Cyclophosphamide for Ocular Inflammatory Diseases

doi:10.1016/j.ophtha.2009.06.060

Ophthalmology

Volume 117, Issue 2, February 2010, Pages 356-365

https://doi.org/10.1016/j.ophtha.2009.06.060 Get rights and content

Purpose

To evaluate the outcomes of cyclophosphamide therapy for noninfectious ocular inflammation.

Design

Retrospective cohort study.

Participants

Two hundred fifteen patients with noninfectious ocular inflammation observed from initiation of cyclophosphamide.

Methods

Patients 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 Measures

Control of inflammation, corticosteroid-sparing effects, and discontinuation of therapy.

Results

The 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.

Conclusions

The 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.

Section snippets

Study Population

The Systemic Immunosuppressive Therapy for Eye Diseases Cohort Study is a multicenter cohort study for identifying long-term treatment adverse events, the methods of which have been described previously.³³ For this report, all patients at 3 academic subspecialty centers with noninfectious ocular inflammation since the inception of the center and an approximate 40% random sample of such patients from a fourth center potentially were eligible. Sampling was carried out because of logistical

Results

Two hundred fifteen patients (77.2% with bilateral ocular inflammation; 381 eyes) were identified who started cyclophosphamide as a single immunosuppressive agent during follow-up, with or without local or systemic corticosteroids and nonsteroidal anti-inflammatory drugs. The demographic and clinical characteristics of this cohort are summarized in Table 1. The overall median age was 61.3 years (range, 11.5–91.4 years). Most patients were white (83.3%) and female (58.1%). The patients with

Discussion

This report confirms the beneficial effects of cyclophosphamide therapy for ocular inflammation. Cyclophosphamide was successful in achieving complete control of inflammation in 49.2% and 76.3% by 6 months and 12 months, respectively. Similarly, corticosteroid-sparing success (sustained control of inflammation while tapering prednisone to 10 mg or less) was gained by 30.1% and 61.2% by 6 and 12 months, respectively. At or before 2 years after initiation of treatment, 63% were able to

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: Manuscript no. 2009-399.

: 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.

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Original articleCyclophosphamide for Ocular Inflammatory Diseases

Purpose

Design

Participants

Methods

Main Outcome Measures

Results

Conclusions

Financial Disclosure(s)

Section snippets

Study Population

Results

Discussion

Am J Ophthalmol

Am J Ophthalmol

Surv Ophthalmol

Best Pract Res Clin Rheumatol

Presse Med

Joint Bone Spine

Ophthalmology

Rev Med Interne

Surv Ophthalmol

J Fr Ophtalmol

Am J Ophthalmol

Ophthalmology

Am J Ophthalmol

Ophthalmology

Ophthalmology

Lancet

Ophthalmology

Am J Med

Treatment of uveitis: overview

Nitrogen mustard therapy of uveitis of unknown etiology [undetermined language]

Rev Clin Esp

Immunosuppressive drugs

Treatment of patients with Wegener's granulomatosis or ANCA-associated vasculitis [in Dutch]

Ned Tijdschr Geneeskd

Wegener's granulomatosis

Curr Opin Rheumatol

Ocular manifestations of Wegener's granulomatosis: analysis of nine cases

Indian J Ophthalmol

Diagnosis and management of systemic Wegener's granulomatosis presenting with anterior ocular inflammatory disease

Br J Ophthalmol

Ocular involvement in Wegener's granulomatosis responding to intravenous cyclophosphamide [letter]

Rheumatology (Oxford)

Wegener's granulomatosis: prospective clinical and therapeutic experience with 85 patients for 21 years

Ann Intern Med

Influence of disease manifestation and antineutrophil cytoplasmic antibody titer on the response to pulse cyclophosphamide therapy in patients with Wegener's granulomatosis

Arthritis Rheum

Diagnosis and therapy of Wegener's granulomatosis based on ocular changes [in Czech]

Cesk Slov Oftalmol

Disease-modifying antirheumatic drugs: using their clinical pharmacological effects as a guide to their selection

Drugs

Polyarteritis nodosa revisited

Curr Rheumatol Rep

New concepts for the therapy of systemic lupus erythematosus [in French]

Rev Med Suisse

Original article
Cyclophosphamide for Ocular Inflammatory Diseases