Real-world multicentre cohort study on choices and effectiveness of immunotherapies in NMOSD and MOGAD.

Background: Recurrent attacks in neuromyelitis optica spectrum disorders (NMOSDs) or myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) can lead to severe disability. We aimed to analyse the real-world use of immunotherapies in patients with NMOSD and MOGAD, focusing on changes in treatment strategies, effects on attack rates (ARR) and risk factors for attacks.
Methods: This longitudinal registry-based cohort study included 493 patients (320 with aquaporin-4 immunoglobulin G (AQP4-IgG) seropositive NMOSD (65%), 44 with AQP4-IgG seronegative NMOSD (9%) and 129 MOGAD (26%)) with 1247 treatments from 19 German and one Austrian centre from the registry of the neuromyelitis optica study group (NEMOS). We analysed unadjusted ARR and implemented survival analyses and Cox proportional hazard regression to assess efficiency and risk factors for subsequent attacks over time.
Results: Rituximab and azathioprine are the most widely used immunotherapies in NMOSD as well as in MOGAD, with changes in distribution over the last decade. Immunotherapy demonstrated significant therapeutic effects in NMOSD but less pronounced effects in MOGAD. Risk factors for attacks included younger age and prior attacks under the same therapy. Efficacy varied among the different immunotherapies, with azathioprine, rituximab and eculizumab showing significant risk reductions in AQP4-IgG seropositive NMOSD.
Conclusions: This study provides insights into the evolving treatment landscape and effectiveness of immunotherapies in NMOSD and MOGAD. Established off-label therapies continue to play an important role, especially for patients with stable disease, with emerging evidence supporting newly approved therapies. Future studies are needed to refine treatment algorithms and address the ongoing uncertainties in MOGAD management.
Competing Interests: Competing interests: VH has received research support from NEMOS e.V. for this project. CT received honoraria for consultation and expert testimony from Alexion Pharma Germany GmbH. None of this interfered with the current report. DE received speaker honoraria and/or travel reimbursement from Alexion, Amgen/Horizon and Merck, all not related to the presented work. DE received speaker honoraria from Alexion. HP has nothing to disclose. JH reports grants from the Friedrich-Baur-Stiftung, Merck and Horizon, personal fees and non-financial support from Alexion, Horizon, Roche, Merck, Novartis, Biogen, BMS and Janssen and non-financial support from the Guthy-Jackson Charitable Foundation and the Sumaira Foundation. AD has received research support from NEMOS e.V. independent of this project. PS received travel support from UCB, received speaker‘s honoraria from Roche and Alexion and served on advisory boards by Alexion. CS has received speaker honoraria from Alexion and travel support from Novartis and UCB. TP has nothing to disclose. KF has nothing to disclose. MR received speaker honoraria and travel reimbursement from Roche, Alexion and Horizon, not related to this study. GL has nothing to disclose. MWH received institutional research support from Myelitis e. V., the German Federal Joint Committee/Innovation Fund, and NEMOS e. V. Speaker honoraria from selpers og, AMGEN/Horizon, and Alexion, and travel grants and compensation for serving on an advisory board from Alexion. DT has nothing to disclose. FB has nothing to disclose. KG has nothing to disclose. MF has nothing to disclose. IS has nothing to disclose. MKK speaker honoraria from BMS, Novartis, Merck. SJ has nothing to disclose. ED has nothing to disclose. LR has nothing to disclose. MS has received consulting and/or speaker honoraria from Alexion, Bayer, Biogen, Bristol-Myers-Squibb/Celgene, Janssen, Merck, Horizon, Roche and Sanofi Genzyme. None of this interfered with the current report. MH has nothing to disclose. AW has nothing to disclose. MP has nothing to disclose. IK has received personal compensation for consulting, serving on a scientific advisory board, speaking or other activities with Alexion, Almirall, Bayer, Biogen, GlaxoSmithKline, Hexal, Horizon, Merck, Neuraxpharm, Roche/Chugai and Sanofi. IK is the editorial board member of BMC Neurology, Frontiers in Neurology and Frontiers in Immunology. KA received travel support from Alexion, Bayer, BiogenIdec, MerckSerono, Novartis, Teva and honoria from Biogen and TEVA; he supported neuroimmunological studies for Alexion, Bayer, BiogenIdec, MerckSerono, Roche and Novartis. MK has nothing to disclose. MG has received consulting and/or speaker honoraria from Biogen, BMS, JJ, Merck, Novartis, Roche, Sanofi Genzyme and Teva. JW has nothing to disclose. PSR has received honoraria for lectures/consultancy from Alexion (Astra Zeneca), Allmiral, Amicus, Biogen, Genzyme, Horizon (AMGEN), Merck, Novartis, Roche and Teva served von advisory boards for Alexion (Astra Zeneca), Amicus, Genzyme, Horizon (AMGEN), Merck, Roche and Sandoz and received research grants from Amicus, Roche, Merck and the Austrian Science Fund (FWF). JPS has nothing to