Advances in Therapy最新文献

Introduction: The aim of this study was to systematically appraise and synthesize real-world data of motor function and safety in Asian patients with spinal muscular atrophy (SMA) treated with nusinersen or risdiplam.

Methods: This study systematically searched PubMed, Cochrane, Embase, CNKI, and Wanfang databases for real-world studies (RWS) published from January 2017 to January 2024. Based on the prespecified study selection and eligibility criteria, RWS evaluating motor function and/or safety outcomes in patients with types 2-4 SMA treated with nusinersen or risdiplam were included, while studies without Asian populations were excluded. The Newcastle-Ottawa Scale (NOS) was used to assess the risk of bias, and a meta-analysis was conducted for each motor function endpoint based on the extracted data.

Results: A total of 26 RWS were included in this review, of which 17 reporting main motor function outcomes were included in the meta-analyses. Intervention in all 17 studies was nusinersen; none included risdiplam. Statistically significant improvement was observed in Revised Upper Limb Module (RULM) [Mean difference (MD) = 2.27 (0.84, 3.71)], Hammersmith Functional Motor Scale Expanded (HFMSE) [MD = 2.62 (1.79, 3.45)] and six-minute walk test (6MWT) [MD = 18.29 (9.12, 27.45)] when treated with nusinersen ≤ 6 months and > 6 months (HFMSE [MD = 4.34 (3.54, 5.14)]; 6MWT [MD = 45.59 (12.92, 78.27)]). Clinically meaningful responses of motor milestones were also observed when treating nusinersen over 6 months: 54.4% (0.305, 0.772) for RULM, 53.0% (0.273, 0.779) for HFMSE and 97.1% (0.819, 1.000) for 6MWT. A total of 19 studies addressed safety outcomes. Reported adverse events were consistent with the expected safety profile for nusinersen.

Conclusion: Our study suggests that nusinersen is associated with a statistically significant and clinically meaningful motor function improvement in Asian patients with types 2-4 SMA in the real-world setting. No unexpected safety concern was observed for nusinersen. Motor function and safety outcomes after risdiplam could not be evaluated in this patient population under real-world settings due to limited studies.

Introduction: This multicenter retrospective study compared the surgical outcomes of Baerveldt glaucoma implant (BGI) surgery with those of Ahmed glaucoma valve (AGV) surgery in patients with neovascular glaucoma (NVG).

Methods: The study included patients with NVG aged ≥ 20 years who had undergone BGI (223 eyes) or AGV (146 eyes) surgery between April 1, 2012 and December 31, 2021 across 10 clinical centers in Japan. Surgical success or failure was the primary outcome measure of this study. We defined surgical failure as a reduction of < 20% in the pre-operative intraocular pressure (IOP) or criterion A (IOP > 21 mmHg), criterion B (IOP > 17 mmHg), or criterion C (IOP > 14 mmHg). In addition, we considered a requirement for re-operation, loss of light perception, and hypotony as surgical failure.

Results: The surgical success rate of the BGI surgery group was significantly higher than that of the AGV group for criteria A (P = 0.01) and B (P = 0.01). Multivariate analysis revealed that AGV surgery showed significant associations with surgical failure for criteria A (hazard ratio, 1.74), B (hazard ratio, 1.72), and C (hazard ratio, 1.34). The overall incidence of postoperative complications was comparable between the two groups. The requirement for re-operation in the AGV surgery group was significantly higher than that in the BGI surgery group (12.3% vs. 5.8%, P = 0.03).

Conclusions: BGI surgery yielded a higher success rate than AGV surgery in patients with NVG for a target IOP of < 21 or < 17 mmHg. No significant differences were observed between the two procedures in terms of the incidence of postoperative complications. Additional glaucoma surgery was required more frequently following AGV surgery. Therefore, BGI surgery may be a more suitable and efficacious option for the management of IOP in patients with neovascular glaucoma compared with AGV surgery.

Introduction: Liver-kidney-metabolic health (LKMH) depends on complex interactions between metabolic dysfunction-associated steatotic liver disease (MASLD), chronic kidney disease (CKD), sex, and reproductive status. This study evaluates in a holistic manner how LKMH, sex, and menopause influence coronary artery calcification (CAC) burden.

Methods: Patients without previous cardiovascular disease were prospectively recruited. Liver fat was assessed via ultrasonography and categorized as mild or moderate-to-severe. CKD was classified using estimated glomerular filtration rate (eGFR). CAC burden was quantified as 0, 1-299, ≥ 300, single-vessel, or multivessel with coronary computed tomography. Stepwise backward multinomial logistic regression was applied for analysis.

