Roflumilast Cream 0.3% in Patients with Chronic Plaque Psoriasis: Pooled PASI and PASI-HD Results from the DERMIS Phase III Trials

St John’s Institute of Dermatology, King’s College London and Guy’s and St Thomas’ NHS Foundation Trust, London SE1 9RT U.K. *Department of Dermatology, Royal Gwent Hospital, Newport NP20 2UB, U.K. Department of Dermatology, Western Infirmary, Glasgow G11 6NT, U.K. The Dermatology Centre, Salford Royal Hospital, University of Manchester, Manchester Academic Health Science Centre, Manchester M6 8HD, U.K. §Psoriasis and Psoriatic Arthritis Alliance, PO Box 111, St Albans AL2 3JQ, U.K. –Department of Dermatology, Cardiff University, School of Medicine, Heath Park, Cardiff CF14 4XN, U.K. **Royal National Hospital for Rheumatic Diseases, Bath BA1 1RL, U.K. Department of Dermatology, Belfast City Hospital, Belfast BT9 7AB, U.K. Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne NE2 4HH, U.K. §§Department of Dermatology, Aberdeen Royal Infirmary, Foresterhill, Aberdeen AB9 2ZB, U.K.

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.

Psoriasis is a chronic scaling and inflammatory skin disease that can affect patients' quality of life and daily functioning. We studied the scores of 85 patients suffering from moderate to severe plaque-type psoriasis, participating in a randomized controlled trial. We compared their scores on a generic quality-of-life instrument with data from two reference populations. We examined associations between clinical severity, as measured by the components of the Psoriasis Area and Severity Index (PASI), and the respective quality-of-life subdimensions, measured by the Medical Outcome Survey Short Form 36 (SF-36), to find out what elements of disease activity are related with impaired quality of life. Compared to the reference population, quality of life was impaired in terms of bodily pain and social functioning. There were no significant correlations between overall disease severity, as measured by PASI, and the SF-36 subdimensions. When examining the PASI components, we found significant correlations between desquamation on the upper limbs and mental health and bodily pain (r = -0.23 and r = -0.28, respectively) and between desquamation on the scalp and mental health (r = -0.29). In conclusion, we found that psoriasis patients had a lower quality of life than a reference population, without a significant relation between disease severity or disease area and quality of life. Yet psoriasis lesions located on visible body parts are significantly correlated with aspects of quality of life.

Evaluation of sPGA × BSA as an Outcome Measure and Treatment Target for Clinical Practice

Updates in psoriasis diagnosis and treatment status in China: results from the National Psoriasis Center Registry.

Roflumilast cream 0.3% in patients with chronic plaque psoriasis: individual patient response from the pooled DERMIS-1 and DERMIS-2 phase 3 trials
 
 James Del Rosso1 on behalf of the authors
 
 INTRODUCTION: Roflumilast cream 0.3% is a highly potent phosphodiesterase 4 inhibitor approved as a nonsteroidal, once-daily treatment for patients with plaque psoriasis. The efficacy and safety of the pooled results of two Phase 3 clinical trials (DERMIS-1 and DERMIS-2) in patients aged ≥2 years with plaque psoriasis have been previously presented. We present individual patient responses using the Psoriasis Area and Severity Index (PASI).
 METHODS: Patients aged ≥2 years with at least mild plaque psoriasis involving 2-20% of 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; IGA of Clear or Almost Clear was a secondary endpoint. PASI was used to measure disease severity; individual patient PASI responses were plotted graphically. Safety and tolerability were also evaluated and have been previously reported.
 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) and IGA of Clear or Almost Clear (48.0% vs. 9.5%; nominal 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). At the first post-treatment timepoint evaluated (Week 2), 85.7% of roflumilast-treated patients had a measurable improvement in PASI, increasing to 95.0% by the last timepoint (Week 8). Roflumilast cream demonstrated low rates of application-site adverse events (AEs), treatment-related AEs, and discontinuations due to AEs, comparable with vehicle. Approximately 96% of patients reported no or mild sensation after the first application of roflumilast cream 0.3%, improving to more than 99% of patients at Week 4 and Week 8, similar to vehicle.
 CONCLUSIONS: Roflumilast cream 0.3% provided greater improvement in IGA Success, IGA of Clear or Almost Clear, and PASI versus vehicle with favorable safety and tolerability in patients with psoriasis in two Phase 3 trials.
 Sponsored by Arcutis Biotherapeutics, Inc.
 ClinicalTrials.gov Identifiers: DERMIS-1: NCT04211363; DERMIS-2: NCT04211389

