Pos0532 Deucravacitinib, an Oral, Allosteric, Tyrosine Kinase 2 (Tyk2) Inhibitor, in Patients With Active Systemic Lupus Erythematosus: Patient-Reported Outcomes in a Phase 2 Trial

Background: Deucravacitinib is a first-in-class, oral, selective, allosteric tyrosine kinase 2 (TYK2) inhibitor approved in the US, EU, and other countries for treatment of adults with moderate-to-severe plaque psoriasis who are candidates for systemic therapy. In PAISLEY, a 48-week, phase 2, randomized controlled trial that assessed deucravacitinib in patients with active systemic lupus erythematosus (SLE), a greater proportion of patients receiving deucravacitinib treatment achieved SLE Responder Index-4 (SRI[4]) responses at Weeks 32 and 48 vs placebo. Objectives: To assess the impact of deucravacitinib on patient-reported outcomes (PROs) in patients with active SLE. Methods: All patients met Systemic Lupus International Collaborating Clinics classification criteria, were seropositive for antinuclear antibody, anti-double-stranded DNA, or anti-Smith antibody, and had Systemic Lupus Erythematosus Activity Index 2000 total score ≥6 points and clinical score ≥4 points. Patients (N = 363) were randomized 1:1:1:1 to placebo (n = 90) or deucravacitinib 3 mg twice daily (BID; n = 91), 6 mg BID (n = 93), or 12 mg once daily (QD; n = 89). Patients assessed pain levels on a numeric rating scale (NRS) and completed the Patient-Reported Outcome Measurement Information System (PROMIS) Fatigue 7a Short Form and 36-Item Short Form Health Survey (SF-36). Patient-reported assessments were recorded on Day 1 regardless of the assessment time relative to the first dose of study medication. Missing data were imputed using control-based pattern imputation. Results were descriptive. Results: Baseline characteristics were comparable across groups. At Week 48, greater mean changes from Day 1 in pain and fatigue were reported with deucravacitinib 3 mg BID, 6 mg BID, and 12 mg QD vs placebo, including achievement of the minimal clinically important differences (MCID) of −1 and −4 for both pain and fatigue with all doses of deucravacitinib vs for pain only with placebo (Figure 1). Patients treated with deucravacitinib reported greater achievement of changes associated with MCID for pain (−1), fatigue (−4), and SF-36 MCS and PCS (−2.5) vs placebo (Table 1). Mean scores (SD) at Week 48 numerically improved with deucravacitinib 3 mg BID, 6 mg BID, and 12 mg QD vs placebo, respectively: Pain NRS: 3.6 (2.7), 3.7 (2.6), 3.6 (2.8), and 4.7 (2.7); PROMIS Fatigue: 52.4 (10.2), 52.6 (10.0), 51.9 (10.6), and 54.4 (10.9); SF-36 PCS: 44.7 (10.0), 44.6 (9.3), 45.1 (11.0), and 41.5 (10.5); and SF-36 MCS: 46.7 (12.6), 46.3 (13.1), 47.3 (12.6), and 45.2 (12.9). Conclusion: Patients with SLE who received deucravacitinib reported improvements over patients who received placebo on pain and fatigue, and in health-related quality of life at Week 48. REFERENCES: NIL. Acknowledgements: This study was sponsored by Bristol Myers Squibb. Disclosure of Interests: Marta Mosca AstraZeneca, Bristol Myers Squibb, GSK, Lilly, Otsuka, and UCB, Laurent Arnaud AbbVie, Alexion, Alpine, Amgen, AstraZeneca, Biogen, Boehringer Ingelheim, Bristol Myers Squibb, GSK, Grifols, Janssen, LFB, Kezar Life Sciences, Lilly, Medac, Novartis, Oséus, Pfizer, Roche-Chugaï, and UCB, Anca Askanase AbbVie, Amgen, AstraZeneca, Bristol Myers Squibb, Celgene, Genentech, GSK, Idorsia, Janssen, Lilly, Pfizer, and UCB, Coburn Hobar Bristol Myers Squibb, Bristol Myers Squibb, Brandon Becker Bristol Myers Squibb, Bristol Myers Squibb, Shalabh Singhal Bristol Myers Squibb, Former employee Bristol Myers Squibb, Subhashis Banerjee Bristol Myers Squibb, Bristol Myers Squibb, Samantha Pomponi Bristol Myers Squibb, Bristol Myers Squibb, Jiyoon Choi Bristol Myers Squibb, Bristol Myers Squibb, Adrian Coles Bristol Myers Squibb, Bristol Myers Squibb, Vibeke Strand AbbVie, Amgen, Arena Pharmaceuticals, AstraZeneca, Bayer, Biosplice, Bioventus, Blackrock Pharmaceuticals, Boehringer Ingelheim, Bristol Myers Squibb, Celltrion, Chemocentryx, Equillium, Eupraxia, Flexion, Galápagos, Genentech/Roche, Gilead, GSK, Horizon Therapeutics, Ichnos Sciences, Inmedix, Janssen, Kiniksa, Kypha, Eli Lilly, Merck, MiMedx, Novartis, Pfizer, Regeneron, Rheos Medicines, Samsung, Sandoz, Sanofi, Scipher, Servier, SetPoint Medical, Spherix, Tonix, and UCB.