Optimizing the treatment sequence: the cumulative clinical benefi t of treatment initiation with deucravacitinib versus apremilast over 52 weeks in patients with moderate to severe plaque psoriasis from the POETYK PSO-1 trial April W. Armstrong,1 Sang Hee Park,2 Viktor Chirikov,3 Pierre Nicolas,2,4 Wei-Jhih Wang,3 Matthew J. Colombo,2 Vardhaman Patel2 1Keck School of Medicine, University of Southern California, Los Angeles, CA; 2Bristol Myers Squibb, Princeton, NJ; 3OPEN Health, Bethesda, MD; 4Bristol Myers Squibb, Boudry, Switzerland Presented at the Fall Clinical Dermatology Conference; October 20—23, 2022; Las Vegas, NV This poster may not be reproduced without written permission from the authors.Email for April Armstrong, MD, MPH: AprilArmstrong@post.harvard.edu Scientifi c Content on Demand To request a copy of this poster: Scan QR code via a barcode reader application QR codes are valid for 30 days after congress presentation date Synopsis • Deucravacitinib is an oral, selective, allosteric tyrosine kinase 2 inhibitor approved by the US Food and Drug Administration for the treatment of adults with moderate to severe plaque psoriasis who are candidates for systemic therapy or phototherapy • In the recent phase 3 clinical trial POETYK PSO-1, patients with moderate to severe plaque psoriasis were randomized 2:1:1 to deucravacitinib, placebo, or apremilast1 — Patients receiving apremilast who did not achieve at least 50% improvement from baseline in Psoriasis Area and Severity Index score (PASI 50) at Week 24 crossed over to deucravacitinib1 • At Week 52, 46.3% of these patients achieved at least 75% improvement from baseline in PASI score (PASI 75), and 42.6% achieved a static Physician Global Assessment (sPGA) score of 0 or 1 (sPGA 0/1)2 — Patients receiving apremilast who achieved PASI 50 at Week 24 continued with apremilast — Patients who received placebo are not represented in this analysis • This study evaluated the cumulative clinical benefit of initiating with deucravacitinib vs apremilast to determine the treatment pathway that provides greater benefit to the patient — The cumulative clinical benefit refl ects the total time patients spend in a state of therapeutic response3 • The results of this study indicate that initiating deucravacitinib as a first-line treatment offers greater benefits over time compared with initiating with apremilast Objective • To evaluate the cumulative clinical benefit of initiating with deucravacitinib vs apremilast from baseline to Week 52 based on data from POETYK PSO-1 Methods • POETYK PSO-1 was a multicenter, randomized, double-blind, placebo- and active comparator–controlled study1 — Patients were aged ≥18 years and had moderate to severe plaque psoriasis (PASI score ≥12, sPGA score ≥3, and body surface area involvement ≥10%) — Coprimary effi cacy endpoints were PASI 75 and sPGA 0/1 — Nonresponder imputation was used for missing data • This post hoc analysis compared data from 2 arms in the POETYK PSO-1 trial (Figure 1) — Deucravacitinib arm: patients initiated with and continued on deucravacitinib, regardless of response status — Apremilast initiators arm: patients initiated with apremilast; at Week 24, PASI 50 responders continued with apremilast while PASI 50 nonresponders crossed over to deucravacitinib • Cumulative clinical benefit from randomization to Week 52 was determined by the total area under the curve of clinical response over 52 weeks (AUC 0–52wk ) in each arm — AUC analysis has been employed to evaluate outcomes over time in clinical trials, as the AUC refl ects the rapidity and durability, as well as the magnitude, of response3-6 • While assessments at discrete time points identify static responses, the AUC approach captures cumulative treatment effects over time — This study determined the AUC using data at a patient level (responder status at each time point over 52 weeks) • Total AUC 0–52wk was calculated separately for each efficacy endpoint, using the trapezoidal rule — Total AUC 0–52wk = 15i=0∑ (Pi+Pi+1)(Ti+1−Ti), where Ti (i = 0, 1, 2, 3, …, 15) denotes the time points of Weeks 0, 1, 2, 4, 8, 12, and 16, then every 4 weeks thereafter through Week 52, and P i denotes the response (yes = 1; no = 0) at each time point, T i • The result was standardized as a percentage of maximum possible AUC 0–52wk (0–5200 [% × weeks]) and aggregated to the population level • Adjusted AUC comparisons between the 2 treatment arms were based on an analysis of covariance (ANCOVA) model, with the following stratification parameters: — Prior use of a biologic treatment (yes/no) — Region (United States, China, Japan, rest of the world [ROW]) — Body weight (<90 kg, ≥90 kg), in the United States and ROW only • Ratios of AUC 0–52wk were calculated, representing the relative cumulative clinical benefit of the 2 treatment pathways for achieving PASI 75 or sPGA 0/1 over the 52-week period Figure 1. Study design comparing data from 2 arms of POETYK PSO-1 Week 0 Week 24 Week 52 Apremilast initiators arm (n = 168) Deucravacitinib arm (n = 332) Initiation of deucravacitinib Continuation of deucravacitinib Initiation of apremilast ≥PASI 50: continuation of apremilast