Cumulative immunosuppressant exposure is associated with diversified cancer risk among 14 832 patients with systemic lupus erythematosus: a nested case-control study

Objectives: Immunosuppressive therapy is necessary to alter the natural course of SLE. However, immunosuppressant-related cancer risk is a major concern. The aim of this study was to determine whether immunosuppressant use is associated with cancer risk in SLE.

Methods: We designed a retrospective nested case-control study within an SLE population based on the National Health Insurance Research Database in Taiwan. We screened 14 842 patients with SLE from 2001 to 2013 and compared patients with SLE complicated by later cancer with patients with SLE but without cancer. The cumulative dose of immunosuppressants was calculated from the SLE diagnosis date to the occurrence of cancer. The immunosuppressants of interest were AZA, CYC, MTX, HCQ and systemic glucocorticoids. Adjusted odds ratios (ORs) for cancer were calculated in conditional Cox regression models after propensity score matching.

Results: The top five types of cancers were breast (16.9%), haematological (11.7%), colorectal (11.0%), lung (10.6%) and hepatobiliary (10.4%) cancers. After matching, this study included 330 cancer patients and 1320 matched cancer-free patients. The adjusted analyses showed an association of a higher cumulative CYC dose (OR = 1.09, 95% CI: 1.04, 1.13) and lower HCQ dose (OR = 0.93, 95% CI: 0.90, 0.97) with cancer risk in comparison with the controls.

Conclusion: Diverse cancer risks are associated with different immunosuppressants in patients with SLE. CYC increases the risk of cancer, and HCQ decreases this risk in SLE patients, both in a dose-dependent manner.