Eculizumab Safe, Tolerable for Refractory Generalized Myasthenia Gravis

woman eyes eyelid myasthenia gravis
woman eyes eyelid myasthenia gravis
Treatment with eculizumab was associated with a significant benefit on quality of life.

Eculizumab is safe, tolerable, and produces similar effects to placebo on activities of daily living for patients with anti-acetylcholine receptor antibody-positive refractory generalized myasthenia gravis, according to results from a phase 3, double-blind, placebo-controlled study.

Patients included in this study were from multiple centers throughout North America, Latin America, Asia, and Europe. All patients had a Myasthenia Gravis-Activities of Daily Living (MG-ADL) score of ≥6 and Myasthenia Gravis Foundation of America class II-IV disease. Researchers randomly assigned participants in a 1:1 ratio to intravenous eculizumab (n=62) or intravenous-matched placebo (n=63) for a total of 26 weeks. Efficacy was evaluated on the basis of the MG-ADL and Quantitative Myasthenia Gravis scores.

In the primary analysis, investigators found no difference between treatment and control in terms of change in the MG-ADL total score from baseline to 26 weeks (least squares mean rank, 56.6 [standard error of the mean, 4.5] vs 68.3 [standard error of the mean, 4.5]; rank-based treatment difference, −11.7 [95% CI, −24.3 to 0.96]; P =.0698). Conversely, eculizumab resulted in a greater benefit than placebo in changing Quantitative Myasthenia Gravis total score from baseline (P =.0129).

According to the 15-item Myasthenia Gravis Quality of Life (MG-QOL15) questionnaire, there was a significant benefit associated with eculizumab vs placebo (P =.0281). The greatest treatment effect was observed by week 12 and was sustained to 26 weeks in sensitivity analyses.

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Rates of upper respiratory tract infections and headache were the 2 most common adverse events in both the eculizumab and placebo groups (16% and 19%, respectively, in both groups). A total of 6 (10%) and 15 (24%) patients receiving eculizumab and placebo, respectively, reported exacerbations of myasthenia gravis.

Although this study demonstrated generally favorable results in regard to eculizumab’s safety and benefits on quality of life, the small sample size reduces the power of the findings.

Despite no significant differences in the study’s primary endpoint, the investigators suggest that inhibition of terminal complement activation with eculizumab, among other therapies, “represents a novel, targeted approach that might prevent damage at the postsynaptic membrane of the neuromuscular junction in patients with anti-acetylcholine receptor antibody-positive refractory generalized myasthenia gravis.”


Howard JF Jr, Utsugisawa K, Benatar M, et al. Safety and efficacy of eculizumab in anti-acetylcholine receptor antibody-positive refractory generalised myasthenia gravis (REGAIN): a phase 3, randomised, double-blind, placebo-controlled, multicentre study [published online October 20, 2017]. Lancet Neurol. doi:10.1016/S1474-4422(17)30369-1