The relationship between cancer and medication exposures in systemic lupus erythaematosus

A case-cohort study

Sasha Bernatsky, L. Joseph, J. F. Boivin, C. Gordon, M. Urowitz, D. Gladman, P. R. Fortin, E. Ginzler, S. C. Bae, S. Barr, S. Edworthy, D. Isenberg, A. Rahman, Michelle Petri, G. S. Alarcón, C. Aranow, M. A. Dooley, R. Rajan, J. L. Sénécal, M. Zummer & 3 others S. Manzi, R. Ramsey-Goldman, A. E. Clarke

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)74-79
Number of pages6
JournalAnnals of the Rheumatic Diseases
Volume67
Issue number1
DOIs
StatePublished - Jan 2008

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Systemic Lupus Erythematosus
Cohort Studies
Immunosuppressive Agents
Neoplasms
Hazards
Pharmaceutical Preparations
Tobacco
Smoking
Azathioprine
Antimalarials
Methotrexate
Geographic Locations
Cyclophosphamide
Glucocorticoids
Aspirin
Tumors
Anti-Inflammatory Agents
Hematologic Neoplasms
Registries
Lung Neoplasms

ASJC Scopus subject areas

  • Rheumatology
  • Immunology

Cite this

Bernatsky, S., Joseph, L., Boivin, J. F., Gordon, C., Urowitz, M., Gladman, D., ... Clarke, A. E. (2008). The relationship between cancer and medication exposures in systemic lupus erythaematosus: A case-cohort study. Annals of the Rheumatic Diseases, 67(1), 74-79. https://doi.org/10.1136/ard.2006.069039

The relationship between cancer and medication exposures in systemic lupus erythaematosus : A case-cohort study. / Bernatsky, Sasha; Joseph, L.; Boivin, J. F.; Gordon, C.; Urowitz, M.; Gladman, D.; Fortin, P. R.; Ginzler, E.; Bae, S. C.; Barr, S.; Edworthy, S.; Isenberg, D.; Rahman, A.; Petri, Michelle; Alarcón, G. S.; Aranow, C.; Dooley, M. A.; Rajan, R.; Sénécal, J. L.; Zummer, M.; Manzi, S.; Ramsey-Goldman, R.; Clarke, A. E.

In: Annals of the Rheumatic Diseases, Vol. 67, No. 1, 01.2008, p. 74-79.

Research output: Contribution to journalArticle

Bernatsky, S, Joseph, L, Boivin, JF, Gordon, C, Urowitz, M, Gladman, D, Fortin, PR, Ginzler, E, Bae, SC, Barr, S, Edworthy, S, Isenberg, D, Rahman, A, Petri, M, Alarcón, GS, Aranow, C, Dooley, MA, Rajan, R, Sénécal, JL, Zummer, M, Manzi, S, Ramsey-Goldman, R & Clarke, AE 2008, 'The relationship between cancer and medication exposures in systemic lupus erythaematosus: A case-cohort study', Annals of the Rheumatic Diseases, vol. 67, no. 1, pp. 74-79. https://doi.org/10.1136/ard.2006.069039
Bernatsky, Sasha ; Joseph, L. ; Boivin, J. F. ; Gordon, C. ; Urowitz, M. ; Gladman, D. ; Fortin, P. R. ; Ginzler, E. ; Bae, S. C. ; Barr, S. ; Edworthy, S. ; Isenberg, D. ; Rahman, A. ; Petri, Michelle ; Alarcón, G. S. ; Aranow, C. ; Dooley, M. A. ; Rajan, R. ; Sénécal, J. L. ; Zummer, M. ; Manzi, S. ; Ramsey-Goldman, R. ; Clarke, A. E. / The relationship between cancer and medication exposures in systemic lupus erythaematosus : A case-cohort study. In: Annals of the Rheumatic Diseases. 2008 ; Vol. 67, No. 1. pp. 74-79.
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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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AU - Gordon, C.

AU - Urowitz, M.

AU - Gladman, D.

AU - Fortin, P. R.

AU - Ginzler, E.

AU - Bae, S. C.

AU - Barr, S.

AU - Edworthy, S.

AU - Isenberg, D.

AU - Rahman, A.

AU - Petri, Michelle

AU - Alarcón, G. S.

AU - Aranow, C.

AU - Dooley, M. A.

AU - Rajan, R.

AU - Sénécal, J. L.

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N2 - 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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