Results: A total of 446 patients (59.2% female, average age 52.9 years) were included. Moderate-to-severe MASLD was independently associated with an increased risk of CAC 1-299 [OR 2.30 (1.21-4.36)], CAC ≥ 300 [OR 4.93 (1.46-16.59)], and single-vessel CAC [OR 2.03 (1.03-4.00)]. Mild MASLD [OR 2.47 (1.20-4.21)], moderate-to-severe MASLD [OR 3.74 (1.76-7.93)], and CKD stage 2 [OR 2.27 (1.26-4.08)] were independently associated with increased multivessel CAC risk. Liver fat content showed a dose-response association with CAC burden. Subgroup analysis revealed that MASLD and CKD increased CAC risk in male but not female patients, with menopause significantly modifying LKMH's effect.

Conclusion: LKMH's impact on CAC burden is significantly influenced by liver fat content, eGFR, sex, and menopause, suggesting that MASLD, CKD, sex, and reproductive status should be integrated into CAC risk prediction models.

Introduction: This study investigates the impact of geographic and socioeconomic barriers on access to transcatheter aortic valve replacement (TAVR).

Methods: Utilizing Medicare data from the US Centers for Medicare and Medicaid Services, this study analyzed TAVR and surgical aortic valve replacement (SAVR) procedures among beneficiaries from 2017 to 2022. Geographic units were defined by 5-digit zip codes, categorized on the basis of TAVR/SAVR volume into four categories: (1) no TAVR or SAVR, (2) no-TAVR zone (SAVR present, no TAVR), (3) low-TAVR zone (TAVR/SAVR ratio ≤ 0.5), and (4) TAVR accessible (TAVR/SAVR ratio > 0.5). The differential distance index (DDI) was developed to measure travel hurdles, calculated as the difference in miles from a patient's zip code center to the treatment hospital (TAVR versus SAVR, CABG (coronary artery bypass grafting), and PCI (percutaneous coronary intervention) comparators). This study maintained a continuous access variable to model outcomes such as the ratio or volume of TAVR/SAVR and the percentage share of TAVR/AVR within each zip code over biennial periods (2017-2018, 2019-2020, 2021-2022). Covariates in the model included population density, area deprivation index (ADI), and calendar time, with an exploration of the interaction between DDI and ADI.

Results: The analysis revealed significant geographic disparities in TAVR access across the USA, with no-TAVR zone and low-TAVR zone areas often featuring lower population densities, higher ADIs, and more rural settings. Increased travel distance (DDI) significantly correlated with lower TAVR utilization, emphasizing distance as a critical barrier. Furthermore, both ADI and DDI emerged as significant predictors of TAVR volume and share, underlining the compound effect of socioeconomic status and geographic distance on healthcare access.

Conclusions: This study highlights the critical role of geographic and socioeconomic barriers in accessing advanced medical treatments like TAVR. Addressing these barriers may ensure equitable healthcare distribution, guiding policymakers and providers towards more accessible healthcare solutions for all populations.

Introduction: Tegoprazan is a potassium-competitive acid blocker, and its systemic exposure is presumably affected by hepatic clearance and bioavailability. This study aimed to investigate the effect of hepatic impairment (HI) on the safety and pharmacokinetics of tegoprazan and metabolite.

Methods: An open-label, multicenter, parallel-group study was conducted in patients with mild (n = 8), moderate (n = 8) and severe (n = 1) HI according to the Child-Pugh classification as well as controls. Healthy subjects (n = 8) were matched to patients with the moderate category based on age, body mass index and sex. Blood and urine samples were obtained to evaluate the concentrations of tegoprazan and metabolite (M1) until 48 h after a single oral administration of 50 mg of tegoprazan.

Results: The geometric mean ratio with a 90% confidence interval of maximum plasma concentration and area under the plasma concentration-time curve for tegoprazan in patients with impaired hepatic function compared to controls were 0.8228 (0.4997-1.3550) and 1.2264 (0.7447-2.0197) in the mild category, 1.0332 (0.6274-1.7015) and 1.7676 (1.0733-2.9109) in the moderate category, and 1.0699 (0.3713-3.0823) and 1.9567 (0.6792-5.6377) in the severe category. The half-life, apparent clearance, renal clearance, and fraction unbound to plasma protein were comparable across study groups. The plasma concentration of M1 increased and decreased faster in the normal group. Tegoprazan was generally well tolerated in patients with HI.

