Anifrolumab for Lupus
Anifrolumab for Lupus
It is well known that the interferon pathway plays an integral role in lupus disease activity. Controlling whether this pathway is active can impact a patient’s experience.
New research published in Arthritis & Rheumatology examined the efficacy of anifrolumab, a type 1 interferon receptor antagonist. According to the study's Richard Furie, M.D., of Hofstra Northwell School of Medicine in New York, the study shows anifrolumab is more effective than other medications in inhibiting interferon.
This was a phase IIb, randomized, double-blind, placebo-controlled study of 305 adults with moderate-to-severe systemic lupus erythematosus. Anifrolumab was shown to substantially reduce disease activity as compared to placebo across multiple clinical endpoints in patients. Patients were randomized to receive intravenous anifrolumab (300 mg or 1,000 mg) or placebo, in addition to standard therapy, every 4 weeks for 48 weeks. The primary end point was the percentage of patients achieving an SLE Responder Index (SRI) response at week 24 with sustained reduction of oral corticosteroids (<10 mg/day and less than or equal to the dose at week 1 from week 12 through 24). The primary end point was met by more patients treated with anifrolumab (34.3% of 99 for 300 mg and 28.8% of 104 for 1,000 mg) than placebo (17.6% of 102) (P = 0.014 for 300 mg and P = 0.063 for 1,000 mg, versus placebo), with greater effect size in patients with a high IFN signature at baseline (13.2% in placebo-treated patients versus 36.0% [P = 0.004] and 28.2% [P = 0.029]) in patients treated with anifrolumab 300 mg and 1,000 mg, respectively.
Dr. Furie spoke with Rheumatology Network about his research.
Q: Why did you research anifrolumab’s impact?
A: For decades, there’s been evidence the interferon pathway is active in lupus patients. The natural thing to do when developing drugs is targeting an active pathway, and interferon has three pathways. The first one has five subsets, including alpha-interferon. All subtypes bind to the same receptor. The downfall has been inhibiting one interferon type leaves four others that can signal the same receptor. Previous studies with other drugs, including sifalimumab, provided hope that inhibiting the interferon pathway might work in treating lupus and its associated conditions, such as active renal disease and joint pain.
Anifrolumab was first tested in a scleroderma study in Japan, before testing it with lupus. Results have shown it’s a better interferon pathway inhibitor than sifalimumab because it binds to all five subtypes. Sifalimumab binds to one, leaving four free to activate cells.
Q: What are the clinical implications of using anifrolumab to treat lupus?
A: Anifrolumab blocks the whole receptor pathway responsible for binding all interferon types. In my study, 300 patients participated globally. There were three treatment arms – placebo, low dose (300 mg), and high dose (1,000 mg) that were given against a background of the standard of care, including steroids, anti-malarials, and other regular lupus medications.
Patient were randomized and given intravenous anifrolumab every four weeks for six months. They were evaluated at six months and one year. At six months, the lower dose worked better than the higher dose. And, at one year, the data were even stronger.