular eruptions that may be accompanied by systemic symptoms. GPP is painful, distressing, and adversely affects patient quality of life (QoL). Spesolimab is a first-in-class anti-IL-36 receptor monoclonal antibody approved for the treatment of GPP flares.

Methods: We describe 4 cases from our respective clinical practices, where individuals with GPP were treated successfully with spesolimab.

Results: Four patient cases of GPP were included; an 18-year-old male, a 58-year-old female; a 36-year-old male, and a 40-year-old female. One patient had a history of GPP, and had experienced 3 prior flares in the preceding year. Two patients had a history of plaque psoriasis. Events preceding the current GPP flare included hydroxychloroquine treatment (n=2), and corticosteroid treatment (n=3). All patients presented with sudden onset of worsening pustular rash (affecting lower extremities [n=1]; extremities and trunk [n=1]; whole body [n=2]). Two patients had systemic symptoms at presentation (1 case: fever, chills, malaise, fatigue; 1 case: severe weakness), and required hospitalization. Two patients received an initial mis-diagnosis of acute generalized exanthematous pustulosis (AGEP). Significant impacts on QoL were reported; all 4 patients were unable to perform normal daily activities; the 18-year-old patient was targeted at school because the skin lesions were perceived to be contagious. The 4 patients received multiple therapies prior to, and concomitantly with, spesolimab treatment, including topical agents, antibiotics, corticosteroids, retinoids, immunosuppressants, and biologics. All 4 patients received two 900 mg intravenous infusions of spesolimab with treatment intervals between 7 and 20 days. Treatment was given at an outpatient infusion center (n=3*), or using a home infusion service (n=1); *1 patient received their first infusion as an inpatient. Significant clinician-assessed improvement in pustules occurred within 1 week of the first spesolimab infusion in 3 patients; the remaining patient reported improvement 1-2 weeks after the second infusion. One of the hospitalized patients experienced 75% improvement in itching, pain, and pustules within 24 hours of the first spesolimab infusion, and was discharged the next day. Spesolimab treatment also improved QoL, with patients experiencing rapid improvements in pain, and their ability to resume their normal daily activities.

Conclusions: These cases demonstrate the efficacy of spesolimab in the real-world, highlighting the ability of spesolimab treatment to rapidly improve GPP symptoms and patient QoL. Administration of spesolimab in an inpatient setting allowed for rapid patient improvement and discharge the next day. These cases also highlight the association of certain drugs as triggers for GPP flares, as well as the importance of AGEP in the differential diagnosis of GPP

Effect of High-Dose Subcutaneous Spesolimab on Skin Manifestations: Results from the Pivotal Effisayil 2 Trial of Flare Prevention in Generalized Pustular Psoriasis

2024-03-05T19:53:27+00:00

Introduction & Objectives: Generalized pustular psoriasis (GPP) is a chronic, rare and potentially life-threatening skin disease, characterized by flares of sterile pustules. Spesolimab, an anti-interleukin-36 receptor monoclonal antibody, is an effective and approved treatment for GPP flares in adults. Effisayil 2 (NCT04399837) was a pivotal, randomized controlled trial that evaluated the efficacy and safety of subcutaneous spesolimab in preventing GPP flares. Here, we report the effect of high-dose spesolimab versus placebo on GPP lesions.

Materials & Methods: Eligible patients with a history of GPP were randomized (1:1:1:1) to receive one of three subcutaneous spesolimab regimens or placebo for 48 weeks. High-dose spesolimab regimen was loading dose 600 mg, followed by maintenance dose 300 mg every 4 weeks. GPP Physician Global Assessment (GPPGA) subscores for erythema, pustules and scaling/crusting, and total score were compared between high-dose spesolimab and placebo groups at baseline and over the treatment period (scale: 0, clear to 4, severe).

Results: Proportion of patients with baseline score of 0 for each GPPGA subscore and total score was generally similar between treatment groups, except erythema; (high-dose spesolimab [n=30] vs placebo [n=31]: erythema, 13.3% vs 22.6%; pustules, 66.7% vs 67.7%; scaling/crusting, 23.3% vs 22.6%; total score, 10.0% vs 12.9%). By Week 4, proportion of patients with scores of 0 increased with high-dose spesolimab versus placebo, (erythema, 33.3% vs 19.4%; pustules, 80.0% vs 41.9%; scaling/crusting, 30.0% vs 19.4%; total score, 26.7% vs 16.1%), and high-dose spesolimab group had fewer flares (10.0% vs 35.5%). This trend was maintained at Week 24 (erythema, 36.7% vs 22.6%; pustules, 63.3% vs 45.2%; scaling/crusting, 36.7% vs 19.4%; total score, 33.3% vs 19.4%) and Week 48 (erythema, 36.7% vs 22.6%; pustules, 66.7% vs 45.2%; scaling/crusting, 43.3% vs 25.8%; total score, 36.7% vs 22.6%). There were no new flares after Week 4 in high-dose spesolimab group; however, flares increased with placebo (45.2% at Week 24; 51.6% at Week 48).

Conclusion: Versus placebo, high-dose subcutaneous spesolimab resulted in a greater proportion of patients maintaining GPPGA scores of 0, a lower proportion having flares at Week 4, and no new flares after Week 4. This was sustained at Weeks 24 and 48.

Assessing Knowledge of Appropriate Sunscreen Guidelines and Skin Cancer Prevention Among New York Yankees Attendees

2024-03-17T15:03:27+00:00

Burnout Among Dermatology Residents and Fellows: A Survey Study

2024-01-30T20:43:19+00:00

Background: Physician burnout is a pressing concern with substantial implications for both providers and the healthcare system. Methods: An 8-minute survey was distributed via email to members of the American Academy of Dermatology Association. Results: The survey revealed burnout is widespread among both dermatology residents and fellows. Conclusion: Residents and fellows expressed a desire for systemic changes in their working conditions.

Triple-Combination Clindamycin Phosphate 1.2%/Adapalene 0.15%/Benzoyl Peroxide 3.1% Gel for Acne: Clinical Efficacy and Application Characteristics

2024-02-27T18:16:50+00:00

Background: Triple-combination therapies for acne including an antibiotic, topical retinoid, and benzoyl peroxide (BPO) are among the most effective, with meta-analyses demonstrating greater efficacy with triple-combinations than dual-combinations or topical monotherapy. However, this benefit may be offset by reduced adherence to a complicated treatment regimen. Here, the clinical efficacy of fixed-dose clindamycin phosphate 1.2%/adapalene 0.15%/BPO 3.1% (CAB) gel is reviewed, and the ease of CAB application is compared with the layered application of its individual active ingredients.

Methods: In a phase 2 (N=741) and two phase 3 (N=183; N=180), double-blind, randomized, 12-week studies, participants aged ≥9 years with moderate-to-severe acne were randomized to receive once-daily CAB or vehicle; the phase 2 study also included treatment arms containing dyad gels (BPO/adapalene; clindamycin phosphate/BPO; clindamycin phosphate/adapalene). Efficacy endpoints included treatment success (percentage of participants achieving ≥2-grade reduction from baseline in Evaluator’s Global Severity Score and clear/almost clear skin) and reductions from baseline in inflammatory (IL) and noninflammatory lesions (NIL). In a split-face study of adults with acne-prone skin (N=25), participant-application of CAB (0.3 cc) was compared to sequential, layered application of benzoyl peroxide cream, adapalene gel, and clindamycin gel (0.1 cc each). IDP-126 and clindamycin gels were compounded with pyranine, which fluoresces under blue light; photos were taken under blue light to assess evenness of product application.

Results: In all three clinical studies at week 12, half of CAB-treated participants achieved treatment success (range: 49.6%-52.5%), significantly greater than with vehicle (8.1%-24.9%; P<0.01, all) or dyads (phase 2 study only; 27.8%-30.5%; P≤0.001, all). Reductions from baseline in both IL and NIL were also significantly greater for CAB vs vehicle (range, IL: 75.7%-80.1% vs 50.4%-59.6%; NIL: 71.0%-73.3% vs 45.8%-49.0%; P<0.001, all) and dyads (IL: 64.0%-69.2%; NIL: 58.7%-61.1%; P<0.01, all vs IDP-126). In the split-face study, 100% of Investigator and participant assessments of evenness of application favored CAB over the three layered products. In addition, all participants rated CAB as both easier and faster to apply, and most (96%) preferred CAB for use at home.

Conclusions: Fixed-dose CAB gel applied more evenly than separate application of its three active ingredients, and demonstrated significantly greater efficacy in the treatment of moderate-to-severe acne than dyad gels or vehicle. By addressing three of the main acne pathogenic pathways in a single, easy-to-apply formulation, CAB may improve efficacy of and adherence to acne treatment.

Funding: Ortho Dermatologics

Efficacy and Safety of Fixed-Dose Triple-Combination Clindamycin Phosphate 1.2%/Adapalene 0.15%/Benzoyl Peroxide 3.1% Gel for Moderate-to-Severe Acne Vulgaris in Children and Adolescents

2024-02-27T18:35:33+00:00

Background: Topical clindamycin phosphate 1.2%/adapalene 0.15%/benzoyl peroxide 3.1% (CAB) gel is the first fixed-dose triple-combination formulation approved for acne vulgaris and is indicated for use in patients aged 12 years and older. As topical acne treatment in pediatric patients may be complicated by tolerability issues and/or a perceived lack of efficacy, the objective of this post hoc analysis was to investigate the efficacy and safety of CAB in children and adolescents.

