In patients with active systemic lupus erythematosus (SLE), treatment with the tyrosine kinase 2 (TYK2) inhibitor deucravacitinib shows statistically significant, sustained clinical efficacy and is well tolerated, according to results of a study presented at the American College of Rheumatology (ACR) Convergence 2022, held between November 10 and 14, in Philadelphia, Pennsylvania.
The investigators of the phase 2, randomized, double-blind, placebo-controlled, 48-week study (ClinicalTrials.gov Identifier: NCT03252587) sought to evaluate the efficacy and safety of deucravacitinib in active SLE.
Eligible patients fulfilled the Systemic Lupus International Collaborating Clinics (SLICC) criteria, tested seropositive, had a Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) score of at least 6, and had a British Isles Lupus Assessment Group (BILAG) index A of at least 1 or more than 2 BILAG B manifestations from the musculoskeletal or mucocutaneous domain.
Patients receiving standard background medications were randomly assigned 1:1:1:1 to placebo, deucravacitinib 3 mg twice-daily, deucravacitinib 6 mg twice-daily, or deucravacitinib 12 mg once-daily. Tapering of oral corticosteroids to 7.5 mg/day was required from weeks 8 to 20, with additional tapering optional from weeks 32 to 40.
The primary study endpoint was the percentage of patients who attained SLE responder index (SRI ) at week 32. Secondary endpoints at week 48 included SRI (4), BILAG-based Composite Lupus Assessment (BICLA), Lupus Low Disease Activity State (LLDAS), decrease in at least 50% from baseline Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI-50), and change from baseline in active (tender and swollen) joint count.
A total of 363 patients were included in the analysis, of whom 275 (76%) completed the 48 weeks of treatment.
At week 32, the primary endpoint was met, with a significantly greater percentage of patients in the deucravacitinib 3-mg, 6-mg, and 12-mg group vs placebo group achieving SRI (4) responses (58.2%, 49.5%, 49.5% vs 34.4%, respectively). The SRI (4) response was sustained in all deucravacitinib groups up to 48 weeks.
At week 48, the deucravacitinib 3-mg group demonstrated statistical significance in BICLA, LLDAS, CLASI-50, and active joint count. The deucravacitinib 6-mg and 12-mg groups demonstrated clinically meaningful differences compared with placebo.
Rates of adverse events (AEs), serious AEs, and AEs of interest were similar between the deucravacitinib groups and the placebo group. The most commonly reported AEs (≥10%) included upper respiratory tract infection, nasopharyngitis, headache, and urinary tract infection. No deaths occurred.
The investigators concluded, “[Deucravacitinib] shows promise as a novel therapy for SLE and warrants further investigation in phase 3 trials.”
Disclosure: Some of the study authors have declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.
June 13, 2022
June 10, 2022
June 10, 2022
June 9, 2022
June 8, 2022
June 8, 2022
Pike M, Merrill J, Morand E, et al. Efficacy and safety of deucravacitinib, an oral, selective, allosteric TYK2 inhibitor, in patients with active systemic lupus erythematosus: a phase 2, randomized, double-blind, placebo-controlled study. Presented at: ACR Convergence 2022; November 10-14; Abstract #1117.