Patient and caregiver perspectives on transitioning to oral prophylaxis in the emerging hereditary angioedema treatment landscape
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ABSTRACT:
SUBMITTER: Soteres D
PROVIDER: S-EPMC8593787 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Remarkable progress has been made in the treatment of bradykinin-mediated angioedema with the advent of multiple new therapies. Patients now have effective medications available for prophylaxis and treatment of acute attacks. However, hereditary angioedema is a burdensome disease that can lead to debilitating and dangerous angioedema episodes associated with significant costs for individuals and society. The burden of treatment must be addressed regarding medication administration difficulties, treatment complications, and adverse side effects. New therapies are being investigated and may offer solutions to these challenges. This article reviews the emerging therapeutic options for the treatment of HAE.
| S-EPMC5585075 | biostudies-literature
Project description:BackgroundHereditary angioedema (HAE) is a rare genetic disorder characterized by unpredictable localized episodes of edema, which is frequently managed with long-term prophylactic medications. Until recently, long-term prophylaxis has predominantly required regular intravenous or subcutaneous administration, however the recent approval of berotralstat (Orladeyo™) offers an orally administered prophylactic which may be associated with a lower burden of treatment compared to injectable options for some patients.Case presentationThis report describes four participants in the APeX-S trial who transitioned from subcutaneously administered lanadelumab (Takhzyro®) to daily oral berotralstat for long-term HAE prophylaxis. Lanadelumab dosing continued after berotralstat commencement in all patients and was tapered before discontinuation in three of the four patients. No substantial increases in HAE attack rates were observed after the transition to berotralstat monotherapy. One patient experienced a treatment-related adverse event (dyspepsia), which was mild and self-resolving.ConclusionsAll four patients described in this case series successfully transitioned from lanadelumab to berotralstat monotherapy for long-term prophylaxis without significant complications and without the use of a complex transition protocol. The decision to transition to berotralstat monotherapy and how the transition should be achieved was discussed between patient and physician, ensuring that the comfort and perspectives of the patients were considered during the treatment transition. This report highlights the importance of individualization of HAE management plans to address both the disease and treatment burdens of HAE, and thus to provide the best possible quality of life for each patient.
| S-EPMC8501591 | biostudies-literature
Project description:Current guidelines recommend short-term prophylaxis (STP) before invasive procedures to prevent hereditary angioedema (HAE) attacks; however, adherence to these guidelines may be variable because this indication lacks Food and Drug Administration approval in the United States.To ascertain the STP experiences of patients with HAE and HAE-treating physicians.Online questionnaires focusing on STP experiences were distributed by the US Hereditary Angioedema Association to the first 250 patients with HAE and to registered HAE-treating physicians. SAS 9.3 was used to perform descriptive statistics and to test the difference between patients who underwent procedures and those who did not using Pearson ?(2) test, Fisher exact test, and 2-sample t test.For the patient survey, 219 respondents met the criteria for HAE type 1 and 2; 37 (17%) underwent 66 invasive procedures, and all reported receiving STP. Eight patients (22%) reported failed STP, but only 3 required on-demand therapy. For STP, anabolic steroids and plasma-derived C1 inhibitor were the most and second-most commonly used, respectively. For the physician survey, 37 physicians reported caring for 433 patients with HAE. Depending on the procedure, 19% to 54% of physicians used STP and 30% to 86% prescribed on-demand therapy; 69% and 78% of physicians prescribed plasma-derived C1 inhibitor as STP for minimally invasive and invasive procedures, respectively. Physicians reported excellent efficacy for the STP treatments used.Physicians reported excellent outcomes using primarily newer STP therapies, namely plasma-derived C1 inhibitor, which was discordant to patient-reported outcomes using older STP therapies, namely anabolic steroids. Well-controlled STP studies are needed to clarify use for patients with HAE in the United States.
