Efficacy and safety of tildrakizumab for the treatment of moderate-to-severe plaque psoriasis of the scalp: A multicenter, randomized, double-blind, placebo-controlled, Phase 3b study.

BACKGROUND: Scalp psoriasis is common and difficult to treat. OBJECTIVE: To evaluate efficacy and safety of tildrakizumab for the treatment of scalp psoriasis. METHODS: In this Phase 3b, randomized, double-blind, placebo-controlled study (NCT03897088), patients with moderate-to-severe plaque psoriasis affecting the scalp (Investigator Global Assessment modified [IGA mod] 2011 [scalp] ≥3, Psoriasis Scalp Severity Index [PSSI] ≥12, ≥30% scalp surface area affected) received tildrakizumab 100 mg or placebo at W0 and W4. The primary endpoint was IGA mod 2011 (scalp) score of "clear" or "almost clear" with ≥2-point reduction from baseline at W16 (IGA mod 2011 [scalp] response). Key secondary endpoints were PSSI 90 response at W12 and W16 and IGA mod 2011 (scalp) response at W12. Safety was assessed from adverse events. RESULTS: Of patients treated with tildrakizumab (n = 89) vs placebo (n = 82), 49.4% vs 7.3% achieved IGA mod 2011 (scalp) response at W16 (primary endpoint) and 46.1% vs 4.9% at W12; 60.7% vs 4.9% achieved PSSI 90 response at W16 and 48.3% vs 2.4% at W12 (all P <0.00001). No serious treatment-related adverse events occurred. LIMITATIONS: Only short-term data are presented. CONCLUSION: Tildrakizumab was efficacious for the treatment of scalp psoriasis with no new safety signals.

Impact of psoriasis disease severity and special area involvement on patient-reported outcomes in the real world: an analysis from the CorEvitas psoriasis registry.

BACKGROUND: The impact of psoriasis in special areas (i.e., scalp, nails, palms, soles, genitals) on patient physical functioning, health-related quality of life (HRQoL), and work abilities has not been fully characterized. We assessed associations between disease severity and special area involvement in psoriasis symptoms, HRQoL, and work/activity impairment. METHODS: Patients with psoriasis from the CorEvitas Psoriasis Registry who initiated systemic treatment between 04/2015-06/2020 were included. Outcomes were change from baseline in psoriasis symptoms, Dermatology Life Quality Index (DLQI), and work/activity impairment at 6 months stratified by baseline disease severity and special area involvement. RESULTS: Among 2620 patients, increasing disease severity was associated with worsening patient-reported outcomes. Patients with (46.0%; N = 1205) versus without (54.0%; N = 1415) psoriasis in special areas reported greater HRQoL and work/activity impairment. Over 6 months, patients with unchanged or worsening disease severity had reduced HRQoL and increased symptom severity; incremental increases in patient HRQoL and decreases in symptom severity were associated with improved disease severity. CONCLUSIONS: Higher disease severity and special area involvement was associated with worse outcomes and impaired work abilities. These data highlight the significant impact that adequate treatment of severe psoriasis and/or special area involvement may have on patient HRQoL and function.

Tildrakizumab in Combination With Topical Halcinonide 0.1% Ointment for Treating Moderate to Severe Plaque Psoriasis.

BACKGROUND: This prospective, open-label study evaluated the effectiveness and safety of tildrakizumab plus topical halcinonide ointment in psoriasis patients. METHODS: Adults (age greater than or equal to 18 years) with moderate to severe plaque psoriasis (body surface area [BSA] greater than or equal to 10%, physician's global assessment [PGA] greater than or equal to 3, psoriasis area severity index [PASI] greater than or equal to 12) received tildrakizumab (100 mg; s.c.) at weeks 0, 4, and 16. Patients with BSA >3% at week 16 received additional halcinonide 0.1% twice daily for 4 weeks (week 20) and were followed for another 4 weeks (week 24); those with BSA less than or equal to 3% were followed to week 24. RESULTS: Twenty-five patients were enrolled (mean age 52.6 years; 68% male). The proportion of all patients achieving BSA less than or equal to 3% was 52.2% at week 16, 73.7% at week 20 (after 4 weeks of adjunctive halcinonide in patients with BSA >3% at week 16), and 84.2% at week 24 (4 weeks after halcinonide discontinuation). PASI 75 was attained in 60.9% of all patients at week 16, and 73.7% at weeks 20 and 24. In patients adding halcinonide, improvements from baseline in mean BSA, PGA, and PGA x BSA increased from week 16 (55%, 29%, and 64%, respectively) to week 20 (78%, 51%, and 88%, respectively), and were maintained through week 24. Quality of life improved with tildrakizumab monotherapy and further with adjunctive halcinonide. Adverse events (AEs) were infrequent. No serious AEs or discontinuations due to AEs were noted. CONCLUSION: Tildrakizumab plus topical halcinonide ointment is safe and effective in controlling psoriasis for patients inadequately responding to tildrakizumab monotherapy.Bagel J, Novak K, Nelson E. Tildrakizumab in combination with topical halcinonide 0.1% ointment for treating moderate to severe plaque psoriasis. J Drugs Dermatol. 2023;22(8):766-772. doi:10.36849/JDD.6830.

