Efficacy Of Rufinamide Research Articles

Therapeutic Drug Monitoring for Rufinamide in Japanese Patients With Epilepsy: Focus on Drug Interactions, Tolerability, and Clinical Effectiveness.

The purposes of this study were to assess drug interactions between rufinamide and concomitant antiepileptic drugs (AEDs) and to identify the therapeutic window for rufinamide. Serum samples (n = 1531) were obtained from 178 patients (aged 2-57 years), and clinical records were retrospectively reviewed to evaluate the safety and efficacy of rufinamide (mean observation time, 1073 ± 846 days). Rufinamide exhibited linear pharmacokinetics at doses of up to 60 mg/kg (range, 50-3200 mg/d). Concomitant use of the enzyme-inducing AEDs such as phenytoin, carbamazepine, and phenobarbital reduced rufinamide concentrations by 43.4%, 13.2%, and 30.3%, respectively. By contrast, concomitant use of valproate significantly elevated rufinamide concentrations. Clinical response was seen in 41 patients (23.0%), with a median therapeutic concentration (interquartile range) of 20.6 mcg/mL (13.3-27.0). There was no difference in the therapeutic concentrations between seizure types, but patients with tonic/atonic seizures tended to have higher rufinamide concentrations. During the study period, adverse events were reported in 64 patients (35.8%), including somnolence, gastrointestinal disorders, dizziness, and irritability/behavior disorders. Conditional logistic regression analysis showed that patients administered a concentration greater than 20 mcg/mL had an 8.6-fold higher incidence of adverse events. Therapeutic drug monitoring for rufinamide is clinically useful for predicting drug interactions between rufinamide and concomitant AEDs. When a patient has tonic/atonic seizures, careful titration is required for concentrations greater than 20 mcg/mL.

Safety and efficacy of rufinamide in children and adults with Lennox-Gastaut syndrome: A post hoc analysis from Study 022

BackgroundLennox-Gastaut syndrome (LGS) is a developmental and epileptic encephalopathy with the first symptoms usually appearing during early childhood. Due to the highly variable underlying etiologies, LGS cannot be considered as one disease but as an electro-clinical entity, often challenging to diagnose early and treat accordingly. The anti-seizure medication, rufinamide, is indicated for the adjunctive treatment of patients with LGS aged ≥1 year. This post hoc analysis assessed the safety and efficacy of adjunctive rufinamide for total and tonic-atonic seizures during Study 022 in children (aged <16 years) and adults (aged ≥16 years). MethodsRandomized, placebo-controlled, phase III Study 022 included patients with a diagnosis of LGS and a history of multiple seizure types (including tonic-atonic or astatic seizures and atypical absence seizures; ≥90 seizures in the month prior to baseline). Assessments included monitoring of treatment-emergent adverse events (TEAEs), percent change in tonic-atonic seizure frequency/28 days during the double-blind phase relative to study baseline (a primary endpoint), and percentage of patients with ≥25%, ≥50%, or ≥75% reduction in seizure frequency relative to baseline. ResultsOf 138 enrolled patients, 74 received rufinamide (<16 years, n = 49 [66%]) and 64 received placebo (<16 years, n = 43 [67%]). Incidence of TEAEs was generally similar between age groups. The frequency (per 28 days) of tonic-atonic seizures was reduced with rufinamide (vs. placebo) in both younger and older patients: age <16 years (−41% vs. −6%), age ≥16 years (−55% vs. +16%) (p < 0.025; both age groups). In patients aged <16 years receiving rufinamide, 38% and 17% achieved ≥50% and ≥75% reductions in tonic-atonic seizure frequency vs. 18% and 3% with placebo, respectively. Corresponding responder rates for patients aged ≥16 years were 52% and 32% (rufinamide) vs. 15% and 5% (placebo), respectively. ConclusionsIn this post hoc analysis, adjunctive rufinamide was well tolerated and improved seizure control in patients with LGS, irrespective of age.