QoolSkin is novel herbal topical medication indicated for the treatment of patients with psoriasis and we endeavored to determine the efficacy of QoolSkin in patients with chronic plaque psoriasis. In an open-label, parallel-group study conducted at four sites in Israel, patients with chronic plaque psoriasis were treated by application of QoolSkin two to three times per day, for a period of 16 weeks. Clinical assessment was performed using the Psoriasis Area and Severity Index (PASI) and the Beer-Sheva Psoriasis Severity Score (BPSS). The study included 100 patients (48 men, 52 women; age 18–65 years). QoolSkin was well tolerated and there were no local or systemic side effects. There was a 19% reduction in PASI, from a mean of 9.8 ± 9.5 before treatment to 8.0 ± 9.6 after treatment (p = 0.09). There was a 20% reduction in BPSS, from a mean of 16.1 ± 9.8 before treatment to 12.8 ± 10.6 after treatment (p = 0.01). The reduction in PASI and BPSS was pronounced in women (32 and 31%, respectively) as compared to men (9 and 11%, respectively). The reduction in PASI and BPSS was parallel to the length of time the patients were treated by QoolSkin. In patients treated by one of the investigators, who applied QoolSkin three times per day and for a long period of time (mean 101.1 days), the reduction in PASI was 32.0% and the reduction in BPSS was 37.8%. In patients with chronic plaque psoriasis, QoolSkin treatment was well tolerated. Application of QoolSkin was associated with a decrease in disease severity, as assessed by the patients and physicians. Application of QoolSkin three times per day for long period is associated with a better response to treatment.

There is a current lack of safe and effective psoriasis therapies that provide patients with lasting remissions after treatment is discontinued. Alefacept, a novel and selective biological agent, has demonstrated durable efficacy in patients with chronic plaque psoriasis, and its efficacy has been correlated with reductions in memory-effector T cells. To demonstrate the efficacy and safety of both one and two 12-week courses of alefacept 7.5 mg given once weekly as an intravenous (IV) bolus injection in patients with chronic plaque psoriasis. Multicentre (51 centres in the USA and Canada), randomized, double-blind, parallel-group study comparing once-weekly alefacept 7.5 mg IV or placebo for two 12-week treatment courses. Each course had a 12-week follow-up phase. Patients were eligible for enrollment if they were > or =16 years of age, had chronic plaque psoriasis for > or =12 months involving > or =10% body surface area, and had CD4+ T-cell counts at or above the lower limit of normal. 553 patients received treatment in Course 1, and 449 were treated in Course 2. The cohorts were well balanced for demographic and baseline disease characteristics. During the treatment and follow-up period of Course 1, 28% of patients treated with alefacept achieved > or =75% reduction in Psoriasis Area and Severity Index (PASI), compared with 8% of placebo-treated patients (P < 0.001). Patients achieving > or =75% reduction in PASI following a single 12-week course of alefacept maintained > or =50% reduction in PASI for a median of over 7 months. Among patients who received a second course of alefacept therapy, 71% achieved > or =50% reduction in PASI, and 40% achieved > or =75% reduction in PASI over two treatment courses. One or two 12-week courses of alefacept were similarly well tolerated. Treatment with alefacept 7.5 mg IV provided highly significant improvements in all measures of psoriasis disease activity compared with placebo. A second course of alefacept provided additional benefit.

AGGRESSIVE WEIGHT LOSS PROGRAM WITH A KETOGENIC INDUCTION PHASE FOR THE TREATMENT OF CHRONIC PLAQUE PSORIASIS

Efficacy and safety of ixekizumab in Chinese patients with plaque psoriasis.

Psoriasis is a chronic immune-mediated disease primarily affecting the skin. The most common subtype is plaque psoriasis, which can affect any body area, with a predilection for the knees, elbows, scalp, lumbosacral region, and genitalia. The European guidelines adopted in Italy recommend systemic therapies for moderate-to-severe psoriasis, defined by a Psoriasis Area and Severity Index (PASI) ≥10, Dermatology Life Quality Index (DLQI) ≥10, and/or Body Surface Area (BSA) ≥10. Over the past two decades, the development of biological agents has revolutionized psoriasis management, targeting specific cytokines, including tumor necrosis factor (TNF)-α, interleukin (IL)-23, and IL-17. Among these, ixekizumab, secukinumab, brodalumab, and bimekizumab are approved for the treatment of moderate-to-severe plaque psoriasis. However, some patients require switching therapy because of primary/secondary ineffectiveness or side effects. We retrospectively analyzed 20 patients who had switched from one anti-IL-17 drug to another, assessing both safety and effectiveness. At baseline, the median PASI score was 10 (interquartile range [IQR] 4.5). After 16 weeks, it decreased to 2 (IQR 5.5), and after one year, it decreased further to 1 (IQR 2). Eight (40%) and six patients (30%) achieved PASI 90 and PASI 100 at 16 weeks, respectively. After one year, sustained effectiveness was observed, with PASI 90 (57.1%), PASI 100 (35.7%), and PASI≤2 (78.6%). No serious adverse events (AEs) or discontinuations due to AEs were observed during the study period. Our study confirms the safety and effectiveness of intra-class switching among IL-17 antagonists within the same class and highlights that switching between different classes of IL-17 inhibitors can be a valid option when patients fail to respond or lose effectiveness with a particular inhibitor. However, a deeper understanding requires further large-scale and long-term studies.

