Deucravacitinib, an Oral, Selective, Allosteric Tyrosine Kinase 2 Inhibitor, in the Phase 3 Clinical Trials in Psoriasis, POETYK PSO-1 and PSO-2: Time to Meaningful Improvements in Itch as Assessed by the Psoriasis Symptoms and Signs Diary

Abstract

Introduction: In the phase 3 POETYK PSO-1 and PSO-2 trials in psoriasis, patients completed the Psoriasis Symptoms and Signs Diary (PSSD) daily, recording the average severity of psoriasis symptoms and signs, including itch, over the past 24 hours. Patients receiving deucravacitinib experienced greater improvement in PSSD scores than patients receiving placebo or apremilast, as previously reported. In this analysis, we evaluate the time to improvement in itch in patients treated with deucravacitinib vs placebo in both POETYK trials.

Methods: In each trial, adults with moderate to severe plaque psoriasis were randomized 1:2:1 to placebo, deucravacitinib 6 mg once daily, and apremilast 30 mg twice daily; at Week 16, patients receiving placebo crossed over to receive deucravacitinib. Adjusted mean score change from baseline for the PSSD itch item was modeled for deucravacitinib vs placebo using an analysis of covariance model with factors for geographic region, body weight, and prior biologic use, and the baseline value as a covariate. Improvements of ≥2 points on individual PSSD items have been established earlier as meaningful to patients. Time to ≥2-, ≥3-, and ≥4-point improvements from baseline to Week 16 on the PSSD itch item was estimated with Kaplan-Meier methods. Cox models estimated hazard ratios (HRs) for these improvements. Missing data for each analysis were imputed using modified baseline observation carried forward methods.

Results: In each trial, significantly greater improvement from baseline in itch score was observed within 2 weeks with deucravacitinib vs placebo. Across both trials, the median (95% confidence interval [CI]) time to ≥2-point and ≥3-point improvements was 6.0 (5.0– 7.0) and 9.0 (8.0–11.0) weeks, respectively, for patients receiving deucravacitinib and not reached for patients receiving placebo (censored at Week 16). Patients receiving deucravacitinib were 3 times more likely to achieve a ≥2-point meaningful improvement in itch score than patients receiving placebo (HR [95% CI]: 3.0 [2.1–4.1] and 3.4 [2.6–4.5] in POETYK PSO-1 and PSO-2, respectively). HRs in favor of deucravacitinib increased as the threshold for improvement increased: at ≥3 points, HRs (95% CI) were 4.0 (2.6–6.1) and 4.9 (3.4–6.9), and at ≥4 points, HRs (95% CI) were 6.5 (3.4–12.4) and 8.8 (5.1–15.2), in POETYK PSO-1 and PSO-2, respectively.

Conclusion: Patients receiving deucravacitinib vs placebo experienced improvement in their itch within 2 weeks of treatment. About half of patients receiving deucravacitinib experienced meaningful improvement in itch within 6 weeks.

Sponsored by: Bristol Myers Squibb.