Complement inhibitors and FcRn blockers improve outcomes in AChR-Ab+ generalized myasthenia gravis

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Journal of neurology Published April 14, 2026 Medically reviewed April 25, 2026 Study authors: Filippakopoulou Eugenia, Gavriilaki Maria, Arnaoutoglou Marianthi, Kimiskidis Vasilios, Di Giovanni … PubMed ↗ DOI ↗ By Dr. Julia Lee, PhD · Oncology, Genomics & Drug Development

Key Takeaway

Consider complement inhibitors and FcRn blockers for AChR-Ab+ gMG with favorable safety.

This meta-analysis evaluated complement inhibitors (eculizumab, ravulizumab, zilucoplan) and FcRn blockers (efgartigimod, rozanolixizumab, batoclimab) in adults with acetylcholine receptor antibody-positive generalized myasthenia gravis, including 739 patients from randomized controlled trials and 588 from open-label extensions, compared to placebo or standard care over up to 156 weeks. Main results showed significantly improved mean changes from baseline versus placebo for Myasthenia Gravis Activities of Daily Living (MD 1.7, 95% CI 1.1-2.3), Quantitative Myasthenia Gravis (MD 2.7, 95% CI 1.8-3.5), Myasthenia Gravis Composite (MD 6.3, 95% CI 5-7.6), MGQoL15r (MD 3.4, 95% CI 1.2-5.6), and Neuro-QoL (MD 4.5, 95% CI 1.2-7.7). Odds of achieving clinically meaningful MG-ADL and QMG improvements were more than doubled (ORs 2.7 and 3.5), with risks of clinical worsening reduced by 72%, rescue therapy use reduced by 48%, and 30% of patients reducing corticosteroid doses. Safety profiles were favorable, with rates of serious adverse events, discontinuations, and tolerability comparable to placebo. Key limitations include lack of reported absolute numbers, funding or conflicts, and causality or certainty notes, and the setting was not reported. In practice, these agents yield clinically meaningful improvements with favorable safety in this population, but clinicians should interpret findings cautiously due to meta-analytic constraints and incomplete long-term evidence.

Study Details

Study typeMeta analysis

EvidenceLevel 1

PublishedApr 2026

PMID41925914

View Original Abstract ↓

BACKGROUND: Antibody status is increasingly used to inform treatment strategies in generalized myasthenia gravis (gMG). We evaluated the efficacy and safety of complement inhibitors and neonatal Fc receptor (FcRn) blockers versus placebo or standard care in adults with acetylcholine receptor antibody-positive (AChR-Ab⁺) gMG. METHODS: We systematically searched MEDLINE, EMBASE, Cochrane Central Register Controlled Trials, and ClinicalTrials.gov through November 2024. Eligible randomized controlled trials (RCTs) informed short-term analyses while long-term outcomes were extracted from open-label extension (OLE) studies. Pooled mean difference (MD) and odds ratio (OR) were calculated using random-effects model. RESULTS: Six RCTs (n = 739) and four OLEs (n = 588) evaluating eculizumab, ravulizumab, zilucoplan, efgartigimod, rozanolixizumab, and batoclimab were included. Both drug classes significantly improved mean changes from baseline versus placebo in Myasthenia Gravis Activities of Daily Living [MD 1.7, 95% confidence interval (CI) 1.1-2.3], Quantitative Myasthenia Gravis [MD 2.7, 95%(CI)1.8-3.5], Myasthenia Gravis Composite [MD 6.3, 95%(CI) 5-7.6], MGQoL15r [MD 3.4, 95%(CI)1.2-5.6], and Neuro-QoL [MD 4.5, 95%(CI)1.2-7.7]. Odds of achieving clinically meaningful MG-ADL and QMG improvements were more than doubled (ORs 2.7 and 3.5). Risks of clinical worsening and rescue therapy use were reduced by 72% and 48%, respectively. Complement inhibitors OLEs showed durable benefit up to 156 weeks; 30% of patients reduced corticosteroid doses. Rates of serious adverse events, discontinuation, and mortality were comparable to placebo. CONCLUSION: In AChR-Ab⁺ gMG, complement inhibitors and FcRn blockers yield clinically meaningful improvements with favourable safety profiles. Complement inhibition additionally confers sustained benefits and corticosteroid-sparing effects in this population over long-term. PROTOCOL REGISTRATION: PROSPERO ID: CRD42024513406.