| S-EPMC4141470 | biostudies-literature
Project description:BackgroundHereditary angioedema (HAE) is an inherited chronic rare disease characterised by recurrent swelling attacks that are associated with significant physical and psychological burden. There is limited understanding of the effect of attack location on this burden and of caregiver burden.ObjectiveOur objective was to capture the relative burden of HAE health and caregiver states, including different attack locations, through a time trade-off (TTO) analysis involving participants from the general public.MethodsQualitative interviews were undertaken to inform vignette development for the TTO study, including vignettes for abdominal, facial, hand and laryngeal attack health states, and an attack-free and caregiver state. Members of the general public in England rated vignettes in TTO interviews, which included a visual analogue scale (VAS) component. For the development of the health state vignettes, qualitative interviews with 15 patients, 5 caregivers and 1 clinical expert were performed. TTO analysis was based on vignette valuation completed by 100 members of the general public.ResultsThe TTO values were as follows: attack-free, 0.783 (standard deviation [SD] 0.316); hand: 0.582 (SD 0.380); facial: 0.483 (SD 0.448); abdominal: 0.345 (SD 0.458); and laryngeal: 0.128 (SD 0.529). The caregiver rating was 0.762 (SD 0.303). V' scores were similar and consistent with TTO values.ConclusionTTO utility values demonstrate that HAE places a significant burden on patients, which is influenced by attack location, and on caregivers. These utility weights can provide important information on quality of life for future economic evaluations of treatments.
| S-EPMC8864034 | biostudies-literature
Project description:BackgroundWith no approved treatments in Japan for the prevention of hereditary angioedema (HAE) attacks, there is a significant unmet need for long-term prophylactic therapies for Japanese patients with HAE. Berotralstat (BCX7353) is an oral, once-daily, highly selective inhibitor of plasma kallikrein in development for prophylaxis of angioedema attacks in HAE patients.MethodsAPeX-J is a phase 3, randomized, double-blind, placebo-controlled, parallel-group, 3-part trial conducted in Japan (University Hospital Medical Information Network identifier, UMIN000034869; ClinicalTrials.gov identifier, NCT03873116). Patients with a clinical diagnosis of type 1 or 2 HAE underwent a prospective run-in period of 56 days to determine eligibility, allowing enrollment of those with ≥2 expert-confirmed angioedema attacks. Patients were randomly assigned (1:1:1) and stratified by baseline attack rate (≥2 vs. <2 expert-confirmed attacks/month between screening and randomization) to receive once-daily berotralstat 110 mg, berotralstat 150 mg, or placebo. The primary endpoint was the rate of expert-confirmed angioedema attacks during dosing in the 24-week treatment period.ResultsNineteen patients were randomized to receive once-daily berotralstat 110 mg (n = 6), berotralstat 150 mg (n = 7), or placebo (n = 6). Treatment with berotralstat 150 mg significantly reduced HAE attacks relative to placebo (1.11 vs. 2.18 attacks/month, p = .003). The most frequently reported treatment-emergent adverse events (TEAEs) in berotralstat-treated patients (n = 13) were nasopharyngitis (n = 4, 31%), abdominal pain, cough, diarrhea, and pyrexia (n = 2 each, 15%).ConclusionsOrally administered, once-daily berotralstat 150 mg significantly reduced the frequency of HAE attacks and was safe and well tolerated, supporting its use as a prophylactic therapy in patients with type 1 or 2 HAE in Japan.
