Advances in Therapy最新文献

Introduction: Malignant pleural mesothelioma (MPM) is a rare malignancy typically attributed to occupational asbestos exposure and associated with dismal survival outcomes. The standard of care for unresectable MPM was platinum-based chemotherapy until the approval of immunotherapy in 2020. We examined treatment patterns, clinical outcomes, health care resource use (HCRU), and costs in patients with MPM to understand disease burden before the first immunotherapy approval.

Methods: This retrospective study used the Surveillance, Epidemiology, and End Results (SEER)-Medicare deidentified database in the US to select patients aged ≥ 65 years who initiated first-line therapy (1L, index event) for advanced MPM (regional extension or distant) diagnosed between 2007 and 2019. Eligible patients had continuous Medicare enrollment from the diagnosis date to ≥ 3 months post-index date, with ≥ 6-month follow-up after 1L initiation. Kaplan-Meier methods were used to estimate real-world time to treatment discontinuation (rwTTD) and overall survival (OS). Data cutoff was December 31, 2020.

Results: Among 554 patients with MPM who initiated 1L, median age was 74 years; most were white (95.0%) and male (73.7%). The most common 1L regimens were platinum-pemetrexed (75.6%), pemetrexed monotherapy (8.5%), and bevacizumab-platinum-pemetrexed therapy (8.1%); the median rwTTD of 1L therapy was 5.3 (95% CI, 4.2-6.3) months. Of 554 patients, 300 (54.2%) initiated second-line therapy (2L), and 120 (21.7%) initiated third-line therapy (3L). Platinum-pemetrexed (25.0%) and gemcitabine (25.0%) were the most common 2L and 3L, respectively. Median OS was 16.3 (95% CI, 15.4-17.8) months, with 5-year survival of 7.9% (95% CI, 5.5-10.9). Mean per-patient-per-month all-cause inpatient admissions, outpatient visits, emergency department visits, and total costs were 0.04, 1.74, 0.18, and $11,432, respectively.

Conclusion: The study highlights a substantial clinical and economic burden among patients with advanced MPM who received 1L chemotherapy in the years preceding immunotherapy approvals, underscoring the need for more effective therapies to improve outcomes.

Introduction: Combining ezetimibe (EZ) and statins is recommended for the treatment of elevated low-density lipoprotein-cholesterol (LDL-C). This subgroup analysis evaluated the efficacy of fixed-dose combination (FDC) therapy with EZ and atorvastatin (AS) versus AS monotherapy on attaining LDL-C goals in Chinese patients with very high risk of atherosclerotic cardiovascular disease (ASCVD) grouped by ASCVD risk, age, and sex.

Methods: Data from the phase III, randomized, double-blind study (NCT03768427) compared EZ10/AS10 mg FDC versus AS20 mg (cohort A), and EZ10/AS20 mg FDC versus AS40 mg monotherapy (cohort B) in Chinese patients with uncontrolled hypercholesterolemia. Proportions of patients attaining 2016 Chinese guideline-recommended LDL-C goals (low/medium risk [< 130 mg/dL], high risk [< 100 mg/dL], very high risk [< 70 mg/dL]) were assessed at weeks 6 and 12. Subgroup analyses by ASCVD risk, age (< 65 and ≥ 65 years), and sex were conducted.

Results: LDL-C goal attainment was significantly higher with FDCs versus AS monotherapy at week 12 (cohort A: 62.7% vs. 35.1%, P = 0.0009; cohort B: 67.5% vs. 31.0%, P < 0.0001). A greater proportion of patients with very high ASCVD risk attained LDL-C goals with FDCs versus AS monotherapy at week 12 (cohort A: 62.3% vs. 33.9%; cohort B: 69.1% vs. 29.5%). LDL-C goal attainment was higher with FDCs versus individual doses of AS at weeks 6 and 12 in both cohorts, regardless of age or sex.

Conclusion: FDCs significantly improved LDL-C goal attainment compared to AS monotherapy in patients with very high ASCVD risk. In the subgroups by age and sex, a higher proportion of patients with uncontrolled hypercholesterolemia attained their LDL-C goals.

Trial registry: Trial registration number NCT03768427.

