Safety and efficacy of fingolimod in patients with relapsing-remitting MS
Treatment, therapies and management
This 24-month placebo-controlled, double-blind phase 3 study was carried out to further assess the efficacy and safety of fingolimod in patients with relapsing-remitting multiple sclerosis.
The researchers randomly allocated 1,083 eligible patients to receive fingolimod 0.5 mg or placebo orally once daily. The primary endpoint was annualized relapse rate at month 24. Secondary endpoints were percentage brain volume change from baseline, time-to-disability-progression confirmed at three months and safety and tolerability of fingolimod. Patients were studied by regular neurological assessments and Extended Disability Status Scale (EDSS) evaluations, by MRI scanning and safety and tolerability assessments.
Patients given fingolimod had lower aggregate annualized relapse rates than those given placebo, but effect on disability progression was not observed. The proportion of patients free of new or newly enlarged T2 lesions and gadolinium-enhancing T1 lesions was higher in the fingolimod groups than it was in the placebo groups. The mean percent brain volume change from baseline was lower with fingolimod than it was with placebo at month 24.
In relation to safety, researchers found a higher incidence of herpes zoster, lower respiratory tract, and influenza infections. Macular oedema was also more common in fingolimod-treated patients, but was reversible on discontinuation of the drug. At treatment initiation, fingolimod was associated with bradycardia and prolongation of the PR interval resulting in cases of Mobitz type I second degree atrioventricular block as well as cases of 2:1 block. The incidence of basal-cell carcinomas was higher, albeit low, in the fingolimod group.
: Calabresi PA, Radue E.
: Lancet Neurol. 2014 Mar 27. pii: S1474-4422(14)70049-3. doi: 10.1016/S1474-4422(14)70049-3. [Epub ahead of print]