Static Physician Global Assessment Research Articles

Real-World Long-Term Effectiveness of Risankizumab Among Patients with Moderate-to-Severe Psoriasis: Analysis from an International Medical Chart Review (RAPID) Study.

Real-world data on the efficacy of risankizumab (RZB) in clinical moderate-to-severe plaque psoriasis (PsO) are limited. The RAPID study assessed real-world clinical and patient-reported outcomes in RZB-treated PsO patients using data collected from dermatologists in Canada, the Czech Republic, Germany, Japan, and Poland. This ongoing, retrospective chart review collected data from medical records of RZB-treated adults with moderate-to-severe PsO (09/2022-06/2023). Eligible patients received RZB, had ≥ 12months of medical records after RZB initiation (index date), and had Psoriasis Area and Severity Index (PASI), Investigator Global Assessment (IGA), or static Physician's Global Assessment (sPGA) scores ≥ 3months before and up to 18months after the index date. The proportion of patients achieving a clear/almost clear PsO (IGA/sPGA = 0/1), PASI ≤ 1, Dermatology Life Quality Index (DLQI) = 0/1, and a 90%/100% improvement from baseline in PASI as well as the mean changes in PASI, DLQI, itch, and skin pain scores at 12 and 18 months were reported for patients with non-missing assessments at baseline and 12months. Most patients (66.4%) were male, 74.0% were biologic naïve, and 73.0% had scalp PsO. Mean baseline IGA/sPGA was 3.7 ± 0.5, with a mean PASI of 23.3 ± 11.8. After 12months, 86.1% of patients reported IGA/sPGA ≤ 1, and 75.7% achieved PASI90; these further increased to 91.1% and 80.5% at 18months. DLQI, itch, and skin pain scores improved over time. These data demonstrated the durable, real-world effectiveness of RZB in patients with moderate-to-severe PsO through continued improvement in disease and symptom severity over 18months, with most of the patients reporting clear/almost clear skin.

Cedirogant in adults with psoriasis: a phase 2, randomized, placebo-controlled clinical trial.

Dysregulated interleukin (IL)-17/IL-23 signaling contributes to psoriasis pathogenesis. Cedirogant is an inverse agonist of retinoic acid-related orphan receptor gamma thymus (RORγt), a key transcription factor responsible for IL-17 synthesis and a regulator of the T helper 17 cell lineage program. To evaluate the efficacy and safety of cedirogant to treat moderate-to-severe psoriasis. In this phase 2b, multicenter, double-blind, 16-week study (NCT05044234), adults aged 18-65 years were randomized 1:1:1:1 to once-daily oral cedirogant 75 mg, 150 mg, 375 mg, or placebo. Assessments included ≥50%/75%/90%/100% improvement from baseline in Psoriasis Area and Severity Index (PASI 50/75/90/100), static Physician Global Assessment 0/1, Psoriasis Symptoms Scale 0, and improvements in itch, adverse events (AEs), pharmacokinetics, and IL-17A/F levels. Efficacy results based on observed cases were summarized descriptively. Of 156 enrolled patients, most were male (70.5%); 39 patients were randomized to each treatment. Only 47 patients completed the study; the study was terminated early due to preclinical findings. At week 16, PASI 75 achievement rates (primary endpoint) were 28.6%, 7.7%, and 41.7% in the cedirogant 75 mg, 150 mg, and 375 mg groups, respectively, and 0% in the placebo group. AE rates were similar in the cedirogant 75 mg, 150 mg, and placebo groups and higher in the cedirogant 375-mg group; most AEs were mild or moderate. Patients with psoriasis who received cedirogant showed PASI improvement and cedirogant was generally well tolerated. Results should be interpreted in the context of early study termination. Cedirogant development has been discontinued.

Bimekizumab for the Treatment of Plaque Psoriasis With Involvement of Genitalia: A 16-Week Multicenter Real-World Experience - IL PSO (Italian Landscape Psoriasis).

