Anifrolumab, an anti-interferon-alpha receptor monoclonal antibody under development by MedImmune, was effective against moderate to severe systemic lupus erythematosus, according to phase 2b trial results.
"The results were the most robust results seen to date in any lupus clinical trial," Richard Furie, MD, in the Division of Rheumatology at Northwell Health in New York, told Healio Rheumatology. "The study confirmed the importance of the pathogenic role of the interferon pathway in extra-renal [systemic lupus erythematosus] SLE."
To assess the efficacy of the drug, Furie and colleagues randomized 305 patients for 48 weeks to receive placebo or 300-mg or 1,000-mg doses of intravenous anifrolumab per 4 weeks. The researchers stratified patients by oral corticosteroid dose, SLE Disease Activity Index 2000 score and type 1 interferon gene signature status. After 24 weeks, the researchers measured the percentage of patients who achieved an SLE Responder Index [SRI] (4) response and who had a sustained reduction of oral corticosteroids — which the researchers defined as corticosteroid dosage of less than 10 mg per day and never going above the week 1 dose after week 12. After 52 weeks, the researchers assessed SRI(4), BILAG-based Composite Lupus Assessment (BICLA), modified SRI(6) and major clinical response, which they defined as maintaining a BILAG 2004 grade of at least C for all organ domains after week 24. They measured these endpoints in a modified intention-to-treat (mITT) population and in a subpopulation of patients with a high interferon signature at baseline.
Compared with placebo, more patients treated with anifrolumab achieved an SRI(4) response and sustained corticosteroid reduction after 24 weeks (17.6% for placebo vs. 34.3% for 300 mg and 28.8% for 1,000 mg), but the 1,000-mg increase was not significant. In patients with a high interferon signature, the increase became significant for the 1,000-mg group (13.2% for placebo vs. 28.2%) and remained significant for the 300-mg group (13.2% vs. 36%). After 52 weeks, more patients treated with anifrolumab achieved SRI(4) response (40.2% for placebo vs. 62.6% for 300-mg and 53.8% for 1,000 mg), BICLA response (25.7% vs. 53.5% and 41.2%, respectively), modified SRI(6) response (28.4% vs. 49.5% and 44.7%) and major clinical response (6.9% vs. 19.2% and 17.3%, respectively). In the safety analysis, more patients treated with anifrolumab acquired herpes zoster (2% vs. 5.1% and 9.5%, respectively) and influenza (2% vs. 6.1% and 7.6%, respectively), while serious adverse event incidence was similar between groups (18.8% vs. 16.2% and 17.1%, respectively). – by Will Offit
Disclosures: Furie reports personal fees from MedImmune. Please see the full study for a list of all other relevant financial disclosures.