| S-EPMC8247297 | biostudies-literature
Project description:BACKGROUND:Effective inhibition of plasma kallikrein may have significant benefits for patients with hereditary angioedema due to deficiency of C1 inhibitor (C1-INH-HAE) by reducing the frequency of angioedema attacks. Avoralstat is a small molecule inhibitor of plasma kallikrein. This study (OPuS-2) evaluated the efficacy and safety of prophylactic avoralstat 300 or 500 mg compared with placebo. METHODS:OPuS-2 was a Phase 3, multicenter, randomized, double-blind, placebo-controlled, parallel-group study. Subjects were administered avoralstat 300 mg, avoralstat 500 mg, or placebo orally 3 times per day for 12 weeks. The primary efficacy endpoint was the angioedema attack rate based on adjudicator-confirmed attacks. RESULTS:A total of 110 subjects were randomized and dosed. The least squares (LS) mean attack rates per week were 0.589, 0.675, and 0.593 for subjects receiving avoralstat 500 mg, avoralstat 300 mg, and placebo, respectively. Overall, 1 subject in each of the avoralstat groups and no subjects in the placebo group were attack-free during the 84-day treatment period. The LS mean duration of all confirmed attacks was 25.4, 29.4, and 31.4 hours for the avoralstat 500 mg, avoralstat 300 mg, and placebo groups, respectively. Using the Angioedema Quality of Life Questionnaire (AE-QoL), improved QoL was observed for the avoralstat 500 mg group compared with placebo. Avoralstat was generally safe and well tolerated. CONCLUSIONS:Although this study did not demonstrate efficacy of avoralstat in preventing angioedema attacks in C1-INH-HAE, it provided evidence of shortened angioedema episodes and improved QoL in the avoralstat 500 mg treatment group compared with placebo.
| S-EPMC6175137 | biostudies-literature
Project description:Aminopeptidase P (APP) plays an important role in the catabolism of kinins in human plasma, mostly for des-Arg(9)-bradykinin. Impaired degradation of this active bradykinin metabolite was found to be associated with a decreased APP activity in hypertensive patients who experienced angioedema while being treated with angiotensin I-converting enzyme inhibitors. The pathophysiology of hereditary angioedema is presently attributed only to a quantitative/qualitative C1 inhibitor (CI-INH) defect with increased bradykinin release.In the context of androgen prophylaxis, increased CI-INH function cannot fully explain protection from angioedema attacks alone because of the limited reversion of the CI-INH defects. Therefore we hypothesized that androgen prophylaxis could enhance plasma APP activity.Patients with hereditary angioedema were investigated for plasma metallopeptidase activities responsible for kinin catabolism (APP, angiotensin I-converting enzyme, and carboxypeptidase N) and for CI-INH function in treated and untreated patients.APP activity was asymmetrically distributed in untreated patients (n = 147): the mean value was significantly lower than the value in a reference healthy and unmedicated population (n = 116; P < or = .001). Prophylaxis with androgen induced a significant increase in APP activity (P < or = .001), whereas it did not affect the other metallopeptidase activities. In both patient groups, APP activity showed a significant inverse relationship to disease severity (P < or = .001).In addition to the effect on circulating CI-INH levels, the increase in APP levels brought on by androgens could contribute to a more effective control of the kinin accumulation considered to be responsible for the symptoms of angioedema.
| S-EPMC4126900 | biostudies-literature
Project description:BackgroundPatients with hereditary angioedema with C1 inhibitor deficiency or dysfunction have burdensome recurrent angioedema attacks. The safety, efficacy, and health-related quality of life (HRQoL) outcomes of C1 inhibitor (C1-INH) prophylaxis (intravenously administered) in patients aged 6-11 years were investigated.MethodsEligible patients were enrolled in a randomized, single-blind, crossover, phase 3 trial. After a 12-week baseline observation period (BOP), patients received 500 or 1000 U C1-INH, twice weekly, for 12 weeks before crossing over to the alternate dose for 12 weeks. The primary efficacy end-point was the monthly normalized number of angioedema attacks (NNA). HRQoL was assessed using the EuroQoL 5-dimensional descriptive system youth version and visual analog scale (EQ-VAS).ResultsTwelve randomized patients had a median (range) age of 10.0 (7-11) years. Mean (SD) percentage reduction in monthly NNA from BOP was 71.1% (27.1%) with 500 U and 84.5% (20.0%) with 1000 U C1-INH. Mean (SD) within-patient difference (-0.4 [0.58]) for monthly NNA with both doses was significant (P = 0.035 [90% CI, -0.706 to -0.102]). Cumulative attack severity, cumulative daily severity, and number of acute attacks treated were reduced. No serious adverse events or discontinuations occurred. Mean EQ-VAS change from BOP to week 9 of treatment (500 U C1-INH, 10.4; 1000 U C1-INH, 21.6) was greater than the minimal important difference, indicating a meaningful HRQoL change.ConclusionsC1-INH prophylaxis was effective, safe, and well tolerated in children aged 6-11 years experiencing recurrent angioedema attacks. A post hoc analysis indicated a meaningful improvement in HRQoL with C1-INH.Trial registrationClinicalTrials.gov identifier NCT02052141.