Comparison of risankizumab and apremilast for the treatment of adults with moderate plaque psoriasis eligible for systemic therapy: results from a randomized, open-label, assessor-blinded phase IV study (IMMpulse).

BACKGROUND: Treatment of psoriasis with risankizumab has demonstrated superior efficacy to other treatments, such as adalimumab, ustekinumab and secukinumab. OBJECTIVES: This study compared the efficacy and safety of risankizumab and apremilast in adults with moderate plaque psoriasis eligible for systemic therapy. It also evaluated the efficacy and safety of switching to risankizumab vs. continuing apremilast in patients who did not achieve ≥ 75% improvement in Psoriasis Area and Severity Index (PASI 75 nonresponders) after 16 weeks of treatment with apremilast. METHODS: This 52-week, phase IV, multicentre, randomized, open-label, efficacy assessor-blinded study (NCT04908475) enrolled patients (aged ≥ 18 years) with a diagnosis of moderate chronic plaque psoriasis (≥ 6 months) and who were candidates for systemic therapy. The enrolled patients (randomized 1 : 2) received subcutaneous risankizumab (150 mg at weeks 0 and 4) or oral apremilast (30 mg twice daily). At week 16, all patients treated with apremilast were re-randomized (1 : 1) to risankizumab or apremilast, stratified by week-16 PASI 75 response. The co-primary outcomes in period A at week 16 were the achievement of ≥ 90% improvement in Psoriasis Area and Severity Index (PASI 90) and static Physician's Global Assessment (sPGA) 0/1 with a two-grade or better improvement from baseline. At week 52, the primary endpoint in period B was the achievement of PASI 90 in PASI 75 nonresponders with apremilast at week 16. Safety was monitored throughout the study. All patients who received one dose of treatment were included in the efficacy and safety analysis. RESULTS: At baseline, 118 and 234 patients were assigned to receive risankizumab and apremilast, respectively. At week 16, PASI 90 was achieved by 55.9% [95% confidence interval (CI) 47.0-64.9] and 5.1% (95% CI 2.3-8.0), and sPGA 0/1 by 75.4% (95% CI 67.7-83.2) and 18.4% (95% CI 13.4-23.3), respectively. In period B, among PASI 75 nonresponders with apremilast at week 16, 83 switched to risankizumab and 78 continued apremilast. At week 52, 72.3% (95% CI 62.7-81.9) who switched to risankizumab achieved PASI 90 vs. 2.6% (95% CI 0.0-6.1) who continued apremilast. The most frequent adverse events (reported in ≥ 5%) in risankizumab-treated patients were COVID-19 infection and nasopharyngitis. Diarrhoea, nausea and headache were most frequent among apremilast-treated patients. CONCLUSIONS: For patients with moderate psoriasis, treatment with risankizumab demonstrated superior efficacy to those treated with apremilast, including those who did not benefit from prior treatment with apremilast. The safety profile of risankizumab was similar to prior studies, and no new safety signals were identified. These results show that, compared with apremilast, risankizumab treatment can significantly improve clinical outcomes in systemic-eligible patients with moderate psoriasis.

Treatment of plaque psoriasis with deucravacitinib (POETYK PSO-2 study): a plain language summary.

WHAT IS THIS SUMMARY ABOUT?: This is a summary of a paper published in a medical journal that describes the results of a study called POETYK PSO-2, which investigated a new treatment for plaque psoriasis. Plaque psoriasis appears on the body as dry, discolored, patches of skin that can be flaky and covered in scales. This can make the skin itch, crack or bleed and make it difficult for people with psoriasis to perform basic everyday tasks. Treatments are available, but some do not always reduce symptoms or may need to be injected or taken multiple times a day, which can be difficult to do, or can have undesirable side effects. Researchers are looking for new treatments for psoriasis. WHAT HAPPENED IN THE STUDY?: Deucravacitinib is a once-daily pill taken by mouth (orally) that was studied as a treatment for moderate to severe plaque psoriasis in two large studies conducted globally, PSO-1 and PSO-2. POETYK PSO-2 was a Phase 3 research study, which is a study that tests a treatment in a large group of participants, that looked at how well deucravacitinib worked in participants with moderate to severe plaque psoriasis compared to a placebo (an inactive pill that has no effect) and an approved psoriasis treatment called apremilast, which is a pill taken twice a day. These medications were tested in adults with moderate to severe plaque psoriasis, which is psoriasis involving 10% or more of their body (equal to 10 or more handprints). The aims of the POETYK PSO-2 study were to find out if treatment with deucravacitinib could improve psoriasis for the participants in the study and to see if there were any side effects. Side effects are events that happened during treatment that may or may not be caused by that treatment. The study also wanted to find out what would happen after stopping treatment with deucravacitinib in participants who had shown major improvements in their psoriasis. WHAT DO THE RESULTS OF THE POETYK PSO-2 STUDY SHOW?: After 4 months of treatment, more participants taking deucravacitinib had significantly greater improvements in psoriasis than those taking placebo or apremilast. The study also showed that participants continued to see these improvements after taking deucravacitinib for up to 1 year. Some participants maintained the improvements in their psoriasis with deucravacitinib after stopping treatment and switching to a placebo. Side effects for participants taking deucravacitinib were generally mild and occurred in similar numbers to those in participants taking placebo. The most common side effects in participants taking deucravacitinib were inflammation of the nose and throat (a common cold) which occurred at a similar rate in participants who took placebo. Clinical Trial Registration: NCT03611751 (POETYK PSO-2 study) (ClinicalTrials.gov).

