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

Burden of illness in patients with treatment refractory myasthenia gravis

“…Because none of the currently available therapies specifically target complement, it is possible that ongoing complement activity may explain why some patients have ongoing disease activity and higher healthcare utilization despite treatment with multiple conventional therapies. Eculizumab, a complement inhibitor, is an emerging therapy that has shown promise in phase 3 clinical trials at reducing self‐reported disease symptoms and disease severity and improving quality of life …”

Correlation between myasthenia gravis−activities of daily living (MG‐ADL) and quantitative myasthenia gravis (QMG) assessments of anti−acetylcholine receptor antibody−positive refractory generalized myasthenia gravis in the phase 3 regain study

“…We recently published a subanalysis of data from a phase 2 pilot crossover study of the terminal complement inhibitor eculizumab in 14 patients with refractory anti−acetylcholine receptor antibody‐positive generalized myasthenia gravis (AChR + gMG) . This subanalysis assessed the correlation between 2 validated, disease‐specific outcome measures, the Quantitative Myasthenia Gravis (QMG) total score (a physician‐assessed measure of muscle strength) and the Myasthenia Gravis−Activities of Daily Living (MG‐ADL) total score (a patient‐reported measure of the effects of MG on daily activities) . For the phase 2 study, the correlation between MG‐ADL and QMG total scores was stronger for change from baseline to 16 weeks than for disease severity at baseline ( R = 0.73 and R = 0.55, respectively) …”

“…The efficacy and safety of eculizumab were demonstrated in patients with refractory AChR + gMG in the 26‐week, phase 3, randomized, double‐blind, placebo‐controlled REGAIN study, ( N = 125; eculizumab, n = 62; placebo, n = 63) . As in the phase 2 study, efficacy measures included the use of the MG‐ADL and QMG scales .…”

Utility of experimental animal models of myasthenia gravis for the elucidation of pathogenic mechanisms and development of new medications

“…The MAC eventually causes severe focal damage to the postsynaptic membranes of NMJ. [33][34][35] In practice, eculizumab, a humanized monoclonal antibody that binds to C5, preventing formation of a C5b-induced MAC, can be prescribed for the treatment of generalized AChR-MG. 36 The second mechanism involved in the pathogenesis of AChR-MG has also been shown with animal models. These morphological changes attenuate postsynaptic sensitivity to the neurotransmitter due to the loss of AChR, resulting in diminished neuromuscular transmission and the manifestation of myasthenic symptoms.…”