Low long-term efficacy and tolerability of add-on rufinamide in patients with Dravet syndrome

Mueller, Arndt; Boor, Rainer; Coppola, Giangennaro; Striano, Pasquale; Dahlin, Maria; Stuelpnagel, Celina von; Lotte, J; Staudt, Martin; Kluger, Gerhard

doi:10.1016/j.yebeh.2011.04.057

Cited by 44 publications

(38 citation statements)

References 25 publications

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“…Limitations common to several previously published post-marketing observational studies of RFM in refractory epilepsy include short follow up times, variable or unspecified time points for efficacy assessment, small sample sizes, populations restricted to one epilepsy type, and the retrospective use of the 50% responder rate outcome measure (Dahlin and Ohman, 2012; Joseph et al, 2011; Kim et al, 2013, 2012; Kluger et al, 2009; Mueller et al, 2011; Olson et al, 2011; Thome-Souza et al, 2014; Vendrame et al, 2010). Particularly in studies reporting efficacy at short assessment times, “honeymoon periods” may not be distinguishable from sustained efficacy, which limits the impact of those studies on clinical decision making.…”

Section: Discussionmentioning

confidence: 99%

“…Since then, a number of studies have investigated the efficacy of RFM in children with other epilepsy types as well, including epileptic spasms and refractory epilepsy more generally (Coppola et al, 2014, 2013, 2011, 2010; Grosso et al, 2014; Joseph et al, 2011; Kim et al, 2013, 2012; Kluger et al, 2010a; Mueller et al, 2011a,b; Olson et al, 2011; Thome-Souza et al, 2014). In addition, RFM now has an indication for adjunctive therapy in refractory partial seizures in adults and adolescents (Brodie et al, 2009).…”

Section: Introductionmentioning

confidence: 99%

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Retention rates of rufinamide in pediatric epilepsy patients with and without Lennox–Gastaut Syndrome

et al. 2015

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Summary Objective To evaluate the effectiveness of rufinamide (RFM) in patients with Lennox–Gastaut Syndrome (LGS) compared to those with other epilepsy syndromes using time to treatment failure (retention rate) as the outcome measure. Methods In this retrospective cohort study, characteristics and outcomes of all patients receiving RFM in 2009 and 2010 were recorded. The primary outcome measure was RFM failure, defined as discontinuation of RFM or initiation of an additional antiepileptic therapy. The secondary outcome measure was discontinuation of RFM. Kaplan–Meier method survival curves were generated for time to RFM failure, for all patients and by the presence or absence of Lennox Gastaut Syndrome (LGS). The impact of age, seizure type, fast or slow drug titration, and concomitant therapy with valproate on retention rate were evaluated using Cox regression models. Results One hundred thirty-three patients were included, 39 (30%) of whom had LGS. For all patients, the probability of remaining on RFM without additional therapy was 45% at 12 months and 30% at 24 months. LGS diagnosis was an independent predictor of time to RFM failure (HR 0.51, 95% CI 0.31–0.83), with a median time to failure of 18 months in LGS compared to 6 months in all others (p = 0.006). Conclusions In a broad population of children with refractory epilepsy, around half will continue taking the medication for at least a year without additional therapy. Patients with LGS are two times more likely to continue RFM without additional therapy compared to those without LGS.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Retention rates of rufinamide in pediatric epilepsy patients with and without Lennox–Gastaut Syndrome

et al. 2015

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“…Only a few pediatric studies have assessed the efficacy and safety/tolerability of RUF in childhood-onset EE and in epileptic syndromes other than Lennox-Gastaut syndrome [17,18,19,20,21]. We observed RUF to be more effective on focal-onset seizures compared to infantile spasms.…”

Section: Discussionmentioning

confidence: 70%

A Pharmacokinetic Study and Correlation with Clinical Response of Rufinamide in Infants with Epileptic Encephalopathies

Marca¹,

Rosati

Falchi

et al. 2013

Pharmacology

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Aim: To evaluate the relationship between the pharmacokinetic (PK) parameters and therapeutic and adverse effects of rufinamide (RUF) in children with epileptic encephalopathies (EE) aged <4 years. Methods: PK analysis was conducted at the steady state using a previously validated liquid chromatography tandem-mass spectrometric method in 15 children aged 6-42 months treated with RUF in add-on. Responders were defined as patients who achieved >50% decrease of seizures. Tolerability was evaluated by analysis of a parental report of adverse effects, a clinical examination and laboratory tests. Results: Maximum plasma concentration (47.40 ± 35.36 mg/l), average plasma concentration (39.94 ± 24.53 mg/l) and half-life (13.66 ± 4.43 h) were extremely variable and considerably higher than those reported in olderchildren treated with the same dose regimen. At the last evaluation, 9 patients (60%) were responders. Conclusion: RUF is efficacious and is well tolerated in children with EE. Nonetheless, a correlation between dose, serum concentration and efficacy could not be demonstrated. The variability in measured concentrations may be related to polytherapy that is necessary for controlling seizures in this very severe form of epilepsy, in which the off-label use of RUF is justified.

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“…La mayoría de casos diagnosticados de forma tardía han recibido antiepilépticos como la carbamacepina, la oxcarbacepina, la lamotrigina o la vigabatrina, que empeoran la epilepsia en los pacientes del espectro Dravet 19,20 . Recientemente se ha encontrado también un empeoramiento de la epilepsia en el 30% de niños tratados con rufinamida 21 . También tiene efectos secundarios más severos la fenitoína 22 y es conveniente evitar los barbitúricos a dosis elevadas, dos fármacos que con frecuencia se utilizan los intensivistas en casos de estatus epiléptico 23 .…”

Section: Discussionunclassified

Crisis con fiebre en el primer año de vida: ¿epilepsia del espectro Dravet?

Sánchez-Carpintero

Núñez

Aznárez

et al. 2012

Anales de Pediatría

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Low long-term efficacy and tolerability of add-on rufinamide in patients with Dravet syndrome

Cited by 44 publications

References 25 publications

Retention rates of rufinamide in pediatric epilepsy patients with and without Lennox–Gastaut Syndrome

Retention rates of rufinamide in pediatric epilepsy patients with and without Lennox–Gastaut Syndrome

A Pharmacokinetic Study and Correlation with Clinical Response of Rufinamide in Infants with Epileptic Encephalopathies

Crisis con fiebre en el primer año de vida: ¿epilepsia del espectro Dravet?

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