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The relationship between cancer and medication exposures in systemic lupus erythematosus: a case-cohort study
  1. Sasha Bernatsky (sasha.bernatsky{at}mail.mcgill.ca)
  1. Research Institute of the McGill University Health Centre, Canada
    1. Jean-Francois Boivin
    1. McGill University, Canada
      1. Lawrence Joseph
      1. Research Institute of the McGill University Health Centre, Canada
        1. Caroline Gordon
        1. University of Birmingham, United Kingdom
          1. Murray Urowitz
          1. Toronto Western Research Institute, Canada
            1. Dafna Gladman
            1. Toronto Western Research Institute, Canada
              1. Ellen Ginzler
              1. SUNY Health Science Center at Brooklyn, United States
                1. Paul Fortin
                1. Toronto Western Research Institute, Canada
                  1. Sang-Cheol Bae
                  1. Hanyang University College of Medicine and the Hospital of Rheumatic Diseases, Korea, Republic of
                    1. Susan Barr
                    1. University of Calgary, Canada
                      1. David Isenberg
                      1. University College London, United Kingdom
                        1. Anisur Rahman
                        1. University College London, United Kingdom
                          1. Michelle Petri
                          1. John Hopkins University, United States
                            1. Graciela Alarcón
                            1. University of Alabama, United States
                              1. Cynthia Aranow
                              1. Columbia University, United States
                                1. Mary-Anne Dooley
                                1. University of North Carolina at Chapel Hill, United States
                                  1. Raghu Rajan
                                  1. McGill University, Canada
                                    1. Jean-Luc Sénécal
                                    1. University of Montreal, Canada
                                      1. Michel Zummer
                                      1. Maisonneuve-Rosemont Hospital, Canada
                                        1. Susan Manzi
                                        1. University of Pittsburg, United States
                                          1. Steve Edworthy
                                          1. University of Calgary, Canada
                                            1. Rosalind Ramsey-Goldman
                                            1. Northwestern University, United States
                                              1. Ann Clarke
                                              1. Montreal General Hospital, Canada

                                                Abstract

                                                Objective: To examine if, in 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 tumor 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, NSAIDs, ASA), 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 on 246 cancer cases and 538 controls without cancer. The adjusted HR for over-all 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 over-all cancer risk. For lung cancer (N=35 cases), smoking was also a prominent risk factor. When looking at hematological 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 five 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 over-all cancer risk, it may contribute to an increased risk of hematological malignancies. Future studies are in progress to evaluate independent influence of medication exposures and disease activity on risk of malignancy.

                                                • cancer
                                                • immunosuppressant
                                                • malignancy
                                                • systemic lupus erythematosus

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