| S-EPMC6851661 | biostudies-literature
Project description:Accurate seizure forecasting is emerging as a near-term possibility due to recent advancements in machine learning and EEG technology improvements. Large-scale data curation and new data element collection through consumer wearables and digital health tools such as longitudinal seizure diary data has uncovered new possibilities for personalized algorithm development that may be used to predict the likelihood of future seizures. The Epilepsy Foundation recognized the unmet need for development in seizure forecasting following a 2016 survey where an overwhelming majority of respondents across all seizure types and frequencies reported that unpredictability of seizures had the strongest impact on their life while living with or caring for someone living with epilepsy. In early 2021, the Epilepsy Foundation conducted an updated survey among those living with epilepsies and/or their caregivers to better understand the use-cases that best suit the needs of our community as seizure forecast research advances. These results will provide researchers with insight into user-acceptance of using a forecasting tool and incorporation into their daily life. Ultimately, this input from people living with epilepsy and caregivers will provide timely feedback on what the community needs are and ensure researchers and companies first and foremost consider these needs in seizure forecasting tools/product development.
| S-EPMC8488220 | biostudies-literature
Project description:BackgroundHereditary angioedema (HAE) is a rare disease characterized by unpredictable, recurring subcutaneous or submucosal swelling. Without effective therapy, HAE can negatively impact patients' quality of life. Management of HAE includes on-demand treatment of attacks and short- and long-term prophylaxis (LTP) to prevent attacks. Newer therapies may be more tolerable and effective in managing HAE; however, therapies such as androgens are still widely used in some countries owing to their relative ease of access and adequate disease control for some patients. This study evaluated the characteristics, treatment patterns, clinical outcomes, and healthcare resource utilization of a multinational cohort of patients with HAE, with a focus on understanding reasons for recommending or discontinuing available therapies.MethodsA retrospective chart review was conducted at 12 centers in six countries and included data from patients with HAE type 1 or 2 who were ≥ 12 years of age at their first clinical visit. The relationship between LTP use and attack rates was evaluated using a multivariable Poisson regression model. Data were collected between March 2018 and July 2019.ResultsData from 225 patients were collected (62.7% female, 86.2% White, 90.2% type 1); 64.4% of patients had their first HAE-related visit to the center prior to or during 2014. Treatment patterns varied between countries. Overall, 85.8% of patients were prescribed on-demand treatment and 53.8% were prescribed LTP, most commonly the androgen danazol (53.7% of patients who used LTP). Plasma-derived C1 inhibitor (Cinryze®) was used by 29.8% of patients for LTP. Patients who received LTP had a significantly lower rate of HAE attacks than patients who did not receive any LTP (incidence rate ratio (95% confidence interval) 0.90 (0.84-0.96)). Androgens were the most commonly discontinued therapy (51.3%), with low tolerability cited as the most frequent reason for discontinuation (50.0%).ConclusionsOverall, findings from this study support the use of LTP in the prevention of HAE attacks; a lower rate of attacks was observed with LTP compared with no LTP. However, the type of LTP used varied between countries, with tolerability and accessibility to specific treatments playing important roles in management decision-making.
| S-EPMC10227962 | biostudies-literature