Tapinarof cream 1% once daily for the treatment of plaque psoriasis: Patient-reported outcomes from the PSOARING 3 trial.

BACKGROUND: Tapinarof cream 1% once daily demonstrated significant efficacy versus vehicle and was well tolerated in two 12-week, phase 3 pivotal trials in adults with mild-to-severe plaque psoriasis. OBJECTIVE: To assess long-term, health-related quality of life and patient satisfaction with tapinarof. METHODS: Patients completing the 12-week trials were eligible for 40 weeks of open-label tapinarof based on Physician Global Assessment score in PSOARING 3, with a 4-week follow-up. Dermatology Life Quality Index was assessed at every visit; Patient Satisfaction Questionnaire responses were assessed at week 40 or early termination. RESULTS: Seven hundred sixty-three (91.6%) eligible patients enrolled; 78.5% completed the Patient Satisfaction Questionnaire. DLQI scores improved and were maintained. By week 40, 68.0% of patients had a DLQI of 0 or 1, indicating no impact of psoriasis on health-related quality of life. Most patients strongly agreed or agreed with all Patient Satisfaction Questionnaire questions assessing confidence in tapinarof and satisfaction with efficacy (62.9%-85.8%), application ease and cosmetic elegance (79.9%-96.3%), and preference for tapinarof versus prior psoriasis therapies (55.3%-81.7%). LIMITATIONS: Open-label; no control; may not be generalizable to all forms of psoriasis. CONCLUSIONS: Continued and durable improvements in health-related quality of life, high rates of patient satisfaction, and positive perceptions of tapinarof cream were demonstrated.

Psoriasis improvements and inflammatory biomarker normalization with secukinumab: the randomized ObePso-S study.

BACKGROUND: The IL-17A inhibitor secukinumab has demonstrated consistent efficacy and safety in patients with moderate-to-severe plaque psoriasis, with normalization of molecular and histopathologic psoriasis markers. OBJECTIVE: To investigate treatment effects of secukinumab on clinical signs and psoriatic inflammation markers over 52 weeks in patients with psoriasis. METHODS: In the ObePso-S study (NCT03055494), patients with psoriasis were randomized 2:1 to receive secukinumab 300 mg (n = 54) or placebo (n = 28), stratified by body weight (<90 or ≥90 kg), for 52 weeks. At Week 12, patients receiving placebo were switched to secukinumab. Psoriasis Area and Severity Index improvement of 90% (PASI90) and Investigator's Global Assessment modified 2011 0/1 responses were assessed at Weeks 12 and 52. Immunohistochemistry for keratin 16 (K16) and gene expression profiles were evaluated in lesional and non-lesional skin biopsies collected at baseline, Week 12, and Week 52. RESULTS: Of patients receiving secukinumab, 55.8% and 59.6% achieved PASI90 at Weeks 12 and 52, respectively. K16 was absent in 93.1% of Week 12 PASI90 responders and 93.6% of Week 52 PASI90 responders, which mirrored the down-regulated expression of psoriatic inflammation. Week 52 PASI90 non-responders experienced regression of clinical and inflammatory marker responses toward baseline levels. Lower control of inflammatory gene expression at Week 12 was associated with suboptimal clinical responses at Week 52. CONCLUSION: Sustained clinical responses with secukinumab were associated with rapid and sustained normalization of K16 and inflammatory gene expression in most patients. Molecular anti-inflammatory effects of secukinumab at Week 12 were associated with clinical responses at Week 52.

Deucravacitinib versus placebo and apremilast in moderate to severe plaque psoriasis: Efficacy and safety results from the 52-week, randomized, double-blinded, phase 3 Program fOr Evaluation of TYK2 inhibitor psoriasis second trial.

BACKGROUND: Deucravacitinib, an oral, selective, allosteric tyrosine kinase 2 inhibitor, inhibits cytokine signaling in psoriasis pathogenesis. OBJECTIVE: The objective of this study was to demonstrate deucravacitinib superiority versus placebo and apremilast in moderate to severe plaque psoriasis based on ≥75% reduction from baseline in Psoriasis Area and Severity Index and a static Physician's Global Assessment score of 0 (clear) or 1 (almost clear) with a ≥2-point improvement from baseline at week 16. METHODS: POETYK psoriasis second trial (NCT03611751), a 52-week, double-blinded, phase 3 trial, randomized patients 2:1:1 to deucravacitinib 6 mg every day (n = 511), placebo (n = 255), or apremilast 30 mg twice a day (n = 254). RESULTS: At week 16, significantly more deucravacitinib-treated patients versus placebo and apremilast patients achieved ≥75% reduction from baseline in Psoriasis Area and Severity Index (53.0% vs 9.4% and 39.8%; P < .0001 vs placebo; P = .0004 vs apremilast) and static Physician's Global Assessment score of 0 or 1 (49.5% vs 8.6% and 33.9%; P < .0001 for both). Efficacy was maintained until week 52 with continuous deucravacitinib. The most frequent adverse event with deucravacitinib was nasopharyngitis. Serious adverse events and discontinuations due to adverse events were infrequent. No clinically meaningful changes were observed in laboratory parameters. LIMITATIONS: The study duration was 1 year. CONCLUSION: Deucravacitinib demonstrated superiority versus placebo and apremilast and was well tolerated in adults with moderate to severe plaque psoriasis.

