Static Physician Research Articles

P65 Clinical characteristics of pruritus in Bangladeshi psoriasis patients

Abstract Background Psoriasis is a chronic systemic autoimmune disease associated with pruritus and seriously affects the quality of life of patients, but published data on its frequency and characteristics are limited. Objectives The purpose of this study is to find out the characteristics of pruritus in patients with different types of psoriasis and its impacts on the quality of life in Bangladesh. Materials and Methods This descriptive cross-sectional study was carried out in the Department of Dermatology and Venereology of Chittagong Medical College Hospital, Bangladesh for the period between March 2021 and August 2022 by using various validated tools like Visual Analog Scale, body surface area (BSA), psoriasis area and severity index (PASI), palmoplantar pustulosis severity index, severity of generalized pustular psoriasis, Static Physician Global Assessment Scale, Dermatology Life Quality Index (DLQI) and Family Reported Outcome Measure (FROM). After developing a questionnaire assessing various aspects of pruritus, we have surveyed 270 patients of psoriasis with different varieties regarding the presence and intensity of pruritus and life quality assessment. Results The mean age of the patients was 38.86 (±14.32) years, and males 182 (67.4%) outnumber females 88 (32.6%). A total of 210 (77.8%) patients reported having pruritus, 110 (40.74%) had moderate pruritus, 82 (30.37%) had mild pruritus, and 18 (6.7%) had severe pruritus. Pruritus was more common in the 21–40 years age group (35%), male sex (53%), low-income group (51%), outside field workers (23%), winter and spring exacerbation (31%), BSA <9% group (45%), palmoplantar psoriasis types (19%) and mild PASI (38%) group. In regards to DLQI, the majority 91 (33.7%) patients had a small effect, 68 (25.2%) had a large effect, 54 (20%) had a moderate effect, 53 (19.6%) had extremely large effect, and 4 (1.5%) had no effect. Conclusion Though pruritus is not specific to psoriasis, this study conveys the severity of pruritus in psoriasis patients in which a physician may encounter in clinical practice to monitor disease severity and optimization of treatment as well as take proper steps to improve the quality of life of patients.

Safety and Efficacy of Deucravacitinib in Moderate to Severe Plaque Psoriasis For Up to 3 Years

Safe and effective long-term treatments for moderate to severe plaque psoriasis are needed. To evaluate the long-term safety and efficacy of deucravacitinib through 3 years (week 148) in the randomized POETYK PSO-1, PSO-2, and nonrandomized long-term extension (LTE) trials. PSO-1/PSO-2 were global, 52-week, randomized, double-blinded phase 3 trials in patients with moderate to severe plaque psoriasis. After completing 52 weeks of treatment in PSO-1/PSO-2, patients could enroll in the prespecified, ongoing, nonrandomized LTE trial. The peak of the global COVID-19 pandemic coincided with the LTE trial. Patient enrollment in the LTE started August 12, 2019; safety and efficacy were assessed through June 15, 2022; and these data were analyzed through June 28, 2024. The PSO-1/PSO-2 trials randomized patients 1:2:1 to oral placebo, deucravacitinib, 6 mg once daily, or apremilast, 30 mg twice daily. Patients enrolling in the LTE trial received open-label deucravacitinib, 6 mg once daily. Safety outcomes were evaluated in patients who received 1 or more doses of deucravacitinib. Efficacy outcomes included 75% or greater or 90% or greater reduction from baseline in Psoriasis Area and Severity Index (PASI 75/90) and static Physician Global Assessment scores of 0 (clear) or 1 (almost clear) (sPGA 0/1) and were assessed in patients who received deucravacitinib treatment from day 1 of the parent trials who continued in the LTE trial. Of 1519 patients who received 1 or more doses of deucravacitinib, 513 received continuous deucravacitinib treatment from day 1 and entered the LTE trial. Exposure-adjusted incidence rates (EAIRs) per 100 person-years were decreased or similar in the 1-year vs 3-year cumulative periods, respectively, for adverse events (AEs) (229.2 vs 144.8; 95% CI, 215.4-243.9 vs 137.1-153.0), serious AEs (5.7 vs 5.5; 95% CI, 4.4-7.4 vs 4.7-6.4), discontinuations due to AEs (4.4 vs 2.4; 95% CI, 3.3-5.9 vs 2.0-3.0), and deaths (0.2 vs 0.3; 95% CI, 0.1-0.8 vs 0.2-0.6). Incidence rates of the most common AEs (EAIR per 100 person-years ≥5) during the 1-year and 3-year cumulative periods, respectively, were nasopharyngitis (26.1 vs 11.4; 95% CI, 23.0-29.8 vs 10.2-12.7), COVID-19 (0.5 vs 8.0; 95% CI, 0.2-1.2 vs 7.1-9.1), and upper respiratory tract infection (13.4 vs 6.2; 95% CI, 11.3-16.0 vs 5.4-7.2). EAIRs for AEs of interest, including herpes zoster, major adverse cardiovascular events, and malignant diseases, remained low and were decreased or comparable between the 1-year and 3-year cumulative periods. Clinical response rates were maintained through 3 years. The findings of this integrated analysis of the phase 3 POETYK PSO-1, PSO-2, and nonrandomized LTE trials demonstrate a consistent safety profile and durable clinical response of continuous treatment with deucravacitinib through 3 years of treatment in patients with psoriasis. ClinicalTrials.gov Identifiers: NCT03624127, NCT03611751, and NCT04036435.

