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

doi:10.1136/bmj.b2480

Published 3 July 2009, doi:10.1136/bmj.b2480
Cite this as: BMJ 2009;339:b2480

Research

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

John H Kempen, associate professor of ophthalmology and epidemiology ¹^,2^,3, Ebenezer Daniel, instructor in ophthalmology ²^,4, James P Dunn, associate professor of ophthalmology⁴, C Stephen Foster, clinical professor of ophthalmology⁶^,7, Sapna Gangaputra, associate researcher in ophthalmology⁴^,8, Asaf Hanish, biostatistical programmer³, Kathy J Helzlsouer, professor of epidemiology⁵^,9, Douglas A Jabs, professor of ophthalmology⁴^,5^,10^,11, R Oktay Kaçmaz, research fellow in ophthalmology⁶^,10, Grace A Levy-Clarke, ophthalmologist¹²^,13, Teresa L Liesegang, research coordinator¹⁴, Craig W Newcomb, biostatistician³, Robert B Nussenblatt, chief of laboratory of immunology¹², Siddharth S Pujari, research fellow in ophthalmology⁶, James T Rosenbaum, professor of ophthalmology, medicine, and cell biology ¹⁴^,15^,16, Eric B Suhler, associate professor of ophthalmology¹⁴^,17, Jennifer E Thorne, associate professor of ophthalmology and epidemiology⁴^,5

¹ Ocular Inflammation Service, Scheie Eye Institute, University of Pennsylvania, Philadelphia, PA, USA, ² Center for Preventive Ophthalmology and Biostatistics, Department of Ophthalmology, University of Pennsylvania, ³ Center for Clinical Epidemiology and Biostatistics, Department of Biostatistics and Epidemiology, University of Pennsylvania, ⁴ Department of Ophthalmology, Johns Hopkins University, Baltimore, MD, USA, ⁵ Department of Epidemiology, Johns Hopkins University, ⁶ Massachusetts Eye Research and Surgery Institute, Cambridge, MA, USA, ⁷ Department of Ophthalmology, Harvard Medical School, Boston, MA, USA, ⁸ Fundus Photograph Reading Center, Department of Ophthalmology, University of Wisconsin, Madison, WI, USA, ⁹ Center for Prevention and Research at Mercy, Mercy Medical Center, Baltimore, ¹⁰ Department of Ophthalmology, Mount Sinai School of Medicine, New York, NY, USA, ¹¹ Department of Medicine, Mount Sinai School of Medicine, ¹² Laboratory of Immunology, National Eye Institute, Bethesda, MD, USA, ¹³ St Luke’s Cataract and Laser Institute, Tarpon Springs, FL, USA, ¹⁴ Department of Ophthalmology, Oregon Health and Science University, Portland, OR, USA, ¹⁵ Department of Medicine, Oregon Health and Science University, ¹⁶ Department of Cell Biology, Oregon Health and Science University, ¹⁷ Portland Veterans’ Affairs Medical Center, Portland

Correspondence to: J H Kempen, Center for Preventive Ophthalmology and Biostatistics, Department of Ophthalmology, University of Pennsylvania, Philadelphia, PA 19104, USA john.kempen{at}uphs.upenn.edu

Context Whether immunosuppressive treatment adversely affectssurvival is unclear.

Objective To assess whether immunosuppressive drugs increasemortality.

Design Retrospective cohort study evaluating overall and cancermortality in relation to immunosuppressive drug exposure amongpatients with ocular inflammatory diseases. Demographic, clinical,and treatment data derived from medical records, and mortalityresults from United States National Death Index linkage. Thecohort’s mortality risk was compared with US vital statisticsusing standardised mortality ratios. Overall and cancer mortalityin relation to use or non-use of immunosuppressive drugs withinthe 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 followup.

Exposures Use of antimetabolites, T cell inhibitors, alkylatingagents, and tumour necrosis factor inhibitors.

Main outcome measures Overall mortality, cancer mortality.

Results Over 66 802 person years (17 316 after exposure to immunosuppressivedrugs), 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. Patientswho used azathioprine, methotrexate, mycophenolate mofetil,ciclosporin, systemic corticosteroids, or dapsone had overalland cancer mortality similar to that of patients who never tookimmunosuppressive drugs. In patients who used cyclophosphamide,overall mortality was not increased and cancer mortality wasnon-significantly increased. Tumour necrosis factor inhibitorswere associated with increased overall (adjusted hazard ratio[HR] 1.99, 95% CI 1.00 to 3.98) and cancer mortality (adjustedHR 3.83, 1.13 to 13.01).

Conclusions Most commonly used immunosuppressive drugs do notseem to increase overall or cancer mortality. Our results suggestingthat tumour necrosis factor inhibitors might increase mortalityare less robust than the other findings; additional evidenceis needed.

© Kempen et al 2009
This is an open-access article distributed under the terms of the Creative Commons Attribution Non-commercial License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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