The best available data so far, generated in a retrospective analysis of 90 patients with NMOSD from the USA22 and of 138 patients with NMOSD from Korea,23 describe greater efficacy of RTX and MMF compared with AZA. (HR=0.4, 95%?CI 0.3 to 0.7, p=0.001) and rituximab (HR=0.6, 95%?CI 0.4 to 1 1.0, p=0.034) reduced the attack risk compared with interferon-, 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 5.1, p=0.009). Every decade of age was associated with a lower risk for attacks (HR=0.8, PF-06463922 95%?CI 0.7 to 1 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). Conclusions Age, antibody status and possibly previous attacks predict further attacks in patients treated for NMOSD. Azathioprine and rituximab are superior to interferon-. Keywords: Neuromyelitis optica spectrum disorder, Therapy, Azathioprine, Rituximab, Aquaporin-4 antibody Introduction Neuromyelitis optica spectrum disorder (NMOSD) is a rare autoimmune disease of the central nervous system, mainly manifesting through recurrent attacks of optic neuritis and longitudinally extensive transverse myelitis.1 Antibodies to aquaporin-4 (AQP4-abs) were identified as pathogenic, and their detection, in addition to typical clinical manifestation, is a hallmark of the recently updated diagnostic criteria. 2C4 The presence of AQP4-abs is also related to prognosis and attack risk.5 6 While a chronic progressive disease course is very rare, inflammatory disease attacks are associated with a high risk of persisting disability, including paraplegia and blindness. 7 8 Attack prevention with immunosuppressive drugs is currently considered the best available treatment.9C11 Besides classical immunosuppressant drugs such as azathioprine (AZA) or mycophenolate mofetil (MMF), rituximab (RTX) has increasingly been used for the treatment of patients with NMOSD since 2005.12C17 More recently, an interleukin-6 receptor inhibitor (SA-237), eculizumab and an anti-CD19 antibody (inebilizumab) are being investigated as alternative therapies.18C21 However, currently only low evidence exists concerning comparative treatment efficacy. The best available data so far, generated in a retrospective analysis of 90 patients with NMOSD from the USA22 and of 138 patients with NMOSD from Korea,23 describe greater efficacy of RTX and MMF compared with AZA. Furthermore, little is known about predictors for treatment response,24 and it is unknown whether AQP4-ab serostatus, gender, age, disease duration and other clinical parameters are associated with attack-free survival under treatment. As long as large prospective cohorts or randomised trials, which are difficult to perform due to the rarity of NMOSD, are lacking, retrospective cohort studies are the best available approach to gain further knowledge about treatment efficacy and predictors of treatment response. Using the NMOSD registry of the German Neuromyelitis Optica Study group (NEMOS), we analysed the efficacy of immunotherapies for attack prevention and predictors for attacks under immunotherapies. Methods Study design and patients This retrospective cohort study was based on the German NEMOS group (www.nemos-net.de) registry established in 2008. At database lock, the registry included 186 patients with neuromyelitis optica (NMO) diagnosed PF-06463922 according to the 2006 Wingerchuk25?criteria or with AQP4-ab-positive NMO spectrum disorder (NMOSD). The local institutional review boards of the participating centres approved the study (first approval from the institutional review board Charit Universit?tsmedizin Berlin EA3/004/08). Last data entry for this analysis varied between centres Comp and was between January 2012 and March 2013. Data collection and processing Data collected at regular clinical visits included demographic data, AQP4-ab status, attacks (onset, treatments?and outcome), long-term treatments (compounds, start/stop dates?and dosages), expanded disability status scale and visual acuity. A detailed description of the cohort and the methods used for data collection, including an on-site data validation (flying doctor-approach), has been published previously.8 For this study, demographic data, long-term treatment data and attack dates were extracted from the database. Treatment data were validated through manual quality checks performed by two authors (JPS?and MK), as well as by automated logical checks. As further analyses relied on exact treatment data, including start and stop dates, patients with insufficient baseline or treatment data were excluded. Definition of treatment episodes For our analyses which PF-06463922 were based on pharmacodynamics and previous treatment experience, we determined the?efficacy of therapeutic interventions after the last dose as PF-06463922 follows: 365 days for alemtuzumab; 180 days for RTX; 90 days for mitoxantrone (Mitox) and intrathecal steroids; 30 days for cyclophosphamide, AZA, ciclosporin A, MMF, natalizumab, intravenous immunoglobulin, fingolimod (FTY), intravenous.