Efficacy and Safety Analysis in Chinese Patients with Moderate-to-Severe Psoriasis from a Phase 3 Trial: Impact of Treatment Withdrawal and Retreatment of Ixekizumab.

In China, approximately 2.3 million people have psoriasis. Continuous treatment is recommended for moderate-to-severe psoriasis. This study aimed to evaluate the outcomes of continuous versus interrupted ixekizumab (IXE) treatment and retreatment with IXE after disease worsening in Chinese patients. In this Phase 3, multicenter, randomized, double-blind, placebo-controlled study, patients were randomized to IXE or placebo at Week 0. At Week 12, IXE responders (static Physician's Global Assessment [sPGA] score, 0 or 1 [0,1]) were re-randomized (2:1) to IXE (IXE/IXE, continuous treatment) or placebo (IXE/PBO, interrupted treatment). After re-randomization, treatment in IXE/PBO patients with disease worsening (relapse, sPGA ≥ 3) was switched to IXE every 4weeks (IXE/PBO + IXEQ4W, retreatment). Efficacy was assessed by evaluating the response rates of Psoriasis Area and Severity Index (PASI) 75/90/100, sPGA (0,1), Dermatology Life Quality Index (DLQI) (0,1), mean PASI, and Itch Numerical Rating Scale (NRS) scores and improvements of special body areas. Safety was evaluated by assessing treatment-emergent adverse events (AEs) and serious AEs. At Week 12, 289 IXE responders were re-randomized to the IXE/IXE group (192 patients) and IXE/PBO group (97 patients). High rates of PASI 75 and sPGA (0, 1) responses were maintained in the IXE/IXE group until Week 60. At Week 60, 88 (90.7%) patients in the IXE/PBO group had disease relapse; the median time to relapse was approximately 20weeks. After 24weeks of retreatment, PASI 75 and sPGA (0, 1) were recaptured (97.2% and 74.6%, respectively, in the IXE/PBO + IXEQ4W group). AEs were comparable in patients who received continuous treatment and retreatment. In Chinese patients who received continuous IXE treatment, high response rates were maintained through 60weeks. Most patients had disease relapse after treatment withdrawal. After retreatment, most of these patients had regained and maintained response since Week 12. NCT03364309.

Comparative Effectiveness of Biologic Classes in Clinical Practice: Month 12 Outcomes from the International Observational Psoriasis Study of Health Outcomes (PSoHO).

Studies directly comparing the effectiveness of different biologics over long observation periods are lacking. As many treatment guidelines are formulated based on drug class, there is a particular need to compare drug classes rather than specific biologic agents. This post hoc analysis compares the effectiveness and durability of biologics that target the interleukin (IL)-17 A ligands or the IL-17 receptor A (IL-17RA) relative to other approved drug classes in patients with moderate-to-severe plaque psoriasis, through 12months in a real-world setting. In the Psoriasis Study of Health Outcomes (PSoHO) (N=1981), patients treated with anti-IL-17A/RA resulted in a higher proportion of patients who achieved the primary outcome [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)] compared to anti-IL-23-, anti-IL-12/23-, and tumor necrosis factor (TNF)-α-treated patients at week 12, month 6, and month 12, except versus anti-IL-23 at month 12. Similar trends were observed for a 100% improvement in PASI score (PASI100), PASI90, and Dermatology Life Quality Index score of 0 or 1 [DLQI (0,1)]. At month 12, the unadjusted response rates across the drug classes were 53.5-69.1% for the primary outcome, 27.6-40.8% for PASI100, 41.7-55.9% for PASI90, and 31.8-33.0% for DLQI (0,1). Regarding the durability of effectiveness, anti-IL-17A/RA patients had the highest response rate, and for the adjusted analysis, using Frequentist Model Averaging (FMA), patients had 1.4-2.6 times higher odds of achieving the primary durability outcome compared to patients treated with any other drug class. Overall, anti-IL-17A/RA had the highest effectiveness of achieving early response to treatment and maintaining that response through 12months compared to other drug classes. The study was registered at the European Network of Centers for Pharmacoepidemiology and Pharmacovigilance (ENCEPP24207).

