The effectiveness and safety of octocog alfa in patients with hemophilia A: up to 7-year follow-up of the real-world AHEAD international study
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PROVIDER: S-EPMC10874143 | biostudies-literature | 2024 Jan
REPOSITORIES: biostudies-literature
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Project description:BackgroundExisting adult patient pharmacokinetic (PK) data from the published Advate vs Kovaltry PK crossover study were used for this validation study. This data set is appropriate for qualification, given that it has not been previously submitted to Web-Accessible Population Pharmacokinetic Service-Hemophilia (WAPPS-Hemo) and will not have impacted the WAPPS-Hemo models for Kovaltry.ObjectiveTo compare the population PK parameters for Kovaltry (BAY 81-8973) derived from the WAPPS-Hemo models with PK parameters derived from noncompartmental analysis (NCA), using a validation PK dataset.MethodsThe qualification data set included Kovaltry factor activity (10 samples per infusion) and anthropometric data for 18 patients. Two analyses were performed comparison of Bayesian forecasting from the WAPPS-Hemo models versus NCA using the full 10-sample data set; and comparison of Bayesian forecasting using the full versus reduced 4- and 3-sample data sets. Agreement between outcomes was assessed by quantifying the variability and bias of the error.ResultsComparison of WAPPS-Hemo models versus NCA led to well-correlated outcomes despite a systematic overprediction of clearance. Population PK models demonstrated greater consistency with NCA on one-stage data, compared with chromogenic data. WAPPS-Hemo model results were consistent in reduced sampling compared to full sampling. Inclusion of a 48-hour time point in the reduced sampling greatly improved the consistency with full sampling.DiscussionQualification of population PK models and their use for Bayesian forecasting in full and reduced sampling is an essential step toward their validation. The evaluations performed in this study support the confidence of PK parameter estimates provided by the models.
| S-EPMC8563921 | biostudies-literature
Project description:BackgroundEfanesoctocog alfa is a new class of factor (F) VIII replacement therapy designed to provide high sustained factor levels for longer by overcoming the von Willebrand factor half-life ceiling.ObjectivesTo assess the pharmacokinetics and safety of standard half-life (octocog alfa) and extended half-life (rurioctocog alfa pegol) FVIIIs and efanesoctocog alfa.MethodsThis phase 1 study (NCT05042440; EudraCT 2021-000228-37) enrolled previously treated adult men with severe hemophilia A. Patients received sequential single 50-IU/kg doses of octocog alfa, rurioctocog alfa pegol, and efanesoctocog alfa after appropriate washout periods between each dose.ResultsThirteen participants were enrolled. Geometric mean elimination half-life of octocog alfa, rurioctocog alfa pegol, and efanesoctocog alfa was 11.0, 15.4, and 43.3 hours, respectively, and area under the FVIII activity-time curve was 1670, 2820, and 10,100 IU × h/dL, respectively. Efanesoctocog alfa maintained mean FVIII activity levels of >40 IU/dL for up to 4 days and at ∼10 IU/dL on day 7. Corresponding times for >40 IU/dL and >10 IU/dL were <1 and <2 days, respectively, for octocog alfa and 1 day and <3 days, respectively, for rurioctocog alfa pegol. No serious treatment-emergent adverse events were reported for efanesoctocog alfa, and no inhibitor development to FVIII was detected.ConclusionEfanesoctocog alfa had 3- to 4-fold longer elimination half-life and 3- to 6-fold greater exposure (area under the FVIII activity-time curve, 6.03 and 3.57 folds) than octocog alfa and rurioctocog alfa pegol. Efanesoctocog alfa provided high sustained FVIII activity in the normal-to-near-normal range (>40 IU/dL) for up to 4 days after the dose and at ∼10 IU/dL on day 7.