Efficacy and safety of rufinamide as adjunctive therapy in patients with Lennox Gastaut syndrome: A systematic review and Meta-analysis

IntroductionRufinamide is an antiseizure medication that acts through sodium channels and is found to be efficacious in patients with Lennox Gastaut syndrome (LGS). However, no systematic review has been conducted in LGS patients to provide an estimate of the efficacy and safety of rufinamide. MethodsDifferent electronic databases were searched for articles describing the use of rufinamide in patients with LGS. For determining primary efficacy outcomes as compared to placebo, we included only studies comparing the efficacy of rufinamide with placebo in LGS patients. We performed an additional analysis to include other uncontrolled studies with a minimum sample size of 20 to provide a more comprehensive estimate of efficacy. ResultsA total of ten studies included 557 patients. Out of them, five studies were placebo-controlled, enrolling a total of 265 patients in the rufinamide group and 203 patients in the placebo group. The average percentage reduction in total seizure frequency per 28 days during the double-blind phase was 29.3% in the rufinamide group compared with 8.3% in the placebo group (difference between the two groups was 20.9%, 95%CI-14.4%-27.3%, p <0.00001). Even for individual seizure types like tonic-clonic seizures, atypical absence seizures, atonic seizures, focal seizures, and myoclonic seizures, rufinamide was more efficacious than placebo(p<0.00001). The number of patients with at least one treatment-emergent adverse effects was significantly higher in rufinamide treated patients (60.2%vs50.7%, p=0.02, RR-1.24(1.03,1.51). ConclusionRufinamide is efficacious as adjunctive therapy in patients with LGS in terms of reduction in total seizure frequency and has mild adverse reaction.

Rufinamidin Dirençli Epilepsi Tedavisindeki Etkinliğinin Araştırılması: Tek Merkez Deneyimi

Resistant epilepsy is a neurological condition that affects the quality of life with high morbidity seen in 10% of childhood epilepsy. Treatment options for resistant epilepsy are very limited. Rufinamide is one of the new 3rd generation antiepileptic drugs. In this study, we aimed to investigate the efficacy of rufinamide in treatment of resistant epilepsy. All patients who received rufinamide treatment in our clinic were included in the study. The efficacy of rufinamide was determined by the variability in seizure frequency. According to the results of our study, rufinamide treatment is more effective in reducing the frequency of seizures in patients followed-up with Lennox-Gastatut syndrome, and it is an effective and reliable additional treatment option in resistant epilepsy patients with non-LGS.

Efficacy and Tolerability of Rufinamide in Epileptic Children Younger Than 4 Years.

Rufinamide, a triazole derivative, is a new-generation antiseizure medication with a novel mechanism of action. We evaluated the efficacy and safety of rufinamide treatment in children with epilepsy younger than 4 years at our center. In this retrospective study, we included children younger than 4 years who had pharmacologically resistant epilepsy and were treated with rufinamide at Boston Children's Hospital between June 2010 and June 2018. Safety and efficacy of rufinamide treatment were assessed immediately prior to initiation of rufinamide and at the last follow-up visit. Responders were defined as patients who had greater than 50% reduction in seizure frequency on follow-up as compared to baseline. We reviewed records of 128 children and included 103 with complete information. Patients consisted of 60 boys (58%), with a median age of 20 months (interquartile range 13-28, range 2-36). Median treatment duration was 15 months, and median rufinamide dosage at the last follow-up was 42 mg/kg/d (interquartile range 34-56). At the last follow-up, seizure frequency decreased (450 vs 90, P<.001) and overall seizure reduction was 54%. Fifty-one patients (49.5%) were responders with 94% seizure reduction, including 20 (19.4%) who achieved seizure freedom. Treatment retention rate at 12 months was 63%. Thirty patients (29%) developed adverse events and 41 patients (39.8%) discontinued rufinamide because of adverse events (15; 14.5%) and lack of efficacy (26; 25%). Rufinamide is effective in reducing seizure frequency in pediatric epilepsy patients younger than 4 years, and overall well tolerated.

What’s hidden behind Lennox-Gastaut syndrome?