Efficacy and Safety of Risankizumab in Patients with Psoriasis Showing Suboptimal Response to Secukinumab or Ixekizumab: Results from a Phase 3b, Open-Label, Single-Arm (aIMM) Study.

Risankizumab has demonstrated superior efficacy compared to other psoriasis treatments, including secukinumab, adalimumab, and ustekinumab; switching to risankizumab from other psoriasis treatments has shown superior clinical and quality of life (QoL) outcomes. We evaluated the efficacy and safety of directly switching patients with moderate-to-severe plaque psoriasis and a suboptimal response to interleukin (IL)-17 inhibitors (secukinumab or ixekizumab) to risankizumab. This 52-week, phase 3b study enrolled patients (≥ 18years) with moderate-to-severe plaque psoriasis who had previously been treated with the recommended dose of secukinumab or ixekizumab for ≥ 6months but did not achieve an optimal response (static Physician's Global Assessment [sPGA] 2/3; body surface are [BSA] 3- < 10%). Patients received subcutaneous risankizumab (150mg) without washout. The primary endpoint was the proportion of patients achieving sPGA of 0/1 at week 16. Secondary endpoints included sPGA 0/1 at week 52, sPGA 0, Dermatology Life Quality Index (DLQI) 0/1, and Psoriasis Symptoms Scale (PSS) 0 at weeks 16 and 52. Safety was monitored throughout the study. The study included 244 patients. sPGA 0/1 was achieved by 57.4% and 62.3% at week 16 and 52. At week 16, sPGA 0, DLQI 0/1, and PSS 0 were achieved by 20.5%, 40.2%, and 20.9%, respectively. At week 52, these proportions increased to 27.1% for sPGA 0, 47.2% for DLQI 0/1, and 27.5% for PSS 0. Most frequently reported adverse events (reported in ≥ 5% of patients) in risankizumab-treated patients were COVID-19 infection (8.6%) and nasopharyngitis (5.7%). No new safety signals were observed. Directly switching to risankizumab improved outcomes and QoL in patients with moderate-to-severe psoriasis who had suboptimal responses to anti-IL-17 inhibitors (secukinumab or ixekizumab). The safety results are consistent with previously reported safety of risankizumab. This study supports the efficacy of risankizumab in patients previously treated with biologics, including IL-17 inhibitors, and suggests a direct switch to risankizumab for improved clinical outcomes and QoL. ClinicalTrials.gov identifier: NCT04102007.

Effectiveness of long-term bimekizumab treatment and predictive factors for responders in moderate-to-severe psoriasis: A 52-week real-world study.

Psoriasis is a chronic, inflammatory skin disease in which the interleukin (IL)-23/IL-17 axis plays a central role. Bimekizumab is a novel antibody that targets both IL-17A and IL-17F. This retrospective study aimed to assess the long-term effectiveness and safety of 52-week treatment with bimekizumab, and to identify predictive factors for short- (16 weeks) and long-term (52 weeks) responders (i.e., achievers of a Psoriasis Area and Severity Index (PASI) score of 100) to bimekizumab in Japanese patients with psoriasis. The study was conducted on 56 Japanese patients (aged ≥ 15 years) with moderate-to-severe psoriasis treated with bimekizumab from May 2022 to March 2024. The therapeutic effectiveness was evaluated by the transition of PASI scores during treatment. Baseline characteristics and clinical and laboratory indexes were compared between responders and poor responders. Treatment-emergent adverse events (TEAEs) were recorded to assess the safety of the treatment. At week 52, the achievement of PASI 100, static Physician's Global Assessment 0/1, and the Dermatology Life Quality Index 0/1 were 72.4%, 94.7%, and 93.3%, respectively. Short-term responders showed lower baseline values of neutrophil-to-lymphocyte ratio, monocyte-to-lymphocyte ratio (MLR), and systemic inflammatory response index compared to poor responders. Long-term responders showed younger age and lower MLR compared to poor responders. TEAEs were mild or moderate, without serious adverse events. Long-term treatment with bimekizumab is effective and safe for psoriasis patients. Lower MLR and younger age might predict long-term response to treatment with bimekizumab, aiding in personalized treatment strategies.