Genital involvement is observed in approximately 60% of patients with psoriasis, presenting clinicians with formidable challenges in treatment. While new biologic drugs have emerged as safe and effective options for managing psoriasis, their efficacy in challenging-to-treat areas remains inadequately explored. Intriguingly, studies have shown that interleukin (IL)-17 inhibitors exhibit effectiveness in addressing genital psoriasis. We aimed to determine the effectiveness profile of bimekizumab in patients affected by moderate-to-severe plaque psoriasis with involvement of genitalia. Bimekizumab, a dual inhibitor of both IL-17A and IL-17F, was the focus of our 16-week study, demonstrating highly favorable outcomes for patients with genital psoriasis. The effectiveness of bimekizumab was evaluated in terms of improvement in Static Physician's Global Assessment of Genitalia (sPGA-G) and Psoriasis Area and Severity Index. Sixty-five adult patients were enrolled. Remarkably, 98.4% of our participants achieved a clear sPGA-G score (s-PGA-g=0) within 16 weeks. Moreover, consistent improvements were observed in PASI scores, accompanied by a significant reduction in the mean Dermatology Life Quality Index (DLQI), signifying enhanced quality of life. Notably, none of the patients reported a severe impairment in their quality of life after 16 weeks of treatment. In our cohort of 65 patients, subgroup analyses unveiled that the effectiveness of bimekizumab remained unaffected by prior exposure to other biologics or by obesity. Our initial findings suggest that bimekizumab may serve as a valuable treatment option for genital psoriasis. Nevertheless, further research with larger sample sizes and longer-term follow-up is imperative to conclusively validate these results.

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

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.
 
 
 
 
 
 
 
 
 
 
 

Real-world data on the effectiveness of brodalumab in patients with moderate-to severe plaque psoriasis in the Greek clinical setting (the BrIDGE study).

Despite that brodalumab's efficacy and safety have been assessed in randomized clinical trials, real-life data remain scarce. BrIDGE was an observational, prospective, single-cohort, multicentre study that recruited patients with moderate-to severe plaque psoriasis in Greece. The primary objective was to assess the proportion of patients who achieved Psoriasis Area and Severity Index (PASI)100 after 24 weeks. Other endpoints included: the maintenance of PASI90/100 through to 104 weeks, the short-term response [PASI75/90/100 and static Physician's Global Assessment (sPGA) 0/1] to brodalumab at 12-16 weeks and time to complete clearance. Moreover, we explored the change in quality of life [Dermatology Life Quality Index (DLQI) 0/1] and adherence to brodalumab. Two hundred patients who were initiating treatment with or switching to brodalumab, were recruited. Analyses were conducted using the as observed data and three imputation approaches were also applied for the missing data (last observation carried forward, 'worst case' and 'best case' scenario). Continuous variables were reported using summary statistics, whereas categorical variables were reported in frequency tables. Based on the 'as observed data', 42.0% of patients achieved PASI100 at Week 24 after 25.9 ± 3.5 weeks and 65% of patients attained PASI100 at Week 104. In total, 70.2%, 47.5% and 32.0% achieved PASI75/90/100, respectively, whereas 72.6% of patients achieved sPGA 0/1, at Weeks 12-16. With respect to sPGA status 82.8%, 89.2% and 92.5% of patients achieved sPGA 0/1 at Weeks 24, 52 and 104, respectively. The time to achieve PASI100 at Weeks 12-16 was 13.7 ± 1.3, 52.1 ± 3.4 weeks at Week 52 and 105.5 ± 4.8 weeks at Week 104. Mean DLQI and Psoriasis Symptom Inventory (PSI) scores decreased by 11.4 ± 7.0 and 15.4 ± 6.5 points from baseline to Week 104, respectively. Adherence to treatment was equal to 98.9%. Brodalumab confers rapid and durable responses, as well as improvements in the quality of life of moderate-to-severe psoriasis patients.

Efficacy and safety of apremilast in pediatric patients with moderate-to-severe plaque psoriasis: 16-week results from SPROUT, a randomized controlled trial

Approved systemic treatment options are limited for pediatric patients with moderate to severe plaque psoriasis. To assess the efficacy and safety of apremilast over 16weeks in pediatric patients with plaque psoriasis. SPROUT (NCT03701763) was a phase 3, multicenter, randomized, double-blind, placebo-controlled study of apremilast in patients aged 6-17years with moderate-to-severe psoriasis (Psoriasis Area and Severity Index [PASI] ≥12, body surface area ≥10%, static Physician Global Assessment [sPGA] ≥3) inadequately controlled by/inappropriate for topical therapy. Patients were stratified by age group and randomized (2:1) to apremilast (20 or 30mg BID based on weight) or placebo for 16weeks, followed by apremilast extension to 52weeks. Of 245 patients randomized (apremilast: 163; placebo: 82), 221 (90%) completed the double-blind phase (apremilast: 149; placebo: 72). Significantly more patients achieved sPGA response and ≥75% reduction in PASI with apremilast than placebo, regardless of baseline age, weight, or disease severity. No new safety signals were observed. Sample size of subgroup analyses. Improvements in global disease activity and skin involvement were significantly greater in pediatric patients treated with apremilast versus placebo. Adverse events were consistent with the known apremilast safety profile.

Comparative Effectiveness and Durability of Biologics in Clinical Practice: Month12 Outcomes from the International, Observational Psoriasis Study of Health Outcomes (PSoHO).

