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

W Winn Chatham, Richard Furie, Amit Saxena, Philip Brohawn, Erik Schwetje, Gabriel Abreu, Raj Tummala, W Winn Chatham, Richard Furie, Amit Saxena, Philip Brohawn, Erik Schwetje, Gabriel Abreu, Raj Tummala

Abstract

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.

© 2020 The Authors. Arthritis & Rheumatology published by Wiley Periodicals LLC on behalf of American College of Rheumatology.

Figures

Figure 1
Figure 1
Flow chart of the open‐label extension (OLE) study design and patient disposition. RCT = randomized controlled trial; IV = intravenous; Q4W = every 4 weeks.
Figure 2
Figure 2
Mean Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI‐2K), Systemic Lupus International Collaborative Clinics/American College of Rheumatology Damage Index (SDI) global score, and Short Form 36 health survey (SF‐36) component summary scores from baseline to week 168. A and B, SLEDAI‐2K score in all patients (A) and by type I interferon gene signature (IFNGS) status (B) during open‐label treatment with anifrolumab. C and D, SDI global score (C) and SF‐36 physical and mental component summary scores (D) during treatment with anifrolumab.
Figure 3
Figure 3
A and B, Mean complement C3 levels (A) and C4 levels (B) over time in the open‐label extension, in patients with abnormal levels at baseline. C, Mean levels of anti–double‐stranded DNA (anti‐dsDNA) by immunoglobulin G enzyme immunoassay (IgG EIA) over time in the open‐label extension, in patients positive for anti‐dsDNA antibodies at baseline. D, Neutralization of type I interferon (IFN) gene signature over time in the open‐label extension, in patients with high IFN gene signature expression at baseline. Color figure can be viewed in the online issue, which is available at http://onlinelibrary.wiley.com/doi/10.1002/art.41598/abstract.

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