Advances in Therapy最新文献

Introduction: Vigabatrin (VGB) is intended for use by caregivers of infants (1 month to 2 years old) diagnosed with infantile spasms (IS). Commercially available vigabatrin powders require caregiver reconstitution prior to oral administration. This study compared the ability of caregivers to accurately provide a targeted dose of vigabatrin using a ready-to-use (RTU) vigabatrin oral solution (VGB-RTU solution) and SABRIL^® (vigabatrin) powder for oral solution, Lundbeck LLC, (vigabatrin powder) without instruction from a healthcare professional.

Methods: A crossover comparative usability study with 30 lay users (15 caregivers with vigabatrin powder experience and 15 oral-syringe/medication preparation naïve users) which required users to deliver a single dose of both VGB-RTU surrogate solution and vigabatrin powder to a sample collection bottle was performed. Doses were measured analytically with a primary endpoint to deliver doses within ± 10% of the target dose of 1125 mg.

Results: All 30 participants administered VGB-RTU solution doses within ± 5% of the target, while only 23/30 of the vigabatrin powder doses were within ± 10%. All naïve users delivered vigabatrin doses using VGB-RTU solution within ± 5% of the target; whereas only 13/15 delivered doses within ± 10% for vigabatrin powder. All experienced vigabatrin users delivered calculated vigabatrin doses using VGB-RTU solution within ± 3%; whereas only 10/15 delivered doses within ± 10% for vigabatrin powder. Users were equally able to accurately deliver the prescribed volumes of both products. Calculated doses of VGB-RTU solution (mg) were significantly less variable (p < 0.0001) and more accurate (p < 0.01) than doses of vigabatrin powder.

Conclusion: Caregivers delivered more accurate and less variable doses of the ready-to-use solution compared to solutions prepared from vigabatrin powders for oral solution. These differences were shown to be due to caregiver errors in reconstituting vigabatrin powders for oral solution.

Introduction: Atrial fibrillation (AF), a common heart rhythm abnormality, is linked to a higher risk of stroke. Traditionally, warfarin has been the primary anticoagulation treatment for reducing the stroke risk. The new standard of treatment by direct oral anticoagulants (DOACs) offers greater benefits including improved efficacy and fewer adverse effects with reduced monitoring. This study aims to evaluate the risk of stroke/systemic embolism (SE) and major bleeding (MB) among patients with AF who switched from warfarin to DOACs.

Methods: This study utilized Medicare data to conduct a retrospective analysis of patients with non-valvular atrial fibrillation (NVAF) who switched from warfarin to DOACs between January 1, 2012, and December 31, 2019. Patients with NVAF aged 65 and older who switched from warfarin and had continuous health plan enrollment were included. Descriptive statistics, propensity score matching (PSM), and Cox proportional hazard (PH) models were utilized to compare the outcomes and assess risks of SE and MB across the DOAC cohorts.

Results: Among 1,843,495 patients with NVAF on warfarin, 171,700 switched to DOACs within 90 days of discontinuation (apixaban: 90,850; rivaroxaban: 67,698; dabigatran: 12,900). The mean follow-up period across DOAC cohorts ranged from 552 to 628 days. After PSM, apixaban showed significantly lower rates of stroke/SE compared to dabigatran (2.99% vs. 3.98%, p < 0.0001) and rivaroxaban (3.08% vs. 3.80%, p < 0.0001). MB rates were also lower with apixaban versus dabigatran (4.29% vs. 5.57%, p < 0.0001) and rivaroxaban (4.07% vs. 6.35%, p < 0.0001). Cox PH models confirmed these findings, with apixaban demonstrating lower risks of stroke/SE [hazard ratio (HR) 0.83, 95% confidence interval (CI) 0.72-0.96 vs. dabigatran; HR 0.91, 95% CI 0.85-0.96 vs. rivaroxaban] and MB (HR 0.79, 95% CI 0.71-0.89 vs. dabigatran; HR 0.68, 95% CI 0.65-0.72 vs. rivaroxaban).

Conclusion: The risk of stroke/SE and MB varies significantly among patients with NVAF switching from warfarin to different DOACs, with apixaban presenting the lowest risk compared to dabigatran and rivaroxaban.

