Drugs - Real World Outcomes最新文献

Background: Wilson's disease (WD) is an autosomal recessive disorder characterized by abnormal copper accumulation, leading to multi-organ damage. The economic impact of WD in Italy has not been comprehensively studied.

Aims: The objectives were to determine the economic burden of WD, describe the demographic and clinical characteristics, and estimate the treatment distribution over time, using real-world data from Italy.

Methods: A retrospective multicenter longitudinal chart review study was conducted across six Italian reference centers for WD management. Patients with at least one visit for WD in 2019-2020 were included. Demographic, clinical, and treatment data were collected from medical records, and healthcare resource utilization and related costs were estimated over a 12-month follow-up. Treatment patterns from diagnosis to 2021 were also described.

Results: A total of 243 patients with WD were included (183 adults, 60 minors). Median age at diagnosis was 11 years in adults and 7 years in minors. At enrollment, hepatic involvement was the most frequent clinical manifestation (84.7% of adults; 80% of minors), while 13.1% of adults and 16.7% of minors were asymptomatic. In adults, use of D-penicillamine and zinc decreased, while trientine tetrahydrochloride use increased over time. In minors, treatment remained stable. The average annual cost per patient was €10,394 for adults (mainly driven by pharmacological treatment) and €1351 for minors. Costs increased with the number of disease manifestations.

Conclusion: The economic burden of WD in Italy varies with disease severity and treatment strategy, highlighting the need for optimized management practices to mitigate costs while enhancing patient care.

Background: Partial response to standard-dose proton pump inhibitors (PPIs) in gastroesophageal reflux disease (GERD) is common, yet real-world data on its burden and management in Indian settings remain limited.

Objective: This study aimed to understand the burden, clinical profile, drug utilization patterns across specialties, the effectiveness of Pantoprazole 80 mg dual delayed-release (DDR) formulation, and management strategies used in the treatment of partial responders with clinically diagnosed GERD in Indian settings.

Methods: This was a multicentric, retrospective observational study. Data on adult patients with GERD with a follow-up duration of at least 4 weeks from baseline were extracted from electronic medical records (EMR) of outpatient settings from five centers, which included drug utilization patterns, clinical and treatment profiles, and effectiveness of PPIs.

Results: Among EMRs of 5205 patients with GERD, 38.0% were on rabeprazole and 36.6% on pantoprazole (mean age: 53.3 years; standard deviation: 14.3 years), and 55.0% were male. Heartburn was the primary complaint in 76.0% of cases. Cardiovascular co-morbidities with dyslipidemia were reported in 66.7% (1742/2610) patients. Pantoprazole and rabeprazole were preferred across specialties, where 31.1% (592/1906) and 17.7% (350/1979) adhered to treatment, respectively. Total burden of partial responders was 41.7%, including patients who switched PPIs, changed PPI dosage, or added other medications. Pantoprazole 40 mg twice daily (BD) showed 49.1% improvement in heartburn and 50.9% in abdominal pain. Pantoprazole 80 mg DDR once daily demonstrated significantly higher symptom relief, with a 60.2% reduction in heartburn (p < 0.001) and a 66.1% reduction in abdominal pain (p < 0.001). These findings suggest that higher-dose pantoprazole therapy may be a clinically effective strategy for managing partial responders to standard-dose PPIs.

Conclusions: A significant proportion of patients with GERD were partial responders to PPIs. Pantoprazole and rabeprazole had high patient adherence across disciplines. Both pantoprazole DDR 80 mg once daily (OD) and 40 mg BD demonstrated significant symptom reduction in partial responders, supporting their use in optimizing GERD management in Indian clinical settings.

Background: The relationship between antidepressants, depression, and the incidence of postpartum hemorrhage (PPH) has been reported in observational studies, but the causal link between these factors remains unknown. Clarifying this relationship is important for treating depression during pregnancy and managing PPH.

