Long-Term Safety and Efficacy of Anifrolumab in Adults With Systemic Lupus Erythematosus: Results of a Phase II Open-Label Extension Study

Arthritis Rheumatol. 2021 May;73(5):816-825. doi: 10.1002/art.41598. Epub 2021 Mar 24.


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 study included adult patients who completed treatment (48 weeks of anifrolumab or placebo; 12-week follow-up) in the MUSE phase IIb randomized controlled trial (RCT). Patients initially received 1,000 mg of anifrolumab intravenously every 4 weeks, which was reduced to 300 mg every 4 weeks based on the benefit/risk profile established in the MUSE trial. Adverse events (AEs) were assessed monthly. Exploratory end points included the SLE Disease Activity Index 2000 (SLEDAI-2K), Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI), pharmacodynamics, and health-related quality of life (HRQoL).

Results: Of the 246 patients who completed the RCT, 218 (88.6%) enrolled in the open-label extension study, of which 139 (63.8%) completed 3 years of treatment. Approximately 69.7% of patients reported ≥1 AE during the first year of open-label extension 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 due to AEs. No new safety signals were identified. Improvement in the 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-double-stranded DNA showed trends toward sustained improvement.

Conclusion: Long-term anifrolumab treatment demonstrates an acceptable safety profile with sustained improvement in SLE disease activity, HRQoL, and serologic measures.

Trial registration: ClinicalTrials.gov NCT01753193.

Publication types

  • Clinical Trial, Phase II
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antibodies, Antinuclear / immunology
  • Antibodies, Monoclonal, Humanized / therapeutic use*
  • Antirheumatic Agents / therapeutic use*
  • Bronchitis / chemically induced
  • Complement C3 / immunology
  • Complement C4 / immunology
  • Female
  • Headache / chemically induced
  • Humans
  • Longitudinal Studies
  • Lupus Erythematosus, Systemic / drug therapy*
  • Lupus Erythematosus, Systemic / immunology
  • Lupus Erythematosus, Systemic / physiopathology
  • Male
  • Middle Aged
  • Nasopharyngitis / chemically induced
  • Respiratory Tract Infections / etiology
  • Treatment Outcome


  • Antibodies, Antinuclear
  • Antibodies, Monoclonal, Humanized
  • Antirheumatic Agents
  • Complement C3
  • Complement C4
  • anifrolumab

Associated data

  • ClinicalTrials.gov/NCT01753193