BACKGROUND: Fingolimod 0·5 mg once daily is approved for treatment of relapsing 
multiple sclerosis (MS). In the phase 3, 2-year FREEDOMS (FTY720 Research 
Evaluating Effects of Daily Oral therapy in MS) study, fingolimod significantly 
reduced annualised relapse rates (ARRs) and the risk of confirmed disability 
progression compared with placebo. We aimed to investigate whether the 
beneficial treatment effect reported for the overall population is consistent in 
subgroups of patients with different baseline characteristics.
METHODS: We did subgroup analyses of ARRs (primary outcome) and confirmed 
disability progression (a secondary outcome) over 24 months in the FREEDOMS 
study, a randomised, double-blind study that included 1272 patients with 
relapsing-remitting MS who were assigned 1:1:1 to fingolimod (0·5 mg or 1·25 mg) 
or placebo once daily for 24 months. Subgroups were predefined, predefined and 
slightly modified, or defined post hoc, by demographic factors (including sex 
and age), disease characteristics (including baseline disability scores, relapse 
rates, and lesion parameters), and response to previous therapy (including 
analyses in patients eligible for fingolimod treatment according to the European 
label). Data were analysed by intention to treat. The FREEDOMS study is 
registered with ClinicalTrials.gov, number NCT00289978.
FINDINGS: Treatment with fingolimod 0·5 mg was associated with significantly 
lower ARRs versus placebo across all subgroups except for patients aged over 40 
years. ARR ratios ranged from 0·76 (95% CI 0·54-1·09; p=0·13) in patients aged 
over 40 years to 0·29 (0·16-0·52; p<0·0001) in patients who had relapse activity 
despite receiving interferon beta during the year before study enrolment. Hazard 
ratios for confirmed disability progression over 24 months with fingolimod 0·5 
mg versus placebo ranged from 0·85 (95% CI 0·53-1·36; p=0·50) in patients with a 
T2 lesion volume of 3300 mm(3) or less to 0·32 (0·14-0·73; p=0·0066) in patients 
with an EDSS over 3·5. In patients who relapsed and had lesion activity despite 
treatment with interferon beta in the previous year, the ARR ratio for 
fingolimod 0·5 mg versus placebo was 0·38 (95% CI 0·21-0·68, p=0·0011), and for 
treatment-naive patients with rapidly evolving severe disease it was 0·33 
(0·18-0·62, p=0·0006). Hazard ratios for confirmed disability progression over 
24 months were 0·68 (0·29-1·62; p=0·39) and 0·73 (0·25-2·07; p=0·55), 
respectively, in these groups.
INTERPRETATION: Patients with relapsing-remitting MS with a wide spectrum of 
clinical and MRI features including subgroups specified by the European label 
can potentially benefit from treatment with 0·5 mg fingolimod.
FUNDING: Novartis.