Methods: Data were pooled from two phase 3 double-blind, randomized, 12-week studies (NCT04214639; NCT04214652). Eligible participants ≥9 years of age with moderate-to-severe acne were randomized (2:1) to once-daily CAB or vehicle gel. This analysis evaluated adolescents aged 12-17 years (CAB: n=123; vehicle: n=50). Endpoints included ≥2-grade reduction from baseline in Evaluator’s Global Severity Score and clear/almost clear skin (treatment success), least-squares mean percent change from baseline in inflammatory/noninflammatory lesions, and treatment-emergent adverse events (TEAEs). Descriptive efficacy and safety data for five children aged 10-11 years enrolled in the study are also summarized (CAB: n=3; vehicle: n=2).

Results: At week 12, 51.5% of CAB–treated participants aged ≥12 years achieved treatment success vs 24.9% with vehicle gel (P<0.01). CAB treatment resulted in significant reductions of >70% in inflammatory and noninflammatory lesion counts in adolescents (78.3% and 73.7%, respectively) vs vehicle (50.5% and 42.9%; P<0.001, both). Most TEAEs were of mild-to-moderate severity, and the most common (>3% in any treatment) treatment-related TEAE was application site pain. Less than 2.5% of participants withdrew due to AEs. For the 5 children aged <12 years, all 3 treated with CAB achieved treatment success, with reductions in inflammatory/noninflammatory lesions ranging from 76%-100%; neither vehicle-treated participant achieved treatment success. Only one CAB–treated younger participant experienced TEAEs (application site pain/dryness, and erythema [all mild/moderate]) and none discontinued the study.

Conclusions: In two pooled phase 3 studies, once-daily CAB gel—the first approved fixed-dose, triple-combination topical formulation for acne vulgaris—was well tolerated and efficacious in pediatric participants with moderate-to-severe acne, with over half achieving treatment success at week 12.

Funding: Ortho Dermatologics

Maintenance Acne Treatment With Topical Tazarotene after Oral Isotretinoin: Overview and Case Reports

2024-03-05T18:22:15+00:00

Introduction: Acne vulgaris is a common dermatologic disorder that may require treatment over months or years. Acne negatively impacts quality of life, and acne of any severity increases the risk of long-term sequelae such as scarring. Common treatments for severe/nodulocystic acne include oral isotretinoin, an oral antibiotic combined with a topical (benzoyl peroxide or a retinoid), an oral combined contraceptive, or oral spironolactone (females). Though oral antibiotics and isotretinoin are not recommended for long-term use, there is scarce guidance or published research on maintenance therapy. Topical retinoids—a mainstay of initial acne treatment—may be prescribed for maintenance once initial oral treatments are complete. Additionally, some retinoids such as tretinoin and tazarotene are indicated for the treatment of fine wrinkles and certain pigmentation disorders, and some studies have shown that adapalene and tazarotene may also reduce acne-induced scarring. Tazarotene 0.045% polymeric emulsion lotion is a well-tolerated retinoid that has demonstrated efficacy in acne treatment and may reduce acne-induced post-inflammatory hyperpigmentation (PIH) and melasma. Further, tazarotene lotion provides rapid and sustained improvements in skin barrier function/moisturization. Herein is presented a report of patients with acne who received maintenance treatment with topical tazarotene 0.045% lotion after an initial course of oral isotretinoin.

Methods: Patients with severe recalcitrant acne vulgaris were treated with once daily oral isotretinoin for at least 20 weeks until deemed clinically clear. All patients received 40 mg isotretinoin once daily for the first 30 days. The dosage was then increased to 1 mg/kg of bodyweight (treatment naïve) or 1.5 mg/kg (repeat treatment). After 20 weeks, patients who achieved clinically clear skin initiated once-daily topical tazarotene 0.045% lotion monotherapy on the day of their last isotretinoin dose. Follow up visits occurred at 6 months and 1-year post-isotretinoin treatment.

Results: Patients (n=12) had a mean age of 17.8 years (standard deviation [SD]: 3.8) and the majority were female (58.3%) and White (66.7%). Oral isotretinoin was used for an average of 24.3 weeks (SD: 6.7), with a mean cumulative dose of 184.6 mg/kg. One patient required a repeat course of isotretinoin prior to tazarotene initiation. Post-isotretinoin, patients received tazarotene 0.045% lotion for an average of 13.0 months (SD: 6.7). No patients relapsed and all showed subjective visual improvements in acne-related scarring with tazarotene maintenance treatment. None discontinued tazarotene lotion due to adverse events.

Conclusions: There is little guidance or research published on acne maintenance treatment after initial oral isotretinoin or other treatments are complete. Topical tazarotene 0.045% polymeric emulsion lotion has previously demonstrated good efficacy, safety, and tolerability with acne and PIH reductions in patients with moderate-to-severe acne, as well as dyspigmentation reductions in patients with melasma and/or PIH. The case reports presented here show that tazarotene 0.045% lotion may be an effective and safe treatment to prevent relapse after initial oral isotretinoin treatment for severe recalcitrant acne.

Funding: Ortho Dermatologics

Efficacy and Safety of Clindamycin Phosphate 1.2%/Adapalene 0.15%/Benzoyl Peroxide 3.1% Gel in Females with Moderate to Severe Acne: Post Hoc Analysis by Age

2024-03-05T18:52:29+00:00

Introduction: While acne is common in adolescents, the overall prevalence in adults is increasing, especially among females. In addition, acne in older females is associated with greater negative impacts on quality of life. Clindamycin phosphate 1.2%/adapalene 0.15%/benzoyl peroxide (BPO) 3.1% (CAB) gel—the first fixed-dose, triple-combination topical product approved for acne—has demonstrated good efficacy, safety, and tolerability in participants with moderate-to-severe acne. The objective of this analysis is to assess the impact of age on efficacy, safety, and tolerability in females with moderate-to-severe acne.

Methods: In one phase 2 (N=741; NCT03170388) and two identically designed phase 3 (N=183; N=180; NCT04214639; NCT04214652), double-blind, randomized, 12-week studies, participants aged ≥9 years with moderate-to-severe acne were randomized to receive once-daily CAB or vehicle gel; the phase 2 study included three additional dyad randomization arms (data not shown). Coprimary endpoints comprised inflammatory and noninflammatory lesion counts and treatment success (≥2-grade reduction from baseline in Evaluator’s Global Severity Score and score of ‘clear’ or ‘almost clear’). Treatment-emergent adverse events (TEAEs) and cutaneous safety and tolerability were also assessed. Pooled data from these studies were analyzed post hoc from female participants categorized by age: 9-24 years (n=274) and ≥25 years (n=121).

Results: At week 12 in both age groups, least-squares mean percent reductions from baseline were >70% in CAB-treated females versus vehicle gel for inflammatory (9-24 y: 77.8% vs 53.8%; ≥25 y: 77.8% vs 60.5%; P<0.01, both) and noninflammatory lesions (9-24 y: 72.8% vs 44.5%; ≥25 y: 73.7% vs 55.2%; P<0.001, both). Half of CAB-treated females in both age groups achieved treatment success at week 12 versus less than one-quarter with vehicle (9-24 y: 54.1% vs 15.6%; ≥25 y: 50.1% vs 22.5%; P<0.01, both). Most TEAEs were mild-to-moderate in severity, with rates similar to the overall pooled phase 2 and 3 populations. Although there were transient increases in the severity of cutaneous safety/tolerability assessments with CAB, scores generally returned to or near baseline levels for most assessments by week 12 in younger and older females. No notable age-related trends in safety were observed.

Conclusions: With greater than 70% lesion reductions and half of participants achieving treatment success by week 12, the innovative, fixed-dose triple combination clindamycin phosphate 1.2%/adapalene 0.15%/BPO 3.1% gel demonstrated good efficacy, safety, and tolerability in both younger and older females with moderate-to-severe acne.

Funding: Ortho Dermatologics

Early Acne Improvements With Fixed-Dose Clindamycin Phosphate 1.2%/ Adapalene 0.15%/Benzoyl Peroxide 3.1% Gel: What to Expect in the First 4 Weeks of Treatment

2024-03-05T19:23:36+00:00

Background: Treatments with fast and substantial acne clearance are highly desirable. While a three-pronged approach may increase treatment efficacy versus monotherapy or dual-combination therapy, it is unknown if triple-combination provides more rapid improvement. CAB gel—clindamycin phosphate (clin) 1.2%/adapalene 0.15%/benzoyl peroxide (BPO) 3.1%—is the first fixed-dose, triple-combination acne topical. Since rapid/substantial acne improvements and fewer side effects can increase adherence, the efficacy and safety of CAB in the first 4 weeks of treatment was evaluated.

Methods: In a phase 2 (N=741; NCT03170388) and two phase 3 (N=183; N=180; NCT04214639; NCT04214652), double-blind, 12-week studies, participants aged ≥9 years with moderate-to-severe acne were randomized to once-daily CAB or vehicle gel; the phase 2 study included 3 additional dyad arms: BPO/adapalene; clin/BPO; and clin/adapalene. Efficacy assessments included least-squares mean percent change from baseline in inflammatory and noninflammatory lesions. Cutaneous safety/ tolerability assessments were graded from 0=none to 3=severe. Post hoc analyses included percentages of participants with one-third and one-half acne lesion reductions.

