Long-term safety of azathioprine for treatment of neuromyelitis optica spectrum disorders

Abstract

Background: Azathioprine is a common first-line therapy for neuromyelitis optica spectrum disorder (NMOSD). Objective: The aim of this study was to determine whether long-term treatment (>10 years) with azathioprine is safe in NMOSD. Methods: We conducted a retrospective medical record review of all patients at the School of Medicine of the University of São Paulo (São Paulo, Brazil) who fulfilled the 2015 international consensus diagnostic criteria for NMOSD and were treated with azathioprine for at least 10 years. Results: Out of 375 patients assessed for eligibility, 19 were included in this analysis. These patients’ median age was 44 years (range=28-61); they were mostly female (17/19) and AQP4-IgG seropositive (18/19). The median disease duration was 15 years (range=10-39) and most patients presented a relapsing clinical course (84.2%). The median duration of treatment was 11.9 years (range=10.0-23.8). The median annualized relapse rates (ARR) pre- and post-treatment with azathioprine were 1 (range=0.1-2) and 0.1 (range=0-0.35); p=0.09. Three patients (15.7%) had records of adverse events during the follow-up, which consisted of chronic B12 vitamin deficiency, pulmonary tuberculosis and breast cancer. Conclusion: Azathioprine may be considered a safe agent for long-term treatment (>10 years) of NMOSD, but continuous vigilance for infections and malignancies is required.

Different monoclonal antibodies and immunosuppressants administration in patients with neuromyelitis optica spectrum disorder: a Bayesian network meta-analysis

“…A retrospective study with the first-line therapy of NMOSD confirmed MMF as the first-line therapeutic option and added that AZA was worth considering if the side effects were tolerable [ 50 ]. Studies have pointed out that the long-term use of AZA or MMF increases the risk of hematologic malignancies [ 51 , 52 ]. Note-worthily, such threats may not spring up in short-term observations and thus could have been severely underestimated as potential side effects.…”

Adverse Events in NMOSD Therapy

“…Azathioprine is a prodrug of 6-mercaptopurine and an immunosuppressive antimetabolite. There are single centre reports on azathioprine in NMOSD with up to 103 patients and two meta-analyses covering 977 and 1016 patients [8][9][10][11][12]. Higher case numbers on adverse events (AEs) have been derived from other indications, in particular, inflammatory bowel disease, rheumatoid arthritis (RA), and the early days of kidney transplantation [13][14][15].…”

“…However, the descriptions of serious infections in NMOSD patients under azathioprine treatment are rare. Elsone et al reported three cases of respiratory infections (out of 103 patients, corresponding to 2.9%), Gomes et al reported on one patient with tuberculosis (out of 19, 5.3%) [9,11]. In inflammatory bowel disease, the reported infection rates range from 2% to 42% [13].…”

“…Regarding NMOSD, Costanzi et al reported three lymphoma cases in 99 patients treated with azathioprine [8]. Gomes et al observed one case of breast cancer (out of 19 patients) [11]. One large review on patients with inflammatory bowel disease found cancer in 7 out of 3931 patients treated with azathioprine, among them two fatal cases with Hodgkin's and hepatosplenic lymphoma [13].…”