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

• Published in: Muscle & nerve Vol. 64; no. 6; pp. 662 - 669
• Main Authors: Nowak, Richard J., Mozaffar, Tahseen, Wilken, Miguel, Saba, Juliet, Bettini, Mariela, De Bleecker, Jan, Van den Abeele, Guy, Mahieu, Délphine, Stevens, Olivier, Geraldo, Jordana Gonçalves, Pozo, Marina, Volpe, Luciana Renata Cubas, Ferreira, Luciana, Cassia Santos, Aline, Andrade, Ana Carolina Amaral, Carrara, Fernanda, Junkerova, Jana, Krogh, Susanne, Autzen, Anne Mette Ostergaard, Erälinna, Juha‐Pekka, Oksaranta, Olli, Szabadosne, Brigitta, Antonini, Giovanni, Puorro, Giorgia, Lopergolo, Diego, Onesti, Emanuela, Frasca, Vittorio, Kanzaki, Akiko, Shimpo, Misa, Morikawa, Miyuki, Shiraishi, Hirokazu, Asada, Shizuka, Amamoto, Shoko, Takada, Kazumi, Suzuki, Yasushi, Akiyama, Tetsuya, Narikawa, Koichi, Fukuda, Yusuke, Sato, Miwako, Nakamori, Masayuki, Yamamoto, Daisuke, Ishiyama, Naoko, Lee, Chang Nyoung, Choi, Mi Song, Jeong, Ha‐Neul, Lee, Hyung Seok, Hwang, Eun Bi, Visser, Marianne, Casasnovas, Carlos, Aguilo, Maria Antonia Alberti, Tejedor, Exuperio Diez, Rivera, Francisco Javier Rodriguez, Fernandez‐Fournier, Mireya, Sastre, Maria, Carbonell, Josep Gamez, Piehl, Fredrik, Hietala, Albert, Sengun, Ihsan, Orsel, Gulsah, Semiz, Cansu, Cavdar, Tugce Kirbas, Sohail, Faisal, Arndt, Heike, Salajegheh, Mohammed, Bravver, Elena, Plevka, Sarah, Guptill, Jeffrey, Hobson‐Webb, Lisa, Pascuzzi, Robert, Mosmiller, Betsy, Ventura, Nicholas, Carter, Cynthia, Sattar, Nadia, Daniels, Kevin, Jeffery, Dennis, Khoury, Julie, Dimitrova, Diana, Seelbach, Jenna, Paulose, Shirley, Bhavaraju‐Sanka, Ratna, Jones, Floyd, Roy, Gulmohor, Mathew, Veena, Echevarria, Laura, Shabbir, Yasmeen, Barohn, Richard, Glenn, Melanie, Johns, Kathryn, Naunton, Kerry, Bilsker, Martin, Karam, Chafic, Vu, Tuan, Gong, Hui, Karimi, Sanaz, Akhter, Salma, Strom, Susan, Bertorini, Tulio, Henderson, Kendrick, Wheeler, Lauren, Nye, Joan
• Format: Journal Article
• Language: English
• Published: Hoboken, USA John Wiley & Sons, Inc 01.12.2021; Wiley Subscription Services, Inc
• Subjects: acetylcholine receptor; Acetylcholine receptors; Activities of Daily Living; Antibodies; Antibodies, Monoclonal, Humanized - adverse effects; Confidence intervals; eculizumab; Humans; Immunosuppressive agents; Immunotherapy; Monoclonal antibodies; Myasthenia; Myasthenia gravis; Myasthenia Gravis - drug therapy; Neuromuscular junctions; Patients; refractory; Rituximab; Rituximab - therapeutic use; Safety; Standard error; Subgroups; myasthenia gravis; acetylcholine receptor; refractory; eculizumab; rituximab
• ISSN: 0148-639X; 1097-4598
• DOI: 10.1002/mus.27422

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.