Advances in Therapy最新文献

Introduction: Several primary and secondary disorders disrupting normal growth pattern are responsible for childhood short stature (SS; height less than 2 standard deviation score [SDS] or the third percentile). Pegylated recombinant human growth hormone (PEG-rhGH) is a long-acting growth hormone which has demonstrated efficacy and safety in pediatric growth hormone deficiency. However, limited data is present on its treatment pattern, extensive population use, and long-term follow-up. Therefore, a real-world study is required to evaluate the efficacy and safety of PEG-rhGH and recombinant human growth hormone (rhGH) in treating childhood SS.

Methods: The proposed study will be an open-label, multicenter, prospective and retrospective, observational study that will recruit Chinese children aged ≥ 2 years with SS. The entire study will be categorized into three cohorts: retrospective, retrospective-prospective, and prospective. The study will recruit 10,000 patients including 3000 patients in the retrospective cohort and 7000 in the retrospective-prospective and prospective cohort, respectively. The total duration of this study will be 16 years. The primary objective will be to evaluate the long-term safety (incidence of all adverse events (AEs) and serious adverse events) of PEG-rhGH and rhGH for the treatment of patients with SS having growth hormone disorder (GHD), idiopathic short stature (ISS), small for gestational age (SGA), Turner syndrome (TS), Prader-Willi syndrome (PWS), Noonan syndrome (NS), deficiency of the short stature homeobox gene on the X-chromosome (SHOX deficiency), and other causes of SS. The secondary objective will be to evaluate the efficacy of PEG-rhGH and rhGH for the treatment of patients with SS with different etiologies.

Planned outcomes: The results may provide the evidence of long-term efficacy and safety of PEG-rhGH and rhGH by analyzing the existing patient data and will also provide a vast array of information, which can be used as reference evidence for the Chinese academic community to design national guidelines or consensus for patients with SS.

Trial registration: The study has been registered at ClinicalTrials.gov (NCT06110910). Date of registration October 31, 2023.

To quantify the impact of Glucagon-like peptide1 receptor-agonists (GLP1-RAs) on asthma control, we analysed people with asthma and obesity, using the Optimum Patient Care Research Database (OPCRD). We identified 10,111 GLP1-RA exposed people and 50,555 unexposed controls. The exposed cohort had higher BMI and more uncontrolled asthma [risk domain asthma control (RDAC) and overall asthma control (OAC)]. The exposed cohort lost more weight and had improved asthma control for both RDAC (odds ratio 2.11 95% CI 1.90-2.36) and OAC (OR 2.10, 95%CI 1.81-2.45) scores. GLP1-RA drugs appear to improve asthma control for people with obesity.

Introduction: The monarchE trial demonstrated that the addition of 2 years of abemaciclib to adjuvant endocrine therapy (ET) significantly reduced the risk of disease recurrence in patients with hormone receptor positive (HR+), and human epidermal growth factor receptor 2-negative (HER2-), node-positive early breast cancer (EBC) at high risk of disease recurrence. Abemaciclib meets a critical unmet need for more effective adjuvant therapy for this patient population. This study evaluates the cost-effectiveness (CE) of abemaciclib plus ET compared to ET alone.

Methods: A five-state cohort transition model, which presents a United Kingdom (UK) perspective, is parameterized using data from the monarchE trial and literature. Cost-effectiveness results are presented in terms of cost/quality-adjusted life year (QALY) over a lifetime time horizon. Various assumptions were tested through sensitivity and scenario analyses and uncertainty was assessed through probabilistic analysis.

Results: Patients receiving abemaciclib plus ET were predicted to experience higher QALYs (11.16 compared to 10.42) at an increased cost (£87,541 compared to £48,625), leading to an incremental cost-effectiveness ratio (ICER) of £52,317 per QALY gain compared to ET alone. The increased costs associated with the addition of abemaciclib were partially offset by a reduction in distant disease recurrence and associated costs. The scenario and sensitivity analyses supported robust base case results.

Conclusion: Despite the ICER exceeding usual willingness-to-pay (WTP) levels in the UK, a consequence of using list prices, the CE model utilizing the latest data cut from the monarchE trial, demonstrated that the upfront cost of abemaciclib reduces the risk of a terminal breast cancer prognosis and its associated cost and quality of life impact. The addition of 2 years of abemaciclib provides an option for the treatment of HR+, HER2-, node-positive, high-risk EBC.

Introduction: Continuous treatment with rifaximin 550 mg (hereafter rifaximin) is associated with lower hospitalization rates in patients with hepatic encephalopathy (HE); however, access barriers may exist. This study assessed gaps in rifaximin access and the impact of treatment gaps, particularly those resulting from claim rejections, on hospitalizations and healthcare costs among patients with HE in the United States.

Methods: The IQVIA PharMetrics^® Plus database linked with Longitudinal Access and Adjudicated Data (2015-2022) were used to identify adults with HE who had ≥ 1 paid rifaximin prescription fill. Rifaximin treatment gaps were assessed during the 12-month period from the first observed attempt at receiving rifaximin (index date). Adjusted number of overt HE (OHE) hospitalizations and healthcare costs were compared over the 6 months following the index date between Cohort 1, who had no gap due to claim rejection and had < 7 days of treatment gap due to other reasons, and Cohort 2, who had ≥ 1 rejection gap or had ≥ 7 days of non-rejection gap.