| S-EPMC10394562 | biostudies-literature
Project description:ObjectivesTo report the final results of the 2-year TAURUS study, assessing weekly prophylaxis dosing regimens of octocog alfa (Kovaltry®/BAY 81-8973) used in standard clinical practice in patients with moderate-to-severe haemophilia A.MethodsTAURUS (NCT02830477) is a phase 4, multinational, prospective, non-interventional, single-arm study in patients of any age with moderate or severe haemophilia A (≤5% factor [F]VIII activity). TAURUS was designed to primarily investigate weekly prophylaxis dosing regimens used in standard clinical practice. Annualised bleeding rates (ABRs), treatment satisfaction and adherence, and safety were also assessed.ResultsOf 302 patients included in the full analysis set, 84.4% (n = 255) maintained their octocog alfa prophylaxis baseline regimen throughout the study, with a majority of patients (76.5%, n = 231) on two times or three times weekly regimens at the end of the observation period (≥1-≤2 years). ABRs, treatment satisfaction, and adherence remained stable during the observation period. Octocog alfa was well tolerated and there were no new or unexpected adverse events.ConclusionsThese data show that a smooth transition is observed when switching to octocog alfa from a previous FVIII treatment, with no safety issues and stable bleeding rates in a real-world setting of patients with moderate-to-severe haemophilia A.
| S-EPMC10092432 | biostudies-literature
Project description:Symptoms control remains challenging for most patients with asthma. This study was conducted to evaluate the level of asthma symptoms control and lung function over 5 years of GINA (Global INitiative for Asthma) implementation. We included all patients with asthma who had been managed following GINA recommendations at the Asthma and COPD Outpatient Care Unit (ACOCU) of the University Medical Center in Ho Chi Minh City, Vietnam from October 2006 to October 2016. Of 1388 patients with asthma managed following GINA recommendations, the proportion of patients with well-controlled asthma significantly improved from 2.6% at baseline to 66.8% at month 3, 64.8% at year 1, 59.6% at year 2, 58.6% at year 3, 57.7% at year 4, and 59.5% at year 5 (p < 0.0001 for all comparisons). The proportion of patients with persistent airflow limitation significantly decreased from 26.7% at baseline to 12.6% at year 1 (p < 0.0001), 14.4% at year 2 (p < 0.0001), 15.9% at year 3 (p = 0.0006), 12.7% at year 4 (p = 0.0047), and 12.2% at year 5 (p = 0.0011). In patients with asthma managed according to GINA recommendations, asthma symptoms control and lung function improved after 3 months and the improvement was sustained over 5 years.
| S-EPMC10222601 | biostudies-literature
Project description:ObjectiveTo determine whether an intensive lifestyle intervention (ILI) designed to sustain weight loss and improve physical fitness in overweight or obese persons with type 2 diabetes was associated with bone loss after 4 years of follow-up.Research design and methodsThis randomized controlled trial of intensive weight loss compared an ILI with a diabetes support and education (DSE) group among 1,309 overweight or obese subjects. Bone mineral density was assessed at baseline and after 1 year and 4 years of intervention.ResultsILI was effective in producing significant weight loss (5.3% vs. 1.8% in ILI and DSE, respectively; P < 0.01) and increased fitness (6.4% vs. -0.8%) at year 4. In men, ILI participants had a greater rate of bone loss during the first year (-1.66% vs. -0.09% per year in ILI and DSE, respectively). Differences between groups were diminished by one-half after 4 years (-0.88% vs. -0.05% per year in ILI and DSE, respectively) but remained significant (P < 0.01). The difference in rate of hip bone loss between groups over 4 years was related to increased weight loss in ILI. Among women, the rate of bone loss did not differ between ILI and DSE after 4 years.ConclusionsA 4-year weight loss intervention was significantly associated with a modest increase in bone loss at the hip in men but not in women.