Background Tumor necrosis factor-alpha (TNF-α) is pivotal in the pathogenesis of psoriasis, an immune-mediated disease. Adalimumab is a fully human, IgG1 monoclonal antibody that inhibits TNF-α. Objectives The aims of this study were to assess the efficacy and safety of adalimumab therapy for patients with moderate to severe plaque psoriasis and evaluate the duration of treatment response after withdrawal from or dosage reduction of adalimumab therapy. Methods In this multicenter, randomized, double-blind, placebo-controlled study, patients with moderate to severe plaque psoriasis received 12-week, open-label therapy with subcutaneous adalimumab, consisting of 80 mg of adalimumab at weeks 0 and 1, followed by 40 mg weekly at weeks 2–11. At week 12, patients who had an improvement in Psoriasis Area and Severity Index (PASI) score of ≥50% were randomized to blinded therapy and received either adalimumab 40 mg every other week (eow) or placebo for an additional 12 weeks. Results A total of 148 patients enrolled. Clinical response was rapid, with a PASI 50 response rate of 28% at week 2 of adalimumab therapy. At week 12, 91.9% (136/148) of patients had achieved ≥50% reduction in PASI (PASI 50) vs. baseline, 76.4% (113/148) had achieved PASI 75, and 47.3% (70/148) had achieved PASI 90. Of patients who were randomized to placebo at week 12, 30.9% (21/68) experienced a relapse (&lt;PASI 50 improvement vs. baseline) by week 24, compared with 16.2% (11/68) of patients who received adalimumab 40 mg eow. In addition, 48.5% (33/68) of patients who were randomized to placebo at week 12 were PASI 75 responded at week 24, compared with 67.6% (46/68) of patients randomized to adalimumab 40 mg eow (p=0.032). And, 27.9% (19/68) of patients who were randomized to placebo at week 12 were PASI 90 responders at week 24, compared with 47.1% (32/68) of patients randomized to adalimumab 40 mg eow (p=0.028). Adalimumab was generally well-tolerated, and the rates of adverse events were comparable between the adalimumab and placebo groups. Conclusions Weekly adalimumab therapy rapidly improved psoriasis during an initial 12-week period. Improvement was sustained in most, but not all patients, despite dosage reduction to every other week. No patients randomized to adalimumab withdrawal (placebo at week 12) experienced rebound, and most maintained &gt;PASI 50 improvement, relative to baseline, during the 3 months following adalimumab discontinuation. Overall, greater efficacy rates at week 24 were observed for patients randomized to continuous adalimumab therapy than for patients who were withdrawn from therapy at week 12.

Product of the Physician Global Assessment and body surface area: A simple static measure of psoriasis severity in a longitudinal cohort

Psoriasis remains an incurable and recurrent condition despite modern treatment. Traditional Unani Medicine recommends numerous formulations for psoriasis, but with little supporting scientific evidence. The study aimed to evaluate the efficacy and safety of Majoon Mundi and Roghan Gul compared to apremilast and coconut oil in managing chronic plaque psoriasis (CPP). The study was a randomized, open-label, standard-controlled clinical trial, with 33 participants. 20 patients completed the 6-week treatment course in the test group, while 10 patients completed the 6-week treatment course in the control group. The study was conducted at the National Institute of Unani Medicine (NIUM), Bangalore, India, from June 2021 to December 2021. Participants aged 18-60 years, of either gender, diagnosed with CPP, and based on psoriasis area and severity index (PASI) score. The participants in the test group received 10 g of Majoon Mundi orally twice daily after meals and Roghan Gul for topical use twice daily, while the participants in the active control group received apremilast orally in a titrated dose and coconut oil as a topical application twice daily. The primary outcome of the study was a reduction in PASI score, and the secondary outcome was a reduction in dermatology life quality index (DLQI) score. Photographic assessments were conducted at the 14th, 28th, and 42nd day of the follow-up period. Intragroup analyses revealed that the test and control groups experienced a statistically significant reduction in PASI and DLQI scores (P < .001). Intergroup analysis showed no statistically significant difference in the reduction of PASI and DLQI scores between groups (P = .772 and .775, respectively). This study found that together, Majoon Mundi and Roghan Gul are as effective as apremilast and coconut oil in decreasing PASI and DLQI scores for managing CPP. apremilast, comparative study, herbal medicine, psoriasis, unani medicine.

Background Tildrakizumab (TIL), a high affinity, humanised, IgG1/κ monoclonal antibody for IL-23p19, recently demonstrated efficacy in patients with chronic plaque psoriasis in two, phase 3 clinical trials. Objectives To examine...