Introduction: Pancreatic enzyme replacement therapy (PERT) is the central management strategy for symptomatic and confirmed exocrine pancreatic insufficiency (EPI). PERT products composed of pancrelipase (under the brand names Creon, Zenpep, Pancreaze, Viokace, Pertzye) differ in formulation-specific attributes and access/coverage considerations. Multiple factors impact healthcare providers' (HCPs) decision-making when selecting an appropriate PERT. The current study's primary objective is to assess real-world EPI management practice and HCP perceptions of PERT products in the United States.

Methods: An online survey was carried out with HCPs who had treated patients with EPI for ≥ 3 years and prescribed PERT products to ≥ 10 patients over a 12-month period. The survey collected de-identified data on HCP characteristics, prescribing patterns, and perceptions of PERT products across the domains of efficacy, convenience, and access. Descriptive statistics were calculated, and HCPs' perceptions were compared across PERT products.

Results: A total of 250 HCPs were surveyed comprising 124 specialists, 95 generalists, and 31 advanced practice providers. HCPs managed a median of 30 patients with EPI on PERT in the 12 months preceding the survey. The most commonly prescribed PERT products were Creon (84.0%), Zenpep (60.4%), and Pancreaze (59.2%), with fewer HCPs prescribing Viokace (27.2%) and Pertzye (16.0%). Specific factors considered in prescribing decisions included improvement in abdominal and bowel symptoms (83.6%), affordability (72.4%), and formulary/insurance coverage (72.0%). A significantly higher proportion of HCPs reported favorable perceptions of Creon over other PERT products. Perceptions of formulary/insurance coverage across PERT products varied, with 8.0-56.0% of HCPs agreeing or strongly agreeing that a prescribed product had good coverage. These findings were generally consistent across different provider types.

Conclusions: HCPs consider multiple factors when prescribing PERT for patients with EPI. HCP perceptions varied across PERT products, and Creon was favorably perceived more often compared to the other therapeutic options. Various factors may contribute to barriers to treatment and should be addressed to improve access.

Introduction: Using data from the OVERCOME study, we examined the influence of household income on access to specialty care and use of recommended acute and preventive treatments for migraine in a large population-based study.

Methods: This analysis from the OVERCOME study, a multicohort, web-based survey (2018-2020) among adults with migraine in the US, examined the influence of annual household income on (1) care-seeking, (2) the highest level of care received (emergency department/urgent care, primary care, specialty care), and (3) use of acute or preventive treatments recommended by the American Headache Society. We used standardized mean differences and logistic regression (LR) models to estimate the magnitude of differences in health care behavior as a function of household income and insurance status.

Results: Among OVERCOME (US) respondents with migraine who provided demographic information (n = 56,667), a higher proportion of people in the lowest income group (< $25,000) received their highest level of migraine care in the emergency department/urgent care setting versus the proportion in the highest income group [≥ $100,000: 12.3% vs 6.5%, standardized mean difference (SMD) = 0.20], and a greater proportion in the highest income group received care in a specialty headache care setting (48.6% vs 36.6% in the lowest income group, SMD = 0.24). The highest income group was more likely to receive a recommended acute treatment [odds ratio (OR) = 1.3, 95% confidence interval (CI) = (1.2, 1.4)] and a recommended preventive treatment [OR = 1.3, 95% CI = (1.2, 1.4)]. Those with health insurance were more likely to receive specialized care [OR = 2.6, 95% CI = (2.4, 2.8)] and recommended acute [OR = 1.9, 95% CI = (1.8, 2.0)] and preventive treatment [OR = 2.1, 95% CI = (1.9, 2.3)]. The effect of insurance was greatest in low-income strata and was not significant in the highest household income group.

Conclusion: Disparities in annual household income may be a barrier to appropriate migraine care, but having health insurance mitigates the effect.

Introduction: Sickle cell pain crises (SCPCs) are debilitating pain events that significantly impact quality of life in patients with sickle cell disease (SCD), but no fit-for-purpose tool exists to capture patients' experiences of them. We developed a patient-reported outcome (PRO) tool to capture patients' SCPC experiences and ensured its content validity through cognitive debriefing (CD) interviews with adolescents and adults with SCD.