Results: At week 4, CAB led to ~55% reductions from baseline in inflammatory acne lesions in the ph2 and pooled ph3 studies, significantly greater than vehicle (~40%) and its 3 dyads (ph2 range: 44.2-47.6%; P<0.05, all). The percentages of participants with one-third and one-half reductions of inflammatory lesions were significantly greater with CAB than vehicle and dyads (P<0.05, all). Similar trends were observed for noninflammatory lesions, though reductions were less pronounced. As expected for retinoids, transient increases from baseline to week 2 in scaling, erythema, itching, burning, and stinging were observed for CAB, BPO/adapalene, and clin/adapalene, with mean scores ≤0.6 (1=mild); no trends in dyspigmentation were observed. Mean scores for all cutaneous assessments were highest for BPO/adapalene, indicating that adding a third product in the fixed-dose CAB gel formulation did not worsen tolerability.

Conclusions: Acne lesion reductions were significantly greater with clin 1.2%/ adapalene 0.15%/BPO 3.1% gel versus its dyads and vehicle gel as early as week 4. More rapid efficacy with this first fixed-dose triple-combination acne product—coupled with its optimized formulation, once-daily dosing, and tolerability—may positively impact treatment adherence.

Funding: Ortho Dermatologics.

Non-invasive Gene Expression Analysis Rules Out Melanoma with High Negative Predictive Value Regardless of Skin Phototype

2024-01-24T00:24:28+00:00

Non-invasive assessment of clinically atypical, pigmented skin lesions to rule out melanoma with a negative predictive value (NPV) of 99% by detecting expression of LINC00518 and PRAME (2-GEP assay) is gaining adoption. These melanomaassociated biomarkers are not known to differ by skin type, race, or ancestry. However, since the test was initially validated in cohorts comprised predominantly of patients with Fitzpatrick skin types I-III, we sought to identify any differences in performance in skin types IV-VI. In the study presented here, we compared 2-GEP assay performance in patients with Fitzpatrick skin types I-III (n=4152) to that in patients with Fitzpatrick skin types IV-VI (n=130) using real-world clinical follow-up data. Median follow-up of over one year was available for approximately 60% of the patients in both groups. Consistent with prior published results, the assay’s NPV for Fitzpatrick I-III patients was 0.9989. Sensitivity and specificity were 0.943 and 0.909, respectively, and positive predictive value (PPV) was 0.15. Among Fitzpatrick IVVI subjects, all three melanomas diagnosed by histopathology were correctly identified by the assay as positive (higher probability of melanoma). NPV in this smaller cohort was 1.0, sensitivity was 1.0, specificity was 0.94, and PPV was 0.3. The 95% confidence intervals for the NPVs in the Fitzpatrick I-III and IV-VI groups (calculated using the Clopper-Pearson Exact Binomial Test) were 0.9972-0.9997 and 0.9697-1.0000, respectively. The 95% confidence interval for the difference between the groups includes 0 (-0.0299 to 0.0028) which indicates that there is no significant difference in the NPVs. Median follow-up times for the Fitzpatrick I-III and IV-VI groups were 368 days and 378 days, respectively. Among patients with Fitzpatrick skin type I-III and negative test results, one patient was diagnosed with melanoma in situ at a 5-month follow-up visit. No melanomas were diagnosed in patients with Fitzpatrick skin type IV-VI whose lesions tested negative.
Additionally, analytical PCR performance in Fitzpatrick I-III and Fitzpatrick IV-VI samples was indistinguishable. These findings indicate that performance of the 2-GEP assay in patients with Fitzpatrick skin types IV-VI does not differ from its performance in patients with Fitzpatrick skin types I-III. During a median follow-up period of over one year, only one melanoma (in situ) was diagnosed among patients whose lesions initially tested negative, further supporting the test’s ability to appropriately guide biopsy decision-making for ambiguous pigmented skin lesions of all skin phototypes.

The 40-gene Expression Profile (40-GEP) Test Identifies Cutaneous Squamous Cell Carcinoma (cSCC) Patients at High Risk of Metastasis within Lower-Staged Tumors to Better Guide Treatment Decisions

2024-01-24T17:32:36+00:00

Introduction- The development of metastases has a profound impact on cSCC patient survival. Lower-stage tumors are those that lack factors that portend higher risk for disease progression and therefore not typically considered for increased surveillance or treatment. However, up to one-third of all metastatic events have been reported for patients originally staged as T1. The 40-GEP test is validated to accurately classify risk for regional and/or distant metastasis in patients with primary cSCC with at least one high-risk factor. The current study investigated whether the 40-GEP test could independently improve identification of lower-staged tumors at increased risk of metastasis.

Methods- In an IRB-approved, retrospective, multi-center study, primary tumor tissue and associated clinical data from patients with cSCC and one or more clinicopathologic risk factors (n=897) were collected. Within this overall cohort, lower Brigham and Women’s Hospital (BWH) T-staged samples (n=444 T1 and n=335 T2a) were evaluated by Kaplan-Meier survival analysis to determine metastasis-free survival (MFS) according to 40-GEP risk class (Class 1-low metastatic risk; Class 2A-higher risk; Class 2B-highest risk).

Results- There was a total of 118 metastatic events in the overall cohort, of which 25% (29/118) and 38% (45/118) occurred in BWH T1 and T2a, respectively. BWH T1 tumors had an overall event rate of 6.5% (29/444), with T1/Class 2B tumors having a 5.1-fold increased event rate of 33.3%. BWH T2a tumors had an overall event rate of 13.4% (45/335), with T2a/Class 2B tumors having a 2.7-fold increased event rate of 36.4%. Stratification by the 40-GEP test resulted in significantly different metastasis rates across all three 40-GEP classes within both the T1 and T2a subsets (log-rank tests, p<0.0001 each subset).

Conclusion- Within a cohort of cSCC patients considered lower risk by current staging alone, the 40-GEP identified patients with a substantial increase in metastatic risk. The observed rates of metastasis over 10% and 20% are clinically actionable for nodal staging or postoperative adjuvant radiation, respectively. Combining clinicopathologic risk assessment with individual biologic risk, as provided by the 40-GEP test, improves the accuracy of risk assessment used clinically as the basis of treatment decisions.

Real-World Evidence Confirms Risk Stratification of the 31-GEP and i31-GEP in Prospectively Tested Patients with Stage I-III Cutaneous Melanoma

2024-01-25T15:43:54+00:00

Introduction: Current American Joint Committee on Cancer (AJCC 8th edition) guidelines in patients with cutaneous melanoma (CM) separate them into risk categories based on the pathological tumor data of Breslow thickness, ulceration status, and sentinel lymph node status. The 31-gene expression profile was developed and prospectively validated to identify patients considered high or low risk by AJCC with low or high-risk tumor biology who may be over- or under-treated by current guidelines. To further advance personalized patient care, the 31-GEP result was integrated with clinical and pathological factors (i31-GEP for risk of recurrence, ROR) to provide a personalized, precise risk of tumor recurrence.

Methods: Patients with stage I-III CM enrolled in the CONNECTION study were prospectively tested with the 31-GEP between 2013 and 2017 (n=1,831). Kaplan-Meier analysis with the log-rank test was used to estimate survival differences between low (Class 1A), intermediate (Class 1B/2A), and high (Class 2) risk groups and the i31-GEP risk groups. The i31-GEP ROR combines Breslow thickness, ulceration, SLN status, mitotic rate, tumor location, age, and the 31-GEP result to provide a personalized estimate of recurrence-free survival (RFS). While guidelines have not established a ROR threshold for determining when to escalate or de-escalate care, the NCCN uses stage IIA versus IIB as the cut-point. This cut-point translates to a 5-year RFS rate of 69.8% and was used for the present analysis. Cox multivariable regression analysis was used to identify predictors of recurrence.

Results: Patients with a Class 1A result had higher 5-year RFS than those with a Class 1B/2A or Class 2B result (94.4% vs. 78.6% vs. 65.5%, p<0.001). The following were significant predictors of recurrence in multivariable analysis: Class 1B/2A (HR=2.07, p<0.001), Class 2B (HR=2.40, p<0.001), positive SLN (HR=4.54, p<0.001), Breslow thickness (HR=1.09, p=0.028), presence of ulceration (HR=1.57, p=0.005), mitotic rate >2/mm2 (HR=1.47, p=0.016), and age (HR=1.02, p<0.001). Patients with a low-risk i31-GEP result had significantly higher 5-year RFS than those considered high risk by the i31-GEP (92.4% vs. 49.7%, p<0.001).

Conclusions: The i31-GEP is validated in a real-world group of prospectively tested patients. The independent i31-GEP ROR test result improves identification of patients whose management should be escalated or de-escalated within current guidelines.

Diagnostic Discordance Among Histopathological Reviewers for Difficult-to-Diagnose Melanocytic Lesions

2024-02-13T20:34:18+00:00

Purpose: Histopathological examination is adequate for most melanocytic neoplasms. However, there is a subset of lesions with uncertain malignant potential that are difficult-to-diagnose where utilization of ancillary tests may be considered to aid in providing a more definitive diagnosis.

Study design: Under an IRB-approved protocol, 3,317 melanocytic lesions underwent independent diagnostic review by up to 9 unique board-certified dermatopathologists. Each lesion received ≥ 3 diagnoses via electronic whole slide images with zoom-in capability as benign, malignant, or unknown malignant potential (UMP). Lesions were subsequently binned according to the results of dermatopathology review in the following manner: concordant (all diagnoses of the same designation); conflicting (both benign and malignant designations); majority (a single designation with the highest number of diagnoses); and equivocal (equal number of different designations). Here we describe the identification of lesions suitable for ancillary testing.

