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Multicenter Study
. 2009 Jul 3:339:b2480.
doi: 10.1136/bmj.b2480.

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

John H Kempen  1 , Ebenezer Daniel, James P Dunn, C Stephen Foster, Sapna Gangaputra, Asaf Hanish, Kathy J Helzlsouer, Douglas A 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 E Thorne
Affiliations
Multicenter Study

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

John H Kempen et al. BMJ. .

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.

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Conflict of interest statement

Competing interests: JTR has received ≤$10 000 for consulting fees or paid advisory boards for Abbott Laboratories (ciclosporin, adalimumab) and Novartis (ciclosporin), and has a research grant from Abbott Laboratories; EBS has received a research grant from Abbott Laboratories; DAJ has received ≤$10 000 for consulting fees or paid advisory boards for Novartis. JTR and EBS have received a research grant from Centocor (infliximab); CSF reports having received fees of ≤$10 000 for speaking at the invitation of Centocor. JTR reports equity ownership/stock options >$10 000 in Amgen (etanercept). JHK, JPD, CSF, JTR, and EBS previously participated in a clinical trial of a competing product, fluocinolone acetonide implant, sponsored by Bausch & Lomb; JHK, JPD, CSF, DAJ, RBN, and JET are participating in an NIH-sponsored study comparing this product with systemic therapy for uveitis, and GAL-C previously participated in this trial; Bausch & Lomb is providing a limited amount of drug product in support of this study.

Figures

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Fig 1 Study profile
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Fig 2 Adjusted relative hazard of all cause mortality for each immunosuppressive agent and class of agents studied
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Fig 3 Adjusted relative hazard of mortality attributed to cancer for each immunosuppressive agent and class of agents studied
See this image and copyright information in PMC

Comment in

References

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