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Abstract
Objective Deucravacitinib, a first-in-class, oral, selective, allosteric tyrosine kinase 2 inhibitor targets select immune pathways relevant to systemic lupus erythematosus (SLE) and is approved in multiple countries for the treatment of adults with moderate-to-severe plaque psoriasis. In the 48-week, double-blind, phase 2 PAISLEY trial for patients with active SLE (NCT03252587), a greater proportion of patients randomized to deucravacitinib 3 mg BID met the primary endpoint of the SLE Responder Index-4 and all key secondary endpoints, including global disease activity measures. This post-hoc subanalysis focuses on musculoskeletal manifestations in the PAISLEY study.
Methods Patients receiving standard-of-care were randomized 1:1:1:1 to placebo (n=90) or deucravacitinib 3 mg BID (n=91), 6 mg BID (n=93), or 12 mg QD (n=89). A 40-joint count measured joint swelling, tenderness, or both. Outcomes included achievement of ≥50% reduction (JC-50) and 100% reduction (JC-100) in active joint count (swollen+tender; AJC-50 and AJC-100, respectively), swollen joint count (SJC), and tender joint count (TJC) in patients with ≥6 joints involved at baseline or patients with any joint involvement at baseline. Responses were reported with a prespecified nonresponder imputation. The 2-sided 95% CI for responses was calculated using the asymptotic (including continuity) method. Results were descriptive.
Results At week 32 (primary endpoint analysis time point), more patients with ≥6 active joints at baseline receiving deucravacitinib achieved AJC-50 vs placebo (placebo, 45.3%; deucravacitinib 3 mg BID, 63.5%; 6 mg BID, 64.6%; 12 mg QD, 56.5%; figure 1A), expanding previously reported JC-50 findings at week 48. Patients with any joint involvement at baseline receiving deucravacitinib achieved AJC-50 more often vs placebo (week 32: placebo, 48.3%; deucravacitinib 3 mg BID, 63.3%; 6 mg BID, 63.4%; 12 mg QD, 53.4%) through week 48 (figure 1B). AJC-100 results were similar to AJC-50 results in both populations through week 48 (figure 1C and 1D). Consistent patterns of higher JC-50 and JC-100 responses with deucravacitinib were observed in separate analyses of SJC and TJC through week 48 (figure 2).
Conclusion Deucravacitinib was associated with reductions in joint counts vs placebo using a range of assessment time points, different joint assessments, and different cutoffs for musculoskeletal involvement at baseline.
AJC-50 and AJC-100 responses from baseline to week 48
JC-50 and JC-100 responses at week 48 for SJC and TJC assessments
Acknowledgements We thank the patients and their families who made this study possible, as well as the clinical teams who participated. This study was sponsored by Bristol Myers Squibb. Professional medical writing assistance was provided by Stephanie V. Koebele, PhD, of SciMentum, Inc, a Nucleus Group Holdings, Inc, company, and funded by Bristol Myers Squibb.
COI Disclosures
MP: Consultancy: AstraZeneca, Bristol Myers Squibb, Pfizer, and UCB
AS: Advisory board: AstraZeneca, Bristol Myers Squibb, Eli Lilly and Company, GSK, and Kezar Life Sciences
RF: Research/grant support and consultancy: Bristol Myers Squibb
PN: Research/grant support and consultancy: AbbVie, Amgen, Bristol Myers Squibb, Celgene, Janssen, Eli Lilly, Novartis, Servatus, and UCB
TD: Research/grant support: AbbVie, Novartis, Bristol Myers Squibb, Janssen, Roche/Genentech, Sanofi, Eli Lilly, UCB, Deutsche Forschungsgemeinschaft, and EU Horizon/HarmonicSS. Advisory boards/panels: AbbVie, Aurinia, Bristol-Myers-Squibb, Eli Lilly, Novartis, Sanofi, and UCB
CH, SP, SB, and TW: Employee and shareholder: Bristol Myers Squibb
RK: Employee: Syneos Health, providing statistical services to Bristol Myers Squibb
JM: Consultancy: AbbVie, Alexion, Amgen, AstraZeneca, Aurinia, Biogen, Bristol Myers Squibb, EMD Serono, Equillium, Genentech, Gilead, GSK, IQVIA, Janssen, Eli Lilly, LFA, Merck, Provention, Remegen, Sanofi, Takeda, and Zenas
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