Results: 30% of lesions were concordant benign and 46.3% were concordant malignant, indicating 76.3% of all lesions were not difficult-to-diagnose. 23.7% of lesions had some level of diagnostic difficulty and/or ambiguity defined by disagreement between reviewers and would be suitable for ancillary testing. Within these ~24%, 7.3% of lesions were majority benign, 4.8% of lesions were majority malignant, 2.7% were majority UMP, 6.9% of lesions were conflicting, and 1.6% of lesions were equivocal.

Conclusions: We demonstrate that in a large cohort of suspicious pigmented lesions, ~24% were difficult-to-diagnose, supporting the need for additional objective diagnostic tools. Patient care would benefit from ancillary testing to aid the diagnosing pathologist in identification of the most appropriate diagnosis to optimize patient management.

Potential conflicts of interest: This study was supported by Castle Biosciences, Inc. GAH and JAP have served as consultants for Castle Biosciences, Inc. MSG is an employee shareholder of Castle Biosciences, Inc. SIE is a consultant and shareholder for Castle Biosciences, Inc. Editorial assistance was provided by Brooke H. Russell, PhD, and Jason H Rogers, MSc, both employee shareholders of Castle Biosciences, Inc.

Efficacy Following Discontinuation of Sonidegib Treatment in Patients With Locally Advanced Basal Cell Carcinoma: Results From the BOLT 42-Month Analysis

2024-02-27T23:43:48+00:00

Introduction: Sonidegib, a Hedgehog (HH) pathway inhibitor, is approved for the treatment of locally advanced basal cell carcinoma (laBCC) not amenable to curative surgery or radiation. The pivotal 42-month BOLT (NCT01327053) study demonstrated sustained efficacy and manageable safety of sonidegib. Prior analyses at 18 months demonstrated clinical benefit persisting beyond sonidegib discontinuation. Pharmacokinetic modeling suggests HH pathway inhibition can be maintained following discontinuation. This analysis presents the efficacy of sonidegib 200 mg daily in patients with laBCC who discontinued treatment without disease progression (PD) at 42 months (end of study).

Methods: BOLT was a randomized, double-blind, placebo-controlled, Phase 2 study. Objective response rates (ORRs; complete response + partial response), duration of response (DOR), and progression-free survival (PFS) were assessed by central and investigator review per modified response evaluation criteria in solid tumors (mRECIST). Adverse events (AEs) were also assessed.

Results: Of the 66 patients with laBCC randomized to sonidegib 200 mg daily, 37 discontinued treatment without PD. The ORRs for these patients per central (57% [n = 20]) and investigator (73% [n = 27]) review were similar to the overall patient population (61% [n = 40] and 71% [n = 47] per central and investigator review, respectively). For patients who discontinued treatment, the median (95% confidence interval [CI]) DOR per central and investigator review was not estimable (NE) and 20.2 months (12.0, NE), respectively. The median PFS (95% CI) per central and investigator review was NE and 22.0 months (16.6, NE), respectively. Most AEs were Grades 1/2 in severity.

Conclusion: In this 42-month analysis among patients with laBCC who received sonidegib 200 mg daily, clinical benefit was observed beyond treatment discontinuation during this study.

Bimekizumab Response Maintenance to 48 Weeks in Patients with Moderate to Severe Hidradenitis Suppurativa: Pooled Responder Analysis from the Phase 3, Double-Blind, Placebo-Controlled, Randomized Clinical Trials BE HEARD I and II

2024-02-26T23:06:01+00:00

N/A

Nevus Sebaceous: A Midline Verrucous Lesion on a Neonate

2023-12-30T02:11:42+00:00

Roflumilast Cream 0.15% in Patients with Atopic Dermatitis: Individual Patient Response from the Pooled INTEGUMENT-1 and INTEGUMENT-2 Phase 3 Trials

2024-01-24T17:04:21+00:00

Introduction: Roflumilast cream 0.15% is a highly selective phosphodiesterase 4 inhibitor under investigation as a once-daily, nonsteroidal treatment for atopic dermatitis (AD). Pooled safety and efficacy results of two Phase 3 clinical trials (INTEGUMENT-1 and INTEGUMENT-2) in patients with AD have been presented previously. Here we present individual patient responses on the Eczema Area and Severity Index (EASI), which is used to assess disease severity in clinical trials.

Methods: INTEGUMENT-1 and INTEGUMENT-2 were identical, randomized, double-blind, vehicle-controlled, 4-week trials of once-daily roflumilast cream 0.15% in patients aged ≥6 with AD (body surface area [BSA] affected: ≥3%). Patients were randomly assigned 2:1 to roflumilast cream 0.15% or vehicle cream. The primary efficacy endpoint was Validated Investigator Global Assessment for AD (vIGA-AD) Success (score of 0 [Clear] or 1 [Almost Clear] plus ≥2-point improvement from baseline, assessed on a five-point scale ranging from 0 to 4 [Severe]) at Week 4. EASI was assessed as a secondary endpoint. Safety and tolerability were also evaluated.

Results: In total, 884 patients received roflumilast 0.15% cream and 453 patients received vehicle cream. Baseline characteristics and demographics were similar between treatment groups. Significantly more roflumilast- than vehicle-treated patients achieved vIGA-AD Success (31.3% versus 14.1%; P<0.0001) and vIGA-AD of Clear or Almost Clear (41.1% vs. 21.4%; P<0.0001) at Week 4. Roflumilast treatment significantly improved itch by 24 hours after first application (P<0.0001). At the first post-treatment timepoint evaluated (Week 1), 84.9% of roflumilast-treated patients had a measurable improvement in EASI. By Week 4, 91.5% of patients had a measurable improvement in EASI. Differences favoring roflumilast were also observed at Week 4 for percentages of patients achieving a 50% reduction in EASI (69.2% vs. 44.4%; P<0.0001), 75% reduction (44.5% vs. 21.2%, P<0.0001), 90% reduction (22.4% vs 8.6%; P<0.0001), and 100% reduction (9.8% vs 4.8%; P<0.002). Roflumilast cream had low rates of application-site adverse events (AEs), treatment-related AEs, and discontinuations due to AEs, comparable with vehicle. On local tolerability assessments, >95% of investigators reported no evidence of irritation at any time point and >90% of patients reported no or mild sensation after applying roflumilast cream on patient-rated local tolerability assessments.

Conclusions: Roflumilast cream 0.15% provided greater improvement in vIGA-AD Success, vIGA-AD of Clear or Almost Clear, itch, and EASI versus vehicle in patients with AD in two Phase 3 trials. Among patients treated with roflumilast cream 0.15%, 91.5% demonstrated an improvement in EASI score by Week 4. Safety and tolerability were favorable, with >90% of roflumilast- and vehicle-treated patients reporting no or mild sensation at the application site at any timepoint.

Sponsored by Arcutis Biotherapeutics, Inc.

ClinicalTrials.gov Identifiers: INTEGUMENT-1 [NCT04773587]; INTEGUMENT-2 [NCT04773600]

Association Between Early Clinical Responses and Long-Term Outcomes With Ruxolitinib Cream Treatment in Mild to Moderate Atopic Dermatitis

2024-02-08T20:58:02+00:00

In the TRuE-AD1/2 studies, patients aged ≥12 years with atopic dermatitis (Investigator’s Global Assessment [IGA] 2/3; 3%–20% affected body surface area) were randomized (2:2:1) to twice-daily 0.75%/1.5% ruxolitinib cream or vehicle for an 8-week, double-blind period followed by a 44-week long-term safety (LTS) period of as-needed ruxolitinib cream. This analysis examines associations between Week 8 responder status to 1.5% ruxolitinib cream with LTS outcomes. At Week 8, 57.0% (244/428) of LTS-evaluable patients applying 1.5% ruxolitinib cream achieved IGA–Treatment Success (IGA-TS; IGA 0/1 with ≥2-grade improvement from baseline); 66.6% (285/428) achieved ≥75% improvement in Eczema Area and Severity Index from baseline (EASI-75); 45.8% (196/428) achieved Itch numerical rating scale 0/1 (NRS 0/1). For patients with ≥2 visits (every 4 weeks) during LTS, mean percentages of visits with clear/almost clear skin were 83.2% vs 59.7%, 82.2% vs 54.9%, and 77.3% vs 70.1% for Week 8 IGA-TS, EASI-75, and Itch NRS 0/1 responders vs nonresponders, respectively. Mean percentages of visits with clear/almost clear skin were similar regardless of time to achieve IGA-TS (83.4%/77.4%/81.9% for those achieving at Week 2/4/8), EASI-75 (80.7%/78.8%/81.6%), and Itch NRS 0/1 (75.8%/70.7%/72.8%). During LTS, mean (SD) cumulative treatment-free days due to complete clearance were 149.2 (86.43) vs 104.0 (89.10), 146.4 (88.43) vs 95.9 (83.55), and 142.6 (87.58) vs 124.4 (91.47) for Week 8 IGA-TS, EASI-75, and Itch NRS 0/1 responders vs nonresponders, respectively. Percentage of treatment-free days between study visits (between Weeks 8 and 12 vs Weeks 48 and 52) among Week 8 responders and nonresponders increased from 44.1% to 50.2% and from 16.3% to 42.3% for IGA-TS; from 41.2% to 49.9% and from 14.9% to 40.6% for EASI-75; from 39.8% to 49.4% and from 29.9% to 46.0% for itch NRS 0/1. In summary, efficacy responses achieved with 8-week ruxolitinib cream treatment are associated with higher disease control in LTS; however, nonresponders approach similar disease control with continued treatment. As-needed ruxolitinib cream monotherapy demonstrated substantial long-term disease control regardless of time to first response achievement.

