Long-term Safety and Efficacy of Anifrolumab in Systemic Lupus Erythematosus: A Meta-Analysis of Randomized Controlled Trials, Extension Studies, and Real-World Cohorts

Objectives: Anifrolumab, a type I interferon receptor antagonist, has shown effectiveness in treating moderate-to-severe systemic lupus erythematosus (SLE). To fully understand its long-term efficacy, glucocorticoid (GC)-sparing potential, and cumulative safety profile in everyday clinical practice, it is essential to combine up to 4 years of long-term extension (LTE) trial data with emerging real-world evidence (RWE). Methods: A systematic literature search was performed across major electronic databases to identify phase 2/3 randomized controlled trials (RCTs), long-term extension (LTE) studies, and RWE cohorts assessing anifrolumab in SLE. Comparative odds ratios (ORs) for RCTs were calculated using the Mantel-Haenszel method, while pooled proportions for single-arm RWE cohorts were estimated using a random-effects model. Primary outcomes included BICLA response, Lupus Low Disease Activity State (LLDAS), GC reduction (to ≤ 7.5 mg/day), and Herpes Zoster (HZ) incidence. Results: Ten studies were included, comprising phase 2/3 RCTs, their LTEs (TULIP-LTE, MUSE-LTE), and four European RWE cohorts. In the RCTs (N = 1,093), anifrolumab significantly improved BICLA responses compared to placebo (pooled OR 1.85, 95% CI 1.42–2.41, p < 0.001) and enhanced the likelihood of achieving a target GC dose of ≤ 7.5 mg/day (OR 2.24, 95% CI 1.52–3.29, p < 0.001). In the pooled RWE cohorts (N = 294), the estimated attainment rate for LLDAS at 6–12 months was notably high at 75.8% (95% CI 68.4–82.5%). Additionally, 72.5% of real-world patients achieved a >50% reduction in GC dosage. Regarding safety, there was no significant increase in overall serious adverse events (SAEs) (OR 0.82, p = 0.25). Although anifrolumab was linked to a higher risk of HZ (OR 3.45, 95% CI 1.95–6.10, p < 0.001), both LTE and RWE data indicated that these cases were mainly mild to moderate and manageable. Conclusion: Anifrolumab offers rapid, strong, and sustained disease control while providing significant GC-sparing effects in both tightly controlled clinical trials and diverse real-world populations. The long-term safety profile remains stable; however, preventative measures, such as HZ vaccination, should be implemented as part of standard care.