A number of epileptologists often diagnose Lennox-Gastaut syndrome, while others almost never do. It is necessary to understand why this is happening, especially since Lennox-Gastaut syndrome, according to literature descriptions, is quite common. Aim. To systematize available data on Lennox-Gastaut syndrome, which will help to improve the quality of diagnosis and management of patients.Materials and methods. Qualitative scientific publications from the International Scientific Databases (ISDS), including peer-reviewed journals and monographs, were selected for the review. The plan of the review included a brief description of the syndrome; seizure types; EEG features; diagnosis criteria; treatment.Results and discussion. None of the seizure types are pathognomonic for Lennox-Gastaut syndrome. The syndrome is considered to be confirmed if typical seizures (predominantly tonic) with typical interictal patterns without atypical EEG characteristics are reported. A diagnosis of the syndrome is considered probable if there are typical EEG patterns of waking and sleeping, but no tonic seizures are detected. The first choice of the treatment is valproate. Possible alternatives are lamotrigine and topiramate. Rufinamide and zonisamide are available as the second line of antiepileptic drugs. Rufinamide should be used when there is no effect from valproate and lamotrigine. Rufinamide also has antiabsance activity.Conclusion. “Classic” Lennox-Gasto syndrome is rare. Cases of “probable” Lennox-Gasto syndrome are much more frequent, and not all criteria of its diagnosis are observed. Taken into account the blurring of the diagnosis criteria for Lennox-Gasto syndrome and data on the efficacy of rufinamide in children with another epilepsies, it is possible to use this drug not only for Lennox-Gasto syndrome, but also for other epileptic syndromes, especially those with dropattacks, tonic seizures and atypical absences.

Rufinamide efficacy and association with phenotype and genotype in children with intractable epilepsy: A retrospective single center study

ObjectiveTo assess long-term efficacy and tolerability of rufinamide in children with epilepsy and a broad spectrum of underlying epileptic etiologies. MethodsPatients with epilepsy treated with rufinamide between 1/1/2009 and 1/1/2018 at Seattle Children’s Hospital were included. Data were collected via retrospective chart review. Rufinamide efficacy was defined as seizure reduction from baseline including seizure free, >50% reduction, any reduction, no reduction, or worsening seizures. Pearson’s chi-square test was used for statistical analysis. Results183 patients (70 females and 113 males) with a broad spectrum of epileptic aetiologies (genetic/metabolic, hypoxic-ischemic, structural and others) were included. 45.9% of the patients had Lennox Gastaut syndrome. Rate of any seizure reduction was at 47.5%, seizure reduction >50% at 35%, and seizure free at 3.3%. Mean rufinamide dosage was 33.9 mg/kg/d (SD = 14.12). Mean duration of treatment was 44.48 months (SD 32.33). Suspected adverse effects occurred at 10.9%, most often as fatigue. Rufinamide achieved better seizure reduction in girls compared to boys [OR = 0.52, 95% CI (0.28, 0.97), p = 0.038]. Seizures were activated in a patient with a SCN1A mutation, fully controlled in a patient with a SCN8A mutation. Patients with certain genetic abnormalities such as DEPDC5, KCNQ2, SPATA5, and 47XYY achieved significant seizure reduction. ConclusionsRufinamide is an effective and well-tolerated drug for long-term treatment in pediatric patients with intractable epilepsy. Certain genotypes such as SCN8A showed good response to rufinamide. Girls seemed to respond better than boys.

Rufinamide efficacy and safety in children aged 1–4 years with Lennox–Gastaut syndrome

PurposeThe treatment options for Lennox–Gastaut syndrome (LGS), a pediatric epileptic syndrome, are limited, especially in younger children. Rufinamide tablets were safe and effective as an add-on treatment in Korean children and adolescents <20 years of age with LGS. This subgroup analysis aimed to evaluate the efficacy and safety of rufinamide tablets in LGS pediatric patients aged 1–4 years. MethodsThis was a retrospective, observational study in LGS patients aged 1–4 years who received 12 weeks of treatment with rufinamide orally as an adjuvant treatment between April and June 2010. The proportion of responders (patients with a ≥50% reduction in seizure frequency after rufinamide treatment) was evaluated according to the type of seizure. The proportion of patients who were seizure-free was also evaluated. Adverse events (AEs) were evaluated after 12 weeks of treatment. ResultsAmong the 15 patients evaluated, one discontinued treatment because of worsening seizures 4 weeks after administration of rufinamide. Seven (46.67%) patients were responders and four patients were seizure-free. There were four responders with convulsive seizures, one each for myoclonic seizures and drop attacks, and spasms. The responder rate was increased to 69.23% by long-term treatment of rufinamide. AEs were experienced by three patients. One patient each experienced somnolence, fatigue, and rash. ConclusionRufinamide tablets were efficacious and well tolerated in LGS patients aged 1–4 years, at doses up to 1000 mg per day, when given as add-on therapy to other antiepileptic drugs.

