Deucravacitinib, a novel cure for patients with active SLE
Australia: Deucravacitinib (DEUC) showed statistically significant and sustained clinical efficacy and safety in patients with active systemic lupus erythematosus (SLE), states a phase 2 trial data published in Annals of the Rheumatic Diseases. DEUC may be a new treatment option for SLE.
Systemic lupus erythematosus is a chronic autoimmune disease.TYK2 mediates the signal of key cytokines involved in lupus pathogenesis. Deucravacitinib (DEUC) is an oral, selective, allosteric TYK2 inhibitor with a unique mechanism of action, distinct from Janus kinase (JAK) 1/2/3 inhibitors. It has already shown efficacy in psoriasis and psoriatic arthritis. It is a topic of discussion among Rheumatologists as a wonder drug for the treatment of a wide range of conditions
The author Eric Morand, Monash University in Victoria, Australia and colleagues conducted a study to evaluate the efficacy and safety of DEUC in patients with active systemic lupus erythematosus (SLE).
The study was a 48-week (wk), randomized, double-blind, placebo (PBO)-controlled, phase 2 trial. Researchers enrolled a total of 363 patients with active SLE and randomized them in 1:1:1:1 to PBO or DEUC (3 mg BID, 6 mg BID, 12 mg QD). The primary endpoint was the proportion of patients achieving SLE Responder Index Level 4 (SRI4) at wk 32. Key secondary endpoints at wk 48 included SRI(4), BICLA, LLDAS, CLASI-50, and change from baseline in the active (tender and swollen) joint count.
Key findings from the trial data,
• At wk 32, a greater proportion of patients achieved SRI(4) responses in DEUC 3 mg BID and 6 mg BID groups compared to PBO
• SRI(4) response was sustained across all DEUC groups for up to 48 wks.
• At wk 48, the DEUC 3 mg BID group demonstrated statistical significance in BICLA, LLDAS, CLASI-50, and active joint count, and the two other DEUC groups demonstrated clinically meaningful differences compared to PBO.
• Rates of adverse events (AEs), serious AEs, and AEs of interest were similar between DEUC and PBO groups. There were no deaths, major cardiac events, thrombotic events, systemic opportunistic infections, or active tuberculosis.
• Malignancies were rare with similar rates of occurrence across all groups.
• There were no meaningful abnormalities in mean levels of haematology and chemistry laboratory parameters.
The authors conclude that DEUC has shown noteworthy and sustained clinical efficacy in SRI (4), improvement across multiple composites and organ-specific measures up to 48 wks and it was well tolerated in active SLE patients. The authors wrote that data shows DEUC as a novel therapy for SLE and warrants further investigation in phase III trials.
Morand E, Pike M, Merrill JT, et alLB0004 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 STUDYAnnals of the Rheumatic Diseases 2022;81:209.