Given the chronic nature of psoriasis (PsO), more studies are needed that directly compare the effectiveness of different biologics over long observation periods. This study compares the effectiveness and durability through 12months of anti-interleukin (IL)-17A biologics relative to other approved biologics in patients with moderate-to-severe psoriasis in a real-world setting. The Psoriasis Study of Health Outcomes (PSoHO) is an ongoing 3-year, prospective, non-interventional cohort study of 1981 adults with chronic moderate-to-severe plaque psoriasis initiating or switching to a new biologic. The study compares the effectiveness of anti-IL-17A biologics with other approved biologics and provides pairwise comparisons of seven individual biologics versus ixekizumab. The primary outcome was defined as the proportion of patients who had at least a 90% improvement in Psoriasis Area and Severity Index score (PASI90) and/or a score of 0 or 1 in static Physician Global Assessment (sPGA). Secondary objective comparisons included the proportion of patients who achieved PASI90, PASI100, a Dermatology Life Quality Index (DLQI) score of 0 or 1, and three different actions of durability of treatment response. Unadjusted response rates are presented alongside the primary analysis, which uses frequentist model averaging (FMA) to evaluate the adjusted comparative effectiveness. Compared to the other biologics cohort, the anti-IL-17A cohort had a higher response rate (68.0% vs. 65.1%) and significantly higher odds of achieving the primary outcome at month12. The two cohorts had similar response rates for PASI100 (40.5% and 37.1%) and PASI90 (53.9% and 51.7%) at month12, with no significant differences between the cohorts in the adjusted analyses. At month12, the response rates across the individual biologics were 53.5-72.6% for the primary outcome, 27.6-48.3% for PASI100, and 41.7-61.4% for PASI90. These results show the comparative effectiveness of biologics at 6 and 12months in the real-world setting. ClinicalTrials.gov identifier EUPAS24207.

Management of Moderate to Severe Plaque Psoriasis with Brodalumab in Daily Practice: Real-World Evidence from the LIBERO Study in the Czech Republic.

Psoriasis is a chronic, immune-mediated inflammatory skin disease. Despite the availability of several therapies, many patients affected by this disease remain untreated, do not have adequate response, or suffer from treatment-related toxic effects. It has been shown that the interleukin (IL)-17 pathway plays a key role in the immunopathogenesis of psoriasis. Brodalumab, the first human monoclonal IgG2 antibody that selectively binds to subunitA of the human IL-17 receptor, blocking interactions with a number of cytokines of the IL-17 family, has confirmed fast onset of action, high complete clearance rates, and sustained efficacy. Nevertheless, there is only a limited amount of published real-world evidence (RWE) data. This was an open-label, multicenter, real-world, prospective, non-interventional, non-controlled (single-arm) observational study (LIBERO-CZ) assessing the management of moderate to severe psoriasis with brodalumab in daily practice for up to 52weeks of treatment. Fifty-four patients (70.4% male, mean age 46.9 ± 13.4years, weight 95.6 ± 22.7kg, disease duration 18.6 ± 12.7years) were enrolled and included in the final analysis. Forty-nine of the patients completed the study and five discontinued prematurely; 51.8% of all the enrolled patients were biologic-naïve. At baseline, 28% patients were classified as severe (psoriasis area severity index (PASI) ≥ 20). Overall, the mean PASI decreased by 15.6 from 16.1 (± 5.0) at baseline to 0.5 (± 1.2) at the last visit. The primary endpoint of an absolute PASI ≤ 3 at week12 (as observed analysis) was achieved by 95.9% of patients. The static Physician's Global Assessment (sPGA) success (defined as clear = 0 and almost clear = 1) at week52 was achieved by 92.1% of patients. PASI75, PASI90, and PASI100 were achieved by 98.0%, 87.8%, and 75.5% of patients, respectively, after approximately 52weeks of treatment. The study also recorded very positive results concerning patient-reported outcomes. LIBERO-CZ confirms the fast onset and high clearance rates of brodalumab in real life in both biologic-naïve and biologic-experienced patients.

Deucravacitinib in Plaque Psoriasis: Maintenance of Response Over 3 Years in the Phase 3 POETYK PSO-1 and PSO-2 Trials