| S-EPMC4170123 | biostudies-literature
Project description:Background The rapid development of early diagnostic methods and systematic treatment for breast cancer have shed lights on the insight of prognosis of breast-conserving therapy versus mastectomy. However, there are relatively few studies with long-term follow-up, large patient cohort and under the contemporary setting in China on the subject of survival of patients undergoing breast conserving therapy versus mastectomy. Methods Data on the cases of breast-conserving therapy and mastectomy for breast cancer from October 1, 2005 to September 31, 2010 were retrieved from the breast cancer database of Chinese PLA General Hospital. The clinicopathological characteristics of patients were compared by chi-square test or Fisher’s exact test. Breast cancer-specific survival, disease-free survival, local recurrence-free survival, loco-regional recurrence-free survival, and distant metastasis-free survival were calculated and compared by Kaplan-Meier survival analysis and log-rank test firstly. And then Cox Proportional-Hazards model was used for multivariate analysis. Results There were 296 patients in the breast-conserving surgery group and 675 patients in the mastectomy group. For patients with invasive breast cancer in the entire cohort, the 10-year breast cancer-specific survival rate of patients in the breast-conserving surgery group at stage I-II was significantly higher than that of the mastectomy group. However, surgical method was not an independent prognostic factor for breast cancer-specific survival, disease-free survival and local recurrence-free survival. Moreover, N stage and luminal B-like subtype were independent prognostic factors for the breast cancer-specific survival of invasive breast cancer in the entire cohort. Conclusions This study suggests that there is no significant difference in breast cancer-specific survival between breast cancer patients undergoing breast-conserving surgery and mastectomy after adjusting for confounding factors. Lymph node staging is the major risk factor affecting patients’ survival. In this case, choosing patients with smaller tumor size, avoiding patients with stage N3, and removing a smaller volume of breast tissue including tumors while ensuring negative margins may reduce the patient’s risk of local recurrence and loco-regional recurrence.
| S-EPMC9346212 | biostudies-literature
Project description: Not available
| S-EPMC7874406 | biostudies-literature
Project description:BackgroundSigns and symptoms of the X-linked disorder, Fabry disease (FD), can occur early during childhood with heterogeneous clinical manifestations including potential cardiac and renal dysfunction. Several studies support the efficacy of the enzyme replacement therapy (ERT) agalsidase alfa, in adults with FD, though published data on the long-term safety and efficacy of agalsidase alfa in children are limited. As early treatment with ERT has the potential to reduce complications arising from disease progression, children in particular could benefit. The objective of this study was to evaluate the safety and efficacy of long-term agalsidase alfa ERT in children with FD.MethodsTKT029 was a 6.5-year open-label, multicenter, extension study of children who completed TKT023 (26-week, open-label, every-other-week, intravenous 0.2 mg/kg agalsidase alfa). TKT029 was divided into two phases (before and after an agalsidase alfa manufacturing process change); only patients who participated in both phases were included in the analysis. Primary endpoints included safety, tolerability, and heart rate variability (HRV). Additional efficacy parameters included left ventricular mass index (LVMI), estimated glomerular filtration rate (eGFR), and plasma/urine globotriaosylceramide (Gb3).ResultsEleven patients participated (phase 1 baseline median [range] age: 10.8 [8.6-17.3] years; 10 [90.9%] males). During TKT029 (6.5 years), all patients experienced ≥1 treatment-emergent adverse event (AE); eight patients had ≥1 possibly/probably drug-related AE. Six patients experienced infusion-related AEs, but none discontinued due to AEs. Eight serious AEs arose (two patients); none were deemed drug-related. No deaths occurred. Three patients developed anti-agalsidase alfa antibodies, with IgG antibodies in one patient that were agalsidase alfa neutralizing, but without apparent clinical impact. Renal (eGFR) endpoints remained generally in normal range. Cardiac endpoints remained stable within normal range for LVMI and a trend towards improved HRV, although some patients experienced a reduction in heart rate. Plasma and urinary Gb3 reductions were maintained.ConclusionsTKT029 represents the longest assessment of ERT in children with FD in a clinical trial setting. Overall, agalsidase alfa was well tolerated and demonstrated a stabilizing clinical effect. Agalsidase alfa may be a useful clinical therapeutic option for long-term treatment initiated during childhood in patients with FD.Trial registrationhttp://ClinicalTrials.gov identifier NCT00084084 .
