Ophthalmic evaluations in clinical studies of fingolimod (FTY720) in multiple sclerosis

Marco A. Zarbin*, Lee M. Jampol, Rama D. Jager, Anthony T. Reder, Gordon Francis, William Collins, Dejun Tang, Xiaoli Zhang

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

123 Scopus citations

Abstract

Purpose: To report outcomes of ophthalmic evaluations in clinical studies of patients receiving fingolimod (Gilenya; Novartis Pharma AG, Basel, Switzerland) for multiple sclerosis (MS). Design: Analysis done on pooled safety data (N = 2615, all studies group) from 3 double-masked, randomized, parallel-group clinical trials (phase 2 core and extension >5 years, and phase 3 FREEDOMS and TRANSFORMS core and extension studies). Participants: Patients aged 18 to 55 years (18-60 years in phase 2 study) diagnosed with relapsing-remitting MS were included. Patients with diabetes mellitus or macular edema (ME) at screening were excluded. Intervention: Participants received fingolimod (0.5/1.25 mg), placebo, or interferon beta for the respective study durations. Ophthalmic examination included detailed eye history (at screening), visual acuity (VA) assessment, dilated ophthalmoscopy, optical coherence tomography (OCT), and fluorescein angiography (FA). Main Outcome Measures: Extensive ophthalmic monitoring was performed for all patients. While being studied, patients with abnormal findings on dilated ophthalmoscopy and OCT compatible with ME were further studied by FA. All locally diagnosed ME cases were centrally reviewed by the retina specialist (M.A.Z.) on the Data and Safety Monitoring Board. Results: Among 2615 patients assessed, 19 confirmed ME cases were observed in fingolimod-treated groups (0.5 mg: n = 4, 0.3%; 1.25 mg: n = 15, 1.2%). Most patients (n = 13, 68%) presented with blurred vision, decreased VA, or eye pain. Macular edema was diagnosed within 3 to 4 months of treatment initiation in most cases (n = 13, 68%); 2 patients had late onset (>12 months) ME. Of the 19 patients with ME, 5 (26%), all treated with fingolimod 1.25 mg, had a history of uveitis compared with 26 (1%) in the all studies group. In most cases (n = 16, 84%), ME resolved after discontinuing the study drug. Eleven patients required topical anti-inflammatory medications. No patient had further vision deterioration. Conclusions: Fingolimod 0.5 mg is associated with a low incidence of ME in MS studies. Patients with a history of uveitis may be at an increased risk of developing ME. An ophthalmic examination before initiating fingolimod therapy and regular follow-up eye examinations during fingolimod therapy are recommended. Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references.

Original languageEnglish (US)
Pages (from-to)1432-1439
Number of pages8
JournalOphthalmology
Volume120
Issue number7
DOIs
StatePublished - Jul 2013

Funding

Funding: The studies were funded by Novartis Pharma AG (Basel, Switzerland) and are registered with Clinicaltrials.gov (Phase 2 core: NCT00333138 ; Phase 2 extension study: NCT00235430 ; FREEDOMS and extension study: NCT00289978 ; TRANSFORMS and extension study: NCT00340834 ). The sponsor participated in the design of the study, conducting the study, data collection, data management, and data analysis, interpretation of the data, preparation, and review and approval of the manuscript. Supported in part by unrestricted grants from the Research to Prevent Blindness, Inc. (New Jersey Medical School, Northwestern University) , the Eye Institute of New Jersey , and the NJ Lions Eye Research Foundation .

ASJC Scopus subject areas

  • Ophthalmology

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