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

Devonshire, Virginia; Havrdová, Eva; Radüe, Ernst Wilhelm; O’Connor, Paul; Zhang-Auberson, Lixin; Agoropoulou, Catherine; Häring, Dieter A.; Francis, Gordon; Kappos, Ludwig

doi:10.1016/s1474-4422(12)70056-x

Cited by 161 publications

(143 citation statements)

References 15 publications

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“…Our findings are partially in contrast with the subgroup analyses of the FREEDOMS and TRANSFORMS trials, where the pre-treatment number of relapses did not affect the on-treatment annualised relapse rate [37,38] and patients with EDSS score ≤3.5 did not have a significant reduction in risk of disability progression compared to placebo [37]. Moreover, subgroup analysis of pivotal trials did not reveal any clear advantage for treatment-naïves with respect to previously treated patients, except for a higher relative reduction in relapse rate for treatment-naive rapidly evolving severe RRMS patients (i.e.…”

Section: Discussioncontrasting

confidence: 99%

Baseline characteristics associated with NEDA-3 status in fingolimod-treated patients with relapsing-remitting multiple sclerosis

Giuliani

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Prosperini

et al. 2017

Mult Scler Demyelinating Disord

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Background: Fingolimod is an efficacious treatment for relapsing-remitting multiple sclerosis (RRMS) and there is class I evidence that it is superior to standard care in reducing relapse rate. However, real-world data investigating its effectiveness and potential predictors of response are still scarce. Objective: To estimate (i) the proportion of fingolimod-treated patients who achieved the no evidence of disease activity (NEDA-3) status; and (ii) to determine which baseline (i.e. at treatment start) clinical and magnetic resonance imaging (MRI) variables were associated with better outcomes. Methods: We collected clinical and MRI data of RRMS patients treated with fingolimod and followed-up for 24 months. The proportion of patients who had NEDA-3 -i.e. absence of relapses, sustained Expanded Disability Status Scale (EDSS) worsening and radiological activity on MRI -was estimated. A Cox proportional hazard model was carried out to investigate which baseline characteristics were associated with the NEDA status at follow-up. Results: We collected data of 201 patients who started fingolimod. Of them, 24 (12%) were treatment-naïve, 115 (58%) were switched after failing a self-injectable drug, and 60 (30%) switching from natalizumab. Five patients who discontinued fingolimod early (within 3 months) (bradycardia, n = 2; leukopaenia, n = 2; macular oedema, n = 1) were removed from the analysis. At follow-up, 118 (60%) patients achieved the NEDA-3 status, while 78 experienced clinical and/or MRI activity. The risk of not achieving the NEDA-3 status was associated with higher baseline EDSS score (hazard ratio [HR] = 1.18, p = 0.024) and more relapses in the 12 months prior to fingolimod start (HR = 1.61, p = 0.014). Conclusion: Our findings suggest that fingolimod may lead to a better control of the disease if started in patients with a less aggressive disease (i.e. fewer pre-treatment relapses and milder disability level), thus supporting its possible role as an early treatment for MS.

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Section: Discussioncontrasting

confidence: 99%

Baseline characteristics associated with NEDA-3 status in fingolimod-treated patients with relapsing-remitting multiple sclerosis

Giuliani

Logoteta

Prosperini

et al. 2017

Mult Scler Demyelinating Disord

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“…In patients who had received IFNb in the year before study entry and had highly active disease defined by relapses alone, fingolimod 0.5 mg significantly reduced the ARR by 71% compared with placebo (0.19 vs. 0.66, respectively; P < 0.001; Fig. 2) [36].…”

Section: When To Switch To Fingolimod or Natalizumabmentioning

confidence: 91%

“…In patients who had received IFNb in the year before study entry and had highly active disease defined by both relapses and MRI activity, fingolimod 0.5 mg significantly reduced the ARR by 62% compared with placebo (0.24 vs. 0.63, respectively; P = 0.001; Fig. 2) [36]. In patients who had received IFNb in the year before study entry and had highly active disease defined by relapses alone, fingolimod 0.5 mg significantly reduced the ARR by 71% compared with placebo (0.19 vs. 0.66, respectively; P < 0.001; Fig.…”

Section: When To Switch To Fingolimod or Natalizumabmentioning

confidence: 95%

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Treatment options for patients with multiple sclerosis who have a suboptimal response to interferon‐β therapy

Freedman

2013

Euro J of Neurology

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Background and purpose: Although the first-line disease-modifying therapies (DMTs) interferon beta and glatiramer acetate have a favourable benefit-to-risk profile, they are only partially effective for treating relapsing-remitting multiple sclerosis (RRMS). The optimization of treatment in patients who do not show a maximum response to first-line therapy is critical for achieving the best long-term outcomes. Treatment strategies for patients with a suboptimal response include switching to another first-line DMT or a second-line DMT. Natalizumab and fingolimod are approved for RRMS with high disease activity in the European Union and Canada. Methods: A comprehensive literature search for articles published between 1990 and April 2012 was undertaken.Results: This review discusses key clinical and safety data for fingolimod and natalizumab, particularly in the patient subgroups for whom these treatments are approved. Benefit-to-risk profiles, including first-dose cardiovascular effects associated with fingolimod and the risk of progressive multifocal encephalopathy with natalizumab, are discussed. Conclusion: A descriptive comparison of fingolimod and natalizumab is provided in the context of the decision-making process of how and when to switch patients who have a suboptimal response to first-line therapy.

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“…While preclinical studies and consistently beneficial effects of fingolimod on atrophy development in phase II and III trials support such an effect, fingolimod failed to show efficacy in primary progressive MS, the pathology of which is thought to be dominated by neurodegeneration [43]. In RR-MS the FREEDOMS and TRANSFORMS studies showed superiority not only to placebo [44][45][46][47], but also to the active comparator intramuscular IFN-1βa [48]. Fingolimod significantly reduced the relapse rate by 38 % and 50 % (for 1.25 mg and 0.5 mg daily, respectively) compared with IFN-1β, and several magnetic resonance imaging (MRI) measures consistently favored fingolimod.…”

Section: Teriflunomidementioning

confidence: 99%

Advances in and Algorithms for the Treatment of Relapsing-Remitting Multiple Sclerosis

2016

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Treatment options in relapsing-remitting multiple sclerosis have increased considerably in recent years; currently, a dozen different preparations of diseasemodifying therapies are available and some more are expected to be marketed soon. For the treating neurologist this broad therapeutic repertoire not only greatly improves individualized management of the disease, but also makes choices more complex and difficult. A number of factors must be considered, including disease activity and severity, safety profile, and patient preference. We here discuss the currently existing options and suggest treatment algorithms for managing relapsing-remitting multiple sclerosis.

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

Cited by 161 publications

References 15 publications

Baseline characteristics associated with NEDA-3 status in fingolimod-treated patients with relapsing-remitting multiple sclerosis

Baseline characteristics associated with NEDA-3 status in fingolimod-treated patients with relapsing-remitting multiple sclerosis

Treatment options for patients with multiple sclerosis who have a suboptimal response to interferon‐β therapy

Advances in and Algorithms for the Treatment of Relapsing-Remitting Multiple Sclerosis

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