disclose. MK has received honoraria from Novartis Pharma, Chugai Pharma and Roche Pharma for presentations unrelated to the topic of this article. FTB has received, over his academic career, research support and travel grants to attend scientific meetings through his institution from the German Science Fund (DFG), German Federal Ministry of Education and Science (BMBF), Bayer-Schering, Diamed, Fresenius, Merck, Novartis, Pfizer, Roche, Sanofi and Teva; speaker fees and compensation for advisory boards from Actelion, Alexion, Bayer, Biogen, CSL Behring, Fresenius, Horizon, Merck, Novartis, Roche, Sanofi-Genzyme, Takeda and Teva. None of these are related to this work. HT received institutional research support and/or consulting/speaker honoraria from Alexion, Bayer, Biogen, Bristol-Myers Squibb, Celgene, Diamed, Fresenius, Fujirebio, GlaxoSmithKline, Horizon, Janssen-Cilag, Merck, Novartis, Roche, Sanofi Genzyme and TEVA. His research is also funded by the Ministry of Education and Research (BMBF), the Ministry of Science, Research and Arts Baden Württemberg (MWK-BW), the German Society of Multiple Sclerosis (DMSG), DMS-Stiftung, AMSEL-Stiftung, Bayern-DMSG and Chemische Fabrik Karl Bucher GmbH. LK received compensation for serving on Scientific Advisory Boards for Alexion, Biogen, Bristol-Myers Squibb, Genzyme, Horizon, Janssen, Merck Serono, Novartis, Roche and Viatris. She received speaker honoraria and travel support from Argenx, Bayer, Biogen, Bristol-Myers Squibb, Genzyme, Grifols, Merck Serono, Novartis, Roche, Santhera and Teva. She receives research support from the German Research Foundation, the IZKF Münster, IMF Münster, Biogen, Immunic AG, Novartis and Merck Serono. BW received grants from the German Ministry of Education and Research, Deutsche Forschungsgemeinschaft, Dietmar Hopp Foundation and Klaus Tschira Foundation, grants and personal fees from Merck, Novartis, Roche and personal fees from Alexion, INSTAND, Roche. OA reports grants from the German Ministry of Education and Research (BMBF) and the German Research Foundation (DFG); grants and personal fees from Biogen and Novartis; and travel support and personal fees from Alexion, Almirall, MedImmune, Merck Serono, Roche, Sanofi, Viela Bio/Horizon Therapeutics and Zambon. IA has received research support from Diamed and Chugai, speaking honoraria, travel grants and compensation for serving on a scientific advisory board from Alexion, Horizon, Roche, Merck and sanofi-aventis/Genzyme, all unrelated to this study. JB-S has received institutional research support from NEMOS e.V., Alexion and Bayer AG, personal compensation from Alexion; speaking honoraria and travel grants from Bayer Healthcare, Horizon/Amgen, Novartis and sanofi-aventis/Genzyme, in addition, compensation for serving on a scientific advisory board of Alexion, Roche and Merck, all unrelated to the presented work. FP provided research support to Neurosciences Clinical Research Center, German Ministry for Education and Research (BMBF), Deutsche Forschungsgemeinschaft (DFG), Einstein Foundation, Guthy Jackson Charitable Foundation, EU FP7 Framework Program, Biogen, Genzyme, Merck Serono, Novartis, Bayer, Roche, Parexel and Almirall, received honoraria for lectures, presentations, speakers from Guthy Jackson Foundation, Bayer, Biogen, Merck Serono, Sanofi Genzyme, Novartis, Viela Bio, Roche, UCB, Mitsubishi Tanabe and Celgene, in addition received compensation for serving on a scientific advisory board of Celgene, Roche, UCB and Merck, is an Academic Editor PLos One and Associate Editor von Neurology Neuroimmunology and Neuroinflammation, all unrelated to the presented work. TK has received speaker honoraria and/or personal fees for advisory boards from Novartis Pharma, Roche Pharma, Alexion/Astra Zeneca, Horizon Therapeutics/Amgen, Merck, Chugai Pharma and Biogen. The institution she works for has received compensation for serving as a member of a steering committee from Roche. Furthermore, she is a site principal investigator in several randomised clinical trials and her institution has received compensation for clinical trials from Novartis Pharma, Roche Pharma and Sanofi Genzyme; all outside the present work. TF reports personal fees from Aslan, Bayer, BiosenseWebster, Bristol Myers Squibb, CSL Behring, Enanta, Fresenius Kabi, Galapagos, Immunic, IQVIA, Janssen, KyowaKirin, Lilly, LivaNova, Minoryx, Novartis, Recordati, Relaxera, Roche, Servier, Viatris, VICO Therapeutics and Vifor for statistical consultancies including data monitoring committees, all outside the submitted work. AB receives funding from the Innovationsausschuss of the German Federal Joint Committee (G-BA; grant 01VSF23040) and the German Federal Ministry of Education and Research (BMBF; grant 01ZZ2102B). He has received consulting and/or speaker fees from Alexion, Argenx, Biogen, Horizon/Amgen, Merck, Novartis, Roche and Sandoz/Hexal, and his institution has received compensation for clinical trials from Alexion, Biogen, Merck, Novartis, Roche and Sanofi Genzyme; all outside the present work. J-PS has nothing to disclose.
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