The regulatory T cell-selective interleukin-2 receptor agonist rezpegaldesleukin in the treatment of inflammatory skin diseases: two randomized, double-blind, placebo-controlled phase 1b trials

Regulatory T cell (Treg) impairment is implicated in the pathogenesis of chronic inflammatory diseases, but relatively little is known about the therapeutic potential of Treg restoration. Here we present clinical evidence for the Treg-selective interleukin-2 receptor agonist rezpegaldesleukin (REZPEG) in two randomized, double-blind, placebo-controlled Phase 1b trials in patients with moderate-to-severe atopic dermatitis (AD) (NCT04081350) or chronic plaque psoriasis (PsO) (NCT04119557). Key inclusion criteria for AD included an Eczema Area and Severity Index (EASI) score ≥ 16 and a validated Investigator Global Assessment for Atopic Dermatitis (vIGA-AD) ≥ 3, and for PsO included a Psoriasis Area and Severity Index (PASI) score of ≥ 12 and a static Physician’s Global Assessment (sPGA) score of ≥ 3. REZPEG is safe and well-tolerated and demonstrates consistent pharmacokinetics in participants receiving subcutaneous doses of 10 to 12 µg/kg or 24 µg/kg once every 2 weeks for 12 weeks, meeting the primary and secondary objectives, respectively. AD patients receiving the higher dose demonstrate an 83% improvement in EASI score after 12 weeks of treatment. EASI improvement of ≥ 75% (EASI-75) and vIGA-AD responses are maintained for 36 weeks after treatment discontinuation in 71% and 80% of week 12 responders, respectively. These exploratory clinical improvements are accompanied by sustained increases in CD25bright Tregs. REZPEG thus represents a homeostatic approach to cutaneous disease therapy and holds clinical potential in providing long-term, treatment-free disease control.

Matching-Adjusted Indirect Comparison of Risankizumab Versus Deucravacitinib in Patients with Moderate-to-Severe Plaque Psoriasis.

Despite advancements in the treatment of psoriasis (PsO), there are few head-to-head studies assessing comparative effectiveness of the newest therapies approved to treat PsO. Our objective was to assess the comparative clinical effectiveness of risankizumab and deucravacitinib in patients with moderate-to-severe PsO. This placebo-anchored matching-adjusted indirect comparison (MAIC) analysis utilized data from UltIMMa-1/2 risankizumab and POETYK PSO-1/2 deucravacitinib trials. Individual patient data from UltiMMA-1/2 were weighted via propensity score to match POETYK PSO-1/2 published summary data. Rate differences between risankizumab and deucravacitinib were assessed for Psoriasis Area and Severity Index (PASI) 75/90/100, the Static Physician Global Assessment (sPGA = 0 or 0/1), and the Dermatology Life Quality Index (DLQI) 0/1. At 16weeks, risankizumab-treated patients demonstrated statistically significantly higher rates of skin clearance and greater improvement in quality of life (QoL) compared to those treated with deucravacitinib. Across all outcomes, risankizumab demonstrated a lower number needed to treat compared to deucravacitinib. Limitations are potential bias due to unobserved/unmeasurable differences and limited generalizability of the results. This indirect comparison demonstrates that risankizumab has higher rates of skin clearance and greater improvements in QoL than deucravacitinib. This study will help inform healthcare providers in their treatment and management strategy of PsO.

Deucravacitinib, an oral, selective, allosteric tyrosine kinase 2 inhibitor, in patients from China mainland, Taiwan, and South Korea with moderate to severe plaque psoriasis: a phase 3 randomized clinical trial.

Deucravacitinib, an oral, selective, allosteric tyrosine kinase 2 inhibitor, is approved in the United States, European Union, Japan, South Korea, China, and other countries for treatment of moderate-to-severe plaque psoriasis. To evaluate the efficacy and safety of deucravacitinib in Asian patients with moderate to severe plaque psoriasis. In the 52-week, blinded, phase 3 POETYK PSO-3 trial (NCT04167462), patients were randomized 1 : 2 to placebo (n = 74) or deucravacitinib 6 mg once daily (n = 146) for 16 weeks followed by deucravacitinib alone. Coprimary endpoints were achievement of ≥ 75% reduction from baseline in Psoriasis Area and Severity Index (PASI 75) and static Physician Global Assessment score of 0 (clear) or 1 (almost clear) (sPGA 0/1) at Week 16. Efficacy and safety were evaluated throughout. At Week 16, significantly higher proportions of patients receiving deucravacitinib versus placebo achieved PASI 75 (68.8% vs. 8.1%; P < 0.0001) and sPGA 0/1 (55.6% vs. 6.8%; P < 0.0001). Response rates with deucravacitinib were maintained through Week 52. Common adverse events included upper respiratory tract infection and nasopharyngitis. Serious adverse event and discontinuation rates were low. Deucravacitinib was efficacious and well tolerated in Asian patients with moderate to severe plaque psoriasis.

Efficacy of Ixekizumab in Chinese Patients with Moderate-to-Severe Psoriasis and Special Body Area Involvement: Sub-analysis of a Randomized, Double-Blind, Multicenter Phase 3 Study.

