| | Cyclophosphamide for Ocular Inflammatory DiseasesReceived 22 March 2009; received in revised form 22 May 2009; accepted 24 June 2009. published online 07 December 2009. PurposeTo evaluate the outcomes of cyclophosphamide therapy for noninfectious ocular inflammation. DesignRetrospective cohort study. ParticipantsTwo hundred fifteen patients with noninfectious ocular inflammation observed from initiation of cyclophosphamide. MethodsPatients initiating cyclophosphamide, without other immunosuppressive drugs (other than corticosteroids), were identified at 4 centers. Dose of cyclophosphamide, response to therapy, corticosteroid-sparing effects, frequency of discontinuation, and reasons for discontinuation were obtained by medical record review of every visit. Main Outcome MeasuresControl of inflammation, corticosteroid-sparing effects, and discontinuation of therapy. ResultsThe 215 patients (381 involved eyes) meeting eligibility criteria carried diagnoses of uveitis (20.4%), scleritis (22.3%), ocular mucous membrane pemphigoid (45.6%), or other forms of ocular inflammation (11.6%). Overall, approximately 49.2% (95% confidence interval [CI], 41.7%–57.2%) gained sustained control of inflammation (for at least 28 days) within 6 months, and 76% (95% CI, 68.3%–83.7%) gained sustained control of inflammation within 12 months. Corticosteroid-sparing success (sustained control of inflammation while tapering prednisone to 10 mg or less among those not meeting success criteria initially) was gained by 30.0% and 61.2% by 6 and 12 months, respectively. Disease remission leading to discontinuation of cyclophosphamide occurred at the rate of 0.32/person-year (95% CI, 0.24–0.41), and the estimated proportion with remission at or before 2 years was 63.1% (95% CI, 51.5%–74.8%). Cyclophosphamide was discontinued by 33.5% of patients within 1 year because of side effects, usually of a reversible nature. ConclusionsThe data suggest that cyclophosphamide is effective for most patients for controlling inflammation and allowing tapering of systemic corticosteroids to 10 mg prednisone or less, although 1 year of therapy may be needed to achieve these goals. Unlike with most other immunosuppressive drugs, disease remission was induced by treatment in most patients who were able to tolerate therapy. To titrate therapy properly and to minimize the risk of serious potential side effects, a systematic program of laboratory monitoring is required. Judicious use of cyclophosphamide seems to be beneficial for severe ocular inflammation cases where the potentially vision-saving benefits outweigh the substantial potential side effects of therapy, or when indicated for associated systemic inflammatory diseases. Financial Disclosure(s)Proprietary or commercial disclosure may be found after the references. Available online: December 6, 2009. 1 The Massachusetts Eye Research and Surgery Institution, Cambridge, Massachusetts 2 Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania, Philadelphia, Pennsylvania 3 Departments of Biostatistics & Epidemiology, University of Pennsylvania, Philadelphia, Pennsylvania 4 Department of Ophthalmology, University of Pennsylvania, Philadelphia, Pennsylvania 5 The Fundus Photograph Reading Center, Department of Ophthalmology, University of Wisconsin, Madison, Wisconsin 6 Department of Ophthalmology, The Johns Hopkins University, Baltimore, Maryland 7 Department of Ophthalmology, Oregon Health & Science University, Portland, Oregon 8 Portland Veterans' Affairs Medical Center, Portland, Oregon 9 Department of Epidemiology, The Johns Hopkins University, Baltimore, Maryland 10 Department of Ophthalmology, Mount Sinai School of Medicine, New York, New York 11 Department of Medicine, Mount Sinai School of Medicine, New York, New York 12 St. Luke's Cataract and Laser Institute, Tarpon Springs, Florida 13 Laboratory of Immunology, National Eye Institute, Bethesda, Maryland 14 Department of Medicine, Oregon Health & Science University, Portland, Oregon 15 Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts  Correspondence: John H. Kempen, MD, PhD, Center for Preventive Ophthalmology and Biostatistics, Department of Ophthalmology, University of Pennsylvania, 3535 Market Street, Suite 700, Philadelphia, PA 19104
Financial Disclosure(s): The author(s) have made the following disclosure(s): C. Stephen Foster - Equity Owner - Eyegate; Consultant, Lecturer - Allergan, Bausch & Lomb; Consultant - Sirion; Lecturer - Alcon, Inspire, Ista, Centocor Douglas A. Jabs - Consultant - Roche, Genzyme Corporation, Novartis, Allergan, Glaxo Smith Kline, Applied Genetic Technologies Corporation, The Emmes Corporation, The Johns Hopkins Dana Center for Preventive Ophthalmology John H. Kempen - Consultant - Lux Biosciences James Rosenbaum - Equity Owner - Amgen; Consultant - Abbott, ESBATech, Lux Biosciences, Centocor, Genentech Supported primarily by the National Eye Institute, Bethesda, Maryland (grant no.: EY014943 [JHK]). Additional support was provided by Research to Prevent Blindness, Inc., New York, New York, and the Paul and Evanina Mackall Foundation, New York, NY. Dr Kempen is a Research to Prevent Blindness James S. Adams Special Scholar Award recipient. Drs. Jabs and Rosenbaum are Research to Prevent Blindness Senior Scientific Investigator Award recipients. Dr. Thorne is a Research to Prevent Blindness Harrington Special Scholar Award recipient. Dr Levy-Clarke previously was supported by and Dr. Nussenblatt continues to be supported by intramural funds of the National Eye Institute. Dr Suhler also received support from the Veterans' Administration, Washington, DC. None of the sponsors had any role in the design and conduct of the report; collection, management, analysis, and interpretation of the data; nor in the preparation, review, and approval of this manuscript. PII: S0161-6420(09)00735-0 doi:10.1016/j.ophtha.2009.06.060 © 2010 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved. | |
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