UCB Pharma (United States)

Hidradenitis suppurativa (HS) is a chronic, inflammatory skin condition which negatively impacts patients' physical and mental wellbeing. The HS Quality of Life questionnaire (HiSQOL©) was developed to assess HS-specific changes in health-related quality of life (HRQoL), one of the six domains of the core outcome set, established by the HS Core Outcomes Set International Collaboration. To evaluate the psychometric properties of HiSQOL total and domain scores and determine interpretation thresholds to guide score interpretation. Blinded, pooled data from two bimekizumab phase III trials (BE HEARD I & II) in adult patients with moderate-to-severe HS were used to conduct a confirmatory factor analysis (CFA) and to assess convergent validity [correlations with other patient-reported outcomes (PROs)], known-groups validity [grouping patients according to Hurley stage, International Hidradenitis Suppurativa Severity Score System (IHS4) and patient global impression of HS severity scale], reliability [Cronbach's α and intraclass correlation coefficients (ICCs)] and responsiveness (sensitivity to change). Clinically meaningful within-patient improvement thresholds were estimated by anchor- and distribution-based analyses. Symptom/impact severity thresholds were estimated by receiver operating characteristic curve analyses. The CFA models supported the relevance of the three subscales and an underlying unidimensional concept, validating the total score derivation from all items. HiSQOL subscale and total scores showed good convergent and known-groups validity, with HiSQOL scores being consistently higher (worse HRQoL outcomes) for patients with higher disease severity. HiSQOL demonstrated good internal consistency (Cronbach's α ≥ 0.81 for all scores) and test-retest reliability (ICC 0.73-0.83 across HiSQOL scores). Correlation coefficients between changes in HiSQOL scores and changes in other PRO scores were all positive and statistically significant (P-values < 0.001), with most exceeding 0.30, demonstrating acceptable responsiveness. Clinically meaningful within-patient improvement thresholds were estimated as: 20-21-point decrease for HiSQOL total score (total possible range 0-68), 5-6-point decrease for symptoms (range 0-16), 4-5-point decrease for psychosocial (range 0-20) and 10-11-point decrease for activities-adaptations (range 0-32). Thresholds for different levels of symptom/impact severity were derived. The HiSQOL subscale and total scores demonstrated robust psychometric properties, supporting the use of HiSQOL to interpret trial results and inform treatment decisions.

Most complex in vitro models (CIVM) and microphysiological systems (MPS) are composed of human cells, with the goal of evaluating diseases, efficacy, safety, and pharmacokinetic ques­tions specifically for humans. The hope with CIVM/MPS is that they will eventually improve our predictivity of clinical responses and reduce or replace animal use in research, supporting the 3Rs concept of only using animals in research when necessary. Given the potential of animal-based models to advance this field by comparing existing in vivo animal data with new animal-based MPS responses, there are currently few CIVM and MPS utilizing animal tissues. Animal-based MPS may also have specific utility for cross-species comparisons or species-specific mechanistic questions on zoonotic diseases, and therapies for animals. Animal-based MPS may help expand in-vitro-to-in-vivo correlations, advance the field, and establish confidence in the predictive nature of such platforms. The IQ MPS-FDA workshop provided an interactive venue for pharmaceutical companies and regulatory agencies such as the U.S. Food and Drug Administration (FDA), NC3Rs (UK), Health Canada, NIH/NCATS, NIHS and PMDA (Japan), Danish Medicines Agency, European Com­mission, NIEHS/NICEATM, HHS, NIST, EURL ECVAM, and the IQ MPS Affiliate, a collaboration of pharmaceutical companies, to jointly discuss considerations of animal-based MPS and applica­tions where animal-based MPS are of potential value.

