Advances in Therapy最新文献

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: While the therapeutic options for Crohn's disease (CD) have broadened swiftly, direct comparative evidence on treatment efficacy remains limited. This study explored the relative efficacy and safety of available treatments based on current evidence.

Methods: A network meta-analysis (frequentist random-effect model) evaluated comparative efficacy of licensed advanced therapies for CD using data on efficacy of maintenance therapy from fully published, randomised, controlled phase 3/3b studies with 48-64-week follow-up periods and placebo or active comparator controls, identified through a systematic literature review (PROSPERO number CRD42023413752). Intravenous (IV) and subcutaneous (SC) infliximab, SC adalimumab, IV and SC vedolizumab, SC ustekinumab, SC risankizumab, and oral upadacitinib were included. Clinical remission and endoscopic response rates attained through maintenance regimens were assessed according to line of use (e.g., first-line and second-or-later line). Safety (serious adverse event rates) was also compared.

Results: Data from nine randomised controlled trials were analysed. SC infliximab 120 mg every 2 weeks (q.2.w.) exhibited the highest risk difference (95% confidence interval) vs. placebo in both first-line and second-or-later-line maintenance treatment for achieving clinical remission (0.38 [0.23-0.53] and 0.51 [0.19-0.83], respectively; 14 and 12 comparator arms, respectively), and endoscopic response (0.39 [0.29-0.49] and 0.35 [0.07-0.63], respectively; 5 comparator arms) compared with other treatments. Differences between therapies did not reach statistical difference. Safety was comparable among treatments in terms of rates of serious adverse events.

Conclusions: The current NMA integrating recently updated phase 3 data in CD indicated that no single treatment significantly outperformed others in achieving clinical remission and endoscopic response, although SC infliximab 120 mg q.2.w exhibited highest numerical efficacy as both a first-line and second-or-later-line maintenance treatment in adult patients with moderate-to-severe CD.

Introduction: Three previous publications have reported real-world comparative effectiveness of fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) and budesonide/glycopyrrolate/formoterol fumarate (BUD/GLY/FORM) in patients with chronic obstructive pulmonary disease (COPD) in the USA. This subgroup analysis assessed treatment with FF/UMEC/VI and BUG/GLY/FORM in patients with COPD who stepped up from dual therapy, stratified by number of prior exacerbations and class of prior dual therapy.

Methods: Propensity score (PS)-weighted patients identified within healthcare claims from the Komodo Research database were used to compare annualized rates and time to first moderate-severe COPD exacerbation between FF/UMEC/VI and BUD/GLY/FORM initiators stepping up from dual therapy, stratified by the type of dual therapy (long-acting muscarinic antagonist plus long-acting β₂-agonist [LAMA/LABA] or inhaled corticosteroid [ICS] plus LABA) and by prior (none or ≥ 1) COPD exacerbation. Results are presented as events per patient year (PPY) and rate ratio (RR) with 95% confidence intervals (CIs).

Results: Approximately 14,000 patients contributed to this analysis, 10,093 FF/UMEC/VI and 3926 BUD/GLY/FORM initiators. Baseline characteristics were well balanced following PS weighting. Step-up to FF/UMEC/VI was associated with a statistically significant reduction in moderate-severe exacerbations compared with step-up to BUD/GLY/FORM irrespective of exacerbation history: no prior exacerbation, n = 7235, 0.48 vs 0.56 PPY, RR [95% CI] 0.86 [0.77, 0.95], P = 0.003; ≥ 1 prior exacerbation, n = 6784, 1.14 vs 1.41 PPY, RR [95% CI] 0.81 [0.74, 0.87], P < 0.001. Step-up to FF/UMEC/VI was also associated with a statistically significant reduction in moderate-severe exacerbations compared with step-up to BUD/GLY/FORM across both subgroups of prior dual therapy: LAMA/LABA, n = 5717, 0.71 vs 0.95 PPY; RR [95% CI] 0.75 [0.67, 0.83], P < 0.001; ICS/LABA, n = 8302, 0.85 vs 0.99 PPY; RR [95% CI] 0.86 [0.79, 0.93], P < 0.001.