Efficacy of rufinamide in childhood refractory epilepsy.

Yıldız EP, Hızlı Z, Bektaş G, Ulak-Özkan M, Tatlı B, Aydınlı N, Çalışkan M, Özmen M. Efficacy of rufinamide in childhood refractory epilepsy. Turk J Pediatr 2018; 60: 238-243. Rufinamide has been used as a new antiepileptic drug in the treatment of drug-resistant epilepsy, in recent years. The objective of this study was to evaluate the reliability of rufinamide and its impact on seizure frequency in patients diagnosed with drug-resistant epilepsy, where seizures could not be controlled with `classical` antiepileptic drugs. We retrospectively reviewed the data of epileptic patients who were followed up between January 2004 and December 2014 in the Pediatric Neurology Department. Patients who were diagnosed with `drug resistant epilepsy` and treated with rufinamide were evaluated. Decrease in seizure frequency and drug side effects were assessed as parameters. A total of 38 patients (14 girls, 24 boys) with a mean age of 8.5 (range, 3.5-17) years were included in the study. The mean follow-up duration was 25.5 (23-29.5) months, while the mean maximal dose of rufinamide was 32.5 (28-42) mg/kg/day. Response to treatment was assessed by the reduction in frequency of seizures. The decrease was < 50% (essentially unresponsive to treatment) in 20 patients and 50‑99% in 8 patients. Ten patients (26.3%) remained seizure-free. The response rate for tonic seizures was 50%. In drop/attacks seizures, this ratio was found as 73%, which was quite high. Patients with myoclonic and tonic-clonic seizures did not significantly benefit from rufinamide. The rate of patients with Lennox-Gestaut syndrome (LGS) who responded very well (reduction in seizure frequency > 50%) was 55.5%. In the LGS group, patients with drop/attacks showed the best response to treatment. Rufinamide was not effective in two patients diagnosed with Dravet syndrome. Rufinamide can be safely used in pediatric patients who use multiple antiepileptic drugs and are unresponsive to the treatment. It was seen to be effective especially in patients diagnosed with LGS and drop/attacks types of seizures.

Dosing considerations for rufinamide in patients with Lennox–Gastaut syndrome: Phase III trial results and real-world clinical data

PurposeLennox–Gastaut syndrome (LGS), a rare, severe form of childhood-onset epilepsy, is difficult to control. Rufinamide is indicated for adjunctive treatment of seizures associated with LGS in adults and pediatric patients aged ≥1 year. In clinical practice, rufinamide dosing and titration may differ from the trial setting. Here, rufinamide clinical trial data are compared with real-world experience to provide insight into optimal dosing and titration strategies. MethodsRufinamide Phase III and open-label extension (OLE) studies were reviewed; effect of titration and dose on adverse events (AEs) and concomitant AED use were analyzed. Real-world studies of rufinamide in LGS were identified via PubMed search. Clinical data were extracted and compared. ResultsResults demonstrated that a rapid titration schedule (7 or 14 days) of rufinamide was tolerable for most patients and resulted in highly significant reductions in total and tonic–atonic seizures, with efficacy and tolerability sustained over 3 years. The most common AEs during the Phase III study – somnolence, vomiting, and pyrexia – occurred during the first 3 weeks of treatment, and a small subset of patients were unable to reach target dose in that time. Use of concomitant AEDs had no clinically significant effect on plasma concentrations of rufinamide. Data from real-world clinical studies are consistent with the Phase III and OLE study results. However, relative to those used in clinical trials, lower doses and slower titration schedules were commonly employed in real-world settings. ConclusionsA lower dose and slower titration schedule (“low and slow”) may reduce incidence of AEs without compromising efficacy of rufinamide in LGS.

