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Objectives: To report the efficacy, safety, and tolerability of fingolimod vs PBO and to evaluate responses in predefined patient subgroups.
Methods: 1083 patients with RRMS were randomly assigned to receive fingolimod 0.5 mg, 1.25 mg, or PBO once daily for 2 y. The primary objective was to demonstrate the superiority of fingolimod 0.5 mg vs PBO in reducing the annualized relapse rate (ARR). Secondary efficacy endpoints included percent brain volume change (PBVC) from baseline and 3-month disability progression. Predefined subgroup analyses assessed the impact of patient characteristics on ARR.
Results: Fingolimod significantly reduced ARR over 2 y compared with PBO. At the approved 0.5 mg dose, fingolimod reduced ARR by 48% vs PBO (ARR ratio: 0.516; P<0.001); a 50% reduction was seen in the 1.25-mg group (ARR ratio: 0.503; P<0.001). There was a 33% reduction in PBVC from baseline to month 24 with fingolimod 0.5 mg vs PBO (P<0.001) and a 53% (P<0.001) reduction in PBVC with the 1.25-mg dose. The risk of 3-month confirmed disability progression was reduced by 17% with fingolimod 0.5 mg vs PBO (P=0.227) and 28% with fingolimod 1.25 mg (P=0.041). Adverse events (AEs) of interest reported more frequently with fingolimod than PBO were hypertension (0.5 mg, 8.9%; 1.25 mg, 12.7%; PBO, 3.1%), lymphopenia (0.5 mg, 7.5%; 1.25 mg, 9.7%; PBO, 0%), increased alanine aminotransferase (0.5 mg, 8.1%; 1.25 mg, 9.5%; PBO, 1.7%), herpes zoster (0.5 mg, 2.5%; 1.25 mg, 3.2%; PBO, 0.8%), and basal cell carcinoma (0.5 mg, 2.8%; 1.25 mg, 1.6%; PBO, 0.6%). Subgroup analyses of ARR by sex, age, treatment history, and baseline disease activity will be presented.
Conclusions: These results from the FREEDOMS II study substantially confirm data from the earlier FREEDOMS I and TRANSFORMS studies and demonstrate the clinical benefits and well-characterized safety profile of fingolimod in MS.