Special body area involvement is common in psoriasis and can be challenging to treat. We investigated the efficacy of ixekizumab (IXE) in Chinese patients with moderate-to-severe psoriasis and fingernail, scalp, or palmoplantar involvement. A post-hoc sub-analysis of a phase 3 trial, in which patients were randomized to receive placebo, IXE 80mg every 2 (IXE Q2W) or 4 (IXE Q4W) weeks. At Week 12, patients classified as IXE responders [static Physician's Global Assessment (sPGA) score of 0 or 1 [0,1)] were re-randomized (2:1) to IXE Q4W or placebo until Week 60. Efficacy was assessed by body-regionspecific parameters including Nail Psoriasis Severity Index (NAPSI), Psoriasis Scalp Severity Index (PSSI), and Palmoplantar Psoriasis Area Severity Index (PPASI). Of 438 patients, 99.1% (434) had≥1 special area involvement [fingernail (76.5%, 335), scalp (97.3%, 426), palmoplantar (27.9%, 122)]. Significantly greater improvements from baseline in NAPSI score were observed with IXE Q4W and Q2W at Week 12 versus placebo (p<0.001 for both). These improvements were further increased and sustained over 60weeks in IXE Q4W and Q2W responders who were re-randomized to IXE Q4W, who achieved a 77.9% and 89.7% improvement from baseline, respectively, at Week 60. Significantly higher proportions of patients receiving IXE Q4W and Q2W achieved NAPSI 50 at Week 12 versus placebo (44.4%, 36.6% vs. 14.1%; p<0.001 and<0.01, respectively). Similarly, significantly higher proportions of patients receiving IXE Q4W and Q2W achieved PSSI 100 and PPASI 100 at Week 12 versus placebo (60.6% and 65.1% vs. 1.2%, and 67.4%, 84.3% vs. 21.4%, respectively; p<0.001 for all comparisons). Improvements across all outcomes were sustained in patients re-randomized to IXE Q4W until Week 60. IXE led to a rapid onset of action and sustained efficacy over 60weeks in Chinese patients with moderate-to-severe psoriasis and special body area involvement. gov identifier, NCT03364309.

Efficacy and safety of vunakizumab in moderate-to-severe chronic plaque psoriasis: A randomized, double-blind, placebo-controlled phase 3 trial

Vunakizumab, a novel anti-interleukin-17A antibody, has shown promising efficacy for moderate-to-severe plaque psoriasis in a phase 2 trial. We conducted a double-blind, randomized phase 3 trial (NCT04839016) to further evaluate vunakizumab in this population. Six hundred ninety subjects were randomized (2:1) to receive vunakizumab 240mg or placebo at weeks 0, 2, 4, and 8. At week 12, subjects on placebo were switched to vunakizumab 240mg (weeks 12, 14, 16, and every 4 weeks thereafter). The co-primary endpoints were ≥90% improvement from baseline in the Psoriasis Area and Severity Index score (PASI 90) and a static Physicians Global Assessment score of 0/1 (sPGA 0/1) at week 12. At week 12, the vunakizumab group showed higher PASI 90 (76.8% vs 0.9%) and sPGA 0/1 (71.8% vs 0.4%) response rates, as well as higher PASI 75 (93.6% vs 4.0%), PASI 100 (36.6% vs 0.0%), and sPGA 0 (38.2% vs 0.0%) response rates (all two-sided P<.0001 vs placebo). Efficacy was maintained through week 52 with continuous vunakizumab. Possible treatment-related serious adverse events occurred in 0.9% of vunakizumab-treated subjects. Chinese subjects only; no active comparator. Vunakizumab demonstrated robust clinical response at week 12 and through week 52, with good tolerability in moderate-to-severe plaque psoriasis.

51101 Deucravacitinib, an oral, selective, allosteric tyrosine kinase 2 (TYK2) inhibitor, in moderate to severe plaque psoriasis: efficacy by baseline static Physician Global Assessment (sPGA) in two phase 3 trials

51101 Deucravacitinib, an oral, selective, allosteric tyrosine kinase 2 (TYK2) inhibitor, in moderate to severe plaque psoriasis: efficacy by baseline static Physician Global Assessment (sPGA) in two phase 3 trials

A randomized phase 3b study evaluating the safety and efficacy of risankizumab in adult patients with moderate-to-severe plaque psoriasis with non-pustular palmoplantar involvement

