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).