Ophthalmic evaluations in clinical studies of fingolimod (FTY720) in multiple
sclerosis.
Author(s): Zarbin MA(1), Jampol LM, Jager RD, Reder AT, Francis G, Collins W, Tang D, Zhang
X.
Affiliation(s): Author information:
(1)Institute of Ophthalmology & Visual Science, New Jersey Medical School, Newark,
New Jersey 07103, USA. zarbin@earthlink.net
Publication date & source: 2013, Ophthalmology. , 120(7):1432-9
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.
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