The objective of this study is to evaluate possible long-term effects of treatment with brivaracetam (BRV) on body weight in children with epilepsy. Post hoc analysis of data from patients (aged 1 month to <17 years) with ≥6 months of BRV treatment in a long-term, open-label trial (N01266 [NCT01364597]). Outcomes included body weight and body mass index (BMI) over time (z-score growth curves), and treatment-emergent adverse events (TEAEs). Previous/ongoing medical conditions that may affect body weight (gastrointestinal and metabolic/nutritional disorders); concomitant antiseizure medications (ASMs) were also evaluated. Two hundred nine patients (mean [standard deviation] age 7.9 [4.6] years) were analyzed. Most (154 [73.7%]) had focal-onset seizures. At study initiation, median (range) BRV dose was 1.0 (0.4-7.5) mg/kg/day. Overall, 189 (90.4%) patients had a previous or ongoing medical condition (gastrointestinal disorders: 43 [20.6%]; metabolism/nutritional disorders: 26 [12.4%]). Most patients followed z-score curves for body weight and BMI during BRV treatment, although there were outliers in both directions. Incidences of appetite/weight-change TEAEs were low. Twenty-three (11.0%) patients had a TEAE of decreased appetite and 14 (6.7%) had a TEAE of weight decreased. Long-term adjunctive BRV was well tolerated in growing children with no indication of detrimental effects on body weight. Brivaracetam is an antiseizure medication (ASM) used to treat seizures in people with epilepsy. Some ASMs can lead to changes in people's appetite and weight. Knowing the effect a drug has on appetite and weight is particularly important in children. We looked at 209 children with epilepsy taking brivaracetam and studied changes in their body weight and body mass index over time. The number of reported side effects related to appetite or weight change was low. There was no apparent long-term effect on their body weight, even when taking their medical history and use of other ASMs into account.

This analysis assessed the effectiveness and tolerability of brivaracetam (BRV) in older (≥65 years of age) and younger (≥16 to <65 years of age) adults with epilepsy. This was a subgroup analysis from EXPERIENCE/EPD332, a pooled analysis of individual patient records from multiple independent, non-interventional studies of patients with epilepsy starting BRV in Australia, Europe, and the United States. Included patients had ≥6 months of follow-up data. Outcomes included responders (≥50 % reduction from baseline in seizure frequency), seizure freedom (no seizures within 3 months before the time point), and continuous seizure freedom (no seizures from baseline) at 12 months; BRV discontinuation during the whole study follow-up; and treatment-emergent adverse events (TEAEs) at 3, 6, and 12 months. Patients with missing data after BRV discontinuation were deemed non-responders/not seizure-free. Analysis populations included the Full Analysis Set (FAS; patients who received ≥1 BRV dose and had seizure type and age documented at baseline) and the modified FAS (FAS patients who had ≥1 seizure recorded during baseline). The FAS was used for all outcomes except seizure reduction. The FAS included 147 (8.9 %) patients aged ≥65 years and 1497 (91.1 %) aged ≥16 to <65 years. Compared with the younger subgroup, patients aged ≥65 years had a longer median epilepsy duration (33.0 years [n = 144] vs 17.0 years [n = 1460]) and lower median seizure frequency at index (2.0 seizures/28 days [n = 129] vs 4.0 seizures/28 days [n = 1256]), and less commonly had >1 prior antiseizure medication (106/141 [75.2 %] vs 1265/1479 [85.5 %]). At 12 months, a numerically higher percentage of patients aged ≥65 years versus the younger subgroup achieved ≥50 % seizure reduction (46.5 % [n = 71] vs 36.0 % [n = 751]), seizure freedom (26.0 % [n = 100] vs 13.9 % [n = 1011]), and continuous seizure freedom (22.0 % [n = 100] vs 10.7 % [n = 1011]). During the whole study follow-up, 43/147 (29.3 %) patients aged ≥65 years and 508/1492 (34.0 %) aged ≥16 to <65 years discontinued BRV. The incidence of TEAEs since the prior visit was similar in both subgroups at 3 months (≥65 years vs ≥16 to <65 years: 38/138 [27.5 %] vs 356/1404 [25.4 %]), 6 months (19/119 [16.0 %] vs 176/1257 [14.0 %]), and 12 months (8/104 [7.7 %] vs 107/1128 [9.5 %]). This real-world analysis suggests BRV was effective in patients aged ≥65 years and ≥16 to <65 years, with numerically higher effectiveness in the older subgroup. BRV was well tolerated in both subgroups.