Objective: We aimed to assess the causal relationship between antidepressants, depression, and PPH using a two-sample Mendelian randomization method.

Methods: Single nucleotide polymorphisms were identified from publicly available genetics summary databases (FinnGen database, access date: 28 December, 2023, version R9, phenocode: ANTIDEPRESSANTS, 195,321 participants; the genome-wide association studies [GWAS] catalog, access date: 3 April, 2024, GWAS ID: ebi-a-GCST90016607; Integrative Epidemiological Unit database, access date: 3 April, 2024, GWAS ID: ieu-a-1187) as alternative exposure factors for antidepressants and depression. Subsequently, inverse variance weighting, Mendelian randomization-Egger regression, weighted median, simple method, and weighted method were employed for Mendelian randomization analyses, and the results were validated for pleiotropy, heterogeneity, and sensitivity.

Results: The analyses employed three sets of genetic tools, comprising two sets of 9 and 32 single nucleotide polymorphisms that are strongly associated with depression and another set of 26 single nucleotide polymorphisms that are associated with antidepressants. The inverse variance weighting indicated that antidepressants are associated with PPH (odds ratio = 1.36, 95% confidence interval 1.10-1.69, p = 0.005). Conversely, none of the five methods of Mendelian randomization analysis identified an effect of depression on PPH.

Conclusions: This Mendelian randomization analysis indicated that antidepressant use is associated with PPH. However, the evidence does not support a causal relationship between depression and PPH.

Background: People with noncommunicable diseases (NCDs) are at a higher risk of contracting vaccine-preventable diseases, such as influenza, with a higher likelihood of severity and complications. However, the immunization rates for the influenza vaccine among this population in the Czech Republic are very low.

Objective: This survey, among adults with NCDs in the Czech Republic, assessed the knowledge, attitudes, and gaps toward vaccination in general and influenza vaccination in particular.

Methods: The survey was conducted between February 2023 and March 2023 among patients with NCDs in the Czech Republic. A structured web-based questionnaire with open-ended questions was administered. This study is a preplanned subgroup ancillary analysis of a previous multicentric study conducted on 1106 patients.

Results: In all, 120 patients were enrolled, with 62% (74) aged between 41 and 60 years. Approximately 30% (36) had taken the influenza vaccine in the last 2 years and 70% (84) had not. Of the total sample, only 46% (55) had a positive opinion about influenza vaccines; this increased to 91% (33) among those vaccinated against the influenza virus. The main drivers of influenza vaccination were general physician (GP) recommendation [50% (18)] and patient initiative [47% (17)]. The main barriers to the influenza vaccine were lack of belief regarding its need [52% (44)], experience of mild severity of influenza [30% (25)], and lack of GP recommendation [25% (21)]. Physicians, dedicated websites, and family members are the most common sources of information regarding influenza. Even among those vaccinated for influenza, only 17% (6) had information about the risk of not taking the vaccine. A high level of dissatisfaction with the information was found among patients not vaccinated against influenza. People wanted more information on who should not receive the influenza vaccination. Unvaccinated patients sought information on side effects and efficacy. Only 40% (48) of the respondents said that they are likely/extremely likely to take an influenza vaccination in the future.

Conclusions: Healthcare practitioners are the key influencers for people to get vaccinated. The dissemination of information about the importance of influenza vaccines for people with NCDs needs to be increased in the Czech Republic.

Background: Intravenous iron replacement therapy for the treatment of iron deficiency anemia is often required in patients with chronic diseases including cancer, heart failure, or chronic kidney disease.

Objective: We aimed to compare healthcare resource utilization and costs for patients treated with intravenous ferric carboxymaltose (FCM) or low-dose iron for iron deficiency anemia.

