A phase II clinical trial has shown that deucravacitinib, an oral, selective, allosteric inhibitor of TYK2, may be an effective and safe treatment for adults with active systemic lupus erythematosus (SLE).
Systemic lupus erythematosus(SLE)
Systemic lupus erythematosus is a chronic autoimmune disease that can affect multiple organ systems in the body. It is characterized by the presence of autoantibodies, inflammation, and tissue damage. Current treatments for SLE include nonsteroidal anti-inflammatory drugs (NSAIDs), corticosteroids, and immunosuppressive agents. However, these treatments have limitations, including side effects and incomplete response rates.
The phase II clinical trial enrolled 363 adults with active SLE from 162 sites in 17 countries. The patients were randomized to receive deucravacitinib at doses of 3 mg twice daily, 6 mg twice daily, 12 mg once daily, or placebo. The primary endpoint of the study was SLE Responder Index 4 (SRI-4) response at week 32. Secondary endpoints 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 plus tender), swollen, and tender joint counts, assessed at week 48.
The results of the study showed that deucravacitinib treatment elicited higher response rates for SRI-4 and other endpoints compared with placebo, with an acceptable safety profile. At week 32, the percentage of patients achieving SRI-4 response was 34% with placebo compared to 58% with deucravacitinib 3 mg twice daily, 50% with 6 mg twice daily, and 45% with 12 mg once daily. The response rates were higher with deucravacitinib treatment for BICLA, CLASI-50, LLDAS, and joint counts compared to the placebo.
The rates of adverse events were similar across groups, except for higher rates of infections and cutaneous events, including rash and acne, with deucravacitinib treatment. However, rates of serious adverse events were comparable, with no deaths, opportunistic infections, tuberculosis infections, major adverse cardiovascular events, or thrombotic events reported.
The study findings suggest that deucravacitinib may be a promising treatment option for adults with active SLE. Deucravacitinib is a selective inhibitor of TYK2, an enzyme that plays a key role in the signaling pathways that lead to inflammation and tissue damage in SLE. By targeting this pathway, deucravacitinib may be able to reduce inflammation and improve disease outcomes in SLE patients.
The phase II clinical trial of deucravacitinib showed promising results in treating active SLE, with higher response rates for several disease activity measures compared to placebo, and an acceptable safety profile. Further studies are needed to confirm these findings and determine the optimal dosing and duration of treatment with deucravacitinib.