Long-term efficacy of eculizumab in refractory generalized myasthenia gravis: responder analyses.

Objective Generalized myasthenia gravis (gMG) is an autoimmune disease that causes disabling weakness via damage to the neuromuscular junction. In most patients, the disease is mediated by autoantibodies to the acetylcholine receptor, which activate the complement cascade. Our objective was to analyze response profiles in adult patients with anti-acetylcholine receptor antibody-positive refractory gMG treated with eculizumab-a terminal complement inhibitor-in the REGAIN study or its open-label extension (OLE). Methods We retrospectively analyzed Myasthenia Gravis-Activities of Daily Living (MG-ADL) and Quantitative Myasthenia Gravis (QMG) scores recorded during REGAIN and its OLE. Early/late responses were defined as improvement in MG-ADL score (≥3 points) or QMG score (≥5 points) at ≤12 or >12 weeks, respectively, after eculizumab initiation. Results The analysis included 98 patients. By Week 12 and conclusion of the OLE, MG-ADL response had been achieved at some point by 67.3% and 84.7% of patients, respectively, and QMG response by 56.1% and 71.4%, respectively. Response was observed over multiple consecutive assessments for most patients. At Week 130, the least-squares mean percentage changes (95% CI) from baseline in MG-ADL score were -61.9% (-69.9%, -53.9%) and -47.5% (-59.0%, -36.0%) in early and late MG-ADL responders, respectively; the least-squares mean percentage changes from baseline in QMG score were -40.8% (-48.3%, -33.4%) and -55.5% (-68.4%, -42.7%) in early and late QMG responders, respectively. Interpretation The findings suggest that, although most patients with refractory gMG will achieve clinical response by Week 12 of eculizumab treatment, first responses can be observed with longer-term treatment.