Methods: This analysis of Optum Research Database administrative claims data included patients with iron deficiency anemia who received intravenous iron from 2017 to 2019 and had diagnoses of cancer, heart failure, or chronic kidney disease. Patients were continuously enrolled for 6-month baseline and 12-month follow-up periods. Follow-up all-cause total costs for FCM and low-dose iron cohorts were compared using generalized linear models; inpatient costs were estimated with two-part models to account for patients without hospitalizations. Models were adjusted for age, sex, geographic region, insurance type, index year, baseline comorbidity scores, and healthcare costs. Sensitivity analyses compared FCM with an iron sucrose subgroup.

Results: For patients with cancer (n = 10,763), mean adjusted all-cause total costs were numerically lower for FCM than low-dose iron by $2369 (cost ratio [CR] 0.97, P = 0.182) and significantly lower for FCM than iron sucrose by $6712 (CR 0.93, P < 0.001). For heart failure (n = 8337), the mean all-cause total cost was numerically lower for FCM than low-dose iron by $2022 (CR 0.97, P = 0.198) and significantly lower for FCM than iron sucrose by $3892 (CR 0.95, P = 0.024). For chronic kidney disease (n = 10,617), the mean all-cause total cost was statistically significantly lower for FCM than low-dose iron by $3623 (CR 0.94, P = 0.006) and iron sucrose by $4161 (CR 0.93, P = 0.004). For all groups, the FCM and low-dose iron cohorts differed in both the odds of having any inpatient costs and the level of inpatient cost (cancer: odds ratio 0.79, P < 0.001; CR 0.88, P < 0.001; heart failure: odds ratio 0.76, P < 0.001; CR 0.89, P < 0.001; chronic kidney disease: odds ratio 0.75, P < 0.001; CR 0.84, P < 0.001). Inpatient cost results were consistent for iron sucrose.

Conclusions: Despite the typically higher drug acquisition cost of FCM versus low-dose intravenous iron, the price differential was offset by the lower inpatient cost incurred in the FCM cohort in each patient population. These findings suggest the potential economic benefit of FCM to reduce inpatient utilization and associated costs to patients and health plans compared with low-dose intravenous iron.

Background: Anaplastic thyroid carcinoma (ATC) is a highly aggressive cancer historically associated with a median survival of about 5 months. Recent advances in tumor genomic testing have identified targetable BRAF mutations in about 35-40% of ATC cases and have shown high levels of programmed death ligand-1 (PD-L1) expression in ATC. These observations have led to clinical trials showing favorable outcomes with targeted therapy and immunotherapy for ATC.

Objective: We aimed to evaluate treatments and outcomes of patients diagnosed with anaplastic thyroid cancer treated at our institution in order to determine the impact of targeted therapy and immunotherapy.

Methods: A retrospective review of ATC patients at a single institution was performed. Data were collected from institutional electronic medical records, including demographic information, treatments administered, and outcomes including survival.

Results: A total of 28 patients were identified within the period under study. Systemic therapy was initiated in 61% of patients. The median overall survival for all patients was 7.3 months. There was a statistically significant improvement in overall survival for patients who received targeted therapy or immunotherapy compared to those who did not.

Conclusions: In this single-institution cohort of 28 patients with ATC, patients who received either targeted therapies or immunotherapy demonstrated markedly improved outcomes. Further clinical trials are required to determine the optimal systemic therapy for this patient population.

Background: Brigatinib, a next-generation anaplastic lymphoma kinase (ALK) inhibitor was licensed for the treatment of ALK-positive metastatic non-small cell lung cancer in 2016. However, real-world evidence on the safety and effectiveness of brigatinib in Latin America remains limited.

Objective: The aim of this study was to assess the safety and effectiveness of brigatinib in the real world in Argentina.

Methods: We conducted a non-interventional cohort study of adult patients (aged ≥  18 years) with a diagnosis of ALK-positive metastatic non-small cell lung cancer not previously treated (first line) or previously treated (second line) with an ALK inhibitor and who received at least one dose of brigatinib between November 2020 and March 2023. The primary outcome was the incidence of treatment-emergent adverse events. Secondary outcomes at the 24-week follow-up were the percentage of patients with an overall best objective response rate of complete or partial response; intracranial objective response rate; progression-free survival; and overall survival.