Introduction: Deucravacitinib, an oral, selective, allosteric tyrosine kinase 2 inhibitor for moderate-to-severe plaque psoriasis, was superior to placebo and apremilast in two global, 52-week, phase 3 trials and maintained long-term efficacy through 2 years with no new safety signals in an ongoing long-term extension (LTE) trial. We report clinical efficacy for up to 3 years (148 weeks) in a subset of patients from these trials.
 Materials: POETYK PSO-1 and PSO-2 randomized patients 1:2:1 to oral placebo, deucravacitinib 6 mg once daily (QD), or apremilast 30 mg twice daily. At Week 52, patients could enter the POETYK LTE and receive open-label deucravacitinib 6 mg QD. Deucravacitinib efficacy, as of June 15, 2022, was evaluated through Week 148 in patients from the pooled PSO-1/PSO-2 populations who received continuous deucravacitinib from Day 1, achieved ≥75% reduction from baseline in Psoriasis Area and Severity Index (PASI 75) at Week 16 (primary endpoint) or at Week 24 (peak response), and entered the LTE. Maintenance of response assessments included PASI 75, PASI 90, and sPGA 0/1 (static Physician Global Assessment of 0 [clear] or 1 [almost clear] with a ≥2-point improvement from baseline), which were reported using modified nonresponder imputation.
 Results: Of patients (N=513) who completed 52 weeks in the parent trials and received continuous deucravacitinib treatment from Day 1, 313 (61.4%) achieved PASI 75 at Week 16 and 336 (66.5%) achieved PASI 75 at Week 24. Among Week 16 PASI 75 responders, PASI 75, PASI 90, and sPGA 0/1 response rates were maintained from Week 52 (87.0%, 60.6%, and 70.8%, respectively) to Week 148 (84.5%, 60.0%, and 62.8%, respectively). Among Week 24 PASI 75 responders, PASI 75, PASI 90, and sPGA 0/1 response rates were maintained from Week 52 (90.2%, 61.6%, and 74.1%, respectively) to Week 148 (86.0%, 60.4%, and 64.5%, respectively).
 Conclusion: Clinical efficacy was maintained with continuous deucravacitinib treatment in most Week 16 and Week 24 PASI 75 responders from the parent trials through 148 weeks, supporting long-term effectiveness of once-daily oral deucravacitinib for 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

Introduction: Deucravacitinib, an oral, selective, allosteric tyrosine kinase 2 inhibitor, is approved in the US, EU, and other countries for the 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 who completed PSO-1/PSO-2. We report safety and efficacy of deucravacitinib 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 once daily (QD), or apremilast twice daily. At Week 52, patients enrolled in the LTE received open-label deucravacitinib 6 mg QD. Safety was evaluated in patients who received ≥1 dose of deucravacitinib using exposure-adjusted incidence rate per 100 person-years (EAIR/PY). Efficacy outcomes (≥75%/≥90% reduction from baseline in Psoriasis Area and Severity Index [PASI 75/90]; static Physician Global Assessment score of 0 [clear] or 1 [almost clear] with a ≥2-point improvement from baseline [sPGA 0/1]) were analyzed using modified nonresponder imputation (mNRI) in patients who received continuous deucravacitinib treatment from Day 1 of the parent trial and were treated in the LTE.
 Results: Of 1519 patients who received ≥1 dose of deucravacitinib (3294.3 PY cumulative exposure), 513 patients received continuous deucravacitinib treatment 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.

Deucravacitinib Long-term Efficacy With Continuous Treatment in Plaque Psoriasis: 2-Year Results From the Phase 3 POETYK PSO-1 and PSO-2 Trials

Introduction: Deucravacitinib, an oral, selective, allosteric tyrosine kinase 2 inhibitor, is approved in the US, EU, and other countries for the treatment of adults with moderate-to-severe plaque psoriasis who are candidates for systemic therapy. Deucravacitinib treatment was superior to placebo and apremilast in the POETYK PSO-1 (NCT03624127) and POETYK PSO-2 (NCT03611751) trials in moderate to severe plaque psoriasis. We evaluated long-term clinical outcomes in patients with ≈2 years (112 weeks) of continuous deucravacitinib exposure.
 Methods: PSO-1 and PSO-2 patients were randomized 1:2:1 to oral placebo, deucravacitinib 6 mg once daily, or apremilast 30 mg twice daily. At Week 52, patients were eligible to enroll in the POETYK long-term extension (LTE; NCT04036435) trial and receive deucravacitinib 6 mg once daily. Efficacy 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) with a ≥2-point improvement from baseline (sPGA 0/1). Efficacy was assessed using modified nonresponder imputation through the data cutoff date of October 1, 2021 (Week 112) in patients receiving continuous deucravacitinib treatment from Day 1 and in patients receiving continuous deucravacitinib treatment who achieved PASI 75 at Week 24. As-observed data and results by treatment failure rules imputation were also analyzed.
 Results: A total of 513 patients received continuous deucravacitinib from Day 1 in PSO-1/PSO-2 until Week 112 in the LTE, including 336 patients who had achieved PASI 75 at Week 24. High clinical response rates achieved at Week 52 in PSO-1/PSO-2 (PASI 75, 73.0%; PASI 90, 46.3%; sPGA 0/1, 58.5%) were maintained at Week 112 in the LTE (PASI 75, 76.2%; PASI 90, 48.3%; sPGA 0/1, 58.4%) among patients receiving continuous deucravacitinib treatment from Day 1. High response rates were also maintained in Week 24 PASI 75 responders (Week 52: PASI 75, 90.3%: PASI 90, 62.1%: sPGA 0/1, 73.8%; Week 112: PASI 75, 89.2%; PASI 90, 61.1%; sPGA 0/1, 70.5%). Results were consistent regardless of data imputation methodology.
 Conclusion: Deucravacitinib was associated with sustained efficacy through 2 years in patients who received continuous treatment from Day 1 and in patients who achieved PASI 75 at Week 24. High clinical response rates achieved at Week 52 were maintained at Week 112. These findings provide additional support for deucravacitinib as an efficacious long-term treatment for moderate to severe plaque psoriasis.