Efficacy of Rufinamide as Adjunctive Treatment for Adults With Lennox-Gastaut Syndrome: Subgroup Analysis From a Phase III Trial (P2.056)

Efficacy of Rufinamide as Adjunctive Treatment for Adults With Lennox-Gastaut Syndrome: Subgroup Analysis From a Phase III Trial (P2.056)

RUFINAMIDE (INOVELON) IN THE TREATMENT OF LENNOX–GASTAUT SYNDROME (A REVIEW OF LITERATURE AND CLINICAL CASE)

Lennox–Gastaut syndrome (LGS) is childhood-onset epileptic encephalopathy manifested by frequent polymorphic seizures, including tonic axial, obvious cognitive impairments, characteristic ECG changes, and therapeutic resistance. Due to the concurrence of several types of seizures in the clinical presentation of the disease and their resistance to drug therapy, great hopes are pinned on the design of novel antiepileptic drugs with fundamentally other mechanisms of action and aimed specially at treating this severe type of epilepsy. The authors review the foreign literature on the new antiepileptic drug rufinamide (Inovelon) registered in Russia in January 2015 to directly treat LGS as adjunctive treatment in children 4 years and older and adults. Multiple trials have demonstrated that rufinamide has efficacy and good tolerability in treating LGS. The authors describe an observed case of the efficacy of rufinamide in a 17-year-old male patient with LGS. Despite the drug resistance of epilepsy and no response to multiple antiepileptic drugs used alone and in different combinations, the incorporation of rufinamide into a treatment regimen had a pronounced therapeutic effect: the frequency of convulsive seizures decreased by 70 %. At the time of writing this paper, the patient has been receiving rufinamide for more 5 months. He has been tolerating the therapy well.

Rufinamide treatment for refractory epilepsy in a largely pediatric population

To determine the safety, tolerability, and efficacy of rufinamide in treating refractory epilepsy in a largely pediatric population. A retrospective chart review was conducted of all patients prescribed rufinamide from December 2008 to July 2010 in the Pediatric Epilepsy Program at Massachusetts General Hospital for Children. Eighty-eight patients on rufinamide with sufficient data for analysis were included in the study. Eight (9.1%) patients had >90% seizure reduction, 40 (45.5%) patients had 50-90% seizure reduction, 19 (21.6%) patients had <50% seizure reduction, and 21 (23.9%) patients had no change in seizure frequency. Generally mild side effects were reported by 28 (31.8%) patients, with the two most common side effects being decreased appetite in seven (8.0%) patients, and somnolence in six (6.8%) patients. Rufinamide appears to be an effective, safe, and well-tolerated antiepileptic drug in the treatment of broad-spectrum intractable epilepsy, expanding outside its specific Food and Drug Administration approved usage in treatment of Lennox-Gastaut syndrome.

Rufinamide as an adjunctive therapy for Lennox–Gastaut syndrome: A randomized double-blind placebo-controlled trial in Japan

To evaluate the efficacy, safety, and pharmacokinetics of rufinamide as an adjunctive therapy for patients with Lennox-Gastaut syndrome (LGS) in a randomized, double-blind, placebo-controlled trial. We conducted a multicenter clinical trial with a 4-week baseline, a 2-week titration, a 10-week maintenance, and either a follow-up visit or entry into an open-label extension. Patients with LGS (4 to 30 years old) taking between one and three antiepileptic drugs were recruited. After the baseline period, patients were randomly assigned to rufinamide or placebo. The primary efficacy variable was the percent change in the tonic-atonic seizure frequency per 28 days. Of the 59 patients, 29 were randomized to the rufinamide group and 30 to the placebo group. The frequency of epileptic seizures was significantly decreased in the rufinamide group than in the placebo group; the median percent change in frequency of tonic-atonic seizures was -24.2% and -3.3%, respectively, (p=0.003) and that of total seizures was -32.9% and -3.1%, respectively (p<0.001). Subgroup analyses indicated that the efficacy of rufinamide was consistent independent of clinical background characteristics. The common treatment-related adverse events in the rufinamide group were decreased appetite (17.2%), somnolence (17.2%), and vomiting (13.8%). Transient seizure aggravations were observed in 13 (22.0%) of the 59 patients, though a causal relationship with rufinamide was suspected in only one patient. All adverse events were mild to moderate in severity. The mean plasma concentration of rufinamide between 1 and 9 within 12h after administration was 17.2 μg/mL. The present results showed a favorable risk-benefit profile for rufinamide as an adjunctive therapy for patients with LGS.

