Tyrosine kinases are enzymes that play central roles in signaling by cytokines involved in the pathogenesis of autoimmune diseases, including lupus. A recent phase 2 clinical trial published by Wiley in Arthritis & Rheumatology has generated promising results for deucravacitinib, an oral inhibitor of tyrosine kinase 2 (TYK2), in patients with active lupus.
In the trial, 363 patients were randomized 1:1:1:1 to placebo or deucravacitinib 3 mg twice daily, 6 mg twice daily, or 12 mg once daily. At week 32, the percentage of patients who experienced a beneficial response (as assessed by various measures of disease activity) was 34% with placebo compared with 58%, 50%, and 45% with the respective deucravacitinib regimens.
Rates of adverse events were similar across groups, except for higher rates of infections and skin-related events, including rash and acne, with deucravacitinib. Rates of serious adverse events were comparable, with no deaths, opportunistic infections, tuberculosis, major adverse cardiovascular events, or thrombotic events reported.
TYK2 transducer signals a unique set of cytokines that are highly relevant to SLE. These results put TYK2 on the map as a target for lupus and encourage further development of deucravacitinib in this disease."
Eric Morand, MBBS, PhD, Corresponding Author, Monash University
Morand, E., et al. (2022) Deucravacitinib, a Tyrosine Kinase 2 Inhibitor, in Systemic Lupus Erythematosus: A Phase II, Randomized, Double-Blind, Placebo-Controlled Trial. Arthritis & Rheumatology. doi.org/10.1002/art.42391.