A Checklist to Aid in Identifying Patients with Atopic Dermatitis Who are Candidates for Systemic Therapy

2024-02-12T17:12:20+00:00

Introduction: The decision to initiate systemic therapy (ST) in patients with atopic dermatitis (AD) is complex, with no criteria that are globally agreed upon. To aid dermatology providers in this decision-making, the “When to Start Systemic Therapy Checklist” was developed. The checklist comprises three components: (A) clinical severity, (B) subjective burden, and (C) lack of treatment response, each with several criteria. Systemic therapy is indicated when at least one criterion in each component is fulfilled. To corroborate the validity of this checklist, we evaluated the agreement between the decision to initiate ST using the checklist, against the reference, CorEvitas AD Registry patients prescribed a ST.

Methods: Adults with moderate-to-severe AD from the prospective, longitudinal CorEvitas AD registry were included in this descriptive analysis (July 2020 – August 2023). Patients were included if they were initiating ST at enrollment (ST group) or not initiating ST at enrollment (non-ST group) but had vIGA-AD® ≥3 and Eczema Area Severity Index ≥12. The checklist criteria were compared against registry outcome measures; when a criterion did not match a measure, either a proxy measure was selected or that part of the questionnaire was excluded. Overall percentage agreement (accord between checklist criteria and ST initiation status [reference standard]) with corresponding 95% confidence intervals (CIs) was calculated.

Results: In the ST group (n=1488), 97.0% of patients met at least one criterion from section A, 94.1% from section B, and 92.1% for either section A or B. In the non-ST group (n=208), 100% of patients met at least one criterion from section A, 92.3% from section B, and 92.3% from either section A or B. Among patients in the ST group who met at least one criterion each from section A and B, overall percentage agreement was 81.7% (95% CI: 79.8%, 83.5%). Section C, which addresses “lack of treatment response” could not be evaluated due to the absence of relevant data in the registry.

Discussion: Nearly all patients initiating ST met at least one criterion from both section A and B of the “When to Start Systemic Therapy Checklist”, demonstrating a strong alignment between the checklist sections A and B and disease burden of AD patients in the registry. Subsequent research is needed to assess section C due to registry limitations. Future analyses should examine why some patients with high disease burden and severity remain untreated with systemics.

Safety of Tralokinumab for the Treatment of Atopic Dermatitis in Patients with Up to 4.5 Years of Treatment: An Updated Integrated Analysis of Eight Clinical Trials

2024-02-26T21:52:20+00:00

Introduction: Clinical trials of up to 52 weeks showed that tralokinumab, a monoclonal antibody that specifically neutralizes interleukin-13, was efficacious and well-tolerated as monotherapy and combination with TCS. Here, we evaluate the long-term safety of tralokinumab in an integrated analysis of seven phase 3 parent trials (PTs) (NCT03131648, NCT03160885, NCT03363854, NCT03562377, NCT03526861, NCT03761537, NCT04587453), and the ongoing, up to 5-year extension study (ECZTEND; NCT03587805).

Methods: Two datasets were analyzed: placebo-controlled (initial 16-week period of the PTs), and all-tralokinumab combining PTs with ECZTEND including patients from first dose until end of tralokinumab exposure or data cut-off (April 30^th, 2022). In the all-tralokinumab dataset, periods on placebo were disregarded. Treatment-emergent adverse events (AEs) were recorded. AEs of special interest (AESIs) were predefined. Proportions of patients with events and incidence rates (IR) per 100 patient-years of exposure (PYE) were calculated. PYE was defined as time until first event or exposure end, whichever came first, and incidence was defined as first event.

Results: 2693 patients (≥12 years) received tralokinumab for up to 238.5 weeks (≈4.5 years) with a median exposure time of 76.5 weeks in the all-tralokinumab dataset. Median age at baseline was 33.0 years (min-max; 12-92). 10.4% of patients were 12-17 years. 2307 patients experienced an AE (IR=202.0), most (97.3%) of which were mild-to-moderate. Serious AEs (SAEs) were reported in 226 patients (IR=4.5); SAEs were considered possibly or probably related by the investigator in 50 patients (IR=0.9). No preferred term level SAEs were reported with an IR≥0.1. Discontinuation of treatment due to AEs was low (IR=2.8). AEs leading to drug withdrawal with an IR>0.1 were dermatitis atopic (IR=0.5) and injection site reaction (ISR) (IR=0.2). Frequently reported AEs in the all-tralokinumab dataset were consistent with the placebo-controlled dataset, including nasopharyngitis (IR=18.4), upper respiratory tract infection (IR=6.9), conjunctivitis (IR=5.0), ISR (IR=3.6), conjunctivitis allergic (IR=2.7), and injection site pain (IR=1.5). AESIs, including eye disorders, skin infections requiring systemic treatment, eczema herpeticum, and malignancies, were observed in the all-tralokinumab dataset at rates similar to or lower than the placebo-controlled dataset.

Conclusion: Long-term use of tralokinumab, for up to 4.5 years, was well-tolerated, and the pattern of AEs was consistent with the initial placebo-controlled treatment period with no new safety signals identified.

Continuous Tralokinumab Treatment over 4 Years in Adults with Moderate-to-Severe Atopic Dermatitis Provides Long-Term Disease Control

2024-02-26T22:06:14+00:00

Introduction: Tralokinumab, a monoclonal antibody that specifically neutralizes interleukin-13, is approved for the treatment of moderate-to-severe AD in multiple countries. Clinical trials of up to 52-week duration showed tralokinumab was effective and well-tolerated as monotherapy and in combination with TCS. ECZTEND (NCT03587805) is an ongoing open-label, 5-yr extension trial investigating the long-term safety and efficacy of tralokinumab ± optional TCS. To assess the efficacy of long-term tralokinumab treatment, we conducted a post hoc interim subgroup analysis restricted to the largest, most homogenous patient population, with the longest treatment duration.

Methods: Adult patients with moderate-to-severe AD who were continuously treated with tralokinumab ± optional TCS for 52 weeks in the phase 3 parents trials (PTs) ECZTRA 1 (NCT03131648) or ECZTRA 2 (NCT03160885) and for up to 152 weeks in ECZTEND as of data cutoff 04/30/2022 were included. Endpoints included proportion of patients achieving IGA 0/1, EASI-75 or EASI-90 relative to PT baseline, EASI ≤7, worst weekly pruritus (itch) NRS ≤4, and DLQI ≤5. Results are presented using observed data (AO). Sensitivity analyses on patients who completed Week152 in ECZTEND (or who withdrew, but were enrolled in the study ≥152 weeks prior to cutoff) were performed using mNRI with discontinuations due to AEs or lack of efficacy imputed as non-responders and a 2-step MI for other missing data.

Results: 347 patients with mean age (SD) of 42.2 (14.5) years and mean EASI (SD) of 30.8 (13.7) at PT baseline were included. After 4 years of total tralokinumab treatment (at Week 152 in ECZTEND), IGA 0/1 [% (n/N)] was observed in 52.6% (92/175) of patients. EASI-75 {% (n/N) [95% CI]} was achieved in 84.5% (147/174) [78.4, 89.1] of patients AO, and 73.4% (254.8/347) [68.6, 78.3] using mNRI. EASI-90 was achieved in 64.4% (112/174) [57.0, 71.1] of patients AO, and 53.4% (185.2/347) [47.8, 59.0] using mNRI. EASI ≤7 was observed in 84.5% (147/174), itch NRS ≤4 in 68.0% (119/175), and DLQI ≤5 in 79.0% (128/162) of patients. The safety profile was favorable and consistent with earlier analyses, with no new safety signals arising with continued tralokinumab use.

Conclusions: Continuous use of tralokinumab ± optional TCS provided long-term disease control over 4 years in adult patients with moderate-to-severe AD.

Progressive and Sustained Disease Control in Patients with Atopic Dermatitis (AD) Aged 12–17 Years Treated with Tralokinumab for 52 Weeks

2024-02-26T22:11:47+00:00

Introduction: The ECZTRA 6 trial showed that tralokinumab 300mg provided progressive and sustained efficacy in adolescent patients with moderate-to-severe AD, and was well tolerated with a reassuring long-term safety profile over 52 weeks.

Objective: To evaluate EASI response and PROs in adolescents from ECZTRA 6 treated with tralokinumab 300mg for the full 52-week treatment period.

Methods: Patients were randomized to tralokinumab 300mg Q2W (n=97) or placebo (n=94) for 16 weeks. At Week 16, patients initiated on tralokinumab and achieving primary endpoints (IGA 0/1 and/or EASI-75) without rescue were re-randomized to tralokinumab 300mg Q2/4W monotherapy for 36 additional weeks; other patients were switched to open-label tralokinumab 300mg Q2W plus optional topical corticosteroids. Post-hoc analyses were conducted by pooling Week 16–52 data for all patients initially randomized to tralokinumab 300mg Q2W.

Results: Greater proportions of tralokinumab- vs placebo-treated patients achieved primary endpoints at Week 16; progressive improvement was seen through Week 52. In addition, pruritus NRS score was improved for a greater proportion of tralokinumab- vs placebo-treated patients from baseline to Week 16, with further improvement up to Week 52. Progressive improvements over time were also observed for proportions of patients with reductions of pruritus NRS ≥4, POEM ≥4, and CDLQI ≥6, from baseline. The safety profile was consistent with prolonged treatment following Week 16.

