USA: A recent study in Wiley’s Arthritis & Rheumatology has shown promising results for deucravacitinib in patients with active lupus. deucravacitinib is an oral inhibitor of tyrosine kinase 2 (TYK2).
The findings from the phase 2 clinical trial showed that treatment with deucravacitinib elicited higher response rates for SLE Responder Index 4 (SRI-4) and other end points versus placebo, having an acceptable safety profile in patients with active systemic lupus erythematosus (SLE).
Tyrosine kinases are enzymes that play central roles in signalling by cytokines involved in the pathogenesis of autoimmune diseases, including 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.
Key findings include:
- At week 32, the percentage of patients achieving
SRI-4 response was 34% with placebo compared to 58% with deucravacitinib 3 mg
twice daily (odds ratio [OR] 2.8 versus placebo), 50% with 6 mg twice daily (OR
1.9 versus placebo), and 45% with 12 mg once daily (OR 1.6). - Response rates were higher with deucravacitinib
treatment for BICLA, CLASI-50, LLDAS, and joint counts compared to placebo. - Rates of adverse events were similar across
groups, except higher rates of infections and cutaneous events, including rash
and acne, with deucravacitinib treatment. - Rates of serious adverse events were comparable,
with no deaths, opportunistic infections, tuberculosis infections, major
adverse cardiovascular events, or thrombotic events reported.
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,” said corresponding author Eric Morand, MBBS, PhD, of Monash University. “These results put TYK2 on the map as a target for lupus and encourage further development of deucravacitinib in this disease.”
Reference:
Eric Morand, Marilyn Pike, Joan T. Merrill, Ronald van Vollenhoven, Victoria P. Werth, Coburn Hobar, Nikolay Delev, Vaishali Shah, Brian Sharkey, Thomas Wegman, Ian Catlett, Subhashis Banerjee, Shalabh Singhal First published: 11 November 2022 https://doi.org/10.1002/art.42391