High persistence and low adverse events burden in cladribine treated MS patients from Argentina.

BACKGROUND: Early initiation with high efficacy therapies seems to be better than an escalation approach in terms of disability prevention in patients with relapsing-remitting MS (RRMS). Although efficacy and safety of cladribine tablets have been shown in clinical trials, real-world evidence (RWE) studies from Latin America are scarce. OBJECTIVE: To describe the baseline characteristics of patients enrolled in the Argentina Patient Support Program (PSP) for cladribine tablets (Adveva®), with at least 1 treatment course, evaluate treatment persistence, adverse event reports from PSP patients and reported relapses characterization. METHODS: Anonymized data routinely collected by Adveva® team of patients that received the first dose of cladribine from April 16th 2018 to March 31st 2021 were analyzed. Treatment persistence was defined as the percentage of patients that initiated year 2 (Y2) from the population of patients with elapsed time since year 1 (Y1) cladribine tablet initiation of at least 18 months. In addition, using the pharmacovigilance data, reported adverse events and the time elapsed from treatment initiation to relapse were analyzed. RESULTS: The present analysis included 269 patients (mean age: 41.7 ± 16 years) that had initiated Y1 of cladribine tablets treatment between April 16th 2018 and March 31st 2021. Although only 29.4% (79/269) of our population was treatment naïve, the ratio of naïve/switch patients that initiated cladribine tablets increased from April 2018-March 2019 to April 2020-March 2021. From the 110 patients with elapsed time since treatment initiation ≥18 months, 101 patients initiated Y2 indicating a persistence level of 91.8%. During follow-up, 425 adverse events were reported, mainly MS relapse (8.9%, 38/425), fatigue (3.8%, 16/425) and headache (3.5%, 15/425). Lymphopenia and infections were rarely reported by RRMS patients treated with cladribine tablets. MS relapse was more frequently reported in patients switching from a previous treatment (87.5%, 27/32) than in the naïve cohort (12.5%, 5/32). CONCLUSIONS: The first real life experience in RRMS patients from Latin America demonstrated that the Adveva® enrolled support program patients have a high persistence level to oral treatment with cladribine tablets. Our results also confirmed the known safety profile of cladribine tablets, with a low incidence of lymphopenia and infections.

Effect of prior treatment status and reasons for discontinuation on the efficacy and safety of fingolimod vs. interferon ß-1a intramuscular: Subgroup analyses of the Trial Assessing Injectable Interferon vs. Fingolimod Oral in Relapsing-Remitting Multiple Sclerosis (TRANSFORMS).

BACKGROUND: Fingolimod demonstrated superior efficacy compared with interferon ß-1a intramuscular in relapsing multiple sclerosis. The impact of treatment history on fingolimod efficacy is unknown. OBJECTIVES: This post-hoc analysis of phase 3 TRANSFORMS data compared the efficacy and safety of fingolimod and interferon ß-1a intramuscular among patient subgroups defined by prior treatment history. METHODS: Annualized relapse rate and safety of once-daily oral fingolimod 0.5mg, 1.25mg, or once-weekly interferon ß-1a 30µg intramuscular for 12 months were analyzed in 1292 patients with relapsing multiple sclerosis according to prior disease-modifying therapy, reason for prior disease-modifying therapy discontinuation (adverse events or unsatisfactory therapeutic effect), and prior disease-modifying therapy duration. RESULTS: Compared with interferon ß-1a intramuscular, fingolimod 0.5mg significantly reduced annualized relapse rate in patients who were treatment naive, received prior interferon-ß treatment, discontinued prior disease-modifying therapy for unsatisfactory therapeutic effect, or had prior disease-modifying therapy duration of ≥1 year (P≤0.05, all comparisons). Similar trends were observed in patients with prior glatiramer acetate treatment. Significant reductions were also seen with fingolimod 1.25mg for treatment-naive and prior interferon-ß-treated patients. CONCLUSIONS: This analysis demonstrates superiority of fingolimod over interferon ß-1a intramuscular regardless of prior (interferon-ß) treatment and prior treatment efficacy and duration. ClinicalTrials.gov identifier: NCT00340834.

