Advances in Therapy最新文献

Introduction: Administration of fecal microbiota spores, live-brpk [Vowst Oral Spores (VOS)], an oral microbiome therapeutic approved for prevention of recurrent Clostridioides difficile infection in adults, requires antibiotic washout using a laxative prior to administration. Patient acceptability of the prerequisite laxative is important. This study assessed psychometric properties of the Antibiotic Washout Patient Satisfaction Scale (AWPSS) which was minimally modified from a previously validated patient satisfaction scale for bowel preparation prior to colonoscopy.

Methods: Patients from the ECOSPOR IV trial who received a laxative preparation prior to oral administration of VOS and were administered the AWPSS were included. Reliability and construct validity of the AWPSS were evaluated.

Results: AWPSS data were available for 110 patients; all completed all 6 items of the AWPSS, supporting its acceptability. Domain 1 mean/median transformed total scores of 105.9/100 [range (best-worst), 0-300] suggested that patients were satisfied with the laxative preparation; a Cronbach's alpha of 0.81 showed acceptable reliability. Almost all patients (97.3%) reported they were able to consume the entire laxative solution as instructed and would take it again if needed (95.5%). Higher satisfaction with the laxative preparation predicted higher acceptability of future use if needed (lower score) with mean/median of 101.7/100 and 195.0/200.00 for those who were willing or not willing to accept, respectively (P = 0.008).

Conclusions: AWPSS is a valid and reliable 6-item patient-reported outcome measure for use in patients requiring a laxative prior to oral microbiome therapy. AWPSS showed antibiotic washout was well tolerated and predicted that patients would be willing to consume the laxative in the future if needed.

Introduction: Infantile hemangioma (IH) is a common benign tumor in infants. While most cases exhibit a self-limiting nature, some require medical treatment to avoid complications. Propranolol is the first-line therapy for IH, it has a high success rate, and is safe to use. Unfortunately, some patients might experience rebound growth after propranolol discontinuation. Currently, it is unclear which factors predict this phenomenon. This study aimed to identify factors affecting the rebound growth of IH after propranolol cessation. We also aimed to identify predictors for an excellent response to oral propranolol.

Methods: We performed a retrospective cohort study using clinical data from all patients referred to our clinic with IH and placed on systemic oral propranolol between January 2009 to December 2023 in the dermatology outpatient clinic of Rambam Healthcare Campus.

Results: Out of a total of 552 patients with IH, 301 received oral propranolol for at least 6 months. A relapse phenomenon was observed in 38 (12.6%) patients. We found a significant association between limb involvement and the least likelihood of hemangioma rebound (p < 0.001). An excellent response to oral propranolol was observed in 57.8% of patients. Younger age at initiation of oral propranolol was associated with an excellent response (p = 0.015). Also, IHs located on the limbs (67) showed a higher rate of excellent response to oral propranolol compared to other anatomical sites (p = 0.02). Interestingly, patients who were treated with a dose of 2 mg/kg/day were associated with excellent response to treatment (p = 0.007).

Conclusions: IHs located on the limbs demonstrated less rebound growth and a better treatment response. When oral propranolol was initiated earlier or when the target dose was 2 mg/kg/day, there was a higher rate of excellent response to treatment.

Introduction: Hyporesponsiveness to erythropoiesis-stimulating agents (ESAs) in patients with anaemia of chronic kidney disease may lead to increased ESA doses to achieve target haemoglobin levels; however, elevated doses may be associated with increased mortality. Furthermore, patients with hyporesponsiveness to ESAs have poorer clinical outcomes than those who respond well to ESAs. Incidence and clinical characteristics of patients with ESA hyporesponsiveness were explored in a real-world setting.

Methods: This was a retrospective study of electronic medical records of adults with stage 5 chronic kidney disease receiving renal replacement therapy and ESA treatment, from 1 January 2015 to 31 December 2021. The primary objective was ESA hyporesponsiveness rate/1000 days, with a hyporesponsive event defined as ESA use at an elevated dose, according to National Institute for Health and Care Excellence (NICE) criteria. Other hyporesponsiveness definitions applied were erythropoietin resistance index-defined ESA hyporesponsiveness (ERI) Kidney Disease Improving Global Outcomes (KDIGO) and a clinical practicality algorithm.

Results: In total, 85,259 patients were included in the analysis; 59.9% were male, median (interquartile range) ESA starting dose was 733.3 (400.0, 1200.0) IU/week and follow-up duration was 2.2 (1.0, 4.2) years. Incidence of ESA hyporesponsiveness varied when applying different definitions; NICE 0.05/1000 days (5.2% of patients), ERI 0.40/1000 days (40.7%), KDIGO 0.15/1000 days (15.4%), and clinical practicality algorithm 0.48/1000 days (47.9%). ESA doses remained higher in hyporesponsive versus responsive patients, yet haemoglobin levels were similar between groups.

