Overall and cancer related mortality among patients with ocular inflammation treated with immunosuppressive drugs: Retrospective cohort study

John H. Kempen, Ebenezer Daniel, James P. Dunn, C. Stephen Foster, Sapna Gangaputra, Asaf Hanish, Kathy J. Helzlsouer, Douglas Jabs, R. Oktay Kaçmaz, Grace A. Levy-Clarke, Teresa L. Liesegang, Craig W. Newcomb, Robert B. Nussenblatt, Siddharth S. Pujari, James T. Rosenbaum, Eric B. Suhler, Jennifer Thorne

Research output: Contribution to journalArticle

Abstract

Context: Whether immunosuppressive treatment adversely affects survival is unclear. Objective: To assess whether immunosuppressive drugs increase mortality. Design: Retrospective cohort study evaluating overall and cancer mortality in relation to immunosuppressive drug exposure among patients with ocular inflammatory diseases. Demographic, clinical, and treatment data derived from medical records, and mortality results from United States National Death Index linkage. The cohort's mortality risk was compared with US vital statistics using standardised mortality ratios. Overall and cancer mortality in relation to use or non-use of immunosuppressive drugs within the cohort was studied with survival analysis. Setting: Five tertiary ocular inflammation clinics. Patients: 7957 US residents with non-infectious ocular inflammation, 2340 of whom received immunosuppressive drugs during follow up. Exposures: Use of antimetabolites, T cell inhibitors, alkylating agents, and tumour necrosis factor inhibitors. Main outcome measures: Overall mortality, cancer mortality. Results: Over 66 802 person years (17 316 after exposure to immunosuppressive drugs), 936 patients died (1.4/ 100 person years), 230 (24.6%) from cancer. For patients unexposed to immunosuppressive treatment, risks of death overall (standardised mortality ratio 1.02, 95% confidence interval [CI] 0.94 to 1.11) and from cancer (1.10, 0.93 to 1.29) were similar to those of the US population. Patients who used azathioprine, methotrexate, mycophenolate mofetil, ciclosporin, systemic corticosteroids, or dapsone had overall and cancer mortality similar to that of patients who never took immunosuppressive drugs. In patients who used cyclophosphamide, overall mortality was not increased and cancer mortality was non-significantly increased. Tumour necrosis factor inhibitors were associated with increased overall (adjusted hazard ratio [HR] 1.99, 95% CI 1.00 to 3.98) and cancer mortality (adjusted HR 3.83, 1.13 to 13.01). Conclusions: Most commonly used immunosuppressive drugs do not seem to increase overall or cancer mortality. Our results suggesting that tumour necrosis factor inhibitors might increase mortality are less robust than the other findings; additional evidence is needed.

Original languageEnglish (US)
Pages (from-to)89-92
Number of pages4
JournalBMJ (Online)
Volume339
Issue number7712
StatePublished - Jul 11 2009

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Immunosuppressive Agents
Cohort Studies
Retrospective Studies
Inflammation
Mortality
Pharmaceutical Preparations
Neoplasms
Tumor Necrosis Factor-alpha
Confidence Intervals
Mycophenolic Acid
Antimetabolites
Dapsone
Vital Statistics
Eye Diseases
Alkylating Agents
Azathioprine
Survival Analysis
Methotrexate
Cyclophosphamide
Cyclosporine

ASJC Scopus subject areas

  • Medicine(all)

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Overall and cancer related mortality among patients with ocular inflammation treated with immunosuppressive drugs : Retrospective cohort study. / Kempen, John H.; Daniel, Ebenezer; Dunn, James P.; Foster, C. Stephen; Gangaputra, Sapna; Hanish, Asaf; Helzlsouer, Kathy J.; Jabs, Douglas; Kaçmaz, R. Oktay; Levy-Clarke, Grace A.; Liesegang, Teresa L.; Newcomb, Craig W.; Nussenblatt, Robert B.; Pujari, Siddharth S.; Rosenbaum, James T.; Suhler, Eric B.; Thorne, Jennifer.

In: BMJ (Online), Vol. 339, No. 7712, 11.07.2009, p. 89-92.

