How Does Fingolimod (Gilenya®) Fit in the Treatment Algorithm for Highly Active Relapsing-Remitting Multiple Sclerosis?

Fazekas, Franz; Băjenaru, Ovidiu; Berger, Thomas; Fabjan, Tanja Hojs; Ledinek, Alenka Horvat; Jakab, Gábor; Komoly, Sámuel; Kobys, Tetiana; Kraus, Jörg; Kurča, Egon; Kyriakides, Theodoros; Lisý, L; Milanov, Ivan; Nehrych, Tetyana; Московко, С.П.; Panayiotou, Panayiotis; Jazbec, Saša Šega; Соколова, Л. И.; Taláb, Radomír; Traykov, Latchezar; Turčãni, Peter; Vass, Karl; Vella, Norbert; Voloshyna, N.P.; Havrdová, Eva

doi:10.3389/fneur.2013.00010

Cited by 23 publications

(21 citation statements)

References 23 publications

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“…6,7 Three landmark phase 3 clinical trials [8][9][10] In the TRANSFORMS study, all patients experienced relapses before randomization, but approximately 45% of the participants were treatment naive. The active comparator to fingolimod in that study was 30 μg of intramuscular interferon beta-1a, which had been shown to be inferior to 44 μg of subcutaneous interferon beta-1a 11 or glatiramer acetate.…”

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confidence: 99%

Comparison of Switch to Fingolimod or Interferon Beta/Glatiramer Acetate in Active Multiple Sclerosis

et al. 2015

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for the MSBase Study Group IMPORTANCE After multiple sclerosis (MS) relapse while a patient is receiving an injectable disease-modifying drug, many physicians advocate therapy switch, but the relative effectiveness of different switch decisions is often uncertain.OBJECTIVE To compare the effect of the oral immunomodulator fingolimod with that of all injectable immunomodulators (interferons or glatiramer acetate) on relapse rate, disability, and treatment persistence in patients with active MS. DESIGN, SETTING, AND PARTICIPANTSMatched retrospective analysis of data collected prospectively from MSBase, an international, observational cohort study. The MSBase cohort represents a population of patients with MS monitored at large MS centers. The analyzed data were collected between July 1996 and April 2014. Participants included patients with relapsing-remitting MS who were switching therapy to fingolimod or injectable immunomodulators up to 12 months after on-treatment clinical disease activity (relapse or progression of disability), matched on demographic and clinical variables. Median follow-up duration was 13.1 months (range, 3-80). Indication and attrition bias were controlled with propensity score matching and pairwise censoring, respectively. Head-to-head analyses of relapse and disability outcomes used paired, weighted, negative binomial models or frailty proportional hazards models adjusted for magnetic resonance imaging variables. Sensitivity analyses were conducted.EXPOSURES Patients had received fingolimod, interferon beta, or glatiramer acetate for a minimum of 3 months following a switch of immunomodulatory therapy. MAIN OUTCOMES AND MEASURESAnnualized relapse rate and proportion of relapse-free patients, as well as the proportion of patients without sustained disability progression. RESULTSOverall, 379 patients in the injectable group were matched to 148 patients in the fingolimod group. The fingolimod group had a lower mean annualized relapse rate (0.31 vs 0.42; 95% CI, 0.02-0.19; P = .009), lower hazard of first on-treatment relapse (hazard ratio [HR], 0.74; 95% CI, 0.56-0.98; P = .04), lower hazard of disability progression (HR, 0.53; 95% CI, 0.31-0.91; P = .02), higher rate of disability regression (HR, 2.0; 95% CI, 1.2-3.3; P = .005), and lower hazard of treatment discontinuation (HR, 0.55; P = .04) compared with the injectable group. CONCLUSIONS AND RELEVANCESwitching from injectable immunomodulators to fingolimod is associated with fewer relapses, more favorable disability outcomes, and greater treatment persistence compared with switching to another injectable preparation following on-treatment activity of MS.

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confidence: 99%

Comparison of Switch to Fingolimod or Interferon Beta/Glatiramer Acetate in Active Multiple Sclerosis

et al. 2015

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“…146 147 In relapsing multiple sclerosis, early attack rate is associated with long term outcomes. 38 140 Several definitions of "highly active" or "aggressive" disease have been proposed for clinical use, [143][144][145][146][147][148][149] or to facilitate subgroup analyses of RCT data, [150][151][152] typically using a combination of two or more clinical relapses together with one or more of relapse severity, presence of multiple gadolinium enhancing MRI lesions, significant T2 lesion burden, or increase in EDSS score within the preceding year.…”

Section: Individual Disability Risk Stratificationmentioning

confidence: 99%

Disease modifying therapies for relapsing multiple sclerosis

Wingerchuk

Weinshenker

2016

BMJ

142

116

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Multiple sclerosis (MS) is a common, disabling, putatively autoimmune neurological disease with worldwide distribution. It typically begins as a relapsing disorder that later evolves to a secondary progressive phase. Inflammatory and neurodegenerative mechanisms seem to operate in both phases, but their relative contributions and interactions are incompletely understood. Disease modifying therapies (DMTs) approved for relapsing multiple sclerosis interfere with a variety of immunological mechanisms to reduce rates of relapse, accumulation of disease burden measured by magnetic resonance imaging (MRI), and decline in neurological function over the two to three year duration of typical randomized controlled trials. Benefits of longer duration of therapy on disability are less clear, as data beyond three years are largely limited to observational studies. However, current DMTs do not slow accrual of disability once progressive multiple sclerosis is established. This review summarizes the evidence about the use of approved DMTs and examines how to individualize treatment despite the absence of validated biomarkers to guide drug selection. Methods such as stratifying patients on the basis of estimated risk for future disability, weighing patient specific factors and preferences, and using objective outcomes to adjudicate treatment success are discussed. Emerging drug therapies and strategies are also reviewed.

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“…Adjusted Cox proportional regression analyses showed that patient group was not independently predictive of time to first relapse (IFN-b/GA-fingolimod HR 5 1. 26 figure 3A). Our analysis had 90% power at the level of a 5 0.05 to detect a difference between groups of 4.7% and 3.3%, respectively, relative to the naive-fingolimod group.…”

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confidence: 92%

“…There are currently no guidelines for the optimal period between natalizumab cessation and fingolimod start, but a period of 3 to 6 months has frequently been recommended. 26,27 Moreover, in certain countries, including Italy, a minimum 3-month washout period is mandated before fingolimod treatment can begin, whereas in other countries, such as Australia, there is a degree of flexibility and a period of 8 weeks washout is often used. Our data suggest that a treatment gap of 2-4 months was an independent predictor of increased relapse risk on fingolimod vs no treatment gap, whereas a treatment gap of 1 day to 2 months was not.…”

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confidence: 99%