Eculizumab in refractory generalized myasthenia gravis previously treated with rituximab: subgroup analysis of REGAIN and its extension study

Muscle Nerve. 2021 Dec;64(6):662-669. doi: 10.1002/mus.27422. Epub 2021 Oct 14.


Introduction/aims: Individuals with refractory generalized myasthenia gravis (gMG) who have a history of rituximab use and experience persistent symptoms represent a population with unmet treatment needs. The aim of this analysis was to evaluate the efficacy and safety of eculizumab in patients with refractory anti-acetylcholine receptor antibody-positive (AChR+ ) gMG previously treated with rituximab.

Methods: This post hoc subgroup analysis of the phase 3 REGAIN study (NCT01997229) and its open-label extension (OLE; NCT02301624) compared baseline characteristics, safety, and response to eculizumab in participants who had previously received rituximab with those who had not. Rituximab use was not permitted within the 6 months before screening or during REGAIN/OLE.

Results: Of 125 REGAIN participants, 14 had received rituximab previously (7 received placebo and 7 received eculizumab). In the previous-rituximab group, 57% had used at least four other immunosuppressants compared with 16% in the no-previous-rituximab group. Myasthenia Gravis Activities of Daily Living total scores from eculizumab baseline to week 130 of eculizumab treatment improved in both the previous-rituximab and no-previous-rituximab groups (least-squares mean -4.4, standard error of the mean [SEM] 1.0 [n = 9] and least-squares mean -4.6, SEM 0.3 [n = 67], respectively; difference = 0.2, 95% confidence interval -1.88 to 2.22). In addition, in both groups, most patients who were treated with eculizumab for 130 weeks achieved a Myasthenia Gravis Foundation of America post-intervention status of minimal manifestations (66.7% and 65.0%, respectively). The eculizumab safety profile was similar between groups and consistent with its established profile.

Discussion: Eculizumab is an effective therapy for patients with refractory AChR+ gMG, irrespective of whether they had received rituximab treatment previously.

Keywords: acetylcholine receptor; eculizumab; myasthenia gravis; refractory; rituximab.

Publication types

  • Clinical Trial, Phase III
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Activities of Daily Living
  • Antibodies, Monoclonal, Humanized* / adverse effects
  • Humans
  • Myasthenia Gravis* / drug therapy
  • Rituximab / therapeutic use


  • Antibodies, Monoclonal, Humanized
  • Rituximab
  • eculizumab

Associated data