Research output: Contribution to journalArticle

Kempen, JH, Daniel, E, Dunn, JP, Foster, CS, Gangaputra, S, Hanish, A, Helzlsouer, KJ, Jabs, D, Kaçmaz, RO, Levy-Clarke, GA, Liesegang, TL, Newcomb, CW, Nussenblatt, RB, Pujari, SS, Rosenbaum, JT, Suhler, EB & Thorne, J 2009, 'Overall and cancer related mortality among patients with ocular inflammation treated with immunosuppressive drugs: Retrospective cohort study', BMJ (Online), vol. 339, no. 7712, pp. 89-92.
Kempen JH, Daniel E, Dunn JP, Foster CS, Gangaputra S, Hanish A et al. Overall and cancer related mortality among patients with ocular inflammation treated with immunosuppressive drugs: Retrospective cohort study. BMJ (Online). 2009 Jul 11;339(7712):89-92.
Kempen, John H. ; Daniel, Ebenezer ; Dunn, James P. ; Foster, C. Stephen ; Gangaputra, Sapna ; Hanish, Asaf ; Helzlsouer, Kathy J. ; Jabs, Douglas ; Kaçmaz, R. Oktay ; Levy-Clarke, Grace A. ; Liesegang, Teresa L. ; Newcomb, Craig W. ; Nussenblatt, Robert B. ; Pujari, Siddharth S. ; Rosenbaum, James T. ; Suhler, Eric B. ; Thorne, Jennifer. / Overall and cancer related mortality among patients with ocular inflammation treated with immunosuppressive drugs : Retrospective cohort study. In: BMJ (Online). 2009 ; Vol. 339, No. 7712. pp. 89-92.
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T1 - Overall and cancer related mortality among patients with ocular inflammation treated with immunosuppressive drugs

T2 - Retrospective cohort study

AU - Kempen, John H.

AU - Daniel, Ebenezer

AU - Dunn, James P.

AU - Foster, C. Stephen

AU - Gangaputra, Sapna

AU - Hanish, Asaf

AU - Helzlsouer, Kathy J.

AU - Jabs, Douglas

AU - Kaçmaz, R. Oktay

AU - Levy-Clarke, Grace A.

AU - Liesegang, Teresa L.

AU - Newcomb, Craig W.

AU - Nussenblatt, Robert B.

AU - Pujari, Siddharth S.

AU - Rosenbaum, James T.

AU - Suhler, Eric B.

AU - Thorne, Jennifer

PY - 2009/7/11

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N2 - Context: Whether immunosuppressive treatment adversely affects survival is unclear. Objective: To assess whether immunosuppressive drugs increase mortality. Design: Retrospective cohort study evaluating overall and cancer mortality in relation to immunosuppressive drug exposure among patients with ocular inflammatory diseases. Demographic, clinical, and treatment data derived from medical records, and mortality results from United States National Death Index linkage. The cohort's mortality risk was compared with US vital statistics using standardised mortality ratios. Overall and cancer mortality in relation to use or non-use of immunosuppressive drugs within the cohort was studied with survival analysis. Setting: Five tertiary ocular inflammation clinics. Patients: 7957 US residents with non-infectious ocular inflammation, 2340 of whom received immunosuppressive drugs during follow up. Exposures: Use of antimetabolites, T cell inhibitors, alkylating agents, and tumour necrosis factor inhibitors. Main outcome measures: Overall mortality, cancer mortality. Results: Over 66 802 person years (17 316 after exposure to immunosuppressive drugs), 936 patients died (1.4/ 100 person years), 230 (24.6%) from cancer. For patients unexposed to immunosuppressive treatment, risks of death overall (standardised mortality ratio 1.02, 95% confidence interval [CI] 0.94 to 1.11) and from cancer (1.10, 0.93 to 1.29) were similar to those of the US population. Patients who used azathioprine, methotrexate, mycophenolate mofetil, ciclosporin, systemic corticosteroids, or dapsone had overall and cancer mortality similar to that of patients who never took immunosuppressive drugs. In patients who used cyclophosphamide, overall mortality was not increased and cancer mortality was non-significantly increased. Tumour necrosis factor inhibitors were associated with increased overall (adjusted hazard ratio [HR] 1.99, 95% CI 1.00 to 3.98) and cancer mortality (adjusted HR 3.83, 1.13 to 13.01). Conclusions: Most commonly used immunosuppressive drugs do not seem to increase overall or cancer mortality. Our results suggesting that tumour necrosis factor inhibitors might increase mortality are less robust than the other findings; additional evidence is needed.

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