Efficacy and safety of rufinamide in children under four years of age with drug-resistant epilepsies

BackgroundStudies on the efficacy and tolerability of rufinamide in infants and young children are scarce. Here we report on an open, retrospective, and pragmatic study about safety and efficacy of rufinamide in children aged less than four years, in terms of seizures types and epilepsy syndromes. MethodsForty children (mean age 39.5 months; range 22–48) were enrolled in the study. The mean follow-up period was 12.2 months (range 5–21). Rufinamide was initiated at a mean age of 26.7 months (range 12–42). Final rufinamide mean dosage was 31.5 mg/kg/day if associated with valproic acid and 44.2 mg/kg/day if not. ResultsThe highest seizure reduction rate was observed in the epileptic spasms (46%) and drop attacks (42%) groups. Seizure reduction was also observed in tonic seizures (35%) and in the focal seizure (30%) groups. In terms of epilepsy syndrome, rufinamide was effective in Lennox–Gastaut syndrome. Results were very poor for those affected by Dravet's syndrome. Globally, responder rate was 27.5%, including two (5%) patients seizure-free. Adverse reactions occurred in 37.5% of children and were mainly represented by vomiting, drowsiness, irritability, and anorexia. Discontinuation rate due to treatment-emergent adverse events was 15%. ConclusionThe present study concludes that rufinamide may be a safe and effective drug for a broad range of seizures and epilepsy syndromes in infants and young children and represents a valid therapeutic option in this population.

Rufinamide Modifies the Gating Process of Human Voltage-Gated Sodium Channels

Lennox-Gastaut Syndrome (LGS) is a severe form of epilepsy manifesting during early childhood. Treatment of the seizures and the ensuing behavioral and mental health problems commonly associated with LGS requires multiple anticonvulsant therapeutics, often with deleterious effects on the patient. Although the relatively new orphan drug rufinamide is gaining importance as an adjunct therapy for LGS, its mode of action remains speculative. To establish the molecular mechanism underlying rufinamide efficacy, we compared its effect on a subset of neuronal human voltage-gated sodium (Nav) channel isoforms (hNav1.1, hNav1.2, hNav1.3, and hNav1.6), several of which are thought to be involved in epilepsy. As a result, we found that a clinically relevant concentration inhibits hNav1.1 activation whereas the recovery from fast inactivation of hNav1.1, hNav1.2, hNav1.3, and hNav1.6 is slowed down. Moreover, experiments with related triazole compounds revealed drug variants with effects comparable to those of rufinamide and suggest that modifications of particular side chains may be exploited to obtain an isoform-specific drug-induced effect on hNav1.1 activation.

Rufinamide efficacy and safety as adjunctive treatment in children with focal drug resistant epilepsy: The first Italian prospective study

Rufinamide is a new antiepileptic drug approved as add-on treatment in Lennox-Gastaut syndrome from the age of 4 years, and for the treatment of focal seizures in adults and adolescents. The aim of this prospective study was to evaluate the safety and efficacy of add-on Rufinamide in the treatment of childhood focal drug resistant epilepsy. We recruited 70 patients for a prospective, add-on, open-label study. Inclusion criteria were: 3 years of age or more; focal drug resistant epilepsy despite the use of three previous AEDs; use of at least one other AED, but no more than three at baseline; more than one seizure per month in the previous 6 months. Rufinamide efficacy was observed up to 12 months of follow-up, with a total responder rate of 38.57%. We found the best results in focal epilepsies due to structural/metabolic etiology (42.6%). The responder rate was similar for focal seizures with secondary generalization, simple focal seizures other than myoclonic jerks, and complex partial seizures. Response to Rufinamide was not related to the age. Our experience suggests that Rufinamide can be effective in reducing focal seizure frequency in children with drug resistant epilepsy, and that it can be considered as a safe drug.