Deucravacitinib, an Oral, Selective, Allosteric Tyrosine Kinase 2 Inhibitor, in Moderate to Severe Plaque Psoriasis: Efficacy by Baseline Body Surface Area (BSA) Involvement and Baseline Psoriasis Area and Severity Index (PASI)

Introduction: Deucravacitinib, an oral, selective, allosteric tyrosine kinase 2 inhibitor, is approved in the US, EU, and other countries for the treatment of adults with moderate-to-severe plaque psoriasis who are candidates for systemic therapy. In the phase 3 POETYK PSO-1 (NCT03624127) and PSO-2 (NCT03611751) trials, deucravacitinib was significantly more efficacious than placebo and apremilast. This analysis evaluated deucravacitinib efficacy by two measures of baseline disease severity, BSA involvement and PASI scores.
 Methods: Patients were randomized 1:2:1 to oral placebo, deucravacitinib 6 mg once daily, or apremilast 30 mg twice daily in both trials, which included 16-week placebo-controlled and 24-week apremilast-controlled periods from Day 1. Of patients randomized to deucravacitinib, those in PSO-1 were treated continuously for 52 weeks; in PSO-2, Week 24 PASI 75 responders were rerandomized to continued deucravacitinib or placebo. Patients randomized to placebo crossed over to deucravacitinib at Week 16 and were treated through Week 52. Efficacy outcomes, including ≥75%/≥90%/100% reductions from baseline in PASI (PASI 75/90/100) and static Physician Global Assessment score of 0 (clear) or 1 (almost clear) (sPGA 0/1), were evaluated using nonresponder imputation in disease severity subgroups defined by baseline BSA involvement (10%-<15%, 15%-<20%, 20%-<30%, ≥30%) and PASI score (12-<15, ≥15). Results are reported through Week 24 in the pooled PSO-1/PSO-2 population (apremilast-controlled) and through Week 52 in the PSO-1 population (continuous deucravacitinib treatment).
 Results: In the pooled PSO-1/PSO-2 population (N=1686), 391 (23.2%) had baseline BSA involvement of 10%-<15% (deucravacitinib, n=194), 371 (22.0%) had 15%-<20% (deucravacitinib, n=183), 391 (23.2%) had 20%-<30% (deucravacitinib, n=198), and 533 (31.6%) had ≥30% (deucravacitinib, n=268). For baseline PASI scores, 387 (23.0%) had a score of 12-<15 (deucravacitinib, n=183) and 1298 (77.0%) had a score of ≥15 (deucravacitinib, n=660). Deucravacitinib-treated patients had comparable PASI 75 response rates across all subgroups at Week 16 (BSA subgroups, 50.5%-58.2%; PASI subgroups, 48.6%-57.0%) and at Week 24 (BSA subgroups, 62.0%-64.1%; PASI subgroups, 59.9%-63.8%), with superior responses versus those in patients receiving placebo or apremilast evaluated in each subgroup. Similar findings were observed for all other efficacy measures. In PSO-1, efficacy was maintained through Week 52 with continuous deucravacitinib treatment across BSA (PASI 75, 67.1%-75.7%; sPGA 0/1, 52.1%-61.2%) and PASI subgroups (PASI 75, 65.6%-73.1%; sPGA 0/1, 54.7%-58.8%).
 Conclusion: Deucravacitinib was efficacious in patients with moderate or severe plaque psoriasis regardless of extent of baseline BSA involvement or PASI scores.

