Cancer occurrence following azathioprine treatment in myasthenia gravis patients: A systematic review and meta-analysis

Treatments of myasthenia gravis (MG) usually include immunosuppressants such as glucocorticoids, tacrolimus, and azathioprine (AZA). In clinical practice, azathioprine therapy is thought to have a potential risk for developing secondary malignancies in myasthenia gravis patients. However, published data on the long-term safety of azathioprine in myasthenia gravis patients are limited and not consistent among studies. To explore cancer occurrence following azathioprine therapy in myasthenia gravis patients in the long term, we searched Medline, EMBASE, and the Cochrane Library for terms related to azathioprine, myasthenia gravis and cancer occurrence. Two investigators independently extracted trial data. A pooled estimate was calculated from fixed-effects meta-analysis. Our analysis included 1650 azathioprine-treated patients and 2481 non-azathioprine-treated patients. All five studies showed some concerns regarding the risk of bias. In a meta-analysis of 5 studies, we observed no significantly elevated risk of cancer occurrence among individuals with prior myasthenia gravis diagnosis who received long-term azathioprine treatment (OR 1.09; 95% CI 0.86-1.38, p = 0.46). Prospective studies are needed to observe the safety of azathioprine.