BackgroundIn plaque psoriasis, palmoplantar areas are more difficult to treat. ObjectiveEvaluate the safety and efficacy of risankizumab (RZB) versus placebo (PBO) for the treatment of palmoplantar psoriasis (PPPsO). MethodsPatients were randomized to RZB or PBO for 16 weeks followed by RZB through week 52. The primary and secondary endpoints were achievement of palmoplantar Investigator’s Global Assessment of “clear” or “almost clear” with ≥2-point reduction from baseline (ppIGA 0/1), achievement of ≥75%, ≥90% and 100% improvement in Palmoplantar Psoriasis Area and Severity Index (PPASI 75, PPASI 90, PPASI 100) and achievement of static Physician Global Assessment of "clear" or "almost clear" with ≥2-point reduction from baseline (sPGA 0/1) at week 16. Safety was based on treatment-emergent adverse events (TEAEs). ResultsRZB demonstrated significant efficacy compared to PBO at week 16 in the patients achieving ppIGA 0/1 (33.3% vs 16.1% [P = .006]), PPASI 75 (42.5% vs 14.9% [P < .001]), PPASI 90 (27.6% vs 5.7% [P < 0.001]), sPGA 0/1 (32.2% vs 11.5% [P < .001]) and PPASI 100 (17.2% vs 1.1% [P < .001]). Results improved through week 52 with no new safety signals. LimitationNo biologic comparator ConclusionsRZB demonstrated safety and efficacy in PPPsO.

Tildrakizumab Real-World Effectiveness and Safety Over 64 Weeks in Patients With Moderate-to-Severe Plaque Psoriasis.

Tildrakizumab is a humanized anti-interleukin-23 p19 monoclonal antibody approved for the treatment of moderate-to-severe plaque psoriasis. This report describes real-world effectiveness and safety of tildrakizumab through 64 weeks of treatment. In this Phase 4, multicenter, uncontrolled, open-label trial (NCT03718299), adults with moderate-to-severe plaque psoriasis received tildrakizumab 100 mg at weeks 0 and 4 and every 12 weeks thereafter through week 52. Effectiveness was assessed from body surface area (BSA) affected and static Physician Global Assessment (sPGA) through week 64 and Psoriasis Area and Severity Index (PASI) through week 52. Adverse events are reported. Of 55 patients enrolled, 45 completed the study and 36 received all doses of tildrakizumab. From baseline to week 64, mean +/- standard deviation BSA decreased by 83.1% (from 14.5 +/- 11.5 to 2.1 +/- 3.6) and sPGA by 67.6% (from 3.2 +/- 0.6 to 1.0 +/-&nbsp;1.0); sPGA x BSA decreased by 89.6% (from 47.0 +/-&nbsp;41.5 to 4.6 +/-&nbsp;9.4; all P&lt;0.001). PASI scores decreased compared to baseline at weeks 4, 16, 28, and 52 (P&lt;0.001). For PASI responses at week 52 compared with baseline, 87.0% achieved greater than or equal to 75% improvement, 56.5% achieved&nbsp;greater than or equal to 90% improvement, and 32.6% achieved 100% improvement. Of 85 treatment-emergent adverse events in 34/55 patients, none were considered related to tildrakizumab treatment. Tildrakizumab treatment was effective in adult patients with moderate-to-severe plaque psoriasis in real-world settings, with no new safety signals. J Drugs Dermatol. 2024;23(8):612-618.&nbsp; doi:10.36849/JDD.8217.

Safety and efficacy of Deucravacitinib for moderate to severe plaque psoriasis: A meta-analysis.

To systematically evaluate the safety and efficacy of Deucravacitinib for moderate to severe plaque psoriasis. Randomized controlled trials (RCTs) of Deucravacitinib for moderate to severe plaque psoriasis in PubMed, Cochrane Library, Embase, and Web of Science were searched from database establishment to April 2023. Literature quality was independently evaluated by two investigators using the Cochrane risk-of-bias assessment tool, and the systematic analysis was made using StateSE15 and RevMan 5.3 software. Four RCTs were included, including 1751 patients with moderate to severe plaque psoriasis. Meta-analysis showed that the differences in efficacy and adverse events (AEs) between the Deucravacitinib group and placebo group were significant (p<0.05). The patients in the Deucravacitinib group took orally 3-12mg daily for 12 sequential weeks or 6mg daily for 52 sequential weeks. Psoriasis Area and Severity Index (PASI) reduced by 75% (PASI 75), (PASI 90), and (PASI 100), static Physician Global Assessment (sPGA) of 0 or 1 (sPGA 0/1), Dermatology Life Quality Index of 0 or 1 (DLQI 0/1), and Psoriasis Symptoms and Signs Diary (PSSD) were significantly higher in the Deucravacitinib group compared to the placebo group, with significant differences (p<0.05). The most frequently encountered AEs after treatment in the Deucravacitinib group was nasopharyngitis. Oral administration of Deucravacitinib is effective for moderate to severe plaque psoriasis. Attention should be paid to the occurrence of AEs, and more RCTs are required to evaluate the relationship between the dose and safety and efficacy.

