Objective:

To evaluate the efficacy of complement inhibitors for treating myasthenia gravis.

Background:

C5 inhibitors, including eculizumab, zilucoplan, and ravulizumab, have been considered to be beneficial for patients with myasthenia gravis, acting by blocking the formation of the membrane attack complex, consequently reducing damage to neuromuscular junction cells and protecting against degradation of acetylcholine receptors. However, their efficacy for this population remains unclear.

Design/Methods:

We systematically searched MEDLINE, Scopus and Cochrane databases until September 25, 2024, for Randomized Controlled Trials (RCT’s) investigating the use of eculizumab, zilucoplan, and ravulizumab in comparison with placebo, for the treatment of myasthenia gravis. Data were examined using the Mantel-Haenszel method and 95% CIs. Heterogeneity was estimated using I² statistics, and RStudio, version 4.3.2, was used for statistical analysis.

Results:

A total of 5 RCT’s and 532 patients were included, of whom 276 (52%) were treated with C5 inhibitors. In this group, 115 (42%) were treated with zilucoplan, 86 (31%) with ravulizumab and 75  (27%) with eculizumab. Compared with placebo, complement inhibitors achieved better rates of Quantitative Myasthenia Gravis decrease (MD -3.52; 95% CI -4.51 to -2.54; P=<0.000001; I² 98%), Myasthenia Gravis-Quality of Life 15 change (MD -4.5; 95% CI -7.85 to -1.14; P=0.0086; I²=99%), Myasthenia Gravis Composite change (MD -3.15; 95% CI -4.08 to -2.22; P<0,000001; I²=71%) and Myasthenia Gravis Activities of Daily Living change (MD -1.87; 95% CI -2.08 to -1.67; P=<0.000001; I²=52%). Additionally, no significant difference was observed in the incidence of headache and diarrhea.

Conclusions:

Our meta-analysis demonstrates that complement inhibitors exhibited greater efficacy than placebo across multiple scores of myasthenia gravis treatment. Furthermore, they did not present significant side effects.