ArticleFrontiers in immunology2026
Complement C5 inhibition in generalized myasthenia gravis is associated with improved survival and increased cardiovascular risk.
Article in Frontiers in immunology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Background: Complement C5 inhibitors are effective disease-modifying therapies for acetylcholine receptor antibody-positive generalized myasthenia gravis (MG), but cardiovascular safety has not been evaluated as a dedicated outcome domain. With increasing and prolonged use, systematic assessment of cardiovascular and thromboembolic risk - including potential differences between individual C5 inhibitors - is needed. Methods: We performed a retrospective cohort study using the TriNetX federated electronic health record network, including adults with generalized MG. Propensity score-matched cohorts compared patients treated with C5 inhibitors with untreated controls (N = 1,094 vs. 1,094), and ravulizumab with eculizumab (N = 330 vs. 330). Outcomes included major adverse cardiovascular events (MACE), thrombotic disorders, acute kidney injury (AKI), arrhythmias, and all-cause mortality over 365 days. Associations were evaluated using risk ratios (RR) and Cox proportional hazards models. Results: After matching, C5 inhibition was associated with increased risk of AKI (6.1% vs 3.2%, p<0.01; RR 1.70) and thrombotic disorders (5.1% vs 2.6%, p=0.002; RR 1.74) compared to no C5-inhibition treatment. All-cause mortality was significantly lower among C5-treated patients after one year (RR 0.54; p=0.045). MACE occurred more frequently with C5 inhibition (8.3% vs 5.5%; p=0.009), with a trend toward higher hazard over time. In agent-specific analyses (ravulizumab vs. eculizumab), ravulizumab was associated with a significantly lower hazard of MACE compared with eculizumab (6.6% vs 11.1%, p=0.041; HR 0.58, while hazards for mortality, thrombotic events, and other cardiovascular outcomes were similar. Conclusions: C5 inhibition in generalized MG is associated with improved survival but increased cardiovascular and thromboembolic risk. Although limited by its retrospective design, this analysis highlights a clinically relevant safety signal and suggests heterogeneity within the C5 inhibitor class. As use of complement inhibition expands, careful longitudinal cardiovascular monitoring will become increasingly important for clinicians managing patients with MG.
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