Conclusions: At Week 16, tralokinumab 300mg Q2W improved EASI and PROs in adolescents with AD, with progressive and sustained improvement seen up to Week 52.

Factors Associated with Persistent Efficacy of Abrocitinib without Flare: A Multivariable Analysis of the JADE-REGIMEN Study

2024-02-27T20:44:08+00:00

Introduction: JADE REGIMEN (NCT03627767) was conducted to evaluate the feasibility of continual, reduced dose or withdrawal of abrocitinib after induction of response in patients with moderate-to-severe atopic dermatitis (AD). This post hoc analysis evaluated patient factors associated with a higher probability of persistent clinical response with abrocitinib, without flare, during a 40-week maintenance period.
Methods: Data were analyzed from patients who responded to abrocitinib 200 mg induction therapy (12 weeks) and were randomly assigned to receive abrocitinib (200 or 100 mg) or placebo in the maintenance period (40 weeks). A multivariable logistic regression model with fixed and random effects was fit to determine factors associated with not experiencing flare by week 52. Fixed effects (factors) considered were randomly allocated treatment, age (<18 vs ≥18 years), race, weight, prior use of systemic agents, AD duration, onset of response in induction (early vs late), Investigator’s Global Assessment score at randomization, body surface area (BSA, ≤50% vs >50%) at baseline, and percentage change in Eczema Area and Severity Index (EASI) at randomization. Backward elimination and stepwise model selection procedures were applied with entry and exit criteria based on a P value threshold of 5%.
Results:1233 patients received abrocitinib 200 mg in the induction period. By week 12, 798 (64.7%) achieved a response and were randomly assigned to receive maintenance treatment for 40 weeks. In total, 356 patients (44.6%) experienced a protocol-defined flare: 16.5% (200 mg), 39.6% (100 mg), and 77.5% (placebo). After model selection, the analysis identified continuation of treatment with abrocitinib 200 mg (odds ratio [OR], 19.51; 95% CI, 11.28-33.75) or reduced-dose abrocitinib 100 mg (5.27; 3.29-8.46) as the greatest predictors of not experiencing flare during maintenance. Not having previously used systemic agents (OR, 1.53; 95% CI, 1.09-2.14), lower baseline BSA (1.55; 1.10-2.17), and greater percentage reduction of EASI during induction (1.35; 1.15-1.59) were also associated with not experiencing flare.
Conclusions: Multivariable analysis of JADE REGIMEN indicated that maintenance treatment with abrocitinib in patients with AD reduced the risk for flare in a dose-dependent manner. Other factors associated with maintaining response to treatment without flare included no previous exposure to systemic agents, lower extent of BSA involvement at baseline, and greater percent change in EASI during induction. These findings may assist clinicians with abrocitinib dosing decisions in the future.

Integrated Safety Analysis of Abrocitinib in 635 Adolescent Patients With Moderate-To-Severe Atopic Dermatitis With Over 1000 Patient-Years of Exposure

2024-02-27T21:02:02+00:00

Introduction: Abrocitinib, an oral, once-daily, Janus kinase 1–selective inhibitor, was efficacious and well tolerated in adolescent patients with moderate-to-severe atopic dermatitis (AD) exposed for approximately 1 year of treatment. Here, we describe the updated long-term integrated safety profile of abrocitinib in adolescent patients in the JADE clinical program.
Methods: A total of 635 adolescent patients (12 to <18 years; exposure: 1011.4 patient-years [PY]) were pooled for safety analysis from the phase 3 JADE clinical trials MONO-1 (NCT03349060), MONO-2 (NCT03575871), TEEN (NCT03796676), and REGIMEN (NCT03627767) and subsequently enrolled in the ongoing phase 3 extension trial JADE EXTEND (NCT03422822; data cutoff: September 25, 2021). Incidence rates (IRs; number of unique patients with events/100 PY) of severe adverse events (SAEs) and AEs of special interest were assessed.
Results: Of the total 635 adolescents, 490 received the same abrocitinib dose throughout exposure (730.6 PY); 289 received abrocitinib 200 mg (424.5 PY) and 201 received abrocitinib 100 mg (306.1 PY). Duration of exposure was ≥96 weeks in 38% and 37%, and ≥144 weeks in 8% and 4% of patients who received abrocitinib 200 mg or 100 mg, respectively. In the 200-mg and 100-mg arms, AEs occurred in 243 (84%) and 153 (76%) patients; 8% (IR [95% CI], 5.87 [3.76-8.74]) and 9% (5.87 [3.48-9.27]) experienced SAEs, and 10% (6.96 [4.69-9.93]) and 8% (5.13 [2.93-8.33]) discontinued the study due to AEs, respectively. IRs of AEs of special interest were 1.84 (95% CI, 0.79-3.62) and 1.28 (0.35-3.27) for serious infection, 2.11 (0.97-4.01) and 1.62 (0.53-3.77) for all herpes zoster (HZ) infections, and 0.69 (0.14-2.03) and 0.32 (0.01-1.77) for opportunistic HZ infections in the 200-mg and 100-mg arms, respectively. One patient (aged 16 years) in the 200-mg arm had a nonfatal venous thromboembolism event (pulmonary embolism; IR, 0.23 [95% CI, 0.01-1.28]); patient had a family history of pulmonary embolism. There were no events of nonmelanoma skin cancer or other malignancies, tuberculosis, or other opportunistic infections (excluding HZ), major adverse cardiovascular events, or deaths.
Conclusions: In this integrated safety analysis using the September 2021 data cut from the ongoing JADE EXTEND trial, abrocitinib had an acceptable long-term safety profile in adolescents with moderate-to-severe AD.

Efficacy of Abrocitinib and Dupilumab in Patients With Moderate-to-Severe Atopic Dermatitis With Severe Itch at Baseline and in Subgroups by Baseline Thresholds of Severe Itch: A Post Hoc Analysis of the JADE COMPARE and JADE DARE Clinical Trials

2024-02-27T21:35:35+00:00

Introduction: In phase 3 trials, abrocitinib provided more rapid and greater itch relief than dupilumab in patients with moderate-to-severe atopic dermatitis (AD). We examined the efficacy of abrocitinib versus dupilumab in patients with severe itch at baseline (BL) and in subgroups by BL thresholds of severe itch.
Methods: Data were pooled from patients treated with abrocitinib 200 mg or dupilumab 300 mg in JADE COMPARE (NCT03720470) and JADE DARE (NCT04345367). Patients with severe itch at BL (Peak Pruritus Numerical Rating Scale [PP-NRS] ≥7), and subgroups by BL PP-NRS 7-10 were assessed for achievement of ≥4-point improvement in PP-NRS (PP-NRS4) and PP-NRS 0/1 (itch free state). Subgroups were also assessed for achievement of Patient Oriented Eczema Measure (POEM) score ≤2 (clear/almost clear AD), and Dermatology Life Quality Index (DLQI) score of 0/1 (no impact on quality of life [QoL]).
Results: This analysis comprised 875 patients (abrocitinib, 453; dupilumab, 422) with severe itch at BL. Median (Q1, Q3) BL score for PP-NRS was 8.0 (7.0, 9.0) in the abrocitinib arm and 8.0 (7.0, 9.0) in the dupilumab arm; 22.0 (19.0, 26.0) and 22.0 (19.0, 27.0) for POEM; 16.0 (11.0, 20.5) and 16.0 (11.0, 20.0) for DLQI. In the overall group, PP-NRS4 responses were greater with abrocitinib versus dupilumab as early as week 2 (56% vs 32%) and sustained through week 16 (73% vs 69%). Stringent PP-NRS 0/1 responses were greater with abrocitinib versus dupilumab at weeks 2 (15% vs 3%) and 16 (35% vs 21%). Across patient subgroups by BL PP-NRS 7-10, greater proportions achieved PP-NRS4 and PP-NRS 0/1 with abrocitinib versus dupilumab at weeks 2 and 16. Greater proportions across subgroups achieved POEM ≤2 with abrocitinib compared with dupilumab at week 16 (BL PP-NRS7, 33% vs 10%; BL PP-NRS8, 29% vs 20%; BL PP-NRS9, 39% vs 16%; BL PP-NRS10, 31% vs 23%). In the overall group, greater proportions achieved DLQI 0/1 with abrocitinib versus dupilumab at weeks 2 (19% vs 6%) and 16 (38% vs 27%). Across subgroups, DLQI 0/1 responses with abrocitinib were generally greater than dupilumab at weeks 2 and 16.
Conclusions: In patients with moderate-to-severe AD who had severe itch at BL, abrocitinib provided more rapid and complete/near complete itch relief and improved QoL than dupilumab as early as 2 weeks of treatment. These results were consistent across subgroups by various BL thresholds of severe itch.

Efficacy Outcomes in Clinical Trials of Atopic Dermatitis Treatments: A Systematic Literature Review

2024-03-01T19:44:01+00:00

Introduction: Complete skin clearance is a key atopic dermatitis (AD) treatment goal. Treatment efficacy in AD trials is evaluated using a range of clinical measures with the Investigator’s Global Assessment (IGA) as a key endpoint. Multiple and varied forms of the IGA scale are utilized across trials, including the Investigator’s Static Global Assessment and the Validated Investigator Global Assessment for AD^TM. IGA scores usually range from 0 (clear) to 1 (almost clear), 2 (mild), 3 (moderate), and 4 (severe), but contain differences in detail assessed. Efficacy endpoints using IGA scales include achieving IGA=0 or 1 with ≥2-point improvement from baseline, or IGA=0. The Eczema Area and Severity Index (EASI) and achievement of ≥75% or ≥90% improvement from baseline (EASI75 and EASI90) are additional gold-standard measurements.

