Purpose

Immunosuppressive drugs play a critical role in treating inflammatory diseases while avoiding corticosteroid-induced side effects. Some immunosuppressants are labelled carcinogenic; the extent of any such effect is important for risk-benefit assessments.

Methods

In this retrospective cohort study, we evaluated incidence of cancer after treatment with immunosuppressive drug classes and individual immunosuppressants in comparison with persons unexposed to immunosuppression. Cancer incidence was ascertained by linkage to twelve state cancer registries from 1996-2015. Cancer incidence was analyzed using Cox regression survival analysis, using 0-, 3- and 5-year lags after immunosuppression began.

Results

10,872 individuals were at risk of incident cancer and resided in one of the 12 states covered; 719 primary cancers were identified through cancer incidence tracing. Tumor Necrosis Factor inhibitor, antimetabolite, calcineurin inhibitor and alkylating agent classes were not associated with statistically significant increases in cancer incidence. Methotrexate was associated with significantly lower overall cancer incidence in the systemic inflammatory disease (SID)-including cohort (adjusted hazard ratio (aHR)= 0.77, 95% confidence interval (CI):0.61-0.98). Other statistically significant overall cancer associations included reduced hazard for adalimumab and chlorambucil and increased hazard for tacrolimus. Etanercept had opposite results in the non-SID and SID-including cohorts.

Conclusions

There is no increased risk of overall or site-specific cancer incidence associated with commonly used immunosuppressive drug classes. Further research may clarify potentially protective or harmful effects of the specific agents associated with reduced or increased cancer incidence.