Efficacy and safety of apremilast in patients with moderate-to-severe genital psoriasis: Results from DISCREET, a phase 3 randomized, double-blind, placebo-controlled trial

Genital psoriasis can be stigmatizing, is highly prevalent among patients with psoriasis, and has limited treatment options. Apremilast is a unique oral immunomodulating phosphodiesterase 4 inhibitor approved for psoriasis treatment. To assess the efficacy and safety of apremilast 30mg twice daily in patients with genital psoriasis. DISCREET, a phase 3, placebo-controlled trial (NCT03777436), randomized patients with moderate-to-severe genital psoriasis (stratified by affected body surface area <10% or ≥10%) to apremilast or placebo for a 16-week period, followed by an apremilast extension period. Week 16 results are presented. Patients were randomized to apremilast (n=143) or placebo (n=146). At Week 16, 39.6% and 19.5% of apremilast and placebo patients, respectively, achieved a modified static Physician Global Assessment of Genitalia response (primary endpoint; score of 0/1, ≥2-point reduction); treatment difference was significant (20.1%, P=.0003). Improvements in genital signs and symptoms, skin involvement, and quality of life were observed. Common treatment-emergent adverse events were diarrhea, headache, nausea, and nasopharyngitis. Lack of active-comparator. Apremilast demonstrated statistically and clinically meaningful genital Physician Global Assessment responses and improvement of signs, symptoms, severity, and quality of life in this first randomized, controlled study of an oral systemic treatment in patients with genital psoriasis.

Long-term safety and efficacy of risankizumab for the treatment of moderate-to-severe plaque psoriasis: Interim analysis of the LIMMitless open-label extension trial up to 5 years of follow-up

Psoriasis is a chronic, inflammatory skin disease often requiring long-term therapy. To evaluate the long-term safety and efficacy of risankizumab in patients with psoriasis. LIMMitless is an ongoing phase 3, open-label extension study evaluating the long-term safety and efficacy of continuous risankizumab 150mg every 12weeks for adults with moderate-to-severe plaque psoriasis following multiple phase 2/3 base studies. This interim analysis assessed safety (ie, monitored treatment-emergent adverse events [TEAEs]) through 304weeks. Efficacy assessments included determining the proportion of patients who achieved ≥90% or 100% improvement in Psoriasis Area and Severity Index (PASI 90/100), static Physician's Global Assessment of clear/almost clear (sPGA 0/1), and Dermatology Life Quality Index of no effect on patient's life (DLQI 0/1) through 256weeks. Among 897 patients randomized to risankizumab in the base studies, 706 were still ongoing at data cutoff. Rates of TEAEs, TEAEs leading to discontinuation, and TEAEs of safety interest were low. At week 256, 85.1%/52.3% of patients achieved PASI 90/100, respectively, 85.8% achieved sPGA 0/1, and 76.4% achieved DLQI 0/1. Open-label study with no placebo or active-comparator group. Long-term continuous risankizumab treatment for up to 5years was well tolerated and demonstrated high and durable efficacy.

Achievement and maintenance of therapeutic response to brodalumab in patients with moderate‐to‐severe plaque psoriasis: An Italian, observational, retrospective and prospective study (BRIGHT study)

AbstractBackgroundBrodalumab, a fully human anti‐interleukin (IL)‐17 monoclonal antibody that blocks IL‐17RA, is approved in Europe for the treatment of adult patients with moderate‐to‐severe plaque psoriasis who are candidates for systemic treatment.ObjectivesThis study evaluated the achievement and maintenance of therapeutic response for 1 year in psoriasis patients treated with brodalumab in the Italian clinical practice.MethodsReal‐world, multicenter, observational, retrospective and prospective study. The retrospective phase ranged from enrolment visit to initiation of brodalumab (12 ± 4 weeks before). The prospective phase ranged from enrolment to a routine follow‐up visit set after 52 ± 4 weeks.ResultsOne hundred eighty‐four patients were eligible and 164 completed the observation period (median 11.9 months; Q1–Q3: 11.4–12.3). At enrolment, the mean duration of disease was 13.9 years (standard deviation; 13.3), 94% of patients (N = 172) had ≥1 clinical manifestation of psoriasis, mainly erythema and itching, and 95.6% had received ≥1 antipsoriatic treatment before brodalumab. Patients who reached an absolute Psoriasis Area and Severity Index (PASI) score ≤3 at week 12 and maintained it ≤3 through week 52 were 97 (64.7%). At week 12, 72.7% of patients achieved PASI 75, 54.5% PASI 90 and 42.0% PASI 100. At Week 52, 92.9% of patients achieved PASI 75, 84.4% PASI 90 and 61.7% PASI 100. A static Physician's Global Assessment (sPGA) score = 0 was obtained by 55.0% of patients after 12 weeks of brodalumab and by 77.0% after 52 weeks. A Dermatology Life Quality Index ≤1 was reported by 71.9% of patients after 12 weeks and by 89.9% after 52 weeks of treatment. No significant outcome differences were shown among patient subgroups defined by previous antipsoriatic treatments (none, systemic other than biologics or biologic) at either brodalumab initiation or any of the subsequent study visits.ConclusionsIn this real‐world setting, brodalumab was rapidly effective on skin lesions and quality of life both in biologic‐naïve and biologic‐experienced moderate‐to‐severe psoriasis patients, with a favourable safety profile.

