Continuous anifrolumab exposure safe, produces sustained SLE disease activity improvement

In the treatment of patients with systemic lupus erythematosus (SLE), long-term use of the type I interferon (IFN) inhibitor anifrolumab leads to sustained improvements in disease activity, quality of life, and serologic measures, according to the results of the open-label extension study.

A total of 246 adult patients completed the MUSE phase IIb randomized controlled trial (48 weeks of anifrolumab or placebo; 12 weeks of follow‐up). Of these, 218 (88.6 percent) participated in the extension study, with 139 (63.8 percent) completing 3 years of treatment.

The patients initially received 1,000 mg of anifrolumab, administered intravenously every 4 weeks. Treatment was de-escalated to 300 mg every 4 weeks based on the benefit-risk profile established in the MUSE trial.

Most patients (69.7 percent) developed at least one adverse event (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 in line with those reported over the 1-year double-blind treatment. AEs seldom led to treatment discontinuation (6.9 percent). Finally, no new safety signals emerged.

In terms of efficacy, the improvement in the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI‐2K) was sustained over 3 years. Moreover, Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI) and Short Form 36 health survey scores remained stable.

Neutralization of type I IFN gene signatures persisted in the IFN‐high population. Additionally, serologic measures including C3, C4, and antidouble‐stranded DNA trended toward sustained improvement.

In light of the findings, long‐term inhibition of the type I IFN pathway with anifrolumab represents a promising novel therapeutic strategy for patients with SLE.