Conclusions: Systemic exposure to tegoprazan tended to be increased in subjects with HI. The difference between patients with mild HI and the controls was deemed not to require dose adjustment for tegoprazan.

Clinical trial registration: ClinicalTrials.gov identifiers: NCT04494269 (31 Jul 2020).

Introduction: This study aimed to demonstrate the interchangeability of biosimilar CT-P17 and European Union reference adalimumab (EU-adalimumab) in a repeated-switch scenario.

Methods: In this ongoing, randomized, double-blind, active-controlled, phase 3 study, adults with moderate-to-severe plaque psoriasis received 80 mg EU-adalimumab on day 1, then 40 mg 1 week later and every other week until week 11. At week 13, patients were randomized (1:1, via an interactive web response system) to continue EU-adalimumab ("continuous" group) or undergo repeated switches between CT-P17 and EU-adalimumab ("switching" group). Dosing was via subcutaneous administration. The primary endpoints were area under the concentration-time curve and maximum serum concentration between weeks 25 and 27 (AUC_tau,W25-27 and C_max,W25-27, respectively). Secondary endpoints comprised additional pharmacokinetic (PK) parameters, efficacy, safety, and immunogenicity. Week 27 findings are presented.

Results: The first patient provided signed informed consent on November 7, 2022. Week 27 visits were completed by August 14, 2023. Of 367 patients enrolled, 346 were randomized (switching group, n = 172; continuous group, n = 174). The ratios of least squares means between groups and associated 90% confidence intervals (CIs) for AUC_tau,W25-27 and C_max,W25-27 were 99.45% (94.11-105.08%) and 100.45% (95.03-106.17%), respectively. For both endpoints, 90% CIs fell within the predefined equivalence margin of 80-125% and criteria were greater than calculated t values, satisfying bioequivalence. Additional PK endpoints and efficacy, safety, and immunogenicity findings were similar between groups. Safety profiles were in line with those previously reported.

Conclusions: Week 27 primary PK results demonstrated bioequivalence, and the overall study results supported the interchangeability of CT-P17 and EU-adalimumab.

Trial registration: ClinicalTrials.gov, NCT05495568.

Introduction: Postoperative nausea and vomiting (PONV) is one of the most common postoperative complications, with particularly high rates in patients undergoing high-risk surgeries such as gynecologic laparoscopy. Although there are many pharmacological and non-pharmacological methods that can prevent PONV, the incidence remains high. This study assessed the effectiveness of a right stellate ganglion block (SGB) in preventing PONV in gynecological laparoscopy patients, while also exploring the potential mechanisms involved.

Methods: Two hundred patients were randomly assigned to either a right SGB under ultrasound guidance 30 min before anesthesia (SGB group) or no treatment (control group). The primary outcome was PONV incidence within 24 h post surgery. Secondary outcomes included nausea and vomiting severity, pain scores, postoperative flatus time, sleep quality, and satisfaction scores.

Results: The incidence of PONV in the SGB group was 38%, significantly lower than the 60% in the control group (P = 0.002). Severity of PONV was also notably reduced in the SGB group (P = 0.004). Resting pain scores in the SGB group at 6 h (0.0 [0.0, 1.0] vs. 0.0 [0.0, 2.0], P = 0.013), 12 h (0.0 [0.0, 1.0] vs. 0.0 [0.0, 2.0], P = 0.027), and 24 h (0.0 [0.0, 1.0] vs. 0.0 [0.0, 2.0], P = 0.011) were lower than in the control group. Post-activity pain scores at 6 h (2.0 [1.0, 3.0] vs. 3.0 [1.25, 4.0], P = 0.000), 12 h (2.0 [1.0, 3.0] vs. 3.0 [1.25, 4.0], P = 0.002), and 24 h (2.0 [1.0, 3.0] vs. 3.0 [2.0, 4.0], P = 0.001) were also lower. The time to first postoperative flatus was shorter in the SGB group (P = 0.033). Overall postoperative satisfaction (P = 0.002) and analgesia satisfaction (P = 0.002) were higher, and sleep quality was improved (P = 0.046).

Conclusion: A right stellate ganglion block reduces PONV, pain, and postoperative flatus time, and improves sleep quality and satisfaction in gynecological laparoscopy patients, proving it to be a safe and effective method.

Trial registration: NCT06426186.

