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Previous Volume 355:1124-1140 September 14, 2006 Number 11 Next

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ABSTRACT

Background Fingolimod (FTY720) is a new oral immunomodulating agent under evaluation for the treatment of relapsing multiple sclerosis.

Methods We randomly assigned 281 patients to receive oral fingolimod, at a dose of 1.25 mg or 5.0 mg, or a placebo once daily, and we followed these patients for 6 months with magnetic resonance imaging (MRI) and clinical evaluations (core study, months 0 to 6). The primary end point was the total number of gadolinium-enhanced lesions recorded on T₁-weighted MRI at monthly intervals for 6 months. In an extension study in which the investigators and patients remained unaware of the dose assignments (months 7 to 12), patients who received placebo underwent randomization again to one of the fingolimod doses.

Results A total of 255 patients completed the core study. The median total number of gadolinium-enhanced lesions on MRI was lower with 1.25 mg of fingolimod (1 lesion, P<0.001) and 5.0 mg of fingolimod (3 lesions, P=0.006) than with placebo (5 lesions). The annualized relapse rate was 0.77 in the placebo group, as compared with 0.35 in the group given 1.25 mg of fingolimod (P=0.009) and 0.36 in the group given 5.0 mg of fingolimod (P=0.01). For the 227 patients who completed the extension study, the number of gadolinium-enhanced lesions and relapse rates remained low in the groups that received continuous fingolimod, and both measures decreased in patients who switched from placebo to fingolimod. Adverse events included nasopharyngitis, dyspnea, headache, diarrhea, and nausea. Clinically asymptomatic elevations of alanine aminotransferase levels were more frequent with fingolimod (10 to 12%, vs. 1% in the placebo group). One case of the posterior reversible encephalopathy syndrome occurred in the 5.0-mg group. Fingolimod was also associated with an initial reduction in the heart rate and a modest decrease in the forced expiratory volume in 1 second.

Conclusions In this proof-of-concept study, fingolimod reduced the number of lesions detected on MRI and clinical disease activity in patients with multiple sclerosis. Evaluation in larger, longer-term studies is warranted. (Clinicaltrials.gov numbers, NCT00333138 [ClinicalTrials.gov] [core study] and NCT00235430 [ClinicalTrials.gov] [extension].)

Source Information

From the Departments of Neurology and Research, University Hospital, Basel, Switzerland (L.K.); Le Centre Universitaire de Santé McGill, Montreal Neurological Institute, McGill University, Montreal (J.A.); Neurology Clinic, San Raffaele Hospital, University Vita e Salute, Milan (G.C.); Neuroimmunology Unit, Hospital Vall d'Hebron, Barcelona (X.M.); Division of Neurology, St. Michael's Hospital, Toronto (P.O.); Department of Neurology, Vrije Universiteit Medical Center, Amsterdam (C.H.P.); Biostatistics and Statistical Reporting (T.H.) and Clinical Development and Medical Affairs (G.K.), Novartis Pharma, Basel, Switzerland; Clinical Development and Medical Affairs, Novartis Pharmaceuticals, East Hanover, NJ (A.A.K.); and Neuroradiology and MS-MRI Evaluation Center, University Hospital, Basel, Switzerland (E.W.R.).

Address reprint requests to Dr. Kappos at the Departments of Neurology and Research, University Hospital, Petersgraben 4, 4031 Basel, Switzerland, or at lkappos{at}uhbs.ch.

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