The effects of the immunosuppressive drug azathioprine (AZA) widely used in multiple sclerosis (MS) before the treatments with interferons or glatiramer acetate

AZA is a possible alternative to interferon beta for treating MS. As concerns have been raised about its safety, mainly due to possible increased risk of cancer, the authors of this review tried to assess the balance between benefits and harms of AZA treatment in MS.
Among the pertinent medical literature only five studies met the methodological quality criteria necessary for their inclusion in this review, comprising a total of 698 participants, with follow-up at one, two and three years.
Taking into account the disability progression and the number of relapses, the authors found evidence that AZA reduced the number of patients who had relapses during the first year of treatment , and at two and three years' follow-up as well. AZA treatment also reduced the number of patients who progressed during the first two to three years of therapy.
Adverse effects such as gastrointestinal disturbances, bone marrow suppression and hepatic toxicity occurred frequently; but they were known and anticipated, thus quite easily managed: withdrawals due to adverse events were few, and mainly due to gastrointestinal intolerance.
Two studies had deaths reported, comprising of four persons in the control group, and eight in the AZA group. These small numbers do not allow a statistical analysis.
Conflicting conclusions on potential risk of cancer in MS patients with long-term AZA treatment have been reported in eight published papers, not considered in the present review because they came from sources other than clinical trials. The presence of patients who developed cancer ( three in the AZA and 1 the placebo group) was reported in two out of five studies considered in this review. Numerous studies of AZA treated patient populations other than MS patients are also available. The whole data, however, does not show an increase in risk of malignancy from AZA. Possible long-term risks may be related to a treatment duration above ten years and cumulative doses above 600 g.