OP0227 EFFICACY OF DEUCRAVACITINIB, AN ORAL, SELECTIVE TYROSINE KINASE 2 INHIBITOR, IN MUSCULOSKELETAL MANIFESTATIONS OF ACTIVE PSORIATIC ARTHRITIS IN A PHASE 2, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED TRIAL

Abstract

Background:Tyrosine kinase 2 (TYK2) is an intracellular kinase that mediates IL-23, IL-12, and IFNα/β signaling. Deucravacitinib is a novel, oral selective inhibitor of TYK2 acting via the TYK2 regulatory domain. Phase 2 results showed deucravacitinib was efficacious and well tolerated versus placebo (PBO) in patients with active psoriatic arthritis (PsA).Objectives:This analysis further evaluated improvements in musculoskeletal disease manifestations in patients in the Phase 2 PsA trial.Methods:The ongoing Phase 2 trial (NCT03881059) enrolled patients who had a PsA diagnosis for ≥6 months, met CASPAR criteria, had active disease (≥3 tender joints, ≥3 swollen joints, C-reactive protein [CRP] ≥3 mg/L), and had at least 1 active skin lesion. Patients either failed or were intolerant to at least 1 nonsteroidal anti-inflammatory drug, corticosteroid, conventional synthetic disease-modifying antirheumatic drug, and/or 1 TNF inhibitor (TNFi; ≤30%). Patients were randomized 1:1:1 to deucravacitinib 6 mg QD or 12 mg QD or PBO, and stratified by TNFi status (experienced vs naive) and body weight (<90 vs ≥90 kg). The primary endpoint, ACR20 response at Week 16, was met and significant improvements in enthesitis vs PBO were observed. The current prespecified subgroup analysis assessed the likelihood of achieving ACR20 response at Week 16 based on study stratification factors. A post hoc analysis evaluated mean change from baseline to Week 16 in ACR components (tender joint count, swollen joint count, Physician’s Global Assessment of PsA, Patients’ Global Assessment of disease activity, Patients’ Global Assessment of pain, high-sensitivity CRP [hCRP], and HAQ-DI score). Analyses were descriptive using data as observed.Results:Patients treated with deucravacitinib were numerically more likely to achieve ACR20 response at Week 16 compared with PBO-treated patients regardless of TNFi experience or body weight, although some of these groups were small (Figure). Improvements for deucravacitinib 6 mg and 12 mg QD versus PBO were observed in all ACR components, with apparent separation occurring as early as Week 4 on, for example, HAQ-DI (mean change from baseline, -0.2 vs -0.2 vs -0.1, respectively) and hCRP (mean change from baseline, -7.4 vs -5.2 vs 0.3, respectively) and maintained through Week 16 (Table).Table 1.Mean (SD) change from baseline for ACR componentsTJCSJCPtGAPainPGAHAQ-DIhCRPBaselineaPBO16.9 (9.8)10.5 (7.7)66.2 (15.8)64.9 (18.2)63.8 (14.8)1.3 (0.6)20.4 (39.1)DEUC 618.1 (10.3)11.9 (7.0)68.2 (16.8)63.6 (21.7)68.2 (14.7)1.3 (0.6)17.6 (23.6)DEUC1219.4 (11.8)11.3 (9.0)63.6 (15.6)63.8 (15.9)63.3 (16.1)1.3 (0.6)16.5 (21.7)Week 16bPBO-4.6 (9.7)-4.3 (8.0)-13.4 (23.5)-13.8 (21.5)-19.9 (21.8)-0.1 (0.4)-3.3 (22.6)DEUC 6-9.3 (9.7)-7.7 (5.8)-28.7 (23.1)-25.3 (26.1)-33.6 (23.0)-0.4 (0.5)-14.2 (24.5)DEUC 12-12.2 (10.2)-8.5 (9.1)-27.6 (25.8)-27.5 (25.0)-32.2 (25.0)-0.4 (0.6)-10.9 (22.8)PBO, n/N=58/66; DEUC 6, n/N=63/70; DEUC 12, n/N=59/67; n/N = number of patients who completed treatment/number of patients randomized; the number of patients with data available for individual components at each time point may vary.aMean (SD). bMean (SD) change from baseline.ACR, American College of Rheumatology; DEUC 6, deucravacitinib 6 mg QD; DEUC 12, deucravacitinib 12 mg QD; HAQ-DI, Health Assessment Questionnaire-Disability Index total score; hCRP, high-sensitivity C-reactive protein; PBO, placebo; PGA, Physician’s Global Assessment of psoriatic arthritis; PtGA, Patients’ Global Assessment of disease activity; QD, once daily; SJC, swollen joint count; TJC, tender joint count.Conclusion:Analyses confirmed the efficacy of deucravacitinib versus PBO across TNFi and body weight subgroups. With deucravacitinib treatment, improvements were displayed in all ACR components.Acknowledgements:This study was sponsored by Bristol Myers Squibb. Professional medical writing assistance was provided by Peloton Advantage, LLC, an OPEN Health company, and funded by Bristol Myers Squibb.Disclosure of Interests:Philip J Mease Consultant of: AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, Galapagos, Gilead, GlaxoSmithKline, Janssen, Novartis, Pfizer, SUN Pharma, UCB, Grant/research support from: AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, Galapagos, Gilead, GlaxoSmithKline, Janssen, Novartis, Pfizer, SUN Pharma, UCB, Atul Deodhar Consultant of: AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Eli Lilly, Galapagos, GlaxoSmithKline, Janssen, Novartis, Pfizer, UCB, Grant/research support from: AbbVie, Eli Lilly, GlaxoSmithKline, Novartis, Pfizer, UCB, Désirée van der Heijde Consultant of: AbbVie, Amgen, Astellas, AstraZeneca, Bayer, Bristol Myers Squibb, Boehringer Ingelheim, Celgene, Cyxone, Daiichi, Eisai, Eli Lilly, Galapagos, Gilead, GlaxoSmithKline, Janssen, Merck, Novartis, Pfizer, Regeneron, Roche, Sanofi, Takeda, UCB Pharma. Director of Imaging Rheumatology BV, Frank Behrens Consultant of: Pfizer, AbbVie, Sanofi, Lilly, Novartis, Genzyme, Boehringer, Janssen, MSD, Celgene, Roche, Chugai, Bristol Myers Squibb, UCB Pharma, Grant/research support from: Pfizer, Janssen, Chugai, Celgene, Roche, Alan Kivitz Shareholder of: Pfizer, Sanofi, GlaxoSmithKline, Gilead Sciences, Inc., Novartis; Paid consultant: AbbVie, Boehringer Ingelheim, Flexion, Janssen, Pfizer, Sanofi, Regeneron, SUN Pharma Advanced Research, Gilead Sciences, Inc, Speakers bureau: Amgen, Horizon, Lilly, Novartis, Pfizer, Sanofi, Genzyme, Flexion, AbbVie, Thomas Lehman Shareholder of: Bristol Myers Squibb, Employee of: Bristol Myers Squibb, Lan Wei Shareholder of: Bristol Myers Squibb, Employee of: Bristol Myers Squibb, Marleen Nys Shareholder of: Bristol Myers Squibb, Employee of: Bristol Myers Squibb, Subhashis Banerjee Shareholder of: Bristol Myers Squibb, Employee of: Bristol Myers Squibb, Miroslawa Nowak Shareholder of: Bristol Myers Squibb, Employee of: Bristol Myers Squibb