Introduction: This study aims to assess the cost-effectiveness of the fall 2023 COVID-19 mRNA XBB.1.5 vaccination campaign in the Netherlands, comparing the XBB1.5 updated mRNA-1273.222 with the XBB1.5 updated BNT162b2 vaccine.

Methods: A 1-year decision tree-based cost-effectiveness model was developed, considering three scenarios: no fall 2023 vaccination, BNT162b2 vaccination, and mRNA-1273 vaccination in the COVID-19 high-risk population in the Netherlands. The high-risk population includes everyone of 60 and older, and younger adults at high risk as identified by the Dutch Health Council. Costs were included from a societal perspective and the modelled period started in October 2023 and ended in September 2024, including life years lost with a lifetime horizon. Sensitivity and scenario analyses were conducted to evaluate model robustness.

Results: In the base case, mRNA-1273 demonstrated substantial benefits over BNT162b2, potentially averting 20,629 symptomatic cases, 924 hospitalizations (including 32 intensive care unit admissions), 207 deaths, and 2124 post-COVID cases. Societal cost savings were €12.9 million (excluding vaccination costs), with 1506 quality-adjusted life years (QALYs) gained. The break-even incremental price of mRNA-1273 compared to BNT162b2 was €16.72 or €34.32 considering a willingness to pay threshold (WTP) of 20,000 or 50,000 euro per QALY gained.

Conclusion: This study provides a comprehensive cost-effectiveness analysis supporting the adoption of the mRNA-1273 vaccine in the national immunization program in the Netherlands, provided that the Dutch government negotiates a vaccine price that is at most €34.32 per dose higher than BNT162b2. Despite limitations, the findings emphasize the substantial health and economic benefits of mRNA-1273 over BNT162b2 in the high-risk population.

Introduction: This article describes the study rationale and design of the real-world multicenter registry study iCaReMe China.

Methods: iCaReMe China is a prospective, multicentric, observational registry study aiming to understand the real-world characteristics of patients with type 2 diabetes (T2D) and/or hypertension (HTN) [combined chronic kidney disease (CKD)] and/or heart failure (HF) and/or CKD, which may provide some evidence for improving quality of care and outcomes of T2D and/or HTN and/or HF and/or CKD in China. A total of approximately 19,000 subjects will be recruited from 110 participating sites in China. Patients will be enrolled in four disease cohorts based on the primary disease conditions. The primary outcome is to describe the sociodemographic, clinical characteristics, disease management patterns, healthcare resource utilization, and clinical outcomes.

Conclusion: iCaReMe China aims to describe the real-world characteristics and treatment patterns of patient with T2D and/or HTN (combined CKD) and/or HF and/or CKD. The data from this prospective registry study will facilitate a better understanding of management strategies, the variations across and within different regions, and associated patient outcomes in China.

Trial registration number: ChiCTR2300073764.

Introduction: Disrupted linkage to care is a major barrier to hepatitis C virus (HCV) elimination leading to high attrition rates. This study aimed to describe (1) flow through the HCV care-cascade (2009-2020), and (2) monthly patterns in HCV care during the coronavirus disease 2019 (COVID-19) pandemic (2020) in Israel.

Methods: Data were obtained from Maccabi Healthcare Services, a 2.6-million-member healthcare provider in Israel. Flow through the HCV care-cascade in 2009-2020 was described from individuals' first positive HCV antibody (Ab+) test to sustained virological response (SVR), and monthly data were obtained on individuals newly attaining a given stage in the HCV care-cascade in 2020.

Results: Among 2809 new patients who were Ab+, 2651 (94.4%) had an HCV polymerase chain reaction (PCR) test, and 1417 (50.4%) were PCR+ during the study. Median time from Ab+ to PCR+ was 3.9 years, with 39.7% PCR+ within 12 months. Median time from PCR+ to HCV treatment was 3.3 years, with 639 (55.5%) of patients who were PCR+ purchasing direct-acting anti-viral agents (DAAs), and 413/416 patients attained SVR. A significant reduction was observed in the time from first HCV detection (Ab+) to HCV confirmation (PCR+) and from PCR+ test to HCV treatment purchase in the pre-DAA era compared to the post-DAA. Monthly data during 2020 (Part B) indicates a decline in the numbers of patients receiving HCV care during the first pandemic-related closure.

Conclusion: Real-world data from a nationally representative healthcare provider database suggest that HCV linkage to care improved over time alongside increased access to DAAs, despite observed declines in access to care in 2020.