Results: During the year following the index date, 94.7% of the 1711 patients experienced a treatment gap, including 34.8% with initiation gaps from first attempt at receiving rifaximin to first paid claim (77.7% of initiation gaps due to rejected claims) and 72.0% with gaps in access during active treatment (14.8% of active treatment gaps due to rejected claims). Compared with Cohort 1 (n = 432; mean age 56.3 years), Cohort 2 (n = 679; mean age 54.8 years) had 1.55 times the incidence rate of OHE hospitalizations [adjusted incidence rate ratio: 1.55 (95% confidence interval: 1.10-2.20)] and incurred US$1579 more in healthcare-associated costs per-patient-per-month (all p < 0.05).

Conclusion: Prescription claim rejections frequently led to delays in rifaximin initiation and gaps in access during active treatment. Access barriers to rifaximin were associated with increased hospitalizations and healthcare costs in patients with HE.

Introduction: AD-REAL is an ongoing 1-year multinational observational cohort study evaluating oral systemic therapies in the management of adults with atopic dermatitis (AD) in a real-world practice across four European countries. Herein, we provide insights on baseline disease characteristics and treatment patterns of patients treated with oral systemic therapies, including baricitinib.

Methods: AD-REAL included adults with moderate-to-severe AD for ≥ 6 months, who were initiated on an oral systemic treatment in clinical practice and enrolled either in the baricitinib or the other oral systemic (OOS) cohort. Here, we report baseline characteristics, including clinician-assessed outcomes (Eczema Area and Severity Index [EASI]) and patient-reported outcomes (PROs), and explore AD subgroups based on body surface area (BSA) ≤ 40% and Itch numerical rating scale (NRS) ≥ 7. Continuous outcomes were reported using mean and standard deviation (SD) and categorical variables using frequencies. Baseline continuous variables with missing data were imputed using the multiple imputation method.

Results: Baseline demographics were consistent across both baricitinib and OOS cohorts. Patients showed long disease duration (26.2 years), refractory to several systemic options, and a moderate EASI mean (SD) score of 17.5 (10.7). The majority (53.7%) presented with severe Validated Investigator Global Assessment (vIGA) and highly impacted Dermatology Life Quality Index (DLQI) score (14.0 [7.1]). At baseline, patients were predominantly female, with AD mainly affecting face/neck (89.4%) and upper extremities (90.3%). About 68.4% presented with BSA ≤ 40 and 33.8% with BSA ≤ 40 and Itch NRS ≥ 7. From those with BSA ≤ 40% and Itch NRS ≥ 7, 63.9% were treated with Janus kinase inhibitors (JAKi).

Conclusion: This analysis provides key information on baseline disease characteristics of patients treated with oral systemics, including baricitinib. Most patients treated with oral systemics in AD-REAL had long-lasting disease, refractory to systemic therapies, with moderate skin affectation but severe itch and impact on quality of life. AD-REAL is the first study to show many patients in real-world practice who are treated with oral systemics present with BSA ≤ 40 and Itch NRS ≥ 7, and most of these patients were treated with JAKi.

Introduction: New maintenance therapies to treat advanced ovarian cancer have added complexity to identifying lines of therapy (LOTs) for real-world evidence (RWE) studies. This study evaluated the performance of a claims-based algorithm that identifies LOTs among patients with ovarian cancer using medical chart review validation.

Methods: The algorithm was developed previously utilizing the Optum Research Database (ORD), a US database that contains administrative claims data. To validate the algorithm, LOT results generated using claims data vs chart data were compared at the patient level by calculating the percent agreement between total number of active and maintenance LOTs, type of therapy (neoadjuvant vs adjuvant classification), and type of regimen (individual drugs). Patients with a diagnosis of ovarian cancer who initiated chemotherapy between December 1, 2014, and September 15, 2017, were included in the study. We report descriptive statistics, the percentage correspondence between medical records and claims data, and kappa statistics to measure the magnitude of agreement.

Results: A total of 294 patients were included in the analysis; 164 received only chemotherapy and no maintenance, 77 received bevacizumab, and 53 patients received poly (ADP-ribose) polymerase inhibitors (PARPi). Mean age was 64.9 years, and 47.3% had stage III cancer. The algorithm demonstrated substantial agreement between claims and medical records for total number of lines of active and maintenance therapy (weighted kappa 0.65 and 0.62 p < 0.0001). There was moderate-to-substantial agreement for neoadjuvant and adjuvant therapy (kappa 0.56 and 0.62 p < 0.0001). The algorithm performed best at identifying early treatment with a regimen match of 82% and 88% agreement for first-line active and first-line maintenance, respectively.

Conclusion: We validated an administrative claims-based algorithm that demonstrates strong concordance with medical records for identifying LOT among patients with ovarian cancer. The algorithm can be applied in future studies to analyze treatment patterns and outcomes.