Deucravacitinib Long-Term Efficacy Through 4 years in Week 16 Placebo Crossover Patients in the Phase 3 POETYK PSO-1, PSO-2, and LTE Program

Introduction: Deucravacitinib, an oral, selective, allosteric tyrosine kinase 2 inhibitor, is approved in the US, EU, and other countries for treatment of adults with moderate to severe plaque psoriasis who are candidates for systemic therapy. Deucravacitinib was efficacious and well tolerated in two global, 52-week, phase 3 POETYK PSO-1 (NCT03624127) and POETYK PSO-2 (NCT03611751) parent 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 4 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 4 years (Week 208; data cutoff, November 1, 2023). 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 208 assessment or discontinued before Week 208. Results: Of 421 patients originally randomized to placebo, 348 crossed over to deucravacitinib at Week 16; 298 completed the parent trials and entered the LTE, with 291 meeting mNRI criteria. Efficacy response rates improved from Week 16 on placebo (PASI 75, 12.0% [95% CI, 8.5%-16.3%]; PASI 90, 3.4% [1.7%-6.2%]; sPGA 0/1, 10.0% [6.8%-14.0%]) through Week 52 on deucravacitinib (PASI 75, 75.2% [70.2%-80.2%]; PASI 90, 47.4% [41.6%-53.1%]; sPGA 0/1, 60.1% [54.5%-65.7%]). Response rates were maintained well through Week 208 (PASI 75, 75.6% [70.0%-81.2%]; PASI 90, 46.6% [40.4%-52.7%]; sPGA 0/1, 55.1% [48.8%-61.4%]). Conclusion: These findings support the long-term efficacy profile of once-daily oral deucravacitinib for treatment of patients with moderate to severe plaque psoriasis.

Deucravacitinib in Plaque Psoriasis: Maintenance of Response Over 4 Years in the Phase 3 POETYK PSO-1, PSO-2, and LTE Trials

Introduction: Deucravacitinib, an oral, selective, allosteric TYK2 inhibitor, was superior to placebo and apremilast in two global, phase 3 trials (POETYK PSO-1 and PSO-2) in moderate to severe plaque psoriasis. At Week 52, patients could enter the POETYK long-term extension (LTE) trial and receive open-label deucravacitinib. Long-term efficacy was maintained through 3 total years of continuous treatment with no new safety signals in the ongoing LTE. Methods: Efficacy was further evaluated through Week 208 (4 years; data cutoff, November 1, 2023) 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 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 score of 0 [clear]/1 [almost clear]). Efficacy is reported using modified nonresponder imputation in patients who reached or discontinued before Week 208. Results: Of 513 patients who received continuous deucravacitinib from Day 1 and entered the LTE, PASI 75 was achieved by 313 (61.0%) and 336 (65.5%) patients at Week 16 and Week 24. Among Week 16 PASI 75 responders, response rates were maintained well from Week 16 to Week 208 (PASI 75: 100%, 84.4%; PASI 90: 55.7%, 57.4%; sPGA 0/1: 82.8%, 65.4%). Among Week 24 PASI 75 responders, response rates were also maintained from Week 24 to Week 208 (PASI 75: 100%, 84.6%; PASI 90: 62.7%, 58.2%; sPGA 0/1: 82.5%, 66.0%). Conclusion: Clinical efficacy was generally maintained with continuous deucravacitinib in the vast majority of Week 16 and Week 24 PASI 75 responders from the parent trials through 4 years, supporting the long-term effectiveness and treatment durability of once-daily oral deucravacitinib for moderate to severe plaque psoriasis.

Cumulative Benefit Over 52Weeks With Deucravacitinib Versus Apremilast in Moderate to Severe Plaque Psoriasis: POETYK PSO-1 Post Hoc Analysis.

Deucravacitinib demonstrated superior efficacy to apremilast in patients with moderate to severe plaque psoriasis in the POETYK PSO-1 and PSO-2 clinical trials. In the study reported here, we aimed to determine the overall 52-week cumulative clinical benefit of treatment initiated with deucravacitinib versus apremilast and to compare the 52-week cumulative benefit of initiating and staying on deucravacitinib versus initiating apremilast and continuing or switching to deucravacitinib at week 24 of treatment. This post hoc analysis of POETYK PSO-1 data (ClinicalTrials.gov identifier: NCT03624127) determined the cumulative clinical benefit of deucravacitinib 6mg once daily and apremilast 30mg twice daily in adults with moderate to severe plaque psoriasis. Patients treated with apremilast who did not achieve a 50% reduction in the Psoriasis Area and Severity Index (PASI 50) at week 24 were switched to deucravacitinib. The cumulative clinical benefit of deucravacitinib versus apremilast over 52weeks was based on cumulative measures of ≥ 75% improvement from baseline in PASI score (PASI 75) and the proportion of patients with a static Physician Global Assessment score of 0 or 1 (sPGA 0/1). Ratios of area under the curve estimates between treatments were calculated and compared based on analysis of covariance regression models. Patients initiating deucravacitinib (N = 332) had a greater cumulative benefit as measured by the PASI 75 and sPGA 0/1 than those initiating apremilast (N = 168). Over 52weeks, those initiating deucravacitinib experienced 50% more benefit as measured by PASI 75 and 58% more benefit as measured by sPGA 0/1 than those initiating apremilast. Results were consistent with the primary analysis when patients were classified by prior systemic and prior biologic therapy exposure. Results from this analysis corroborate the primary efficacy analysis supporting the use of deucravacitinib compared with apremilast for moderate to severe plaque psoriasis, regardless of prior systemic or biologic use.

