- 作者：Marco A. Zarbin ; Lee M. Jampol ; Rama D. Jager ; Anthony T. Reder ; Gordon Francis ; William Collins ; Dejun Tang ; Xiaoli Zhang
- 刊名：Ophthalmology
- 出版年：2013
- 出版时间：July, 2013
- 年：2013
- 卷：120
- 期：7
- 页码：1432-1439
- 全文大小：1534 K
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.