Methotrexate for Ocular Inflammatory Diseases

Received 15 October 2008; received in revised form 4 April 2009; accepted 7 April 2009. published online 14 September 2009.

Purpose

To evaluate the outcome of treatment with methotrexate for noninfectious ocular inflammation.

Design

Retrospective cohort study.

Participants

Patients with noninfectious ocular inflammation managed at 4 tertiary ocular inflammation clinics in the United States observed to add methotrexate as a single, noncorticosteroid immunosuppressive agent to their treatment regimen, between 1979 and 2007, inclusive.

Methods

Participants were identified from the Systemic Immunosuppressive Therapy for Eye Diseases Cohort Study. Demographic and clinical characteristics, including dosage, route of administration of methotrexate, and main outcome measures, were obtained for every eye of every patient at every visit via medical record review by trained expert reviewers.

Main Outcome Measures

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

Results

Among 384 patients (639 eyes) observed from the point of addition of methotrexate to an anti-inflammatory regimen, 32.8%, 9.9%, 21.4%, 14.6%, 15.1%, and 6.3%, respectively, had anterior uveitis, intermediate uveitis, posterior or panuveitis, scleritis, ocular mucous membrane pemphigoid, and other forms of ocular inflammation. In these groups, complete suppression of inflammation sustained for ≥28 days was achieved within 6 months in 55.6%, 47.4%, 38.6%, 56.4%, 39.5%, and 76.7%, respectively. Corticosteroid-sparing success (sustained suppression of inflammation with prednisone ≤10 mg/d) was achieved within 6 months among 46.1%, 41.3%, 20.7%, 37.3%, 36.5%, and 50.9%, respectively. Overall, success within 12 months was 66% and 58.4% for sustained control and corticosteroid sparing (≤10 mg), respectively. Methotrexate was discontinued within 1 year by 42% of patients. It was discontinued owing to ineffectiveness in 50 patients (13%); 60 patients (16%) discontinued because of side effects, which typically were reversible with dose reduction or discontinuation. Remission was seen in 43 patients, with 7.7% remitting within 1 year of treatment.

Conclusions

Our data suggest that adding methotrexate to an anti-inflammatory regimen not involving other noncorticosteroid immunosuppressive drugs is moderately effective for management of inflammatory activity and for achieving corticosteroid-sparing objectives, although many months may be required for therapeutic success. Methotrexate was well tolerated by most patients, and seems to convey little risk of serious side effects during treatment.

Financial Disclosure(s)

The authors have no proprietary or commercial interests in any of the materials discussed in this article.

Available online: September 12, 2009.

1 The Fundus Photograph Reading Center, Department of Ophthalmology, University of Wisconsin, Madison, Wisconsin

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

3 Department Epidemiology, The Johns Hopkins University, Baltimore, Maryland

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

5 The Department of Biostatistics and Epidemiology, The University of Pennsylvania, Philadelphia, Pennsylvania

6 The Department Ophthalmology, The University of Pennsylvania, Philadelphia, Pennsylvania

7 The Department of Ophthalmology, Oregon Health & Science University, Portland, Oregon

8 The Department of Medicine, Oregon Health & Science University, Portland, Oregon

9 The Massachusetts Eye Research and Surgery Institute, Cambridge, Massachusetts

10 The Department of Ophthalmology, The Mount Sinai School of Medicine, New York, New York

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

12 The Laboratory of Immunology, National Eye Institute, Bethesda, Maryland

13 The Portland Veterans' Affairs Medical Center, Portland, Oregon

14 The 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

Manuscript no. 2008-1221.

Financial Disclosure(s): The authors have no proprietary or commercial interest in any of the materials discussed in this article.

Supported primarily by National Eye Institute Grant EY014943 (JHK). Additional support was provided by Research to Prevent Blindness and the Paul and Evanina Mackall Foundation. 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 was previously supported by and Dr Nussenblatt continues to be supported by intramural funds of the National Eye Institute.

PII: S0161-6420(09)00373-X

doi:10.1016/j.ophtha.2009.04.020

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