ucb-34714 and Intellectual-Disability

Approximately one quarter of people with an intellectual disability (PwID) have epilepsy of whom nearly three-quarters are pharmaco-resistant. There are higher reported neuropsychiatric side-effects to anti-seizure medication (ASM) in this group. Levetiracetam (LEV) is a first-line ASM with a stronger association with neuropsychiatric symptoms for PwID than other ASMs. Brivaracetam (BRV) is a newer ASM. Recent studies suggest a beneficial effect of swapping people who experience neuropsychiatric events with LEV to BRV. However, there is limited evidence of this for PwID. This evaluation analyses real world outcomes of LEV to BRV swap for PwID compared to those without ID.. We performed a multicentre, retrospective review of clinical records. Demographic, clinical characteristics and reported adverse events of patients switched from LEV to BRV (2016-2020) were recorded at 3 months pre and 6- and 12-month post-BRV initiation. Outcomes were compared between PwID and those without and summarised using cross-tabulations and logistic regression models. A Bonferroni correction was applied.. Of 77 participants, 46 had ID and 52% had a past psychiatric illness. 71% participants switched overnight from LEV to BRV. Seizure reduction of > 50% was seen in 40% patients. Psychiatric illness history was predictive of having neuropsychiatric side-effects with LEV but not BRV (p = 0.001). There was no significant difference for any primary outcomes between PwID versus without ID.. Switching from LEV to BRV appears as well tolerated and efficacious in PwID as those without ID with over 90% still on BRV after 12 months.

Topics: Anticonvulsants; Case-Control Studies; Drug-Related Side Effects and Adverse Reactions; Epilepsy; Humans; Intellectual Disability; Levetiracetam; Substance Abuse, Intravenous; Treatment Outcome

Patients with intellectual disability (ID) are often excluded from clinical trials, and little is known about the best approach to treat their epilepsy. Brivaracetam (BRV) is a new antiepileptic drug (AED) for adjunctive treatment in patients with focal-onset seizures with or without secondary generalization. We analyzed the efficacy and tolerability of BRV in patients with ID and epilepsy who either had or had not previously received treatment with levetiracetam (LEV). Data on efficacy and tolerability were retrospectively collected. After the initial start of BRV in our tertiary epilepsy center, we analyzed medical records at 0, 3, 6 and 12 months of follow-up. 116 patients were included (mean age = 34.9 years, 44% female). All had complete data of 3-month follow-up, 76 of 6-month follow-up, and 39 patients of 1-year follow-up. Median starting dose of BRV was 50.0 mg/day and the mean number of concomitant AEDs was 2.6. Seizure reduction and no side effects were reported in more than half of all patients. The most reported side effects were somnolence, dizziness and aggression. Retention rates for BRV were 84.4%, 75.5% and 58.1% after 3, 6 and 12 months, respectively. Seizure reduction and side effects did not differ significantly between the groups with or without previous LEV treatment. We demonstrate that BRV is effective and well tolerated in patients with epilepsy and ID, even in those where previous LEV treatment failed.

Topics: Adolescent; Adult; Aged; Anticonvulsants; Child; Dizziness; Epilepsy; Fatigue; Female; Headache; Humans; Intellectual Disability; Male; Middle Aged; Pyrrolidinones; Retrospective Studies; Sleepiness; Treatment Outcome; Young Adult

Clinical studies suggest that the antiepileptic drug (AED) brivaracetam (BRV) is associated with fewer behavioral and psychiatric adverse events (AEs) compared with levetiracetam (LEV) in treating epilepsy. There are, however, few comparative studies of treatment-emergent AEs between patients on BRV with preexisting psychiatric or behavioral comorbidities to those without. Our study compared longer-term tolerability over a 26-month period between these patient groups and assessed the overall efficacy of BRV as add-on therapy. Patients with intellectual disabilities in whom the prevalence of epilepsy is higher, are often excluded from randomized controlled trials, and our study further assessed comparative effectiveness between this patient group and those with normal range intellect. We collected prospective data on 134 patients prescribed add-on BRV for epilepsy at a tertiary UK center over a 26-month period. All patients had previously received LEV. Sixty-three patients were on LEV at the start of the data collection period. Levetiracetam was withdrawn and switched to BRV in 39 patients because of inefficacy and 24 patients because of behavioral or psychiatric side effects. Seventy-three patients (54%) had a preexisting psychiatric or behavioral disorder compared with 64 patients (46%) without. The retention rate at last follow-up [mean: 11 months (0.5-26 months)] was 60% in the psychiatric/behavioral disorders group versus 67% in those without (p = 0.68). Forty-one patients had diagnosed intellectual disabilities. The retention rate was 66% in this group versus 62% in patients without intellectual disabilities (p = 0.36). The commonest treatment-emergent AEs were somnolence (26%), aggression (23%), and depression (9%). There were similar frequencies reported for these specific events across the groups. The proportion with a 50% responder rate was 29% in patients with focal epilepsy and 47% in patients with generalized and combined focal and generalized epilepsies. However, fifteen patients (11%) reported increased seizure activity leading to withdrawal of treatment. This study showed evidence that BRV may be an effective adjunctive therapy in patients with drug-resistant focal or generalized epilepsies whose seizures have previously not responded or tolerated LEV therapy. We demonstrated a higher incidence of treatment-emergent AEs leading to lower retention rates compared with previous studies across all patient groups. There were, however, no signifi

Topics: Adolescent; Adult; Aged; Anticonvulsants; Behavioral Symptoms; Comorbidity; Drug Therapy, Combination; Epilepsies, Partial; Epilepsy, Generalized; Female; Humans; Intellectual Disability; Levetiracetam; Male; Mental Disorders; Middle Aged; Prospective Studies; Pyrrolidinones; Treatment Outcome; Young Adult

The purpose of this study was to evaluate the tolerability and efficacy of brivaracetam (BRV) in residential patients at our epilepsy centre.. We assessed retrospectively 33 patients (14 females; mean age 38.2 years, with range 17-63 years) with intellectual disability (ID) and drug-resistant epilepsy using an industry-independent, non-interventional study design based on standardized daily seizure records. Mean seizure frequency was compared between the 3-month baseline period and subsequent 3-month treatment period. Evaluation, including calculation of retention rate, was carried out for the intervals 3-6 and 9-12 months after brivaracetam initiation. Responders were defined as having a 50% reduction in seizure frequency. The Clinical Global Impression scale (CGI) was applied to allow assessment of qualitative changes in seizure severity, and the Aggressive Behaviour Scale (ABS) gave further insights into challenging behaviour.. The responder rate was 19%, and one non-responder attained an improvement in CGI score. The retention rate after 12 months was 37%. Brivaracetam treatment was stopped because of adverse events (n = 3), lack of efficacy (n = 8) or both (n = 6). Thirteen patients experienced behavioural changes, with aggressive behaviour being the commonest effect. We also observed ataxia (n = 2), gastrointestinal disorder (n = 3) and sedation (n = 2). The ABS showed deterioration, or new occurrence, of aggressive behaviour in 13 patients.. Brivaracetam seems to be effective in a small number of patients suffering from difficult-to-treat epilepsy and intellectual disability. Challenging behaviour was documented in a relevant number of patients, with psychiatric illness being a risk factor for this.

Topics: Adolescent; Adult; Anticonvulsants; Behavior; Drug Resistant Epilepsy; Female; Humans; Intellectual Disability; Male; Middle Aged; Pyrrolidinones; Retrospective Studies; Risk Factors; Seizures; Treatment Outcome; Young Adult