Safety and Efficacy of Eculizumab in Patients with Refractory Myasthenia Gravis

Book about Myasthenia gravis and medication, injection, syringe and pills
There was a rapid and sustained clinical response in patients treated with eculizumab for anti-acetylcholine receptor-positive refractory generalized myasthenia gravis.

In patients with anti-acetylcholine receptor-positive (AChR+) refractory generalized myasthenia gravis (MG), treatment with eculizumab, a humanized monoclonal antibody that binds to the human C5 complement protein, was associated with rapid and sustained clinical response, according to study results published in Neurology.

While immunosuppressive therapies are effective for most patients with MG, up to 15% show an inadequate response and are considered to have refractory MG. An interim analysis of the REGAIN study ( Identifier: NCT01997229) showed that the benefits of eculizumab were sustained for 3 years in patients with AChR+ refractory generalized MG.

The objective of the current study was to report the final data on the efficacy of eculizumab in patients with refractory generalized MG during REGAIN and up to open-label week 130 using Myasthenia Gravis Foundation of America (MGFA). MGFA post-intervention status can be used to assess changes in a patient’s condition after treatment. This includes improvement, worsening or no change in clinical manifestations from before treatment.

The analysis included 117 patients who completed the REGAIN study and continued into the open-label extension ( Identifier: NCT02301624). Of these, 56 participants were treated with eculizumab in the REGAIN study and continued the active medication in the open label extension, and 61 participants received placebo during the REGAIN trial and switched to eculizumab in the open-label study.

At week 26, improved status was more common with eculizumab compared with placebo (60.7% vs 41.7%, respectively), while worsening was reported in 1 eculizumab-treated patient and 5 placebo-given patients. A greater proportion of patients treated with eculizumab than placebo achieved an MGFA post-intervention status of minimal manifestations (25.0% vs 13.3%, respectively; common odds ratio, 2.3; 95% CI: 1.1-4.5).

At week 130 of the open-label study, results indicated improved status in most patients of both groups: 80 percent of patients who were treated with eculizumab and continued it in the open-label extension, compared with 94.3% of those who switched from placebo to eculizumab. At this point, 57.1% of patients achieved an MGFA post-intervention status of minimal manifestations.

The safety profile of eculizumab was consistent with its known profile. Study researchers reported no new safety signals. The most common adverse events with eculizumab were headache (44.4%) and nasopharyngitis (38.5%).  Worsening of MG and MG crisis, reported in 15.4% and 3.4% of patients, respectively, were the most common serious adverse events.

The open-label design of the extension study was the chief limitation of this analysis.

“These findings further support the long-term effectiveness of eculizumab for use in patients with AChR+ [anti-acetylcholine receptor-positive] refractory gMG [generalized MG],” concluded the study researchers.

Disclosure: This clinical trial was supported by Alexion Pharmaceuticals. Please see the original reference for a full list of authors’ disclosures.


Mantegazza R, Wolfe GI, Muppidi S, et al. Post-intervention status in patients with refractory myasthenia gravis treated with eculizumab during REGAIN and its open-label extension. Neurology. Published online November 23, 2020. doi:10.1212/WNL.0000000000011207