Outcomes of Biologic Use in Asian Compared with Non-Hispanic White Adult Psoriasis Patients from the CorEvitas Psoriasis Registry.

INTRODUCTION: Real-world data are limited comparing Asian and White patients with psoriasis using biologic therapy. This study compared the 6-month effectiveness of biologic therapy between Asian and White plaque patients with psoriasis in the CorEvitas Psoriasis Registry. METHODS: Analyses included biologic initiations and 6-month follow-up visits from self-identified Asian (n = 293) and White (n = 2314) patients in the USA/Canada (4/2015-4/2020). Outcomes included: Psoriasis Area Severity Index (PASI) 75, disease activity measures [body surface area (BSA) ≤ 1, BSA ≤ 3, PASI90, PASI100, Investigator's Global Assessment (IGA) 0/1], and patient-reported outcomes [Dermatology Life Quality Index (DLQI) 0/1, itch, fatigue, skin pain, EuroQoL visual analog scale (EQ-VAS), patient global assessment, Work Productivity Activity and Impairment (WPAI) domains]. Unadjusted regression models were used to calculate odds ratios (OR) and 95% confidence intervals (CI) for achievement of binary outcomes and difference in mean change in continuous outcomes (ß, 95% CI) at 6 months, followed by adjustment for age, sex, body mass index, alcohol, smoking, health insurance, education, comorbidities, scalp psoriasis morphology, psoriatic arthritis, biologic class, previous biologics, and baseline outcome value. RESULTS: Asians had lower proportions of women (32.8% versus 49.1%) and obesity (27.3% versus 54.5%), and higher proportions on Medicaid (19.9% versus 8.8%), graduated college (50.9% versus 40.1%) and never smoked (67.1% versus 44.1%). In unadjusted analyses, Asians had 52% higher odds of achieving PASI75 versus White patients (OR 1.52; 95% CI 1.15, 2.02). After adjustment, the association was attenuated (OR 1.11; 0.81, 1.52). Secondary outcomes experienced similar patterns except for DLQI: Asians had 33% lower odds of achieving DLQI 0/1 in both the unadjusted (OR 0.67; 0.50, 0.90) and adjusted (OR 0.67; 0.49, 0.92) models. CONCLUSION: Unadjusted differences in biologic therapy effectiveness between Asians compared with White patients were likely explained by differences in demographic, lifestyle, and psoriatic disease characteristics between groups. However, Asians still experienced lesser improvements in skin-related quality of life, even after adjustment.

Effect of Roflumilast Cream vs Vehicle Cream on Chronic Plaque Psoriasis: The DERMIS-1 and DERMIS-2 Randomized Clinical Trials.