Methods: In this non-interventional, qualitative research study, a targeted literature review (TLR) was conducted to create preliminary items and a preliminary conceptual model (CM) of SCPCs in patients with SCD. Next, an item-generation session was held with clinical experts, followed by hybrid concept elicitation (CE) and CD interviews with patients over three waves; the preliminary items and CM were refined iteratively after each wave. SCPC and impact disturbance ratings were summarised using descriptive statistics. CD responses were analysed on the basis of a semi-structured discussion guide.

Results: The TLR identified 12 articles describing 47 concepts related to pain, anatomical sites, duration, frequency, and impacts of SCPCs. In CE interviews, patients described various aspects of their SCPC experience, including anatomical sites affected, pain characteristics, and duration. CD interviews confirmed the content validity of the eDiary, with patients finding most questions and response options clear and useful. The diary was modified on the basis of patient feedback per wave.

Conclusion: The SCPC eDiary is a novel PRO instrument that captures the frequency, severity, and impact of home-managed pain crises. Future studies should assess its real-world use and performance in clinical settings.

The prevalence of obesity continues to rise, with notable increase in stage III obesity in North America. The accumulation of excess adipose tissue can impair health with cardiovascular disease being the leading cause for increased mortality in people with obesity. The chronicity of the condition makes sustainable weight loss and improved health difficult for many with lifestyle changes alone, often necessitating the need for pharmacotherapy and bariatric surgery. Bariatric surgery remains the most efficacious treatment for obesity, despite improved pharmacotherapies. However, its low acceptability and accessibility render it an underutilized treatment. Meanwhile, the use of obesity pharmacotherapy, especially glucagon-like peptide 1 receptor agonists (GLP1RA) has become widespread with significant weight loss and improved health outcomes in randomised control trials. The real-world effectiveness of GLP1RA is hindered by issues including cost and tolerability. This narrative review discusses strategies to improve the effectiveness of pharmacotherapy and bariatric surgery and posits that bariatric surgery will continue to play an important role in obesity treatment in the GLP1RA era.

Endometriosis is a chronic, debilitating condition characterized by heterogenous clinical manifestations. It has a prevalence of 5-10% in women of reproductive age, and 30-50% of individuals with endometriosis are affected by infertility. There are multiple mechanisms through which endometriosis can lead to infertility: reduced ovarian reserve, distorted pelvic anatomy, chronic inflammation, altered immunity, dyspareunia, and/or altered hormonal and cell-mediated endometrial function. The revised American Society for Reproductive Medicine (rASRM) classification was one of the initial methods to stage disease severity. The Endometriosis Fertility Index (EFI) score, based upon the rASRM score and other factors, can help guide management. Medical treatment for endometriosis is predominantly contraceptive; therefore, surgery and medical reproduction techniques are the mainstay of management for endometriosis-related infertility. The evidence regarding the benefit of surgery for endometriosis-related infertility is conflicting; however, ablative techniques for endometriomas may enhance conception spontaneously and via assisted reproduction techniques (ART). Medically-assisted reproduction techniques include intra-uterine insemination and ovarian stimulation, as well as ART such as in vitro fertilization or intracytoplasmic sperm injection. ART has similar outcomes in individuals with rASRM stage I to II endometriosis as it does in individuals without endometriosis; however, live birth rate, mean number of oocytes retrieved, and clinical pregnancy rate are reduced in individuals with rASRM stages III-IV. Ultimately, endometriosis-related infertility treatment plans should be patient-centered, individualized, and holistic, considering alternative factors which may influence which treatment option can be offered.

Immune thrombocytopenia (ITP) is a rare autoimmune disease that results in low platelet counts and an increased risk of spontaneous bleeding due to impaired blood clotting. Several therapeutic approaches can be used to treat patients with ITP. However, many patients either lose response in the long term or are unable to maintain a response after treatment discontinuation, necessitating chronic treatment and multiple lines of therapy. Here, two patients with ITP share their experience, each providing a firsthand description of their ITP diagnosis, symptoms, management, and perspectives on the future. These stories are complemented by a clinical review of ITP pathophysiology, symptoms, and treatments presented by two expert hematologists who care for patients with ITP. The physician perspective reinforces the challenges faced by patients in everyday life and highlights the remaining areas of concern regarding the treatment of chronic ITP.