| S-EPMC4260255 | biostudies-literature
Project description:AimsStress echocardiography is widely used to assess patients with chest pain. The clinical value of a positive or negative test result to inform on likely longer-term outcomes when applied in real-world practice across a healthcare system has not been previously reported.Methods and resultsFive thousand five hundred and three patients recruited across 32 UK NHS hospitals between 2018 and 2022, participating in the EVAREST/BSE-NSTEP prospective cohort study, with data on medical outcomes up to 2023 available from NHS England were included in the analysis. Stress echocardiography results were related to outcomes, including death, procedures, hospital admissions, and relevant cardiovascular diagnoses, based on Kaplan-Meier analysis and Cox proportional hazard ratios (HRs). Median follow-up was 829 days (interquartile range 224-1434). A positive stress echocardiogram was associated with a greater risk of myocardial infarction [HR 2.71, 95% confidence interval (CI) 1.73-4.24, P < 0.001] and a composite endpoint of cardiac-related mortality and myocardial infarction (HR 2.03, 95% CI 1.41-2.93, P < 0.001). Hazard ratios increased with ischaemic burden. A negative stress echocardiogram identified an event-free 'warranty period' of at least 5 years in patients with no prior history of coronary artery disease and 4 years for those with disease.ConclusionIn real-world practice, the degree of myocardial ischaemia recorded by clinicians at stress echocardiography correctly categorizes risk of future events over the next 5 years. Reporting a stress echocardiogram as negative correctly identifies patients with no greater than a background risk of cardiovascular events over a similar time period.
| S-EPMC11781832 | biostudies-literature
Project description:BackgroundEating disorders are often characterised as disabling, chronic or relapsing conditions with high mortality rates. This study reports follow-up outcomes for patients seen at the Maudsley Centre for Child and Adolescent Eating Disorders (MCCAED), whose end of treatment outcomes are reported in a separate paper.MethodsThree-hundred-and-fifty-seven former patients, who received evidence-based treatment for an eating disorder as a child or adolescent in MCCAED between 2009 and 2014 were eligible to participate. Current contact information was available for 290, of whom 149 (51.4%) consented to follow-up. Participants were sent links to online questionnaires, with additional demographic information extracted from medical records. Descriptive analyses of key socioeconomic and health outcomes were performed on data collected.ResultsMean length of follow-up was 6 years 11 months. Ten (6.7%) participants reported a current diagnosis of an eating disorder at follow-up. The great majority reported no (63.8%) or minimal (26.8%) interference from eating disorder difficulties. More than half (53.6%) reported other mental health diagnoses with most reporting no (33.8%) or minimal (50.7%) interference from those difficulties. One third (33.3%) had sought help for an eating disorder and around 20% received prolonged/intensive treatment during the follow-up period. Approximately 70% had sought treatment for other mental health difficulties (mostly anxiety or depression) and 35.4% had substantial treatment. At follow-up more than half (55.5%) reported doing generally well, and around two-thirds reported general satisfaction with their social well-being (65%). The majority (62.7%) had a good outcome on the Morgan Russell criteria, which was consistent with low self-reported ratings on EDE-Q, and low impact of eating disorder or mental health symptoms on work and social engagement. Most of the former patients who had day and/or inpatient treatment as a part of their comprehensive integrated care at MCCAED did well at follow-up.ConclusionsYoung people seen in specialist eating disorder services do relatively well after discharge at longer-term follow-up especially regarding eating disorders but less favourably regarding other mental health difficulties. Few reported a diagnosable eating disorder, and the great majority went on to perform similarly to their peers in educational and vocational achievements.
| S-EPMC8817149 | biostudies-literature