Objective: To examine if, in systemic lupus erythaematosus (SLE), exposure to immunosuppressive therapy (cyclophosphamide, azathioprine, methotrexate) increases cancer risk.
Methods: A case–cohort study was performed within a multi-site international SLE cohort; subjects were linked to regional tumour registries to determine cancer cases occurring after entry into the cohort. We calculated the hazard ratio (HR) for cancer after exposure to an immunosuppressive drug, in models that controlled for other medications (anti-malarial drugs, systemic glucocorticoids, non-steroidal anti-inflammatory drugs (NSAIDs), aspirin), smoking, age, sex, race/ethnicity, geographic location, calendar year, SLE duration, and lupus damage scores. In the primary analyses, exposures were treated categorically (ever/never) and as time-dependent.
Results: Results are presented from 246 cancer cases and 538 controls without cancer. The adjusted HR for overall cancer risk after any immunosuppressive drug was 0.82 (95% CI 0.50–1.36). Age ⩾65, and the presence of non-malignancy damage were associated with overall cancer risk. For lung cancer (n = 35 cases), smoking was also a prominent risk factor. When looking at haematological cancers specifically (n = 46 cases), there was a suggestion of an increased risk after immunosuppressive drug exposures, particularly when these were lagged by a period of 5 years (adjusted HR 2.29, 95% CI 1.02–5.15).
Conclusions: In our SLE sample, age ⩾65, damage, and tobacco exposure were associated with cancer risk. Though immunosuppressive therapy may not be the principal driving factor for overall cancer risk, it may contribute to an increased risk of haematological malignancies. Future studies are in progress to evaluate independent influence of medication exposures and disease activity on risk of malignancy.
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Funding: SB was sponsored by the Canadian Institutes of Health Research (CIHR) Junior Investigator Award; Fonds de la Recherche en Santé du Québec (FRSQ); Lupus Canada Fellowship; and Canadian Arthritis Network Scholar Award. LJ was sponsored by a CIHR Senior Investigator Award. PRF was sponsored by Arthritis Centre of Excellence University of Toronto, Arthritis & Autoimmunity Research Centre, University Health Network, Lupus Canada; and Investigator Award The Arthritis Society (TAS)/CIHR. MP was sponsored by The Hopkins Lupus Cohort supported by NIH AR437337 and the Johns Hopkins University Clinical Research Centre M01-RR00052. GSA was sponsored by NIAMS P01AR49084 and GCRC M01-RR00032 (UAB). CG was sponsored by financial support for the Birmingham UK lupus cohort provided by Lupus UK. J-LS was sponsored by CIHR MOP-62687. AC was sponsored by the Singer Family Fund for Lupus Research; FRSQ National Scholar Award; TAS 99-105; CIHR MOP-57816, MOP-62817, MOP-74630; and National Cancer Institute of Canada 013135. RR-G was sponsored by the Arthritis Foundation, Clinical Science Grant, Arthritis Foundation Greater Chicago Chapter NIH RO-3 CA 110904, AR 02138, AR 48098; and Lupus Foundation of Illinois Chapter Grant.
Competing interests: None
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