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VBCR - August 2016, Vol 5, No 4 - Lupus
Alice Goodman

London, United Kingdom—Evidence is mounting in support of using the investigational monoclonal antibody anifrolumab in patients with severe systemic lupus erythematosus (SLE). Results from the phase 2b MUSE trial—which were first presented at the 2015 American College of Rheumatology Annual Scientific Meeting, and then in greater detail at the recent 2016 European League Against Rheumatism Annual Congress—show that in patients with moderate-to-severe SLE, anifrolumab reduces disease activity across a wide range of clinical end points, and is safe and tolerable.

Going forward, AstraZeneca will use the dose of intravenous (IV) anifrolu­mab 300 mg every 4 weeks in phase 3 trials. Investigators are excited about having this potential new tool in the armamentarium.

“Anifrolumab is promising for patients who do not respond to currently available therapies,” said principal investigator Richard Furie, MD, Chief, Division of Rheumatology, Northwell Health, Great Neck, NY. “Substantial benefits were seen across multiple global and organ-specific disease activity measures, with acceptable safety and tolerability. I am excited about this compelling evidence that blocking type 1 interferons (IFNs) is a promising strategy for the treatment of SLE, provid­ing much needed hope for the SLE community.”

Anifrolumab is an investigational human monoclonal antibody that binds to subunit 1 of the type 1 IFN receptor, inhibiting all activity of type 1 IFNs, which play a central role in SLE. Anifrolumab is currently in phase 3 trials, and has been granted a fast track designation for SLE by the FDA.

MUSE was a randomized, double-blind, placebo-controlled trial of 305 adults with moderate-to-severe SLE. All patients were treated with standard-of-care medications, and, in addition, were randomized to receive IV anifrolumab 300 mg every 4 weeks; standard of care plus IV anifrolumab 100 mg every 4 weeks; or IV placebo every 4 weeks, for 48 weeks.

Patients were stratified by SLE Disease Activity Index 2000 (DAI-2K) score, oral corticosteroid dose, and IFN gene signature (ie, high vs low, based on a 4-gene expression assay).

The primary end point was the percentage of patients who achieved an SLE Responder Index 4 (SRI4) at day 169, with a sustained reduction in oral corticosteroid use between days 85 and 169. Secondary efficacy was SRI4 at day 365.

The rates of SRI4 at day 169 were 34.3% for the 300-mg dose group, 28.8% for the 1000-mg dose group, and 17.6% for patients receiving placebo (P = .014 for the 300-mg dose vs placebo; P = .063 for the 1000-mg dose vs placebo).

The rates of SRI4 at day 365 were 51.5% for the 300-mg dose group, 38.5% for the 1000-mg dose group, and 25.5% for patients receiving placebo (P <.01 for the 300-mg dose vs placebo; P = .048 for the 1000-mg dose vs placebo). Low disease activity at day 365—as measured by SLEDAI-2K scores <2—was achieved by 35.4% of the 300-mg group and 32.7% of the 1000-mg group, versus 17.6% of the placebo group (P = .004 for the 300-mg dose vs placebo; P = .012 for the 1000-mg dose vs placebo).

Even more robust activity was observed in the 75% of patients who had a high type 1 IFN gene signature at baseline, Dr Furie emphasized.

These patterns were replicated for all disease measures, including major clinical response, oral corticosteroid taper, as well as quality of life. The best responses were observed with IV anifrolumab 300 mg every 4 weeks, and that is the dose being used going forward in phase 3 trials.

At least 1 adverse event was reported in 85.3% of all treated patients (including patients receiving placebo). A greater number of adverse events of interest were reported in patients receiving anifrolumab (ie, dose-dependent increases in herpes zoster and influenza cases). The safety was deemed acceptable.

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