Introduction: This study explored the effects of four different surgical methods in the treatment of cesarean scar pregnancy (CSP).

Methods: In this multicenter retrospective analysis of 359 patients, the surgical indices, the time taken for the serum human chorionic gonadotropin level to return to normal, the recovery time of menstruation, and the incidence of postoperative adverse reactions were comparatively analyzed. The clinical efficacies of various preoperative treatment methods to block the blood supply to CSP tissues and those of four different surgical methods to treat CSP, namely, curettage, hysteroscopic surgery, laparoscopic surgery, and vaginal surgery, were evaluated in this study.

Results: Hysteroscopic pregnancy tissue removal in patients with type I CSP was found to be associated with low cost, rapid postoperative recovery, and a low incidence of postsurgical complications. Among patients with type II-III CSP, the operation success rate (96.97% for type II and 88.46% for type III) in those who underwent uterine artery embolization + curettage was lower than that in patients from the other groups (all 100%). Among patients with type III CSP who underwent transvaginal ligation of the descending uterine artery + hysteroscopic removal of the pregnancy tissues, three patients (12.5%) underwent hysteroscopic surgery under transumbilical single-port laparoscopic surveillance so as to avoid uterine perforation considering that the pregnancy tissue was only 1 mm away from the uterine plasma membrane layer.

Conclusion: Hysteroscopic surgery without pretreatment can be adopted for patients with type I CSP. In contrast, patients with type II and III CSP should be initially pretreated with vascular ligation to prevent intraoperative bleeding, followed by laparoscopic or vaginal surgery.

Trial registry: Clinical Trial Registry Number ChiCTR2000040357.

Introduction: This retrospective claims analysis characterized contemporary ulcerative colitis (UC) treatment patterns and investigated the economic burden of UC in Japan.

Methods: This study used anonymized claims data in the Medical Data Vision database. Patients were included if they had a confirmed UC diagnosis and ≥ 1 claim of systemic treatment for UC (index date) between June 2018 and December 2022, in addition to continuous enrollment for ≥ 6 months before and ≥ 12 months after the index date. Patients were excluded if they were aged < 18 years at index or if they had claimed systemic UC treatment during the pre-index period, had a confirmed diagnosis of Crohn's or Behçet's disease, or had a record of colectomy during the pre-index period. Outcomes of interest were treatment patterns, healthcare resource utilization (HCRU), and UC-related costs per person per month (PPPM). Further exploratory analyses were conducted to understand whether real-world treatment patterns with conventional therapy were optimally aligned with guideline recommendations. Two definitions of suboptimal treatment with conventional therapies were identified: prolonged treatment with corticosteroids (i.e., consecutive use for  > 90 days) and corticosteroid cycling (i.e., three or more ≥ 30-day corticosteroid courses over 1 year, with a ≥ 60-day gap between courses).

Results: Overall, 15,429 patients were included. The most frequently observed class of first-line treatment was 5-aminosalicylic acid monotherapy (75.0%); treatment modification was observed in 39.7% of patients. Within 1 year of follow-up, patients had a mean (SD) of 9.8 (6.8) outpatient visits, and a hospital stay was reported in 23.9% of patients. Mean total cost PPPM was ¥76,374. Of patients with ≥ 1 course of corticosteroids, 39.8% received suboptimal treatment with conventional therapies. HCRU and total costs were higher for patients with versus without suboptimal treatment with conventional therapies.

Conclusions: Japanese patients with UC would benefit from treatment options that can reduce costs, HCRU, and suboptimal treatment with conventional therapies.

Introduction: Fabry disease (FD) is a rare lysosomal storage disorder that is associated with pain and progressive damage to the renal, cardiac, and cerebrovascular systems. Enzyme replacement therapy (ERT) is one of the treatment options for FD and the most recently approved ERT agent, pegunigalsidase alfa, has shown clinical efficacy in three phase 3 clinical trials of adults with FD: BALANCE, BRIDGE, and BRIGHT. Recent published guidelines support the mapping of health utility state data to the EuroQol-5 Dimension-3 Level (EQ-5D-3L) index to align with the preferred methodology used by the National Institute for Health and Care Excellence (NICE). Therefore, the primary objective of this study was to estimate EQ-5D-3L values in clinical trials of pegunigalsidase alfa for FD for future cost-utility analyses.

