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The relationship between cancer and medication exposures in systemic lupus erythaematosus: a case–cohort study
  1. S Bernatsky1,
  2. L Joseph2,
  3. J-F Boivin1,
  4. C Gordon4,
  5. M Urowitz5,
  6. D Gladman5,
  7. P R Fortin5,
  8. E Ginzler6,
  9. S-C Bae7,
  10. S Barr8,
  11. S Edworthy8,
  12. D Isenberg9,
  13. A Rahman9,
  14. M Petri10,
  15. G S Alarcón11,
  16. C Aranow12,
  17. M-A Dooley13,
  18. R Rajan14,
  19. J-L Sénécal15,
  20. M Zummer16,
  21. S Manzi17,
  22. R Ramsey-Goldman,
  23. A E Clarke2
  1. 1
    Division of Clinical Epidemiology, Research Institute of the McGill University Health Centre, Montreal, Quebec, Canada
  2. 2
    Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, Quebec, Canada
  3. 3
    Department of Rheumatology, University of Birmingham, UK
  4. 4
    Division of Health Care & Outcomes Research, Toronto Western Research Institute, Toronto, Ontario, Canada
  5. 5
    Division of Rheumatology, Department of Medicine, SUNY Health Science Center at Brooklyn, New York, USA
  6. 6
    Department of Internal Medicine, Division of Rheumatology, Hanyang University College of Medicine and the Hospital of Rheumatic Diseases, Seoul, Korea
  7. 7
    Division of Rheumatology, Department of Medicine, University of Calgary, Calgary, Alberta, Canada
  8. 8
    Centre for Rheumatology Research - Department of Medicine, University College London, UK
  9. 9
    Division of Rheumatology, Department of Medicine, Johns Hopkins University, Baltimore, Maryland, USA
  10. 10
    Division of Clinical Immunology and Rheumatology, Department of Medicine, University of Alabama, Birmingham, Alabama, USA
  11. 11
    Department of Medicine, Columbia University, New York, USA
  12. 12
    Department of Medicine, Thurston Arthritis Research Center, The University of North Carolina at Chapel Hill, North Carolina, USA
  13. 13
    Department of Oncology, McGill University Health Centre, Montreal, Quebec, Canada
  14. 14
    Division of Rheumatology, Centre Hospitalier de l’Universite de Montreal, Department of Medicine, University of Montreal School of Medicine, Montreal, Quebec, Canada
  15. 15
    Department of Rheumatology, Maisonneuve-Rosemont Hospital, Montreal, Quebec, Canada
  16. 16
    Division of Rheumatology and Clinical Immunology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
  17. 17
    Division of Rheumatology, Northwestern University, Feinberg School of Medicine, Chicago, Illinois, USA
  1. Dr Sasha Bernatsky, Division of Clinical Epidemiology, McGill University Health Centre, 687 Pine Avenue West, V-Building, Montreal, Québec H3A 1A1, Canada; sasha.bernatsky{at}mail.mcgill.ca

Abstract

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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Footnotes

  • 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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