Efficacy and safety of azathioprine for neuromyelitis optica spectrum disorders: A meta-analysis of real-world studies

Objective This study aimed to perform a meta-analysis of the efficacy and safety of azathioprine (AZA) for neuromyelitis optica spectrum disorders (NMOSD), considering the potential predictive factors related to patient response to AZA in this disease. Methods We performed a systematic online query in PubMed, EMBASE, The Cochrane Library, ClinicalTrials.gov, China National Knowledge Infrastructure, WANFANG DATA, and CQVIP DATA. The available studies on the use of AZA in NMOSD patients were included. Results We analyzed a total of 21 studies including 1016 patients. Results demonstrated that AZA significantly decreased annual relapse rate (ARR) by 1.164 (95% confidence intervals (CI), -1.396 to -0.932; p < 0.001). Subgroup analysis showed that AZA significantly decreased ARR in both low-dose group (effect size (ES): -1.545) and moderate-dose group (ES: -2.026). AZA therapy also resulted in a significant reduction of 1.117 (95% CI: -1.668 to -0.566; p < 0.001) in expanded disability status scale (EDSS) score. AZA did not affect EDSS score in the low-dose subgroup (ES: -0.535; p = 0.209) or the moderate-dose subgroup (ES: -0.709; p = 0.064). During AZA therapy, 47% of patients did not experience any relapses (95% CI, 39% to 54%). In addition, 13% of patients developed leukopenia, 11% had elevated liver enzyme levels, 8% experienced nausea or vomiting, 5% developed pancytopenia and 6% died during follow-up. Conclusion AZA is effective in reducing relapse and improving patients’ neurological function. However, liver function monitoring and routine blood monitoring remain necessary. Within the safe upper limit, a higher dose of AZA may be associated with a better efficacy for NMOSD.