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

Ophthalmology. 2013 Jul;120(7):1432-9. doi: 10.1016/j.ophtha.2012.12.040. Epub 2013 Mar 24.

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.

Trial registration: ClinicalTrials.gov NCT00235430 NCT00289978 NCT00333138 NCT00340834.

Publication types

  • Case Reports
  • Clinical Trial, Phase II
  • Clinical Trial, Phase III
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Double-Blind Method
  • Female
  • Fingolimod Hydrochloride
  • Fluorescein Angiography
  • Humans
  • Immunosuppressive Agents / adverse effects*
  • Immunosuppressive Agents / therapeutic use
  • Macular Edema / chemically induced*
  • Macular Edema / diagnosis
  • Macular Edema / physiopathology
  • Male
  • Middle Aged
  • Multiple Sclerosis / drug therapy*
  • Ophthalmoscopy
  • Propylene Glycols / adverse effects*
  • Propylene Glycols / therapeutic use
  • Sphingosine / adverse effects
  • Sphingosine / analogs & derivatives*
  • Sphingosine / therapeutic use
  • Tomography, Optical Coherence
  • Treatment Outcome
  • Uveitis / complications
  • Visual Acuity / physiology
  • Young Adult

Substances

  • Immunosuppressive Agents
  • Propylene Glycols
  • Fingolimod Hydrochloride
  • Sphingosine

Associated data

  • ClinicalTrials.gov/NCT00235430
  • ClinicalTrials.gov/NCT00289978
  • ClinicalTrials.gov/NCT00333138
  • ClinicalTrials.gov/NCT00340834