Importance: Once-daily roflumilast cream, 0.3%, a potent phosphodiesterase 4 inhibitor, demonstrated efficacy and was well tolerated in a phase 2b trial of patients with psoriasis. Objective: To evaluate the efficacy of roflumilast cream, 0.3%, applied once daily for 8 weeks in 2 trials of patients with plaque psoriasis. Design, Setting, and Participants: Two phase 3, randomized, double-blind, controlled, multicenter trials (DERMIS-1 [trial 1; n = 439] and DERMIS-2 [trial 2; n = 442]) were conducted at 40 centers (trial 1) and 39 centers (trial 2) in the US and Canada between December 9, 2019, and November 16, 2020, and between December 9, 2019, and November 23, 2020, respectively. Patients aged 2 years or older with plaque psoriasis involving 2% to 20% of body surface area were enrolled. The dates of final follow-up were November 20, 2020, and November 23, 2020, for trial 1 and trial 2, respectively. Interventions: Patients were randomized 2:1 to receive roflumilast cream, 0.3% (trial 1: n = 286; trial 2: n = 290), or vehicle cream (trial 1: n = 153; trial 2: n = 152) once daily for 8 weeks. Main Outcomes and Measures: The primary efficacy end point was Investigator Global Assessment (IGA) success (clear or almost clear status plus ≥2-grade improvement from baseline [score range, 0-4]) at week 8, analyzed using a Cochran-Mantel-Haenszel test stratified by site, baseline IGA score, and intertriginous involvement. There were 9 secondary outcomes, including intertriginous IGA success, 75% reduction in Psoriasis Area and Severity Index (PASI) score, and Worst Itch Numeric Rating Scale score of 4 or higher at baseline achieving 4-point reduction (WI-NRS success) at week 8 (scale: 0 [no itch] to 10 [worst imaginable itch]; minimum clinically important difference, 4 points). Results: Among 881 participants (mean age, 47.5 years; 320 [36.3%] female), mean IGA scores in trial 1 were 2.9 [SD, 0.52] for roflumilast and 2.9 [SD, 0.45] for vehicle and in trial 2 were 2.9 [SD, 0.48] for roflumilast and 2.9 [SD, 0.47]) for vehicle. Statistically significantly greater percentages of roflumilast-treated patients than vehicle-treated patients had IGA success at week 8 (trial 1: 42.4% vs 6.1%; difference, 39.6% [95% CI, 32.3%-46.9%]; trial 2: 37.5% vs 6.9%; difference, 28.9% [95% CI, 20.8%-36.9%]; P < .001 for both). Of 9 secondary end points, statistically significant differences favoring roflumilast vs vehicle were observed for 8 in trial 1 and 9 in trial 2, including intertriginous IGA success (71.2% vs 13.8%; difference, 66.5% [95% CI, 47.1%-85.8%] and 68.1% vs 18.5%; difference, 51.6% [95% CI, 29.3%-73.8%]; P < .001 for both), 75% reduction in PASI score (41.6% vs 7.6%; difference, 36.1% [95% CI, 28.5%-43.8%] and 39.0% vs 5.3%; difference, 32.4% [95% CI, 24.9%-39.8%]; P < .001 for both), WI-NRS success (67.5% vs 26.8%; difference, 42.6% [95% CI, 31.3%-53.8%] and 69.4% vs 35.6%; difference, 30.2% [95% CI, 18.2%-42.2%]; P < .001 for both). The incidence of treatment-emergent adverse events was 25.2% with roflumilast vs 23.5% with vehicle in trial 1 and 25.9% with roflumilast vs 18.4% with vehicle in trial 2. The incidence of serious adverse events was 0.7% with roflumilast vs 0.7% with vehicle in trial 1 and 0% with roflumilast vs 0.7% with vehicle in trial 2. Conclusions and Relevance: Among patients with chronic plaque psoriasis, treatment with roflumilast cream, 0.3%, compared with vehicle cream resulted in better clinical status at 8 weeks. Further research is needed to assess efficacy compared with other active treatments and to assess longer-term efficacy and safety. Trial Registration: ClinicalTrials.gov Identifiers: NCT04211363, NCT04211389.

Adjunctive Use of Halobetasol Propionate-Tazarotene in Biologic-Experienced Patients With Psoriasis.

Not all patients with psoriasis achieve a satisfactory response to their initial biologic monotherapy. Switching to a new biologic may be associated with new safety issues and additional costs. In this study, we assessed the effectiveness and safety of adjunctive halobetasol propionate (HP) 0.01%-tazarotene (TAZ) 0.045% lotion in adult patients with moderate to severe plaque psoriasis who had been receiving biologic monotherapy for 24 weeks or more but had inadequate responses. All participants received HP-TAZ lotion once daily for 8 weeks, then once every other day for 4 weeks, in addition to their ongoing biologics. This real-world study demonstrated that HP-TAZ lotion adjunctive to ongoing biologics is safe and effective and potentially a more economical alternative to switching biologics for patients with psoriasis with inadequate responses to biologic monotherapy.

Baseline Demographics and Severity and Burden of Atopic Dermatitis in Adult Patients Initiating Dupilumab Treatment in a Real-World Registry (PROSE).

INTRODUCTION: Dupilumab was initially approved in 2017 as the first biologic therapy for atopic dermatitis (AD). We characterized adults with AD initiating dupilumab in a real-world setting in the USA/Canada. METHODS: PROSE is an ongoing, longitudinal, prospective, observational, multicenter registry of patients with AD initiating dupilumab per country-specific prescribing information. We report baseline data (day of first dupilumab injection) for patients enrolled from April 2018 through July 2019. RESULTS: Among 315 patients (mean age 42.5 years, 55.2% female), the median AD duration was 17.0 years; 65.4% reported a history of type 2 inflammatory comorbidities (e.g., allergic rhinitis, asthma), and 93.3% reported treatment(s) for AD in the previous year, including topical corticosteroids (90.8%), systemic corticosteroids (36.2%), and nonsteroidal systemic therapies (14.0%). In total, 89.2% had an Overall Disease Severity score of 3 (moderate) or 4 (severe). Other mean disease severity scores included the following: Eczema Area and Severity Index 16.9 (range 0-72), body surface area affected 26.8%, Patient-Oriented Eczema Measure 18.5 (range 0-28), Dermatology Life Quality Index 12.7 (range 0-30), and pruritus Numerical Rating Scale score 6.9 (range 0-10). CONCLUSION: Patients initiating dupilumab have longstanding moderate-to-severe AD with significant disease burden and frequent type 2 comorbidities. GOV IDENTIFIER: NCT03428646.

Adjunctive Use of Calcipotriene 0.005%/Betamethasone Dipropionate 0.064% Foam in Patients With Psoriasis Treated With Ixekizumab.

