ArticleFrontiers in immunology2026
Real-world efficacy of eculizumab in generalized myasthenia gravis patients with poor early response to efgartigimod: a prospective cohort study.
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
Objective: The management of generalized myasthenia gravis (gMG) poses a therapeutic challenge. Efgartigimod, a neonatal Fc receptor (FcRn) inhibitor, has significant efficacy in patients with positive acetylcholine receptor (AChR) antibodies. However, approximately 30% of patients exhibit a poor early response. This study aimed to explore whether the complement C5 inhibitor, eculizumab, can bring clinical benefits to patients who have a poor early response to efgartigimod, thereby investigating potential sequential treatment strategies. Methods: We first conducted a prospective study to rigorously evaluate and longitudinally follow up 103 patients with gMG who received one treatment cycle of efgartigimod, ultimately enrolling 18 patients who demonstrated an inadequate response to the therapy. Then, these patients received eculizumab induction (900 mg weekly for four weeks) followed by maintenance dosing (1200 mg every two weeks or extended to once every three weeks). Clinical outcomes were assessed using MG-specific activities of daily living (MG-ADL) and quantitative myasthenia gravis (QMG) scores. Safety was evaluated through adverse event reporting. Results: Significant clinical improvements were observed during the induction phase, with mean MG-ADL scores demonstrating a reduction from 7.9 ± 3.9 before eculizumab to 2.6 ± 1.7 [-5.3 (95% CI: -7.6 to -3.0); P < 0.001], while QMG scores dropped from 14.1 ± 6.6 to 6.5 ± 3.2 [-7.4 (95% CI: -10.2 to -4.7); P < 0.001]. All patients achieved clinically meaningful improvement (≥2-point MG-ADL reduction), with four patients reaching minimal symptom expression (MSE, defined as an MG-ADL score ≤1-point) by week 4. Among the 12 patients who completed the 16-week follow-up, seven patients (58.3%) achieved minimal symptom expression. Glucocorticoid doses were successfully reduced to ≤5mg per day in seven patients. Two mild adverse events (urinary tract infection and limb edema) were reported. Conclusion: Eculizumab exhibited rapid and significant efficacy in patients with gMG who were poor early response to efgartigimod, and exhibited a favorable safety profile. These findings suggest that complement inhibition may serve as a potential sequential therapy when FcRn antagonist modulation failure.
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