Aquaporin-4 serostatus does not predict response to immunotherapy in neuromyelitis optica spectrum disorders.

BACKGROUND: Debate exists about whether neuromyelitis optica spectrum disorder seronegative disease represents the same immune-mediated attack on astrocytic aquaporin-4 as in seropositive disease. OBJECTIVE: We investigated whether response to common treatments for neuromyelitis optica spectrum disorder differed by serostatus, as assessed by change in annualized relapse rate. METHODS: We performed a multicenter retrospective analysis of 245 patients with neuromyelitis optica spectrum disorder who were treated with either rituximab or mycophenolate mofetil as their first-line immunosuppressive treatment for disease prevention. Patients were followed for a minimum of 6 months following treatment initiation. RESULTS: In those started on rituximab, the pre-treatment annualized relapse rates for seropositive and seronegative patients were 1.81 and 1.93, respectively. On-treatment annualized relapse rates significantly declined to 0.32 (seropositive; p < 0.0001) and 0.12 (seronegative; p = 0.0001). In those started on mycophenolate mofetil, the pre-treatment annualized relapse rates for seropositive and seronegative patients were 1.79 and 1.45, respectively. On-treatment annualized relapse rates declined to 0.29 (seropositive; p < 0.0001) and 0.30 (seronegative; p < 0.005). CONCLUSION: In this international collaboration involving a large number of neuromyelitis optica spectrum disorder patients, treatment was effective regardless of serostatus. This suggests that treatment should not differ when considering these treatments.

Anti-aquaporin-4 titer is not predictive of disease course in neuromyelitis optica spectrum disorder: A multicenter cohort study.

BACKGROUND: Neuromyelitis optica spectrum disorder (NMOSD) is a rare autoimmune disease associated with a serological antibody to aquaporin-4 (AQP4) detectable in up to 80% of patients. The enzyme-linked immunosorbent assay (ELISA) is one of the most popular methods of testing for anti-AQP4 antibodies that results with a titer in which < 3 Units/ml is negative, 3-5 is borderline and 5+ is positive. The value of the positive titer in predicting long term disease course is currently unknown. METHODS: This is a retrospective analysis of NMOSD patients from five centers around the world: Baltimore, USA, Philadelphia, USA, Shanghai, China, Berlin, Germany, and Medellin, Columbia, where ELISA titers on anti-AQP4 antibody testing is available. Inclusion criteria include a diagnosis of NMOSD and seropositive anti-AQP4 antibody test with titer = /> 3 Units/ml. Patients were stratified into three groups by titer: 3-30 Units/ml (low), 31-100 Units/ml (medium), and 101+ Units/ml (high). Demographic factors such as age at onset, race, and sex were collected along with clinical features such as annualized relapse rate, duration of disease, location of relapses, and treatment history. RESULTS: A total of 139 NMOSD patients met criteria for inclusion in this study, stratified into three groups by titer: 42 subjects with low titers of 3-30 Units/ml, 30 subjects with medium titers of 31-100 Units/ml and 67 subjects with high titers of 101 or greater ELISA Units/ml. The average age at onset, sex and race distribution were not significantly different among the groups. The number of patients untreated in each group was similar (< 25%) as was the average annualized relapse rate (0.591-0.821 relapses/year). With an average of 10 years follow up, the average disability level was not different among the three titer groups (EDSS range 3.03-3.48). The distribution of lesions, as well as their preventive treatment regimens did not differ significantly. CONCLUSION: Beyond a positive/borderline/negative result, the titer of the anti-AQP4 antibody ELISA assay is not predictive in the disease course for patients with NMOSD. Low titer patients experience the same disease course as medium-titer and high-titer anti-AQP4 antibody patients with NMOSD.