Journal Article

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

Tumani, Hayrettin, Zeltner, Lena, Krumbholz, Markus, Mayer, Christoph, Wildemann, Brigitte, Gahlen, Anna, Stangel, Martin, Lauda, Florian, Kümpfel, Tania, Young, Kim Lea, Faiss, Jürgen, Jarius, Sven, Stellmann, Jan-Patrick, Schwab, Matthias, Paul, Friedemann, Hofstadt-van Oy, Ulrich, Pache, Florence, Hartung, Hans-Peter, Angstwurm, Klemens, Marziniak, Martin, Ziemann, Ulf, Havla, Joachim, Kleinschnitz, Christoph, Aktas, Orhan, Fischer, Katrin, Berthele, Achim, Neuhaus, Oliver, Trebst, Corinna, Ruprecht, Klemens, Ringelstein, Marius, Friede, Tim, Linker, Ralf Andreas, Kleiter, Ingo, Then Bergh, Florian, Geis, Christian, Schuster, Simon, Zettl, Uwe, Hellwig, Kerstin, Hemmer, Bernhard, Borisow, Nadja

2017

Overview

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.

• Publisher: BMJ Publishing Group LTD,Journal of Neurology, Neurosurgery, and Psychiatry
• Subject: 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