Rufinamide as an adjuvant treatment in children with Lennox-Gastaut syndrome

PurposeTo evaluate the efficacy of rufinamide as an add-on treatment in children and adolescents with Lennox-Gastaut syndrome (LGS). MethodsThe study was an open-label, observational clinical trial of rufinamide as an add-on treatment in intractable LGS patients. This intent-to-treat trial included 4 weeks of scheduled titrated doses and a 12-week maintenance phase with a target dose of 20–40mg/kg rufinamide, adjusted according to its effectiveness and tolerability after a baseline period of 4 weeks. The primary outcome was measured by the seizure-reduction rate according to individual seizure type over the 12-week maintenance period. ResultsOne hundred and twenty-eight patients with LGS who were determined to be unresponsive to one or more antiepileptic drugs or dietary therapy were enrolled. Of the 128 patients enrolled, 112 (87.5%) completed the study. After add-on rufinamide treatment, 46 patients (35.9%) achieved a more than 50% reduction in seizure frequency and 10 (7.8%) patients became seizure-free. When we identified those who responded with an at least 50% reduction in seizure frequency, 39.4% of the responders reported reductions in convulsive seizures, 36.4% in drop attacks, 33.3% in myoclonic seizures, and 20.0% in epileptic spasms. Overall, 32.8% of patients reported adverse effects, which were mostly mild and transient in nature. The most common adverse effects were fatigue (15 patients, 11.7%) and poor appetite (9 patients, 7.0%). Twenty-one (16.4%) patients experienced an increased seizure frequency. ConclusionsRufinamide appears to be a safe and effective adjuvant treatment for many cases of intractable LGS.

Rufinamide from clinical trials to clinical practice in the United States and Europe

Rufinamide is a triazole derivative structurally unrelated to other antiepileptic drugs that is indicated for the adjunctive treatment of seizures associated with Lennox-Gastaut syndrome (LGS) in patients aged ≥4 years. Originally granted orphan drug status, marketing authorisation was obtained on the basis of a randomised, double-blind, placebo-controlled trial conducted in 138 LGS patients. An open-label extension study subsequently demonstrated that rufinamide's efficacy and tolerability were maintained over the longer term (median duration of treatment, 432 days). Recently published reports from Europe and the United States have described the use of adjunctive rufinamide to treat LGS in clinical practice. These data complement the clinical trial results, by providing information on the efficacy and tolerability of rufinamide when used on an individualised basis in real-world practice, under less tightly restricted conditions in terms of patient population and dosing strategies. A comparison of the data reveals that a "lower and slower" dosing strategy tends to be adopted in clinical practice, in comparison with the clinical trial, which does not appear to compromise efficacy, but may provide improvements in tolerability. Individual case reports provide additional valuable information on how rufinamide is being used to treat different seizure types associated with LGS. Since clinical experience with rufinamide is currently at an early stage, there are still unanswered questions relating to its use, and it is likely that its place in the adjunctive treatment of LGS will evolve as further data emerge.

Efficacy of Rufinamide in Drug-Resistant Epilepsy: A Meta-analysis

Rufinamide is a new orally active antiepileptic drug that has been found to be effective in the treatment of partial seizures and drop attacks associated with Lennox-Gastaut syndrome. We performed a quantitative analysis of the efficacy of this new antiepileptic drug from all double-blind, add-on, randomized, placebo-controlled clinical trials published to date. Data from 918 patients were studied. The number of patients per study varied from 25 to 262. Rufinamide was efficacious in doses up to 45 mg/kg daily when provided as adjunctive therapy in patients with Lennox-Gastaut syndrome and other drug-resistant epilepsies. Further studies are needed to confirm and expand these findings.