Immunotherapies in neuromyelitis optica spectrum disorder: efficacy and predictors of response

• Published in: Journal of neurology, neurosurgery and psychiatry Vol. 88; no. 8; pp. 639 - 647
• Main Authors: Stellmann, Jan-Patrick, Krumbholz, Markus, Friede, Tim, Gahlen, Anna, Borisow, Nadja, Fischer, Katrin, Hellwig, Kerstin, Pache, Florence, Ruprecht, Klemens, Havla, Joachim, Kümpfel, Tania, Aktas, Orhan, Hartung, Hans-Peter, Ringelstein, Marius, Geis, Christian, Kleinschnitz, Christoph, Berthele, Achim, Hemmer, Bernhard, Angstwurm, Klemens, Young, Kim Lea, Schuster, Simon, Stangel, Martin, Lauda, Florian, Tumani, Hayrettin, Mayer, Christoph, Zeltner, Lena, Ziemann, Ulf, Linker, Ralf Andreas, Schwab, Matthias, Marziniak, Martin, Then Bergh, Florian, Hofstadt-van Oy, Ulrich, Neuhaus, Oliver, Zettl, Uwe, Faiss, Jürgen, Wildemann, Brigitte, Paul, Friedemann, Jarius, Sven, Trebst, Corinna, Kleiter, Ingo
• Format: Journal Article
• Language: English
• Published: England BMJ Publishing Group LTD 01.08.2017; Journal of Neurology, Neurosurgery, and Psychiatry
• Series: Research paper
• Subjects: Adult; Aquaporin 4 - immunology; Aquaporins; Autoantibodies - blood; Azathioprine - therapeutic use; Cohort Studies; Data collection; Datasets; Drug dosages; Female; Follow-Up Studies; Germany; Glatiramer Acetate - therapeutic use; Humans; Immunotherapy; Immunotherapy - methods; Interferon-beta - therapeutic use; Long-Term Care; Male; Medical prognosis; Middle Aged; Mitoxantrone - therapeutic use; Monoclonal antibodies; Neuro-Inflammation; Neurology; Neuromyelitis Optica - drug therapy; Neuromyelitis Optica - immunology; Prognosis; Recurrence; Registries; Retrospective Studies; Rituximab - therapeutic use; Survival analysis; Treatment Outcome; Rituximab; Therapy; Neuromyelitis optica spectrum disorder; Azathioprine; Aquaporin-4 antibody
• ISSN: 0022-3050; 1468-330X
• DOI: 10.1136/jnnp-2017-315603

ObjectiveTo analyse predictors for relapses and number of attacks under different immunotherapies in patients with neuromyelitis optica spectrum disorder (NMOSD).DesignThis is a retrospective cohort study conducted in neurology departments at 21 regional and university hospitals in Germany. Eligible participants were patients with aquaporin-4-antibody-positive or aquaporin-4-antibody-negative NMOSD. Main outcome measures were HRs from Cox proportional hazard regression models adjusted for centre effects, important prognostic factors and repeated treatment episodes.Results265 treatment episodes with a mean duration of 442 days (total of 321 treatment years) in 144 patients (mean age at first attack: 40.9 years, 82.6% female, 86.1% aquaporin-4-antibody-positive) were analysed. 191 attacks occurred during any of the treatments (annual relapse rate=0.60). The most common treatments were rituximab (n=77, 111 patient-years), azathioprine (n=52, 68 patient-years), interferon-β (n=32, 61 patient-years), mitoxantrone (n=34, 32.1 patient-years) and glatiramer acetate (n=17, 10 patient-years). Azathioprine (HR=0.4, 95% CI 0.3 to 0.7, p=0.001) and rituximab (HR=0.6, 95% CI 0.4 to 1.0, p=0.034) reduced the attack risk compared with interferon-β, whereas mitoxantrone and glatiramer acetate did not. Patients who were aquaporin-4-antibody-positive had a higher risk of attacks (HR=2.5, 95% CI 1.3 to 5.1, p=0.009). Every decade of age was associated with a lower risk for attacks (HR=0.8, 95% CI 0.7 to 1.0, p=0.039). A previous attack under the same treatment tended to be predictive for further attacks (HR=1.5, 95% CI 1.0 to 2.4, p=0.065).ConclusionsAge, antibody status and possibly previous attacks predict further attacks in patients treated for NMOSD. Azathioprine and rituximab are superior to interferon-β.