Comparison of the efficacy of azathioprine and rituximab in neuromyelitis optica spectrum disorder: a randomized clinical trial
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Neuromyelitis optica spectrum disorder (NMOSD) often follows a relapsing course. As disability in NMOSD is attack-related, effective treatments are needed. We aimed to compare the efficacy of azathioprine (AZA) and rituximab (RIT) as maintenance therapy in NMOSD patients. An open, randomized clinical trial was conducted during September 2015 to December 2016, in Isfahan, Iran. Initially, 100 NMOSD patients were approached, 86 entered the study, and 68 cases completed the trial. All patients had a relapsing–remitting course with expanded disability extended scale (EDSS) ≤7 (median 2.75, range = 0–7). Patients were randomized into two groups, which did not differ according to age, gender distribution, and disease duration. In the AZA group, 35 patients [20 aquaporin-4 (AQP4)-IgG positive] were started on 50 mg/day oral AZA and increased to 2–3 mg/kg/day (with oral prednisolone as adjunctive therapy). In the RIT group, 33 patients (13 aquaporin-4-IgG positive) received 1 g intravenous rituximab and repeated 2 weeks later and then every 6 months. Annualized relapse rate (ARR) was measured as the primary outcome and EDSS as the secondary outcome after 12 months of intervention. The mean ARR [standard deviation (SD)] in the AZA group decreased from 1 (0.38) to 0.51 (0.55) (P value <0.001) and in the RIT group decreased from 1.30 (0.68) to 0.21 (0.42) (P value <0.001). ARR after intervention minus ARR before intervention [mean (SD)] was 1.09 (0.72) in RIT group and 0.49 (0.59) in AZA group (P value <0.001). EDSS after intervention minus EDSS before intervention [mean (SD)] was 0.98 (1.14) in RIT group and 0.44 (0.54) in AZA group (P value <0.001). Nineteen patients (54.3%) in AZA group and 26 patients (78.8%) in RIT group became relapse-free after intervention (P value = 0.033). AZA and RIT can both effectively decrease ARR and EDSS in NMOSD patients. RIT was significantly more effective than AZA treatment.
Trial Registration Name of registry: clinicaltrials.gov; ID: NCT03002038; URL: https://clinicaltrials.gov/ct2/show/NCT03002038.
KeywordsNeuromyelitis optica spectrum disorder Azathioprine Rituximab Randomized clinical trial Comparative study Efficacy
We want to thank vice-chancellor for research and technology of Isfahan University of Medical Sciences for funding and supporting this project (Grant number: 395275).
Dr. ZN contributed in designing the study, conducting the study, data collection, data interpretation, critically reviewing the manuscript, and approving the final manuscript as submitted. Dr. SB contributed in designing the study, data collection, data analysis, data interpretation, preparing the first draft of the manuscript, and approving the final manuscript as submitted. Prof. VS contributed in the first idea of the study, designing the study, supervising the study, conducting the study, data interpretation, critically reviewing the manuscript, and approving the final manuscript as submitted. Dr. NA contributed in the first idea of the study, designing the study, conducting the study, data interpretation, critically reviewing the manuscript, and approving the final manuscript as submitted. Dr. FA contributed in the first idea of the study, designing the study, conducting the study, data interpretation, critically reviewing the manuscript, and approving the final manuscript as submitted.
Compliance with ethical standards
Conflicts of interests
Nothing to report.
This study was approved by the regional bioethics committee of Isfahan University of Medical Sciences (approval code:195105) and therefore have been performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki.
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