Methods: A mixed effects model was developed to predict values derived from EQ-5D-3L for the following health states used in cost-utility analyses: no Fabry clinical event (FCE)/no pain-related adverse event (AE), pain-related AE, cardiac FCE, cerebrovascular FCE, and renal FCE.

Results: The baseline EQ-5D-3L utility value had a statistically significant (p < 0.0001) impact on utility values, whereas study, age, sex, disease type, treatment arm, kidney function, and serious AE were not statistically significant. Health state utility values with 95% confidence intervals (CI) for the final model were as follows: no FCE/no pain-related AE, 0.8005 (0.7675, 0.8334); pain-related AE, 0.7737 (0.7262, 0.8211); cardiac FCE, 0.7189 (0.6274, 0.8103); cerebrovascular FCE, 0.7923 (0.6633, 0.9212); and renal FCE, 0.6881 (0.3887, 0.9874).

Conclusions: The utility values generated by the present study are generally in line with EQ-5D values in the FD literature and can be used to inform both economic evaluations and our understanding of the impact that FD has on quality of life.

Trial registration: NCT03018730, NCT02795676, NCT03180840.

Hypertension, dyslipidemia, and type 2 diabetes are highly prevalent and poorly controlled cardiometabolic diseases in the Middle East. Therapeutic non-adherence and therapeutic inertia are major contributors to this suboptimal disease control. Regardless of the cardiometabolic disease, evidence-based solutions may be used to improve therapeutic non-adherence and overcome inertia, and thereby help to alleviate the heavy burden of cardiovascular disease in the Middle East. Such solutions include the routine and early use of single-pill combinations, educational initiatives for patients, and multidisciplinary team-based care. This article highlights these and other potential solutions for therapeutic non-adherence and inertia, as discussed at the 2024 Evidence in the Cardiometabolic Environment (EVIDENT) Summit. There is now a 'call-to-action' from healthcare providers and other stakeholder groups to ensure that the solutions discussed at this meeting are implemented within health systems in the Middle East to significantly improve cardiovascular outcomes.Infographic available for this article.

Randomized phase III trials showed that using trifluridine/tipiracil (FTD/TPI) in patients with pre-treated metastatic colorectal cancer (mCRC) conferred survival benefit versus placebo. Here, we investigated the effectiveness and safety of FTD/TPI and sought to identify prognostic factors among the mCRC population in Hong Kong.

A non-interventional, retrospective, multicenter cohort study enrolled patients with mCRC who received FTD/TPI in seven public hospitals in Hong Kong between 2016 and 2020. Overall survival (OS) was the primary endpoint; treatment duration and occurrence of neutropenia were secondary endpoints. We also performed a post hoc analysis to identify factors influencing OS and treatment duration.

Overall, 456 patients were included (median age, 64.0 years; 57.5% men). Approximately half (225/456; 49.3%) had RAS wild-type tumors; the median treatment duration was 12.4 weeks (95% confidence interval [CI] 11.1–13.1). Median OS was 7.59 months (95% CI 7.00–8.21). Overall, 289 (63.4%) patients developed neutropenia of any grade and 159 (34.9%) developed grade ≥ 3 neutropenia. Neutropenia at 1 month occurred in 193 (43.1%) patients. The use of granulocyte colony-stimulating factor for neutropenia was reported for 42 (9.2%) patients. The development of neutropenia, absolute neutrophil count decrease of ≥ 2 grades in 1 month, absence of liver metastasis, and RAS wild-type status were associated with significantly longer OS and, except for RAS wild-type status (not analyzed), longer treatment duration (p < 0.05 for all comparisons).

Our data show that treatment with FTD/TPI offers survival benefits in patients with refractory mCRC in Hong Kong consistent with randomized controlled trials and other real-world studies. Furthermore, the prognosis in patients receiving FTD/TPI appears to be significantly better in those who develop neutropenia, with RAS wild-type status, or those without liver metastases, despite a higher rate of dose reduction in the real-world setting.