Deucravacitinib Shows Promise for Systemic Lupus Erythematosus in Phase 2 Trial

Eric Morand, MBBS, PhD

On the heels of its approval for use in patients with plaque psoriasis, new research from a phase 2 trial is providing insight into the effects of the oral tyrosine kinase 2 inhibitor (TYK2) among a patient population with systemic lupus erythematosus (SLE).

Presented at the American College of Rheumatology (ACR) Convergence 2022, the results of the trial, which included more than 360 individuals from more than 15 countries, demonstrate use of deucravacitinib was associated with greater response rates for SLE Responder Index 4 (SRI-4) response at week 32 as well as improvements in other end points of note compared with placebo therapy, with investigators also highlighting an acceptable safety profile for the agent.

“TYK2 transducer signals a unique set of cytokines that are highly relevant to SLE,” said corresponding author Eric Morand, MBBS, PhD, of Monash University, in a statement. “These results put TYK2 on the map as a target for lupus and encourage further development of deucravacitinib in this disease."

A member of the JAK inhibitor family that mediates signaling of IL-23, IL-12, and Type I IFN, deucravacitinib has captured the attention of rheumatologists and specialists in rheumatic disease for its potential in treating a variety of chronic conditions as a result of its effect on inflammatory markers. As a result, deucravacitinib has become the focus of research endeavors in plaque psoriasis, psoriasis, ulcerative colitis, and, in the current study, SLE.

To examine use of the agent in SLE, investigators designed the phase 2 trial as a quadruple-masked, randomized, double-blind, placebo-controlled study, with the intent of randomizing adult patients with SLE in a 1:1:1:1 ratio to receive deucravacitinib 3 mg twice daily, 6 mg twice daily, 12 mg once daily, or placebo.

The primary outcome of interest for the study was SRI-4 response at week 32. Secondary outcomes of interest, which were assessed at week 48, included SRI-4, British Isles Lupus Assessment Group–based Composite Lupus Assessment (BICLA) response, Cutaneous Lupus Erythematosus Disease Area and Severity Index 50 (CLASI-50), Lupus Low Disease Activity State (LLDAS), and improvements in active, swollen, and tender joint counts. The trial also included multiple safety outcomes of interest, such as rate of adverse events and incidence of death or major adverse cardiovascular events.

Overall, 363 individuals underwent randomization in the study. Of these, 90, 91, 93, and 89 individuals were randomized to the placebo, deucravacitinib 3 mg twice daily, deucravacitinib 6 mg twice daily, and deucravacitinib 12 mg once daily, respectively. Of the 363 included in the study, 75.8% completed the 48 weeks of treatment.

Upon analysis, results suggested the proportion of patients achieving SRI-4 response was 34% among those receiving placebo therapy, which was lower than the 58% achieved with deucravacitinib 3 mg twice daily (OR, 2.8 [95% CI, 1.5-5.1]; P <.001), 50% achieved with 6 mg twice daily (OR, 1.9 [95% CI, 1.0-3.4]; P=.02), and 45% achieved with 12 mg once daily (OR, 1.6 [95% CI, 0.8-2.9]; P=.08). Further analysis indicated response rates were higher with deucravacitinib treatment for BICLA, CLASI-50, LLDAS, and joint counts when compared with placebo therapy.

In safety analyses, results indicated rates of adverse events were similar with placebo therapy and deucravacitinib, except higher rates of infections and cutaneous events, including rash and acne, observed with deucravacitinib. In regard to serious adverse events, results suggested rates were comparable between the study arms, with deaths, opportunistic infections, tuberculosis infections, major adverse cardiovascular events, or thrombotic events reported among either arm.

This study, “Deucravacitinib, a Tyrosine Kinase 2 Inhibitor, in Systemic Lupus Erythematosus: A Phase II, Randomized, Double-Blind, Placebo-Controlled Trial,” was presented at ACR Convergence 22 and simultaneously published in Arthritis and Rheumatology.