Objective: To compare differences in efficacy outcomes in recent clinical trials of FDA-approved AD treatments for adults and children.

Methods: A systematic literature search was conducted using MEDLINE, Embase, Cochrane Library, and hand search to identify AD trials published in English language between January 1, 2016 and August 16, 2023. Trials could include patients with any severity of AD who were treated with topical therapies (crisaborole, ruxolitinib), injectable systemics (dupilumab, tralokinumab), or oral systemics (upadacitinib, abrocitinib) according to approved indications. Efficacy outcomes of IGA=0 or 1 with ≥2-point improvement, IGA=0, EASI75, and EASI90 were categorized and summarized by AD severity, treatment type, and age groups in the trials.

Results: Of 50 publications identified, 40 (80%) reported randomized controlled trials, 2 (4%) single-arm trials, and 8 (16%) open-label extension trials. By patient age groups, 11 publications were on children (<12 years), 8 on adolescents (12–17 years),15 on patients ≥12 years, and 17 on adults (≥18 years). Moderate to severe AD was the most frequently studied severity (38/50 publications), of which all trials were either as systemic monotherapy or systemic therapy combined with a topical. Topical monotherapy for mild to moderate AD only was reported in 8/50 publications. For topicals, achievement of IGA=0 (clear) was not reported for any age group, and no trials reported EASI90 for children <12 years. For injectable systemics, no outcome was reported for IGA=0 (clear) in children <12 years. For oral systemics, no outcomes were reported for children <12 years.

Conclusions: This literature search of AD trial publications on FDA-approved treatments from 2016 onwards revealed several gaps in available outcomes data. There were no trials that assessed a topical therapy for moderate to severe AD, and complete disease clearance (IGA=0) was not demonstrated for any topicals. The findings reinforce the unmet need for a topical AD treatment that can provide high efficacy including complete clearance without restriction based on age or disease severity.

Funding Support: Dermavant Sciences, Inc.

Transungual Penetration and Antifungal Activity of Seven Prescription and Over-the-Counter Topical Antifungals: In Vitro Comparison

2024-02-27T18:49:12+00:00

Background: Onychomycosis is typically caused by dermatophytes of the species Trichophyton. Topical antifungals must penetrate the nail to reach the infection, though this can be inhibited by keratin binding within the nail. These in vitro experiments compared penetration of commercially available topical antifungals through keratin-free cellulose disks versus human nails to inhibit Trichophyton growth.

Methods: Seven topical antifungals were tested: 3 FDA-approved products indicated for the treatment of onychomycosis (ciclopirox 8% lacquer; efinaconazole 10% solution; tavaborole 5% solution) and 4 over-the-counter (OTC) products for fungal infections (tolnaftate 1% solutions [Formula 3, Formula 7, Tolcylen] and undecylenic acid 25% solution [Terpenicol]). Antifungal efficacy was assessed via cellulose disk diffusion assay. Each product was applied to a 6-mm cellulose disk and placed in the center of an agar plate (85 mm radius) seeded with a clinical isolate of T. rubrum or T. mentagrophytes (2 strains each; 3 replicates/strain for each product). After 4-7 days incubation, the zone of inhibition (ZI)—defined as the radius of the area of no fungal growth—was recorded. To assess the impact of nail penetration on antifungal efficacy, products were applied to the tops of human cadaverous great toenails and allowed to dry. Five 4-mm disks were punched from the middle of each nail and placed treated side up on seeded plates prior to measurement of ZI (5 replicates/strain for each product). In both experiments, results were averaged across the 2 strains of each fungal species and untreated nails served as negative controls.

Results: Among FDA-approved topicals in the cellulose disk diffusion assay, efinaconazole and tavaborole demonstrated maximal inhibition (ZI=85 mm) against both T. rubrum and T. mentagrophytes; for ciclopirox, average ZIs were lower (59.0 mm; 55.7 mm, respectively). For OTC products, ZIs were 31.2-57.8 mm against T. rubrum and 25.7-47.7 mm against T. mentagrophytes. In the nail penetration assay, average ZI for FDA-approved topicals against both species was greatest for efinaconazole (T. rubrum: 82.1 mm; T. mentagrophytes: 63.8 mm), followed by tavaborole (63.5 mm; 39.1 mm) and ciclopirox (7.4 mm; 3.6 mm). Average ZI of OTC products ranged from 10.5-34.2 mm against both species. ZIs were generally not affected by nail thickness.

Conclusions: Our data show that FDA-approved and OTC topical antifungals penetrate cellulose disks more efficiently than cadaver nails, suggesting that keratin in the nails hampers nail penetration. Among all antifungals tested, ability to penetrate human toenails and inhibit growth of both T. rubrum and T. mentagrophytes was greatest for efinaconazole, followed by tavaborole. These results indicate superior transungual penetration of efinaconazole compared to the other antifungals, perhaps due to lower keratin binding in the nail.

Funding: Ortho Dermatologics

Concealing Meets Healing in the Treatment of Toenail Onychomycosis: A Review of Concurrent Nail Polish Use With Topical Efinaconazole 10% Solution

2024-03-05T18:02:43+00:00

Introduction: Females are more likely than males to seek help or treatment for onychomycosis and are more likely to camouflage affected nails with nail polish. Between 2016 and 2022, over half of prescriptions for topical efinaconazole 10% solution were written for females, suggesting that there may be particular interest in the interaction between nail polish use concurrent with efinaconazole treatment for onychomycosis.

Methods: Review in vitro data on effects of nail polish on nail penetration of efinaconazole 10% solution and clinical studies on the impact of nail polish use on efficacy of topical efinaconazole in the treatment of toenail onychomycosis.

Results: Only 4 small studies have assessed interactions between efinaconazole 10% solution and concurrent nail polish use. In vitro, penetration of efinaconazole 10% solution through cadaverous human nails coated with traditional nail polish was similar to penetration through uncoated nails. In a 1-year clinical study, once-daily efinaconazole treatment for 48 weeks was associated with improvements in onychomycosis severity and clear toenail growth that were similar for participants who used traditional nail polish and those who did not use nail polish. In a second, 6-month clinical study, participants received once-daily efinaconazole treatment concurrent with monthly gel nail polish pedicures. After 6 months, 100% of participants tested negative for fungal infection (mycological cure) and all participants experienced visible improvements in their treated toenails. In clinical and in vitro studies, efinaconazole application was associated with degradation of traditional nail polish texture and appearance as well as color transfer to the applicator and unused medication. In contrast, efinaconazole did not affect the duration, quality, or texture of gel nail polish.

Conclusions: Application of nail polish did not prevent penetration of efinaconazole 10% solution through human nails or its successful use in the treatment of toenail onychomycosis. Further, efinaconazole did not impact the texture or appearance of gel-polished nails. To our knowledge, these findings represent the only available data on topical treatment of toenail onychomycosis with concurrent nail polish use, and may be of particular importance when selecting treatment options for female patients with onychomycosis.

Funding: Ortho Dermatologics

VP-102 Tolerability Evaluated by Concomitant Analgesic Medication Usage in Two Phase 3 Trials for Molluscum Contagiosum

2024-02-27T15:23:32+00:00

Background: Drug tolerability is the degree to which a patient can tolerate a drug's adverse effects. VP-102, a drug-device combination product containing cantharidin (0.7%), a vesicant, is approved for treatment of molluscum contagiosum (molluscum) in patients >2. Local skin reactions (LSRs) are expected, including pain. In Phase 3 trials, 97% of LSRs were mild to moderate. The discontinuation rate due to an adverse reaction was 2.3%:0.5% (drug:vehicle) treated subjects, respectively. This post-hoc analysis evaluated VP-102 tolerability based on analgesic usage over the study course.

Methods: VP-102 or vehicle was applied to all baseline and new lesions once every 21 days until complete clearance, or up to a maximum of 4 applications. Acetaminophen or ibuprofen were permitted for application site pain and/or other Adverse Reactions.

Results: Overall incidence of pain at any time for a VP-102 subject was 62.7% (195/311), with the majority [(60.5%),188/311] as mild to moderate. 18.6% (58/311) of VP-102 and 1.4% (3/216) of vehicle treated subjects received an analgesic, including 15.8% (49/311) for an LSR after the first VP-102 application.

Median VP-102 analgesic use for LSR pain (range) was 2 (1-14) days for the entire study, and 2 (1-9) days after the first application. 29% of participants who reported analgesic usage took medication ≤1 day. Analgesic usage for AEs other than LSR pain (≥ 5% of participants) included 6% (19/311) for application site vesicles. There were no treatment-related SAEs reported.

Conclusions: In this largely pediatric population, VP-102 was well-tolerated, with a short duration of elective analgesic use.

Roflumilast Cream 0.3% for the Treatment of Recalcitrant Lichen Nitidus

2024-02-23T17:08:51+00:00

Introduction:

Lichen nitidus is a rare chronic inflammatory condition that presents as shiny, flat-topped papules. The pathophysiology of lichen nitidus is not well understood but has been theorized to stem from allergens that cause antigen presenting cells to activate, thus causing a cell-mediated response that ultimately creates the distinct inflammatory papules¹. Cytokines produced by this cell-mediated response may cause an increase in T-helper 2 cells which have the potential to produce the superficial dermal granulomas seen in lichen nitidus². Currently, no FDA approved treatments for lichen nitidus exist. Due to the inflammatory nature of the disease, off-label therapies may include topical corticosteroids, topical calcineurin inhibitors and UV light¹. Lichen nitidus can be a chronic condition and in cases where long term topical corticosteroid use is required, has been associated with hypopigmentation in African Americans. Roflumilast cream 0.3% is a highly selective, non-steroidal and potent topical phosphodiesterase 4 (PDE4) inhibitor approved in 2022 by the FDA for the treatment of psoriasis, including intertriginous disease. Here, we report the case of a 51-year-old African American patient with lichen nitidus that is pruritic and refractory to typical off-label treatments including emollients, triamcinolone and clobetasol. The patient was started on roflumilast cream 0.3% daily with complete resolution of lesions and pruritus in 4 weeks.