Deucravacitinib: The First FDA-Approved Oral TYK2 Inhibitor for Moderate to Severe Plaque Psoriasis.

The objective of this study was to review the safety and efficacy of deucravacitinib, a tyrosine kinase 2 (TYK2) inhibitor for moderate to severe plaque psoriasis. Literature was reviewed from MEDLINE and Clinicaltrials.gov up to December 2022 using the terms "deucravacitinib" and "BMS-986165." Relevant articles in English relating to the pharmacodynamics, pharmacokinetics, efficacy, and safety of deucravacitinib were included. A total of 6 trial results were included. Deucravacitinib showed clinical efficacy across all the phase II and III clinical trials. Excluding the long-term extension study, there were 2248 subjects across all studies, with 63.2% of patients receiving deucravacitinib 6 mg daily. Of these subjects, the average proportion achieving a PASI 75 (a reduction of greater than 75% in the Psoriasis Area and Severity Index) at week 16 was 65.1%. Patients receiving deucravacitinib 6 mg once daily had a higher rate of achieving both PASI 75 response and a Static Physician's Global Assessment (sPGA) score of 0 or 1, compared with oral apremilast 30 mg twice daily. The safety profile of deucravacitinib includes mild adverse events (AEs), most commonly nasopharyngitis, with serious AEs reported ranging from 1.35% to 9.5%. While many available therapies for moderate to severe plaque psoriasis rely on an injectable dosage form or extensive monitoring, deucravacitinib can potentially reduce patient medication-related burden. This review summarizes the efficacy and safety of oral deucravacitinib for the treatment of severe plaque psoriasis. Deucravacitinib shows a consistent efficacy and safety profile as the first oral TYK2 inhibitor approved for adult patients with moderate to severe plaque psoriasis who are eligible for systemic therapy or phototherapy treatment.

Measurement properties of the Patient Global Assessment numerical rating scale in moderate-to-severe psoriasis.

Patient Global Assessment (PtGA) has been recommended as one of the core domains in psoriasis clinical trials. Among multiple versions of PtGA, the single-question 11-point PtGA numeric rating scale (NRS) remains to be validated in patients with plaque psoriasis. To evaluate the psychometric charateristics of a 11-point PtGA NRS for disease severity in patients with moderate-to-severe plaque psoriasis. Data were analyzed from 759 patients with moderate-to-severe psoriasis in the Shanghai Psoriasis Effectiveness Evaluation CoHort (SPEECH), a prospective, multicenter, and observational registry assessing the comparative effectiveness and safety of biologics (adalimumab, ustekinumab, secukinumab or ixekizumab), conventional systemic therapies (acitretin or methotrexate), or phototherapy. The test-retest reliability of the PtGA NRS showed good agreement (intraclass correlation coefficient range 0.79-0.83). No floor or ceiling effects of PtGA NRS were observed. The PtGA NRS was significantly correlated with Psoriasis Area and Severity Index (PASI), static Physician Global Assessment (sPGA), body surface area, Dermatology Quality of Life Index (DLQI), and Hospital Anxiety and Depression Scale. Relatively large correlations of PtGA NRS with PASI and DLQI Symptoms and feelings domain (all correlations ≥ 0.4 except at baseline) supported convergent validity. The presence of psoriatic arthritis or joint symptoms had no significant association with the PtGA NRS. In multivariate regression analyses, the PtGA NRS at baseline was predicted by age, lesion extent, lesion intensity, patients' symptoms and feelings, and impact on work or school. The PtGA NRS displayed known-groups validity with the PASI, sPGA and DLQI score bands. The PtGA NRS was responsive to change in PASI and DLQI after treatment. Anchor- and distribution-based approaches supported -3 as the minimal important difference for PtGA NRS. An absolute PtGA NRS ≤ 2 during follow-ups was concordant with the state of minimal disease activity based on PASI 90 or PASI 90 plus DLQI 0/1. Sensitivity analysis using subgroup comparison and multiple imputation model yielded consistent conclusions. The PtGA NRS showed good reliability, validity, and responsiveness in patients with psoriasis, and was feasible in clinical trials and daily practice.

Anti-interleukin-17 and anti-interleukin-23 biologic drugs for genital psoriasis: a single-center retrospective comparative study.

