Comparative efficacy and acceptability of novel biologics in the treatment of myasthenia gravis: systematic review and network meta-analysis of randomized trials

BACKGROUND: Myasthenia gravis (MG) is a chronic autoimmune disorder affecting the neuromuscular junction. The emergence of molecular therapies, such as monoclonal antibodies, B-cell-depleting agents, and chimeric antigen receptor T-cell-based therapies, has the potential to transform the treatment landscape for myasthenia gravis. The clinical efficacy of novel biologics in the treatment of individuals with myasthenia gravis is still a subject of debate. The objective was to compare and rank the efficacy and acceptability of novel biologics in the treatment of individuals with MG through a network meta-analysis. METHODS: This systematic review and network meta-analysis (NMA) involved a comprehensive search for published randomized controlled trials (RCTs) across several databases, including PubMed, Web of Science, Embase, Cochrane Library, SinoMed, CNKI, Wanfang, and VIP, covering articles published from inception until July 3, 2024. We included randomized controlled trials involving patients with myasthenia gravis. The main outcome was the overall symptomatology. Random-effects pairwise meta-analyses and network meta-analyses (NMAs) were conducted to compute standardized mean differences (SMDs) or risk ratios with 95% confidence intervals (CIs). The research process did not include individuals with lived experience. The studies' quality was evaluated utilizing the risk-of-bias assessment tool created by the Cochrane Collaboration. Network meta-analysis was performed utilizing Stata 16 and R4.2.3. RESULTS: Eleven RCTs including 840 participants with myasthenia gravis were eligible. Belimumab improvement of the MG-ADL score is compared to placebo (MD = - 3.29, 95% CI (- 5.78, - 0.80), P < 0.05). Compared to placebo, batoclimab enhanced the QMG score (MD = - 4.46, 95% CI (- 7.57, - 1.35), P < 0.05) and the MGC score (MD = - 3.58, 95% CI (- 6.68, - 0.47), P < 0.05). Eculizumab improvement of the MG-QoL 15r score is compared to placebo (MD = - 7.10, 95% CI (- 12.20, - 2.00), P < 0.05). Regarding adverse reactions, we found no difference in the network comparison of novel biologics compared to placebo, but this conclusion requires further validation through rigorous research. CONCLUSIONS: This study provides an updated, relative rank-order efficacy of novel biologics therapies for myasthenia gravis. These data may help inform the design and sample size calculation of future clinical trials and assist selection of combination therapy. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42024559757.