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Phase II study of oral fingolimod (FTY720) in multiple sclerosis: 3-year results. Mult Scler

Department of Neurology, Università Vita-Salute San Raffaele, Milan, Italy.
Multiple Sclerosis (Impact Factor: 4.86). 12/2009; 16(2):197-207. DOI: 10.1177/1352458509357065
Source: PubMed

ABSTRACT In a 6-month, placebo-controlled trial, oral fingolimod (FTY720) 1.25 or 5.0 mg, once daily, significantly reduced MRI inflammatory activity and annualized relapse rate compared with placebo in patients with relapsing multiple sclerosis (MS). The objectives were to monitor the 36-month, interim efficacy and safety results of the ongoing extension of this study. In the extension (months 7-36), placebo-treated patients were re-randomized to either dose of fingolimod; fingolimod-treated patients continued at the same dose. During months 15-24, all patients receiving fingolimod 5.0 mg switched to 1.25 mg. Of the 250 patients who entered the extension study, 173 (69%) continued to month 36. Most patients were free from gadolinium-enhanced lesions (88-89%) or new T2 lesions (70-78%) at month 36. Patients receiving continuous fingolimod treatment had sustained low annualized relapse rates of 0.20-0.21, and 68-73% remained relapse-free at month 36. Over 36 months, nasopharyngitis (34%), headache (30%), fatigue (19%) and influenza (18%) were the most commonly reported adverse events. Pulmonary function remained stable and blood pressure was stable after an initial increase (3-5 mmHg) during the first 6 months of fingolimod treatment; serious adverse events included infections and skin cancer. The low MRI and clinical disease activity at 6 months were maintained at 36 months with fingolimod, which was generally well tolerated by most patients. The efficacy and safety of oral fingolimod are being further evaluated in a large phase III MS study programme.

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    • "In clinical practice, due to its presumed superiority over interferon beta, fingolimod is one of the first line therapeutic choices for highly active RRMS. Besides the positive effect on clinical outcome, previous clinical trials (Kappos et al., 2006; Comi et al., 2010) as well as the following phase III studies FREEDOMS, TRANSFORMS and FREEDOMS II have shown effects of fingolimod on magnetic resonance imaging (MRI) outcomes: Gadolinium (Gd) enhanced lesions, the morphological correlates of clinical as well as subclinical relapses, were reduced in the fingolimod treatment group compared to the patients receiving interferon beta-1a or placebo. Gd enhancement indicates BBB leakage, which is one of the initial steps in the pathophysiological cascade resulting in a MS plaque. "
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    • "Phase II and the aforementioned phase III clinical trials have shown that FTY720 is generally well tolerated and the reported adverse effects are, further to adverse effects due to immunosuppression, also of a cardiovascular nature. Besides transient effects on heart rate (bradycardia ) and atrioventricular conduction, a moderate increase in BP of approximately 3–5 mmHg in 4–6% of treated patients was observed that persisted during treatment (Cohen et al., 2010; Comi et al., 2010; Kappos et al., 2010). In addition , one case of severe peripheral arterial vasospasm was reported in a patient after 7 days of FTY720 treatment (Schwarz et al., 2010). "
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