OBJECTIVE: To examine the effectiveness and safety of adjunctive treatment with calcipotriene 0.005%/betamethasone dipropionate 0.064% (Cal/BD) foam in adult patients with chronic plaque psoriasis who have localized residual plaques after ≥24 weeks of treatment with ixekizumab biologic therapy. METHODS: This study was a prospective, open-label, single-arm study of adult patients with moderate-to-severe chronic plaque psoriasis who had suboptimal response after ≥24 weeks of treatment with ixekizumab (residual 3–8% body surface area [BSA] involvement). All patients continued treatment with ixekizumab and received once-daily Cal/BD foam for 4 weeks, followed by every other day for weeks 8 to 12. The primary endpoint was treat-to-target BSA ≤1% at week 4. Additional endpoints included the Physician’s Global Assessment (PGA) score, PGA×BSA, and the patient-reported Dermatology Life Quality Index (DLQI). Safety evaluations included assessments of adverse events (AEs) and local skin reactions. RESULTS: Among 25 enrolled patients, 36% were female, and the mean age was 50 years. After 4 weeks of daily Cal/BD foam, 56% of patients achieved the treat-to-target goal of ≤1% BSA. Mean % BSA involvement, mean PGA score, and composite PGA×BSA score decreased 4 weeks after the addition of Cal/BD foam. Improvements in disease severity outcomes were maintained after reducing Cal/BD dosing frequency. Cal/BD was generally safe and well-tolerated, with no serious AEs reported. CONCLUSION: In real-world clinical practice, for patients with moderate-to-severe plaque psoriasis who had residual plaques following ≥24 weeks of ixekizumab monotherapy, adjunctive treatment with Cal/BD foam was associated with notable and sustained improvements in disease control. J Drugs Dermatol. 2022;21(3): 235-240. doi:10.36849/JDD.6396.

Bimekizumab Self-Injection Devices: Two Multicenter, Randomized, Open-Label Studies on Self-Administration by Patients With Psoriasis.

BACKGROUND: Bimekizumab is a monoclonal IgG1 antibody that selectively inhibits interleukin (IL)-17F in addition to IL-17A. OBJECTIVES: To assess patients' ability to self-inject bimekizumab subcutaneously using a 1 mL safety syringe or auto-injector. METHODS: DV0002 and DV0006 were sub-studies of BE BRIGHT, a multicenter, phase 3 open-label extension study. Patients with moderate to severe plaque psoriasis received bimekizumab 320 mg (2x160 mg injections) every 4 or 8 weeks and were randomized 1:1 to the safety syringe or the auto-injector. The ability of patients to safely and effectively self-inject bimekizumab was assessed at 8 weeks (primary endpoint) and immediately after self-injection training at Baseline (secondary endpoint). Patient experience was evaluated using the pain visual analog scale (VAS; 0–100 mm; 100 being worst pain), and the Self-Injection Assessment Questionnaire (SIAQ; 0–10; 10 being most positive experience). RESULTS: All evaluable patients in DV0002 (n=125) and DV0006 (n=86) safely and effectively self-injected bimekizumab at Week 8. All evaluable patients in DV0002 who used the safety syringe (n=64) and 97.1% (n=66/68) who used the auto-injector, as well as all evaluable DV0006 patients (n=88) also self-injected bimekizumab safely and effectively at Baseline. Median VAS scores were low (range: 7.0–20.0), and median pre-injection and post-injection SIAQ scores were high (range: 5.8–10.0 and 7.1–10.0, respectively) across both devices, sub-studies, and timepoints. CONCLUSIONS: Both devices provide a safe and effective option for patients to self-administer bimekizumab. Furthermore, patients reported a positive self-injection experience. TRIAL REGISTRATION: NCT03766685 J Drugs Dermatol. 2022;21(2):162-171. doi:10.36849/JDD.6274THIS ARTICLE HAD BEEN MADE AVAILABLE FREE OF CHARGE. PLEASE SCROLL DOWN TO ACCESS THE FULL TEXT OF THIS ARTICLE WITHOUT LOGGING IN. NO PURCHASE NECESSARY. PLEASE CONTACT THE PUBLISHER WITH ANY QUESTIONS.

Secukinumab dosing every 2 weeks demonstrated superior efficacy compared with dosing every 4 weeks in patients with psoriasis weighing 90 kg or more: results of a randomized controlled trial.