BackgroundSeizure clusters are underresearched and associated with adverse outcomes in patients with epilepsy. This study was a noninterventional, retrospective claims-based analysis using the Wisconsin Health Information Organization (WHIO) All-Payer Claims Database to characterize the epilepsy population in Wisconsin, with a focus on prevalence, treatment patterns, and healthcare resource utilization (HCRU) in patients with seizure clusters prior to the introduction of nasal spray rescue medications. This timeframe allows characterization of a historical baseline for future comparisons with newer treatments. MethodsFour cohorts were defined: (1) all-epilepsy (all patients with epilepsy); and subcohorts of: (2) patients receiving a monotherapy antiseizure medication (ASM); (3) patients receiving ASM polytherapy; and (4) patients treated for seizure clusters (ie, those taking rescue medications and ≥ 1 ASM). Primary outcomes were HCRU over a 12-month follow-up period, which were descriptively analyzed. ResultsBetween 2017 and 2019, 16,384 patients were included in the all-epilepsy cohort; 11,688 (71.3 %) were on monotherapy, 3,849 (23.5 %) were on polytherapy, and 526 (3.2 %) were treated for seizure clusters. Twelve-month retentions to the ASM treatments were 46.7 % (7,895/16,904) in the all-epilepsy cohort, and 40.0 % (4,679/11,688) and 40.1 % (1,544/3,849) in the monotherapy and polytherapy subcohorts, respectively. Rescue medication prescriptions were obtained 1,029 times by the 526 patients in the treated seizure cluster subcohort, with infrequent refill rates (mean 1.6–1.9 times/year). A higher proportion of patients in the treated seizure cluster subcohort had epilepsy-related outpatient visits (89.7 %), other visits (71.3 %), and hospitalizations (25.3 %) than patients in the monotherapy (72.2 %, 50.2 %, 19.3 %, respectively) and polytherapy (83.3 %, 63.3 %, 22.8 %, respectively) subcohorts. Mean (standard deviation) all-cause ($114,717 [$231,667]) and epilepsy-related ($76,134 [$204,930]) costs over 12 months were higher in the treated seizure cluster subcohort than the monotherapy ($89,324 [$220,181] and $30,745 [$145,977], respectively) and polytherapy ($101,506 [$152,931] and $49,383 [$96,285], respectively) subcohorts. ConclusionsPatients treated for seizure clusters incurred higher all-cause and epilepsy-related costs and epilepsy-related HCRU than other subcohorts and had infrequent rescue medication refills. The findings of this analysis highlight the need for appropriate treatment for those patients with epilepsy experiencing seizure clusters. The effect of newer rescue medications to alter these findings will be explored in a follow-up study. Regardless, specialist providers with expertise in treating refractory epilepsy and seizure cluster patients may help to reduce the burden of seizure clusters.

