Objective: To investigate long-term safety and tolerability of anifrolumab, a human monoclonal antibody to the type I interferon (IFN) receptor subunit 1, in patients with moderate to severe systemic lupus erythematosus (SLE).
Methods: This 3-year, multinational, open-label extension (OLE) enrolled adult patients who completed treatment (48 weeks anifrolumab or placebo; 12-week follow-up) in the MUSE phase 2b randomized controlled trial (RCT). Patients initially received intravenous anifrolumab 1000 mg every 4 weeks, reduced to 300 mg every 4 weeks based on the benefit/risk profile established in MUSE. Adverse events (AEs) were assessed monthly. Exploratory endpoints included SLE Disease Activity Index 2000 (SLEDAI-2K), SLICC Damage Index (SDI), pharmacodynamics, and health-related quality of life (HRQoL).
Results: Of 246 patients who completed the RCT, 218 (88.6%) enrolled in the OLE; 139/218 (63.8%) completed 3 years of treatment. Approximately 69.7% of patients reported ≥1 AE during the first year of OLE treatment. Frequency and patterns of serious AEs and AEs of special interest over 3 years were consistent with those reported for 1 year of treatment in the RCT. Few patients (6.9%) discontinued treatment because of AEs. No new safety signals were identified. Improvement in SLEDAI-2K was sustained over 3 years. SDI and Short Form 36 Health Survey scores remained stable. Neutralization of type I IFN gene signatures was maintained in the IFN-high population, and C3, C4, and anti-dsDNA showed numeric trends toward sustained improvement.
Conclusion: Long-term anifrolumab treatment demonstrated an acceptable safety profile with sustained improvement in disease activity, HRQoL, and serologies.
Keywords: biologicals; disease activity; systemic lupus erythematosus (SLE).