BACKGROUND: Obesity is a common comorbidity of psoriasis and can attenuate response to biologic treatment. OBJECTIVES: To investigate the efficacy, safety and tolerability of secukinumab 300 mg every 2 weeks (Q2W) vs. secukinumab 300 mg every 4 weeks (Q4W) in patients with a higher bodyweight. METHODS: In this multicentre, double-blind, parallel-group trial, 331 patients with moderate-to-severe chronic plaque psoriasis weighing ≥ 90 kg were randomized to receive secukinumab 300 mg Q2W or secukinumab 300 mg Q4W. Patients who did not achieve Psoriasis Area and Severity Index (PASI) 90 at week 16 on the Q4W regimen were reallocated to remain on the Q4W regimen or uptitrate to Q2W. RESULTS: At week 16, Q2W dosing (n = 165) led to significantly higher PASI 90 responses vs. Q4W [n = 166; 73.2% vs. 55.5%, one-sided P-value = 0.0003, odds ratio estimate (95% confidence intervals): 2.3 (1.4-3.8)]. At week 52, higher efficacy responses were maintained in the Q2W arm (n = 165) vs. Q4W (n = 83); PASI 75: 88.9% vs. 74.8%; PASI 90: 76.4% vs. 52.4%; PASI 100: 46.7% vs. 27.3%; Investigator's Global Assessment 0/1: 75.9% vs. 55.6% and Dermatology Life Quality Index 0/1: 66.1% vs. 48.8%. PASI 90 nonresponders at week 16 who uptitrated to Q2W (n = 31) showed higher efficacy responses at week 32 (16 weeks post-uptitration, PASI 90: 38.7% vs. 16.5%) vs. those who remained on Q4W (n = 40). Safety results were comparable across treatment arms and consistent with the established secukinumab safety profile. CONCLUSIONS: Secukinumab 300 mg Q2W demonstrated superior and sustained efficacy compared with Q4W in patients with moderate-to-severe plaque psoriasis weighing ≥ 90 kg. PASI 90 nonresponders derived additional benefits from uptitration to a Q2W regimen (ClinicalTrials.gov identifier: NCT03504852). What is already known about this topic? Obesity is a common comorbidity of psoriasis and can attenuate response to biologic treatment. Secukinumab is a fully human monoclonal antibody that selectively neutralizes interleukin-17A in the treatment of moderate-to-severe plaque psoriasis. Subgroup analyses of previous study results and pharmacokinetic/pharmacodynamic modelling data suggest that heavier patients may benefit from higher exposure to secukinumab through an increased dosing frequency [300 mg every 2 weeks (Q2W) vs. every 4 weeks (Q4W)]. What does this study add? Over 52 weeks, secukinumab 300 mg Q2W demonstrated superior efficacy compared with secukinumab 300 mg Q4W in patients with moderate-to-severe plaque psoriasis weighing ≥90 kg, with comparable safety results, consistent with the established secukinumab safety profile. In patients who did not achieve PASI 90 at week 16 on the Q4W regimen, uptitration to the Q2W regimen at week 16 resulted in improved efficacy responses through week 52 after switching.

Efficacy, safety, usability, and acceptability of risankizumab 150 mg formulation administered by prefilled syringe or by an autoinjector for moderate to severe plaque psoriasis.

BACKGROUND: Risankizumab is approved for treatment of moderate to severe plaque psoriasis. Availability of a patient-controlled single self-injection of risankizumab may improve adherence and long-term management of psoriasis. OBJECTIVE: To investigate efficacy, safety, and usability of a new risankizumab 150 mg/mL formulation administered as a single subcutaneous injection via prefilled syringe (PFS) or autoinjector (AI). METHODS: Efficacy, safety, usability, and acceptability of risankizumab 150 mg/mL PFS or AI were investigated in adults with moderate to severe psoriasis in two phase 3 studies. Study 1 was a multicenter, randomized, double-blinded, placebo-controlled study that investigated 150 mg/mL risankizumab PFS; study 2 was a multicenter, single-arm, open-label study that investigated 150 mg/mL risankizumab AI. RESULTS: At week 16, risankizumab 150 mg/mL demonstrated efficacy vs. placebo (Psoriasis Area and Severity Index ≥90% improvement (PASI 90), 62.9% vs. 3.8%; static Physician Global Assessment (sPGA) 0/1, 78.1% vs. 9.6%; both p< .001) in study 1; in study 2, PASI 90 and sPGA 0/1 were 66.7%, and 81.5%, respectively. All patients successfully self-administered study treatments via PFS or AI. Acceptability of self-injection was high in both studies. Efficacy and safety of risankizumab 150 mg/mL were comparable with results from previous risankizumab phase 3 studies using the 90 mg/mL formulation. CONCLUSIONS: The efficacy, safety, and usability of 150 mg/mL risankizumab delivered as a single PFS or AI injection support use of this new formulation in patients with moderate to severe plaque psoriasis. CLINICAL TRIALS: NCT03875482 and NCT0387508.

Efficacy of guselkumab versus secukinumab in subpopulations of patients with moderate-to-severe plaque psoriasis: results from the ECLIPSE study.

PURPOSE: Guselkumab, an interleukin (IL)-23 inhibitor, effectively treats moderate-to-severe plaque psoriasis. MATERIALS AND METHODS: ECLIPSE, was a Phase 3, multicenter, 56-week, double-blinded, active-comparator study of guselkumab vs. secukinumab (IL-17A inhibitor) in patients with moderate-to-severe psoriasis. Patients were treated with guselkumab 100 mg (n = 534) or secukinumab 300 mg (n = 514) through week 44. Efficacy (at least a 90% and 100% improvement from baseline in Psoriasis Area and Severity Index [PASI 90 and PASI 100], Investigator's Global Assessment [IGA] 0/1, and IGA 0) was analyzed across subpopulations defined by baseline: age (<45, 45 to <65, and ≥65 years old), body weight, body mass index (BMI), psoriasis disease severity (body surface area, disease duration, PASI, and IGA), psoriasis by body regions (head, trunk, upper and lower extremities), and prior psoriasis medication history at week 48. RESULTS: Overall, 1048 patients were randomized. At week 48, numerically greater proportions of patients achieved PASI 90, PASI 100, IGA 0/1, and IGA 0 with guselkumab vs. secukinumab regardless of baseline age, body weight, BMI, disease severity, body region, and prior medication. The largest differences were in patients ≥65 years old and patients weighing >100 kg. CONCLUSIONS: Guselkumab treatment provided greater efficacy vs. secukinumab at week 48 in most subpopulations of patients with psoriasis.

