Anifrolumab and deucravacitinib combo shows promise in patients with lupus

Type I interferon (IFN) is a powerful immune activator that is present at high levels in the majority of patients with lupus, an autoimmune disease. In Arthritis & Rheumatology, researchers report positive results from the first placebo-controlled long-term trial of anifrolumab-a human monoclonal antibody that targets the type I IFN receptor-in patients with lupus.

In the long-term extension trial of two earlier phase 3 trials, patients continued anifrolumab 300 mg, switched from anifrolumab 150 mg to 300 mg, or were re-randomized from placebo to either anifrolumab 300 mg or continued placebo, administered every 4 weeks, with all patients also receiving standard therapy. Anifrolumab was administered as an intravenous infusion.

Treatment with anifrolumab was well tolerated and had an acceptable long-term safety profile, while sustaining reduction in lupus disease activity and reducing or eliminating the need for steroid medications.

Another recent phase 2 clinical trial which I'm going to talk about also published in Arthritis & Rheumatology has generated promising results for deucravacitinib, an oral inhibitor of tyrosine kinase 2 (TYK2), in patients with active lupus. Tyrosine kinases are enzymes that play central roles in signaling 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 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.

Reference:

"A Randomized, Placebo-controlled Phase 3 Extension Trial of the Long-term Safety & Tolerability of Anifrolumab in Active Systemic Lupus Erythematosus." Kenneth C. Kalunian, Richard Furie, Eric F. Morand, Ian N. Bruce, Susan Manzi, Yoshiya Tanaka, Kevin Winthrop, Ihor Hupka, Lijin (Jinny) Zhang, Shanti Werther, Gabriel Abreu, Micki Hultquist, Raj Tummala, Catharina Lindholm,and Hussein Al-Mossawi. Arthritis & Rheumatology; Published Online: November 12, 2022 (DOI: 10.1002/art.42392).

"Deucravacitinib, a Tyrosine Kinase 2 Inhibitor, in Systemic Lupus Erythematosus: A Phase 2, Randomized, Double-Blind, Placebo-Controlled Trial." 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. Arthritis & Rheumatology; Published Online: November 12, 2022 (DOI: 10.1002/art.42391).