ObjectiveTo describe patients’ use of opioids in the year preceding and year following new diagnosis of ankylosing spondylitis (AS), psoriatic arthritis (PsA), or rheumatoid arthritis (RA), compared with patients without the/se diseases.MethodsThis study used US IBM® MarketScan® Commercial Claims and Encounters (CCAE) and Medicaid data and included three cohorts, comprised of incident cases of AS, PsA, or RA (2010–2017). Three matched comparator patients (without the incident disease) were selected for each patient within the disease cohort. Opioid use and appropriate treatment exposure (as defined by US guideline recommendations) in the 12-month baseline and follow-up periods were evaluated using descriptive analyses.ResultsPrevalence of claims for opioids was higher for disease cohorts vs. comparators in CCAE; 36.4% of patients with AS, 29.5% with PsA, and 44.4% with RA did not have any claim for guideline-appropriate therapy in follow-up. Prevalence of claims for opioids was also higher for disease cohorts vs. comparators in Medicaid; 30.6% of patients with AS, 36.6% with PsA, and 65.4% with RA did not have any claim for guideline-appropriate therapy in follow-up.ConclusionsIn patients with AS, PsA, or RA, there was high reliance on opioids at and around the time of diagnosis. Significant proportions of patients were not on appropriate treatment as defined by professional society post-diagnosis guidelines; this discordance between actual patient therapies and treatment recommendations may suggest a need for better awareness of appropriate pain management and treatment strategies in rheumatic diseases.Key Points• This study analysed opioid use among patients with ankylosing spondylitis (AS), psoriatic arthritis (PsA), or rheumatoid arthritis (RA), and adds to current knowledge by expanding beyond assessment of opioid use at diagnosis, to the year before and after diagnosis.• Opioid use was found to be highly prevalent in AS, PsA, and RA in the year prior to diagnosis and, interestingly, was still seen during the year after diagnosis.• Opioids are neither disease modifying, nor a targeted/recommended treatment for chronic autoimmune diseases. In addition to their association with significant economic costs, opioids are potentially hazardous and are not better than alternative treatments with superior safety profiles.• The reasons behind opioid prescribing patterns should be explored further to support movement to targeted therapies.

To evaluate the long-term safety and efficacy of zilucoplan, a macrocyclic peptide complement component 5 inhibitor, up to 96 weeks in patients with acetylcholine receptor autoantibody-positive (AChR Ab+) generalized myasthenia gravis (gMG) in an interim analysis of RAISE-XT (NCT04225871).

ObjectiveTo assess the effectiveness and tolerability of brivaracetam (BRV) in adults with epilepsy by specific comorbidities and epilepsy etiologies.MethodsEXPERIENCE/EPD332 was a pooled analysis of individual patient records from several non-interventional studies of patients with epilepsy initiating BRV in clinical practice. Outcomes included ≥ 50% reduction from baseline in seizure frequency, seizure freedom (no seizures within prior 3 months), continuous seizure freedom (no seizures since baseline), BRV discontinuation, and treatment-emergent adverse events (TEAEs) at 3, 6, and 12 months. Analyses were performed for all adult patients (≥ 16 years of age) and stratified by comorbidity and by etiology at baseline (patients with cognitive/learning disability [CLD], psychiatric comorbidity, post-stroke epilepsy, brain tumor−related epilepsy [BTRE], and traumatic brain injury−related epilepsy [TBIE]).ResultsAt 12 months, ≥ 50% seizure reduction was achieved in 35.6% (n = 264), 38.7% (n = 310), 41.7% (n = 24), 34.1% (n = 41), and 50.0% (n = 28) of patients with CLD, psychiatric comorbidity, post-stroke epilepsy, BTRE, and TBIE, respectively; and continuous seizure freedom was achieved in 5.7% (n = 318), 13.7% (n = 424), 29.4% (n = 34), 11.4% (n = 44), and 13.8% (n = 29), respectively. During the study follow-up, in patients with CLD, psychiatric comorbidity, post-stroke epilepsy, BTRE, and TBIE, 37.1% (n = 403), 30.7% (n = 605), 33.3% (n = 51), 39.7% (n = 68), and 27.1% (n = 49) of patients discontinued BRV, respectively; and TEAEs since prior visit at 12 months were reported in 11.3% (n = 283), 10.0% (n = 410), 16.7% (n = 36), 12.5% (n = 48), and 3.0% (n = 33), respectively.ConclusionsBRV as prescribed in the real world is effective and well tolerated among patients with CLD, psychiatric comorbidity, post-stroke epilepsy, BTRE, and TBIE.