Phase 3 Trials of Tapinarof Cream for Plaque Psoriasis.

BACKGROUND: Tapinarof cream is a topical aryl hydrocarbon receptor-modulating agent under investigation for the treatment of psoriasis. Tapinarof modulates the expression of interleukin-17 and the skin-barrier proteins filaggrin and loricrin. METHODS: We conducted two identical phase 3 randomized trials of tapinarof in patients with mild-to-severe plaque psoriasis. Adults with a baseline Physician's Global Assessment (PGA) score of 2 (mild) to 4 (severe) (on a scale from 0 to 4, with higher scores indicating more severe psoriasis) and a percent of total body-surface area affected of 3 to 20% were randomly assigned in a 2:1 ratio to use tapinarof 1% cream or vehicle cream once daily for 12 weeks. The primary end point, PGA response, was a PGA score of 0 (clear) or 1 (almost clear) and a decrease from baseline of at least 2 points at week 12. Secondary efficacy end points at week 12 were a reduction of at least 75% in the Psoriasis Area and Severity Index (PASI) score, a PGA score of 0 or 1, the mean change from baseline in the percent of body-surface area affected, and a reduction of at least 90% in the PASI score. Patient-reported outcomes were the mean changes from baseline to week 12 in the proportion of patients who had a decrease of at least 4 points in the Peak Pruritus Numeric Rating Scale (PP-NRS) score (range, 0 [no itch] to 10 [worst imaginable itch]), the PP-NRS total score, the Dermatology Life Quality Index total score, and the Psoriasis Symptom Diary score. RESULTS: In trials 1 and 2, a total of 692 and 674 patients, respectively, were screened, with 510 and 515 patients being enrolled. A PGA response occurred in 35.4% of the patients in the tapinarof group and in 6.0% of those in the vehicle group in trial 1 and in 40.2% and 6.3%, respectively, in trial 2 (P<0.001 for both comparisons). Results for secondary end points and patient-reported outcomes were generally in the same direction as those for the primary end point. Adverse events with tapinarof cream included folliculitis, nasopharyngitis, contact dermatitis, headache, upper respiratory tract infection, and pruritus. CONCLUSIONS: Tapinarof 1% cream once daily was superior to vehicle control in reducing the severity of plaque psoriasis over a period of 12 weeks but was associated with local adverse events and headache. Larger and longer trials are needed to evaluate the efficacy and safety of tapinarof cream as compared with existing treatments for psoriasis. (Funded by Dermavant Sciences; PSOARING 1 and 2 ClinicalTrials.gov numbers, NCT03956355 and NCT03983980, respectively.).

Serious Gastrointestinal-Related Adverse Events Among Psoriasis Patients Treated With Guselkumab in VOYAGE 1 and VOYAGE 2.

BACKGROUND: Anti-interleukin (IL)-17 biologic agents used to treat psoriasis are associated with onset/exacerbation of inflammatory bowel disease (IBD). OBJECTIVES: To determine the incidence of IBD or serious gastrointestinal-related adverse events (GI SAEs) in patients with moderate-to-severe psoriasis treated with guselkumab, an IL-23p19 inhibitor that indirectly inhibits IL-17, through 4 years in the phase 3 VOYAGE 1 and VOYAGE 2 trials. METHODS: Patients were randomized to guselkumab 100 mg every-8-weeks or placebo→guselkumab (week 16), or adalimumab. In VOYAGE 1, all patients received open-label guselkumab starting at week 52. In VOYAGE 2, eligible patients were treated with guselkumab or placebo based on clinical response starting at week 28 and received open-label guselkumab starting at week 76. Cumulative incidence rates of IBD and other GI SAEs were calculated as events per 100 patient-years (PY) through week 204. IBD was defined as AEs of Crohn’s disease or ulcerative colitis. Data were summarized for all guselkumab-treated patients for years 1-4. RESULTS: Of 1721 guselkumab-treated patients, 1612 were exposed for ≥1 year, 1545 for ≥2 years, 1454 for ≥3 years, and 661 for ≥4 years. For all patients through week 204, the cumulative rate of GI SAEs was 0.45/100PY. Event rates remained stable with longer duration of exposure, ranging from 0.36 to 0.57/100PY. No new or exacerbated cases of IBD were reported. CONCLUSIONS: No cases of IBD were observed and rates of GI SAEs were low through 4 years of treatment with guselkumab in two large trials of patients with psoriasis. J Drugs Dermatol. 2021;20(8):855-860. doi:10.36849/JDD.6216 THIS ARTICLE HAD BEEN MADE AVAILABLE FREE OF CHARGE. PLEASE SCROLL DOWN TO ACCESS THE FULL TEXT OF THIS ARTICLE WITHOUT LOGGING IN. NO PURCHASE NECESSARY. PLEASE CONTACT THE PUBLISHER WITH ANY QUESTIONS.