Julien Poupart1, Jonathan Giovannelli1, Romain Deschamps1, Bertrand Audoin1, Jonathan Ciron1, Elisabeth Maillart1, Caroline Papeix1, Nicolas Collongues1, Bertrand Bourre1, Mickael Cohen1, Sandrine Wiertlewski1, Olivier Outteryck1, David Laplaud1, Sandra Vukusic1, Romain Marignier1, Hélène Zephir2. 1. From the Department of Neurology (J.P., J.G., O.O., H.Z.) and U995-LIRIC-Lille Inflammation Research International Center, Inserm, Univ Lille (J.G., H.Z.), CHU Lille; Department of Neurology (R.D.), Fondation Ophtalmologique Adolphe de Rothschild, Paris; CNRS, CRMBM UMR 7339 (B.A.), Aix-Marseille Université; Service de Neurologie (B.A.), Pôle de Neurosciences Cliniques, APHM, Hôpital de la Timone, Marseille; Department of Neurology (J.C.), Hôpital Purpan, CHU de Toulouse; Department of Neurology (E.M., C.P.), Hôpital de la Pitié Salpêtrière, AP-HP, Paris; Biopathologie de la Myéline, Neuroprotection et Stratégies Thérapeutiques (N.C.), INSERM U1119, Fédération de Médecine Translationnelle de Strasbourg (FMTS), Université de Strasbourg; Département de Neurologie (N.C.) and Centre d'Investigation Clinique, INSERM U1434 (N.C.), Centre Hospitalier Universitaire de Strasbourg; Department of Neurology (B.B.), Hôpital Charles Nicolle, CHU Rouen; Centre de Ressources et Compétences Sclérose en Plaques, Neurologie (M.S.), Université Nice Côte d'Azur, CHU Pasteur 2, Nice; Department of Neurology (S.W., D.L.), CHU Nantes; Service de Neurologie, Sclérose en Plaques, Pathologies de la Myéline et Neuro-inflammation (S.V., R.M.), Hôpital Neurologique Pierre Wertheimer Hospices Civils de Lyon; Centre de Référence des Maladies Inflammatoires Rares du Cerveau et de la Moelle (R.M.), Lyon; and INSERM U1028 (R.M.), CNRS UMR 5292, Center for Research in Neuroscience of Lyon, Lyon1 University, France. 2. From the Department of Neurology (J.P., J.G., O.O., H.Z.) and U995-LIRIC-Lille Inflammation Research International Center, Inserm, Univ Lille (J.G., H.Z.), CHU Lille; Department of Neurology (R.D.), Fondation Ophtalmologique Adolphe de Rothschild, Paris; CNRS, CRMBM UMR 7339 (B.A.), Aix-Marseille Université; Service de Neurologie (B.A.), Pôle de Neurosciences Cliniques, APHM, Hôpital de la Timone, Marseille; Department of Neurology (J.C.), Hôpital Purpan, CHU de Toulouse; Department of Neurology (E.M., C.P.), Hôpital de la Pitié Salpêtrière, AP-HP, Paris; Biopathologie de la Myéline, Neuroprotection et Stratégies Thérapeutiques (N.C.), INSERM U1119, Fédération de Médecine Translationnelle de Strasbourg (FMTS), Université de Strasbourg; Département de Neurologie (N.C.) and Centre d'Investigation Clinique, INSERM U1434 (N.C.), Centre Hospitalier Universitaire de Strasbourg; Department of Neurology (B.B.), Hôpital Charles Nicolle, CHU Rouen; Centre de Ressources et Compétences Sclérose en Plaques, Neurologie (M.S.), Université Nice Côte d'Azur, CHU Pasteur 2, Nice; Department of Neurology (S.W., D.L.), CHU Nantes; Service de Neurologie, Sclérose en Plaques, Pathologies de la Myéline et Neuro-inflammation (S.V., R.M.), Hôpital Neurologique Pierre Wertheimer Hospices Civils de Lyon; Centre de Référence des Maladies Inflammatoires Rares du Cerveau et de la Moelle (R.M.), Lyon; and INSERM U1028 (R.M.), CNRS UMR 5292, Center for Research in Neuroscience of Lyon, Lyon1 University, France. helene.zephir@chru-lille.fr.
Abstract
OBJECTIVE: To compare the efficacy and the risk of severe infectious events of immunosuppressive agents used early as first-line therapy in patients with neuromyelitis optica spectrum disorder (NMOSD). METHODS: We retrospectively included patients with NMOSD and a seropositive status for aquaporin 4 or myelin oligodendrocyte glycoprotein antibodies beginning first-line immunosuppressants within 3 years after the disease onset. The main outcome was occurrence of relapse after the initiation of immunosuppressants; the secondary outcome was the annual relapse rate (AAR). RESULTS: A total of 136 patients were included: 62 (45.6%) were treated with rituximab (RTX), 42 (30.9%) with mycophenolate mofetil (MMF), and 23 (16.9%) with azathioprine (AZA). Compared with RTX-treated patients, the risk of relapse was higher among MMF-treated patients (hazard ratio [HR], 2.74 [1.17-6.40]; p = 0.020) after adjusting for age at disease onset, sex, antibody status, disease duration, ARR before treatment, corticosteroid intake, and relapse location. We did not observe any difference between RTX-treated and AZA-treated patients (HR, 2.13 [0.72-6.28]; p = 0.17). No interaction was found between the antibody status and immunosuppressive treatments. ARR was lower with RTX than with MMF (p = 0.039), but no difference was observed with AZA. We observed 9 serious infectious events with MMF, 6 with RTX, and none with AZA. CONCLUSIONS: The use of first-line RTX in NMOSD appears more effective than MMF in suppressing clinical activity, independent of the antibody status. CLASSIFICATION OF EVIDENCE: That study provides Class III evidence that for patients with NMOSD, first-line RTX is superior to MMF to reduce the risk of relapse.
OBJECTIVE: To compare the efficacy and the risk of severe infectious events of immunosuppressive agents used early as first-line therapy in patients with neuromyelitis optica spectrum disorder (NMOSD). METHODS: We retrospectively included patients with NMOSD and a seropositive status for aquaporin 4 or myelin oligodendrocyte glycoprotein antibodies beginning first-line immunosuppressants within 3 years after the disease onset. The main outcome was occurrence of relapse after the initiation of immunosuppressants; the secondary outcome was the annual relapse rate (AAR). RESULTS: A total of 136 patients were included: 62 (45.6%) were treated with rituximab (RTX), 42 (30.9%) with mycophenolate mofetil (MMF), and 23 (16.9%) with azathioprine (AZA). Compared with RTX-treated patients, the risk of relapse was higher among MMF-treated patients (hazard ratio [HR], 2.74 [1.17-6.40]; p = 0.020) after adjusting for age at disease onset, sex, antibody status, disease duration, ARR before treatment, corticosteroid intake, and relapse location. We did not observe any difference between RTX-treated and AZA-treated patients (HR, 2.13 [0.72-6.28]; p = 0.17). No interaction was found between the antibody status and immunosuppressive treatments. ARR was lower with RTX than with MMF (p = 0.039), but no difference was observed with AZA. We observed 9 serious infectious events with MMF, 6 with RTX, and none with AZA. CONCLUSIONS: The use of first-line RTX in NMOSD appears more effective than MMF in suppressing clinical activity, independent of the antibody status. CLASSIFICATION OF EVIDENCE: That study provides Class III evidence that for patients with NMOSD, first-line RTX is superior to MMF to reduce the risk of relapse.