Although most individuals with refractory generalized myasthenia gravis (MG) achieve clinical response (assessed by Myasthenia Gravis–Activities of Daily Living [MG-ADL] or Quantitative Myasthenia Gravis [QMG] scores) after 12 weeks with eculizumab treatment, some individuals may need a longer treatment period to achieve a clinical response. This data comes from the 6-month double-blind placebo-controlled REGAIN study (NCT01997229) and its open-label extension (NCT02301624).
Post hoc analysis demonstrated the sustained efficacy of eculizumab in adults with antibodies to the acetylcholine receptor (antiAChR+) who had generalized MG. By week 12 and the end of the open-label extension, clinical response as measured by MG-ADL was achieved by 67.3% and 84.7% of participants, respectively. The response as measured by the QMG was achieved by 56.1% and 71.4%, respectively.
A difference was seen in people who responded to eculizumab within 12 weeks and those who responded only after more than 12 weeks of treatment. Individuals who took longer to respond had less change in the MG-ADL score (least squares mean change -47.5% vs -61.9%) and on the QMG score (least squares mean change -40.8 vs -55.5 respectively (P<.0001 for all measures]). Those who were late vs early responders were more likely to have longer disease duration (10.46 versus 5.46 years, respectively; P=.0002) as well as differences in baseline mean QMG score (18.6 versus 15.1, respectively; P=.0223).
These results suggest that individuals with higher baseline QMG scores and longer duration of disease may take more than 12 weeks to respond to treatment with eculizumab. These results also raise the question of whether or not 12 weeks in the appropriate time point at which to consider an individual as a responder or nonresponder to eculizumab.
Early/late responses were defined as improvement in MG-ADL score (≥3 points) or QMG score (≥5 points) occurring at ≤12/>12 weeks, respectively, after baseline (eculizumab initiation).
These data were presented during the online presentation of the Muscular Dystrophy Association Clinical and Scientific Congress on March 24, 2020 in lieu of the annual meeting that was canceled due to the 2020 COVID-19 pandemic.
Duriel I. Hardy, MD, and Sona Narula, MD
Donna Stephenson, MD
Danielle S. Takacs, MD, and Eli M. Mizrahi, MD