Results: Of the 39 patients included in the study (n = 22 [first line]; n = 17 [second line]), 12 patients (30.7%) experienced treatment-emergent adverse events, with the most frequent being increased levels of transaminases (7.6%), increased level of blood creatine phosphokinase (5%) and hypokalaemia (5%). Most adverse events (85.7%) were mild to moderate. Effectiveness outcomes at 24 weeks in patients treated with brigatinib first line or second line, respectively, were as follows: overall objective response rate: 81.8% and 70.5%; intracranial objective response rate (in patients with brain metastases at baseline): 66.6% and 88.8%; progression-free survival: 93.8% and 82.4%; overall survival: 100% and 87.5%.

Conclusions: Brigatinib was demonstrated to be a safe and effective treatment option for ALK-positive metastatic non-small cell lung cancer in routine clinical practice in Argentina.

Clinical trial registration: NCT04887519.

Background: In early 2022, new treatment recommendations for heart failure (HF) were introduced in Sweden.

Objective: This study aims to evaluate and analyze the pharmaceutical treatment patterns of HF patients over time in Sweden, in relation to the updated treatment recommendations.

Methods: This observational study is based on registry data. The study population consisted of patients ≥18 years old who, at any time between 2017 and 2023, had an HF diagnosis, defined using ICD-10 code I50 (n = 212,757). Descriptive statistics were presented for the study population. Based on data from the national drug prescription registry, the treatment patterns between 2021 and 2023 were analyzed using biannual datasets before and after the introduction of treatment recommendations.

Results: The mean age of the study population was 79 years and 56% were men. The utilization of quadruple therapy and SGLT2 inhibitors, both as monotherapy and in combination, increased over time, with a rising trend already apparent prior to the introduction of the updated treatment recommendations. At the end of 2023, about 30% of the incident HF population had at least tried quadruple therapy. Furthermore, a growing number of diverse treatment pathways among HF patients was observed over time, which may indicate an increased consideration for individualized treatment.

Conclusions: Even though the implementation of the treatment recommendations for HF is not yet optimal, this study found a notable adoption of quadruple therapy in Sweden. There was an increased use of SGLT2 inhibitors and quadruple therapy, beginning even before the introduction of the updated Swedish treatment recommendations.

Background: Multiple sclerosis (MS) is a heterogeneous disease that may manifest differently among racial/ethnic groups, influencing response to disease-modifying therapy (DMT). Data on natalizumab (NTZ) effectiveness in people with MS (PwMS) based on race/ethnicity are limited.

Objective: The aim of this study was to evaluate the effectiveness of NTZ on relapse onset and rate, and to assess MS-related healthcare encounters and costs in Black, Hispanic, Asian, and White PwMS.

Methods: This was a retrospective analysis of the Komodo Health Claims Database, including adult patients in the US with one or more MS claim at index date (January 1, 2016-August 31, 2022). Patients were followed from first NTZ exposure through end of study, end of insurance eligibility, gap in index DMT > 45 days, or DMT switch. Annualized relapse rate (ARR), time to first relapse, and MS-related healthcare encounters and costs were compared in the 12 months pre/post NTZ initiation and while on treatment across racial strata.

Results: The study included 3244 PwMS (Black, n = 632; Hispanic, n = 382; Asian, n = 49; White, n = 2181). Mean post-index NTZ exposure was 15.5-19.2 months. Post-index ARRs were significantly reduced across racial/ethnic groups (p < 0.001). The adjusted Kaplan-Meier estimated proportion of relapse-free patients at 2 years for all racial/ethnic groups was not significantly different from the White group. Significant differences were observed in annualized MS-related healthcare cost rates but not in annualized MS-related encounter rates before and after NTZ initiation across the racial/ethnic groups.

Conclusion: NTZ was effective across racial/ethnic groups although not significantly different between groups.