Relapse and disability outcomes in patients with multiple sclerosis treated with fingolimod: subgroup analyses of the double-blind, randomised, placebo-controlled FREEDOMS study

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• 作者：Virginia Devonshire ; MD^a ; Eva Havrdova ; MD^b ; Prof Ernst Wilhelm Radue ; MD^c ; Paul O'Connor ; MD^d ; Lixin Zhang-Auberson ; MD^e ; Catherine Agoropoulou ; PhD^e ; Dieter Adrian Hä ; ring ; PhD^e ; Gordon Francis ; MD^f ; Prof Ludwig Kappos ; MD^c ; ^{lkappos@uhbs.ch} ; for the FREEDOMS study group^&Dagger ;
• 刊名：Lancet Neurology
• 出版年：2012
• 期刊代码：300_14744422
• 类别：med
• 出版时间：May, 2012
• 卷：11
• 期：5
• 页码：420-428
• 文件大小：211 K

摘要

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Summary

Background

Fingolimod 0路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路5 mg or 1路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 , number .

Findings

Treatment with fingolimod 0路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路76 (95%CI 0路54-1路09; p=0路13) in patients aged over 40 years to 0路29 (0路16-0路52; p<0路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路5 mg versus placebo ranged from 0路85 (95%CI 0路53-1路36; p=0路50) in patients with a T2 lesion volume of 3300 mm³ or less to 0路32 (0路14-0路73; p=0路0066) in patients with an EDSS over 3路5. In patients who relapsed and had lesion activity despite treatment with interferon beta in the previous year, the ARR ratio for fingolimod 0路5 mg versus placebo was 0路38 (95%CI 0路21-0路68, p=0路0011), and for treatment-naive patients with rapidly evolving severe disease it was 0路33 (0路18-0路62, p=0路0006). Hazard ratios for confirmed disability progression over 24 months were 0路68 (0路29-1路62; p=0路39) and 0路73 (0路25-2路07; p=0路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路5 mg fingolimod.

Funding

Novartis.