Genital psoriasis affects 3-33% of patients with psoriasis during the course of the disease, usually leading to a severe reduction in the patient's quality of life. This study aims to retrospectively assess the effectiveness of interleukin (IL)-23 and IL-17 inhibitors in a real-life population affected by moderate-to-severe plaque psoriasis with genital involvement coming from our dermatology department. A total of 86 patients with a diagnosis of moderate-tosevere plaque psoriasis with severe genital involvement were enrolled. Patient characteristics, psoriasis area and severity index (PASI), and static physician global assessment of genitalia (sPGAG) at each visit were recorded. During the treatment, the mean PASI decreased from 12.8 to 0.63 at week 52; a PGA of 0/1 was reached by 97.40% at week 52 and by 100% of patients (37/37) at week 104. No significant differences between IL-23 and IL-17 inhibitors were observed; indeed, the bio-naïve group of patients demonstrated a superior response compared to the group of bioexperienced patients.Our findings confirmed that IL-23 and IL-17 inhibitors are safe and effective therapeutic options for the treatment of genital psoriasis.

Clinical Utility of Deucravacitinib for the Management of Moderate to Severe Plaque Psoriasis.

Psoriasis is a chronic, immune-mediated skin condition with significant detriments to physical/mental health. While systemic therapies are available for the treatment of moderate-to-severe psoriasis, patients can experience therapeutic failure, loss of efficacy, or medical contraindications that require other therapeutic options. With the recent approval of deucravacitinib, a first-in-class TYK2 small molecule inhibitor administered orally for psoriasis patients, we reviewed data from randomized controlled trials (RCTs) to synthesize its clinical utility. To our knowledge, this is the first systematic review and meta-analysis of deucravacitinib comparing its clinical efficacy to placebo in psoriasis. A literature search was conducted in PubMed (MEDLINE), Embase, and the Cochrane Central Register of Controlled Trials to identify RCTs studying deucravacitinib in human patients with moderate-to-severe psoriasis. One placebo-controlled Phase II RCT and two placebo-controlled/active-comparator Phase III RCTs were included for review. Patients (N=1953) treated with deucravacitinib 6 mg daily showed marked improvement in disease severity (Psoriasis Area and Severity Index (PASI), static Physician Global Assessment (sPGA) and quality-of-life outcomes compared to patients administered comparator (apremilast) and placebo. Clinical improvement given deucravacitinib was noted for scalp psoriasis but not fingernail psoriasis. Meta-analysis (deucravacitinib, n=888; placebo, n=466) comparing rates of clearance (sPGA 0/1) demonstrated superior efficacy of deucravacitinib compared to placebo (odds ratio, 12.87; 95% confidence interval, 8.97-18.48; χ2=4.08, I2=51%). Deucravacitinib was well-tolerated, with similar rate of occurrence and type of adverse events reported among patients treated with placebo or apremilast at Week 12-16. No cardiovascular events, serious infections, or lab abnormalities were noted. Deucravacitinib possesses good efficacy, with no report of safety concerns associated with prior JAK inhibitors used for psoriasis. Meta-analysis demonstrated deucravacitinib's superiority compared to placebo, indicating its promising clinical utility. Further studies are needed to observe long-term safety and efficacy, and to compare deucravacitinib to existing treatments.

Efficacy of ixekizumab in patients with moderate-to-severe plaque psoriasis and prediabetes or type 2 diabetes.

Patients with psoriasis have an increased prevalence of type 2 diabetes when compared to the general population. Research suggests that type 2 diabetes (T2D) as well as obesity may have an impact on patients' response to treatment. This post-hoc analysis reports the efficacy of ixekizumab in treating moderate-to-severe psoriasis in patients with prediabetes or T2D. UNCOVER-1, UNCOVER-2, and UNCOVER-3 were three Phase 3, multicenter, randomized, double-blind, placebo-controlled trials that evaluated the efficacy and safety of ixekizumab in adult patients with moderate-to-severe psoriasis. Patients were aged ≥18 years with chronic moderate-to-severe psoriasis (defined as ≥10% body surface area affected, static Physician Global Assessment ≥3, and Psoriasis Area and Severity Index [PASI] ≥12 at screening and baseline) who were candidates for phototherapy or systemic therapy. UNCOVER-1, UNCOVER-2, and UNCOVER-3 participants received ixekizumab as per label (that is, an initial dose of two subcutaneous injections [160 mg in total] at Week 0, followed by 80 mg every 2 weeks through Week 12 and 80 mg every 4 weeks thereafter through Week 60). The proportions of patients with prediabetes, T2D and normoglycemia that achieved PASI75, PASI90, and PASI100 at Week 60 were similar. Results suggest that patients with T2D were slower to achieve PASI100 than patients with prediabetes or those with normoglycemia. Ixekizumab had no effect on any metabolic markers in patients receiving the treatment. Despite the higher rate of obesity and extreme obesity in patients with prediabetes and T2D, ixekizumab was an efficacious treatment in treating patients with psoriasis.