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

by Selleckchem | Sep 05 2023

Introduction: 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.

Objective: 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.

Methods: 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.

Results: 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.

Conclusion: 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.

Comments:

Disclaimer: The following response is based on the information provided in the introduction and should not be considered as a substitute for professional medical advice or guidance. It is always recommended to consult with a healthcare professional for specific treatment options and decisions.

Summary: According to the systematic review and meta-analysis of randomized controlled trials (RCTs), deucravacitinib, a first-in-class TYK2 small molecule inhibitor, shows promising clinical utility for the treatment of moderate-to-severe psoriasis. The review included one Phase II RCT and two Phase III RCTs comparing deucravacitinib to placebo in patients with psoriasis. The results indicate that deucravacitinib, administered orally at a dose of 6 mg daily, led to marked improvements in disease severity, quality of life, and static Physician Global Assessment (sPGA) scores compared to placebo. However, it should be noted that deucravacitinib did not show significant efficacy in treating fingernail psoriasis, but it did show improvement in scalp psoriasis.

A meta-analysis, comparing deucravacitinib (n=888) to placebo (n=466), revealed that deucravacitinib was significantly more effective in achieving clearance (sPGA 0/1) compared to placebo. The odds ratio for clearance was 12.87 (95% confidence interval: 8.97-18.48), indicating the superior efficacy of deucravacitinib.

Regarding safety, deucravacitinib was well-tolerated, with a similar incidence of adverse events when compared to placebo or the active comparator, apremilast, over a 12- to 16-week treatment period. Notably, no cardiovascular events, serious infections, or laboratory abnormalities were reported.

Conclusion: Based on the available evidence from RCTs, deucravacitinib demonstrates good efficacy and a favorable safety profile for the treatment of moderate-to-severe psoriasis. The meta-analysis further supports the superior efficacy of deucravacitinib compared to placebo. However, more studies are required to evaluate the long-term safety and efficacy of deucravacitinib and to compare it with existing treatments for psoriasis. It is essential to consult with healthcare professionals to determine the most suitable treatment options for individual patients.