Conclusion: Patients newly initiating FF/UMEC/VI following prior treatment with ICS/LABA or LAMA/LABA experienced a significantly lower rate of moderate-severe COPD exacerbations than those newly initiating BUD/GLY/FORM irrespective of number of prior exacerbations or prior dual therapy class.

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.

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.

Introduction: Hematologic response is well established in systemic light chain (AL) amyloidosis treatment, but hepatic response patterns remain unclear. This study explored hepatic response dynamics in hepatic-involved patients with AL amyloidosis who achieved hematologic partial response within 24 months post-treatment.

Methods: Using two- and four-level hepatic response criteria (two-level: hepatic organ response [hepatic OR], hepatic no response [hepatic NR]; four-level: hepatic complete response [hepaCR], hepatic very good partial response [hepaVGPR], hepatic partial response [hepaPR], hepatic no response [hepaNR]), responses were assessed at 3, 6, 12, and 24 months.

Results: Among 137 patients (median follow-up: 55.0 months), hepatic OR and ≥ hepaPR plateaued at 24 months, with hepatic OR achieved in 75.6% (65/86), hepaCR in 10.5% (9/86), hepaVGPR in 16.3% (14/86), and hepaPR in 38.4% (33/86). The two-level hepatic response better predicted overall survival than the four-level criteria. Patients achieving hepatic OR within 24 months had significantly better prognosis than non-responders (log-rank p = 0.008; HR, 2.782; 95% CI, 1.260-6.141), with no impact from response speed. Hematologic complete response (CR_H) at 3 months predicted higher likelihood of 24-month hepatic OR (OR 2.571, 95% CI, 1.387-4.767, p = 0.003).

Conclusion: The study highlights the importance of monitoring hepatic response dynamics, identifying 3-month CR_H and 24-month hepatic OR as key treatment milestones. A graphical abstract is also available with this article.

Introduction: Metastatic castration-resistant prostate cancer (mCRPC) presents significant treatment challenges. Although androgen deprivation therapy (ADT) has been the standard treatment for metastatic prostate cancer for over 80 years, its efficacy is often limited to the initial treatment phase for most patients. Recent clinical trials have investigated various therapeutic options for mCRPC; however, real-world evidence is essential for a comprehensive understanding of the current treatment landscape and to identify unmet clinical needs.

Methods: A multi-country, retrospective, non-interventional study was conducted across 31 centres in Latin America, the Middle East and Asia. Adults diagnosed with mCRPC between January 2016 and December 2018 were enrolled as the study subjects. Treatment patterns were thoroughly analysed, including those used when patients were at the metastatic castration-sensitive prostate cancer (mCSPC) and non-metastatic castration-resistant prostate cancer (nmCRPC) settings.

Results: Among 795 enrolled patients with mCRPC (most aged ≥ 65 years), significant attrition was observed between treatment lines: approximately 50% of patients on first-line (1L) therapy advanced to second line (2L) but only 23.5% proceeded to third line (3L). New hormonal agent (NHA)-based therapies were the most prevalent choice for 1L and 2L, with post-chemotherapy NHA being the most common 1L-2L sequence. Disease progression, the primary reason for discontinuation across all regimens, occurred in > 60% of patients during mCRPC treatment. Generally, median real-world progression-free survival (rwPFS) decreased with each subsequent line of therapy. This study also highlights the inadequacy of prostate cancer screening in these regions.

Conclusion: This study offers valuable insights into the current treatment landscape of patients with mCRPC in non-US and non-European settings within a real-world context.

Clinicaltrials:

Gov id: NCT04801186.

Background: Virtual reality (VR) technology has become more mature and accessible in recent years. In the context of alcohol use disorder (AUD), it can be used for various therapeutic contexts, such as exposure therapy, diagnostics, and improved interactivity. Although promising, the data regarding its effectiveness vary; therefore, caution is warranted when it is introduced. This review aims to illustrate the current state of research on virtual reality in alcohol use disorder therapy.

