On the heels of its approval for use in patients with plaque psoriasis, new research from a phase 2 trial provides insight into the effects of the oral tyrosine kinase 2 (TYK2) inhibitor in a population of patients with systemic lupus erythematosus (SLE).
Presented at the American College of Rheumatology (ACR) Convergence 2022, results from the trial, which included more than 360 people from more than 15 countries, demonstrate that deucravacitinib use was associated with higher response rates elevated for the SLE Responder Index 4 (SRI-4) response at week 32 as well as notable improvements in other endpoints over placebo treatment, with the researchers also pointing to an acceptable safety profile for the agent .
“The TYK2 transducer signals a unique set of cytokines 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 in lupus and encourage the further development of deucravacitinib in this disease.”
A member of the family of JAK inhibitors that mediate IL-23, IL-12, and type I IFN signaling, deucravacitinib has caught the attention of rheumatologists and rheumatic disease specialists for its potential in the treatment of various chronic conditions as a result of its effect on inflammatory markers. As a result, deucravacitinib has become the focus of research efforts in plaque psoriasis, psoriasis, ulcerative colitis, and, in the present study, SLE.
To examine the agent’s use in SLE, researchers designed the Phase 2 trial as a quadruple masked, randomized, double-blind, placebo-controlled study with the intention of randomizing adult patients with LES 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 endpoint of interest for the study was SRI-4 response at week 32. Secondary endpoints of interest, which were assessed at week 48, included SRI-4 response, British Isles Lupus Assessment Group–Based Composite Lupus Lupus Erythematosus Disease Area and Severity Index 50 (CLASI-50), Lupus Low Disease Activity State (LLDAS) and improvement in active, swollen and painful joint counts. The trial also included several safety outcomes of interest, such as the rate of adverse events and the incidence of death or major adverse cardiovascular events.
A total of 363 people were randomized in the study. Of these, 90, 91, 93, and 89 people were randomized to receive 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.
After analysis, the results suggested that the proportion of patients achieving an SRI-4 response was 34% among those receiving placebo treatment, which was lower than the 58% achieved with deucravacitinib 3 mg twice daily (OR, 2.8 [95% CI, 1.5-5.1]; P<.001 achieved with mg twice daily ci>P= 0.02), and 45% achieved with 12 mg once daily (OR, 1.6 [95% CI, 0.8-2.9]; P=.08). Further analysis indicated that response rates were higher with deucravacitinib treatment for BICLA, CLASI-50, LLDAS and joint count compared to placebo treatment.
In safety analyses, results indicated that rates of adverse events were similar with placebo and deucravacitinib treatment, except for higher rates of infections and skin events including rash and acne, seen with deucravacitinib. Regarding serious adverse events, the results suggest that the rates were comparable between the study arms, with deaths, opportunistic infections, tuberculosis infections, major adverse cardiovascular events or thrombotic events reported in both arms.
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.