Case Report:

We report the case of a 51-year-old African American patient presenting to the clinic with a history of firm, pruritic, white colored papules on both of his hands that made it hard for him to drive. These lesions had been present for 2 years and did not respond to previous treatment with emollients and topical corticosteroids including triamcinolone cream 0.1% and clobetasol ointment 0.05% both twice daily. A biopsy was performed and demonstrated lymphocytic infiltrate in the upper dermis and the classic “claw and ball” configuration consistent with lichen nitidus. The patient was subsequently started on topical roflumilast 0.3% daily which resulted in complete resolution of lesions and pruritus within 4 weeks.

Conclusion:

We reported a case of a 51-year-old African American papules on both hands that were consistent with lichen nitidus. In this case, the patient’s lichen nitidus was refractory to topical corticosteroids and emollients. Long term corticosteroid use is also associated with hypopigmentation in this population. After starting topical roflumilast 0.3% daily, the patient reported complete resolution of the lesions and puritus. This report suggests reduction of inflammation with roflumilast cream 0.3%, can offer a treatment option for patients with lichen nitidus.

Bimekizumab Versus Secukinumab Continuous Maintenance of PASI 90 and PASI 100 Responses through One Year in Patients with Moderate to Severe Plaque Psoriasis: Post-HOC Results from the BE RADIANT Phase 3b Trial

2024-03-18T14:49:23+00:00

Introduction: Bimekizumab (BKZ) is a monoclonal IgG1 antibody that selectively inhibits interleukin (IL)-17F in addition to IL‑17A.^[1] Secukinumab (SEC) is a widely used monoclonal IgG1 antibody that targets IL-17A. BE RADIANT was the first phase 3 study to compare inhibition of IL-17A and IL-17F with inhibition of IL-17A alone. Patient (pt) surveys have confirmed that maintaining a long-lasting response is a key treatment goal for patients who have already achieved skin clearance.^[2,3]

Here, we assess the efficacy of BKZ vs SEC in continuously maintaining an improvement of ≥90% in the Psoriasis Area and Severity Index (PASI 90), and PASI 100 responses, at every visit from Week (Wk)16 to Wk48 of treatment in pts with moderate to severe plaque psoriasis.

Procedure/study: BE RADIANT was a phase 3b, randomized trial, consisting of a 48-week double-blinded, active comparator-controlled period followed by an open-label extension.^[4] Pts were randomized 1:1 to BKZ 320 mg every 4 wks (Q4W) or SEC (weekly to Wk4 then Q4W). At Wk16, BKZ-randomized pts either continued to receive BKZ 320 mg Q4W or switched to BKZ 320 mg every 8 wks (Q8W). This analysis includes pts who achieved PASI 90 or 100 at Wk16 and continued to receive study medication at Wk16 or later, reported with BKZ dose groups pooled. We report the proportion of responders who continued to achieve their response at every study visit up to and including Wk48. Missing data were imputed as non-response.

Results: At baseline, 373 pts were randomized to BKZ, and 370 were randomized to SEC. At Wk16, 319/373 (85.5%) BKZ-randomized and 273/370 (73.8%) SEC-randomized pts achieved PASI 90; 230/373 (61.7%) and 180/370 (48.6%) achieved PASI 100. PASI 90 was continuously maintained at each study visit from Wk16–Wk48 by 242/319 (75.9%) BKZ-treated and 177/273 (64.8%) SEC-treated Wk16 responders. PASI 100 was continuously maintained through Wk48 by 139/230 (60.4%) BKZ-treated and 93/180 (51.7%) SEC-treated Wk16 responders.

Conclusion: A higher proportion of pts treated with BKZ continuously maintained their Wk16 PASI 90 and PASI 100 responses at every visit during the first treatment year compared to SEC.

Funding: UCB Pharma. Medical writing support: Costello Medical.

A New Peptide Skin-Brightening Facial Cream Demonstrated Clinical Improvement in Jawline Sagging, Discoloration and Overall Photodamage

2024-02-15T03:06:37+00:00

Besides fine lines and wrinkles, chronological aging leads to discoloration, age spots, and more importantly, sagging and loss of elasticity on facial skin. There are ample consumer needs to reduce age spots and skin sagging with an increasing desire for effective topical solutions that can provide meaningful benefits in these areas. A new microdipeptide (acetyl dipeptide) technology was developed that demonstrated the potential to reduce skin inflammation and stimulate the skin’s supporting matrix. This clinical study was designed to test the effectiveness of a facial cream with a unique blend of microdipeptide technology along with brightening and firming ingredients to reduce the key signs of facial aging with twice daily use. The 16-week study included 43 healthy female subjects, ages 40-70 with diverse skin tones, and having mild to moderate jawline sagging with fine lines and/or hyperpigmentation by expert visual grading (3 to 6 on a 0 to 9 scale). Visual grading exhibited statistically significant reduction in all targeted skin aging signs starting at week 8, and continuing improvement to week 16, including jawline sagging (19%), laxity (19%), lift/ firmness (15%), as well as improved evenness of skin tone (16%), hyperpigmentation (14%) and overall photodamage (23%) (mean percent change, p< 0.05). Consumer perception questionnaires also revealed improvement after 16 weeks of use with tighter/tauter jawlines (88%), increased firmness (93%), skin elasticity (93%), refined facial contour (88%), less sagging (95%), and more lifted (91%) and volumized appearance (98%). Furthermore, subjects also indicated brighter skin (95%), increased radiance (93%), less discoloration (86%), fading dark spots (77%), reduced fine lines (93%) and wrinkles (95%), skin looks younger (95%), and overall less noticeable aging signs (95%). Clinical photography supported both the clinical grading and consumer perception of benefits. In addition, these clinical outcomes are further supported by in vitro and ex vivo investigations showing the microdipeptide activity on inhibiting the expression of inflammatory cytokines and inducing multiple matrix building biomarkers, beyond elastin, pro-collagen and hyaluronic acid to include decorin and fibronectin. Gene expression profiling showed changes associated with skin barrier and extracellular matrix organizations, therefore mimicking a younger-looking skin. These results demonstrated that this peptide facial cream was well-tolerated and effective in improving jawline sagging, facial skin firmness, skin brightening, and reducing the overall signs of aging.

Clinical Efficacy and Patient Reported Impacts of Roflumilast Foam 0.3% in Seborrheic Dermatitis: An Analysis of STRATUM Data for Patients Unresponsive or Intolerant to Topical Corticosteroids

2024-01-24T16:49:54+00:00

Objective. Roflumilast foam 0.3% has demonstrated efficacy and tolerability in a Phase 3 clinical trial of moderate-to-severe seborrheic dermatitis (SD) patients (STRATUM). The aim of this subgroup analysis is to assess the efficacy and patient-reported quality of life (QOL) effects of roflumilast vs vehicle in patients with an inadequate response, intolerance, or contraindication to topical corticosteroids (TCS).

Methods: Patients 9 years or older with at least moderate seborrheic dermatitis (Investigator Global Assessment [IGA] ≥ 3) were randomized 2:1 to roflumilast or vehicle for 8 weeks. Patients reporting a history of inadequate response, intolerance, or contraindication to topical corticosteroids (TCS) were included in this subgroup analysis. The primary efficacy endpoint was IGA success (Clear or Almost Clear with at least a 2-grade improvement) at Week 8. QOL was assessed using the Dermatology Life Quality Index (DLQI) for patients aged ≥17 years. QOL endpoints included percentage change from baseline in DLQI score, achievement of a minimal important difference (MID; defined as at least a 4-point reduction in DLQI score), and patients achieving a DLQI score of 0 or 1 by treatment group at weeks 2, 4, and 8. Differences in change from baseline DLQI scores were assessed using the Kruskal-Wallis rank sum test. The Cochran–Mantel–Haenzel test was used to assess differences in the proportion of patients achieving binary endpoints between treatments.

Results: 189 patients (129 roflumilast, 60 vehicle) were included in the subgroup analysis. At Week 8, 78.8% of roflumilast patients achieved IGA success vs. 48.3% of vehicle patients (odds ratio [OR] 3.45; 95% confidence interval [CI]: 1.62, 7.36; p<0.001). At each time point, percentage change from baseline in DLQI score was significantly larger for roflumilast-treated patients relative to vehicle (p≤0.001). Treatment with roflumilast significantly increased the odds of achieving an MID in DLQI across all time points (OR: 6.97; 95% confidence interval [CI]: 3.97, 12.24; p<0.001) and achieving a DLQI score of 0 or 1 (OR: 2.46; 95% CI: 1.58, 3.81; p<0.001).

Conclusions: Roflumilast foam 0.3% provided significant and meaningful efficacy with improved QOL in patients with moderate-to-severe SD who had a prior history of an inadequate response, intolerance, or contraindication to TCS. Clinical improvement aligned with patient-reported outcomes at all key assessment periods.