Tyrosine kinase 2 inhibitor (deucravacitinib) for psoriasis: A systematic review and network meta-analysis of randomized controlled trials

Objective: Deucravacitinib is a tyrosine kinase-2 inhibitor that shows promise as an emerging treatment option for psoriasis. We aimed to evaluate the efficacy and safety of different doses of deucravacitinib versus placebo or apremilast on psoriasis treatment. Methods: We performed a systematic review and pairwise and network meta-analyses of randomized controlled trials published in Web of Science, SCOPUS, EMBASE, PubMed, and Cochrane Central databases from the inception of databases until 31 st March 2023. We used the risk ratio for dichotomous outcomes, and the mean difference with corresponding 95% confidence interval for continuous outcomes. We registered our protocol in PROSPERO (ID: CRD42023413976). Results: We analyzed four randomized controlled trials involving 2,156 patients randomly assigned to receive placebo, 60 mg of apremilast once daily, or various doses of deucravacitinib (3 mg every other day, 3 mg once daily, 3 mg twice daily, 6 mg twice daily, or 12 mg once daily). Deucravacitinib achieved significantly better outcomes compared with placebo across multiple efficacy measures, including the Psoriasis Area and Severity Index score (P &lt; 0.01), Static Physician’s Global Assessment score (P &lt; 0.01), Psoriasis Symptoms and Signs Diary score (P &lt; 0.01), Dermatology Life Quality Index score (P &lt; 0.01), and scalp-specific Physician’s Global Assessment score (P &lt; 0.01). When comparing 3 mg of deucravacitinib twice daily with 60 mg of apremilast once daily, deucravacitinib exhibited superior outcomes in terms of the Psoriasis Area and Severity Index (P &lt; 0.01), Dermatology Life Quality Index (P &lt; 0.01), Static Physician’s Global Assessment (P &lt; 0.01), and scalp-specific Physician’s Global Assessment scores (P &lt; 0.01). Conclusion: Deucravacitinib and apremilast show promising efficacy as psoriasis treatments. While adverse events were more common with these treatments compared with placebo, the incidence of serious adverse events did not significantly differ between the intervention and placebo groups.

Consistent Efficacy of Apremilast in Patients with Psoriasis Regardless of Baseline Disease Severity or Special Area Involvement: Subgroup Analysis from PROMINENT.

Psoriasis involvement in special areas (e.g., scalp or nails) is associated with a great disease burden yet it is often inadequately treated with topical treatments. The efficacy and tolerability of apremilast plus existing topical therapy in Japanese patients with mild to moderate plaque psoriasis were demonstrated in PROMINENT, a phase 3b, multicenter, open-label, single-arm study. We evaluated the efficacy of apremilast across disease severities and special areas involved in these patients. In PROMINENT, patients received apremilast 30mg twice daily for 16weeks in addition to their existing topical therapy, with the option of topical therapy reduction at the discretion of their physician while continuing apremilast treatment from Weeks 16 to 32. We performed a post hoc analysis, assessing apremilast efficacy and safety in Japanese patients stratified by baseline static Physician Global Assessment (sPGA) score (2 [mild] or 3 [moderate]) and special area involvement. Of patients with baseline sPGA = 2 and sPGA = 3, 62.7% and 30.7%, respectively, achieved sPGA score 0 or 1 at Week 32. At Week 32, improvements in skin, nail, scalp, and quality of life assessments were observed regardless of baseline sPGA score. Improvements in these endpoints at Week 32 were also observed in patients with special area (scalp or nail) involvement (n = 134). Incidence of adverse events was similar between patients with baseline sPGA = 2 and sPGA = 3. Apremilast in combination with topical therapy may be a beneficial treatment for Japanese patients, who have limited systemic treatment options for mild to moderate psoriasis or psoriasis in special areas. NCT03930186.