Long-term Risk of Malignancy Among Patients Treated With Immunosuppressive Agents for Ocular Inflammation: A Critical Assessment of the Evidence

Accepted 29 April 2008. published online 06 June 2008.

Purpose

To critically assess potentially carcinogenic effects of immunosuppressive therapy in the ocular inflammation setting.

Design

Focused evidence assessment.

Methods

Relevant publications were identified by MEDLINE and EMBASE queries and reference list searches.

Results

Extrapolation from transplant, rheumatology, skin disease, and inflammatory bowel disease cohorts to the ocular inflammation setting suggest that: 1) alkylating agents increase hematologic malignancy risk and cyclophosphamide increases bladder cancer risk, but less so with ≤18 months' duration of therapy and hydration, respectively; 2) calcineurin inhibitors and azathioprine probably do not increase total cancer risk to a detectable degree, except perhaps some other risk factors (uncommon in ocular inflammation patients) might interact with the former to raise risk; 3) tumor necrosis factor (TNF) inhibitors may accelerate diagnosis of cancer in the first six to 12 months, but probably do not increase long-term cancer risk; and 4) changes in risk with methotrexate, mycophenolate mofetil, and daclizumab appear negligible, although nontransplant data are limited for the latter agents. Immunosuppression in general may increase skin cancer risk in a sun exposure–dependent manner.

Conclusion

Use of alkylating agents for a limited duration seems justifiable for severe, vision-threatening disease, but otherwise cancer risk may be a relevant constraint on use of this approach. Antimetabolites, daclizumab, TNF inhibitors, and calcineurin inhibitors probably do not increase cancer risk to a degree that outweighs the expected benefits of therapy. Monitoring for skin cancer may be useful for highly sun-exposed patients. Data from ocular inflammation patients are needed to confirm the conclusions made in this analysis by extrapolation.

a Ocular Inflammation Service, Scheie Eye Institute, The University of Pennsylvania, Philadelphia, Pennsylvania

b Center for Preventive Ophthalmology and Biostatistics, Department of Ophthalmology, The University of Pennsylvania, Philadelphia, Pennsylvania

c Center for Clinical Epidemiology and Biostatistics, Department of Biostatistics and Epidemiology, The University of Pennsylvania, Philadelphia, Pennsylvania

d Department of Ophthalmology, The Johns Hopkins University, Baltimore, Maryland

e Department of Epidemiology, The Johns Hopkins University, Baltimore, Maryland

f St Luke's Cataract and Laser Institute, Tarpon Springs, Florida

g Laboratory of Immunology, National Eye Institute, Bethesda, Maryland

h Department of Ophthalmology, Oregon Health and Science University, Portland, Oregon

i Department of Medicine, Oregon Health and Science University, Portland, Oregon

j Portland Veterans' Affairs Medical Center, Portland, Oregon

k Massachusetts Eye Research and Surgery Institute, Cambridge, Massachusetts

l Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts

m Department of Ophthalmology, Mount Sinai School of Medicine, New York, New York

n Center for Prevention and Research at Mercy, Mercy Medical Center, Baltimore, Maryland

Inquiries to John H. Kempen, Center for Preventive Ophthalmology and Biostatistics, Department of Ophthalmology, University of Pennsylvania, 3535 Market St., Suite 700, Philadelphia, PA 19104

PII: S0002-9394(08)00337-1

doi:10.1016/j.ajo.2008.04.035

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