Atypical antipsychotic metabolism and excretion.

BACKGROUND: The metabolic/biotransformation pathways of atypical antipsychotics (aripiprazole, clozapine, iloperidone, olanzapine, paliperidone, quetiapine, risperidone, and ziprasidone) have been characterized and reviewed. However, comparisons of excretory pathways remain unexplored. OBJECTIVE: To analyze the excretion profile of atypical antipsychotic agents and compare the overall magnitude of metabolism (changed vs. unchanged drug) and route of excretion (feces vs. urine). Secondary objectives include providing: 1) dosing information in hepatic and renal impairment, and 2) context of the specific enzymes and pathways involved in each agents' biotransformation. METHODS: Published literature and each manufacturer's radiolabeled drug absorption, distribution, metabolism and excretion data and U.S. prescribing information were reviewed. RESULTS: With the exception of paliperidone, atypical antipsychotics undergo extensive metabolism (i.e.,

Adjunctive therapy with oxcarbazepine in children with partial seizures. The Oxcarbazepine Pediatric Study Group.

OBJECTIVE: To evaluate the safety and efficacy of oxcarbazepine (OXC) as adjunctive therapy in children with inadequately controlled partial seizures on one or two concomitant antiepileptic drugs (AEDs). BACKGROUND: OXC has shown antiepileptic activity in several comparative monotherapy trials in newly diagnosed patients with epilepsy, and in a placebo-controlled monotherapy trial in hospitalized patients evaluated for epilepsy surgery. DESIGN: A total of 267 patients were evaluated in a multicenter, randomized, placebo-controlled trial consisting of three phases: 1) a 56-day baseline phase (patients maintained on their current AEDs); 2) a 112-day double-blind treatment phase (patients received either OXC 30-46 mg/kg/day orally or placebo); and 3) an open-label extension phase. Data are reported only from the double-blind treatment phase; the open-label extension phase is ongoing. METHODS: Children (3 to 17 years old) with inadequately controlled partial seizures (simple, complex, and partial seizures evolving to secondarily generalized seizures) were enrolled. RESULTS: Patients treated with OXC experienced a significantly greater median percent reduction from baseline in partial seizure frequency than patients treated with placebo (p = 0.0001; 35% versus 9%, respectively). Forty-one percent of patients treated with OXC experienced a > or =50% reduction from baseline in partial seizure frequency per 28 days compared with 22% of patients treated with placebo (p = 0.0005). Ninety-one percent of the group treated with OXC and 82% of the group treated with placebo reported > or =1 adverse event; vomiting, somnolence, dizziness, and nausea occurred more frequently (twofold or greater) in the group treated with OXC. CONCLUSION: OXC adjunctive therapy administered in a dose range of 6 to 51 mg/kg/day (median 31.4 mg/kg/day) is safe, effective, and well tolerated in children with partial seizures.

Electroclinical signs of benign neonatal familial convulsions.

Benign neonatal familial convulsions comprise a distinct epileptic syndrome with an autosomal mode of transmission. The electroclinical signs of seizures in this syndrome are not yet well defined. In 3 children from two families presenting with benign neonatal familial convulsions, 14 seizures were recorded during electroencephalographic (EEG)-video sessions. All seizures occurred during sleep, after a short arousal reaction. Seizures started with bilateral, symmetrical flattening of the EEG for 5 to 19 seconds; simultaneously there was apnea and tonic motor activity. The EEG flattening was followed by a long (1-2-minute) bilateral discharge of spikes and sharp waves; simultaneously, there were vocalizations, chewing, and focal or generalized clonic activity. The prominence of EEG and motor abnormalities varied between the left and the right from one seizure to the next in any given child. The seizures stopped without EEG or clinical postictal depression. These electroclinical observations suggest that the convulsions of benign neonatal familial convulsions are a form of generalized tonic-clonic seizure whose expression may be asymmetrical, probably because of the immaturity of the corpus callosum or other structures ensuring seizure synchronization.