Methods: In accordance with the PRISMA and Cochrane guidelines, publications focusing on implementing virtual reality to treat alcohol use disorder, published since 2015, were investigated. These included trials, prototype presentations, and expert interviews.

Results: Thirty-two publications were identified, 19 of which were trials, with 653 participants. The results indicate that VR has been researched in various therapeutic contexts. In virtual cue-exposure therapy (CET), trials suggest that virtual reality can effectively increase craving and anxiety after one-time use and reduce craving after multiple uses. In diagnostics, trials demonstrate that it is possible to distinguish between heavy and light consumers based on the choices made in virtual reality, leading to a more standardized approach. In virtual approach-avoidance therapy (AAT), trials indicate increased effectiveness in the use of VR compared to the usual two-dimensional approach regarding craving. Non-trial publications focus on the inclusion of specific technologies, such as biofeedback, design choices, and ethical considerations.

Conclusions: Despite promising results, current research is limited. From a therapeutic perspective, the limitations are the variety of approaches to development and use, the heterogeneous designs, inconsistent trial results, and the lack of long-term data on abstinence, effectiveness, and potential risks for patients. Technologically, the adaptation of virtual environments and the inclusion of biofeedback devices require more research. Methodically, the interdependence of scientific disciplines increases the complexity. Since virtual reality has been used in other types of therapy with success (e.g., phobia and anxiety treatment) and a growing body of literature presents promising findings, there is a strong incentive to continue research on using virtual reality in treating alcohol use disorder.

Introduction: Efsubaglutide alfa is a novel, long-acting GLP-1RA, which imparts human homology, molecular flexibility and enhanced GLP-1 receptor-specific binding. This drug-free, observational follow-up evaluated remission and durability of glycemic control in drug-naïve T2D participants who had completed 52 weeks of once-weekly efsubaglutide alfa in the SUPER-1 randomized trial.

Methods: Adults who completed SUPER-1 with HbA1c ≤ 7.0% discontinued all glucose-lowering therapy and entered a 52-week, medication-free observation. The primary endpoint was diabetes remission, defined as HbA1c < 6.5% (American Diabetes Association criteria, ADA 2021) measured ≥ 3 months after the last efsubaglutide dose. Kaplan-Meier (KM) analysis was employed to estimate the probability of maintaining HbA1c < 7% over 12 months post-treatment. Continuous glucose monitoring (CGM) assessed changes in time in range (TIR). Factors contributing to diabetes remission were analyzed using logistic regression and subgroup KM analyses.

Results: Twenty-nine participants were enrolled; at 3 months post-discontinuation, the diabetes remission rate was 60% (12/20). The probabilities of maintaining HbA1c < 7% at 6- and 12-month post-treatment were 58.1% (17/29; 95% CI 39.0-73.1%) and 41.4% (12/29; 95% CI 24.0-58.0%), respectively. Efsubaglutide alfa treatment during the 52-week period significantly improved TIR (baseline: 46.4%; 52 week: 89.1%, p < 0.001). TIR levels off therapy were 70.1% at 3 months, 68.1% at 6 months and 64.1% at 12 months. Patients who achieved remission had relatively lower baseline HbA1c and higher body mass index (BMI) values before treatment, demonstrating significantly greater reductions in waist circumference (- 3.3 cm) and postprandial glucose (PPG) levels compared to those who did not remit. Post-treatment HbA1c levels and improvements in homeostasis model assessment of β-cell (HOMA-β) scores were strongly associated with a higher probability of remission (p = 0.03 and 0.05, respectively). Body weight remained stable throughout the 12-month drug-free observation without rebound.

Conclusions: Efsubaglutide alfa demonstrated efficacy in achieving stable glycemic control and drug-free diabetes remission. Enhanced β-cell function emerged as a key factor contributing to long-term remission.

Trial registration: ClinicalTrials.gov identifier, NCT06605287.