Conclusion: The results from this study, which applied multiple hyporesponsiveness definitions to a large, geographically diverse population of patients with anaemia of CKD, showed variation in ESA hyporesponsiveness incidence rates depending on definitions used and higher ESA doses in hyporesponsive versus responsive patients. These results underscore the need for individualised clinical assessment and thorough evaluation when considering ESA dose adjustments to reach haemoglobin targets. Graphical abstract available for this article.

Trial registration: NCT05530291.

Introduction: The phase 3 XTEND-1 trial (NCT04161495) demonstrated that efanesoctocog alfa prophylaxis provided superior bleed protection compared with pre-trial factor VIII (FVIII) prophylaxis in patients with severe haemophilia A. The aim of this study was to indirectly compare the efficacy of efanesoctocog alfa with non-factor replacement therapy emicizumab in adolescent and adult patients with severe haemophilia A without inhibitors.

Methods: A systematic literature review was conducted to identify phase 3 trials of emicizumab. Matching-adjusted indirect comparisons were used to compare annualised bleeding rates (ABRs) for any, treated, joint, and spontaneous bleeds, and joint health (measured using Hemophilia Joint Health Score [HJHS]), between efanesoctocog alfa and emicizumab. Estimated effects for different emicizumab regimens were pooled using random-effect meta-analysis to evaluate the overall difference in bleed outcomes between efanesoctocog alfa and emicizumab.

Results: One emicizumab trial was included (HAVEN 3), which investigated three dosing regimens. In meta-analyses, efanesoctocog alfa once-weekly (Q1W) was associated with significantly lower ABRs for any (incidence rate ratio [95% CI] 0.33 [0.20; 0.53]), any treated (0.49 [0.30; 0.80]) and treated joint (0.51 [0.28; 0.91]) bleeds compared with emicizumab Q1W in non-inhibitor patients with prior prophylaxis or on-demand treatment. Efanesoctocog alfa Q1W was also associated with a significantly better improvement from baseline in HJHS Joint Score (mean difference [95% CI] -2.06 [-3.97; -0.14]) and Total Score (-2.37 [-4.36; -0.39]) versus emicizumab Q1W or every 2 weeks.

Conclusion: Efanesoctocog alfa prophylaxis was associated with significantly lower rates of any, treated, and joint bleeds and improved joint health compared with emicizumab in patients with severe haemophilia A.

Introduction: Socioeconomic determinants are increasingly important factors in the integrated management of atrial fibrillation (AF). The impact of loneliness status on AF recurrence remains unclear.

Methods: We conducted a cohort study based on patients with AF undergoing catheter ablation from 2017 to 2022. The Chinese version of the De Jong Gierveld scale (DJGLS) for evaluating loneliness degree was used. Multivariate Cox regression was performed to identify the independent risk factors for recurrent AF. A multivariate model was used to estimate the hazard ratio (HR) with 95% confidence interval (CI) when adjusting the known risk covariates in several kinds of subgroups.

Results: Nine hundred fifty-five patients with AF and mean age > 65 years finished long-term follow-up. The AF cluster with severe/extreme loneliness tended to live alone according to DJGLS scores. Multivariate Cox regression showed that loneliness status is an independent risk factor for AF recurrence by using a multivariate model with adjustments of some covariates (moderate loneliness: HR 2.02; 95% CI 1.47-2.77, P < 0.001; severe/extreme loneliness: HR 5.28; 95% CI 3.56-7.84, P < 0.001). Survival analysis demonstrated that patients with AF with a more severe degree of loneliness are more likely to have AF recurrence in the long-term follow-up (log-rank test, P < 0.001). Restricted cubic spline (RCS) showed a mainly non-linear relationship between feeling lonely and AF recurrence (P overall < 0.001, P non-linear = 0.195). Receiver-operator characteristic curve (ROC) and time-dependent ROC curve indicated that the diagnostic value of loneliness status in predicting AF recurrence is stable and acceptable.

Conclusion: A more severe degree of loneliness was positively associated with increased risk of AF recurrence. Loneliness status showed an acceptable diagnostic value in discriminating AF recurrence as an independent tripartite variable.

Introduction: In the Phase 3 XTEND-1 trial, (NCT04161495) efanesoctocog alfa prophylaxis provided superior bleed protection versus pre-study factor VIII (FVIII) replacement therapy in patients with severe haemophilia A. The aim of this study was to indirectly compare bleed outcomes between efanesoctocog alfa and standard/extended half-life (SHL and EHL) FVIII replacement therapies in adolescent and adult patients with severe haemophilia A without inhibitors.

Methods: A systematic literature review was conducted to identify Phase 3 trials of EHL and SHL FVIII replacement therapies for comparison with efanesoctocog alfa data from XTEND-1. Matching-adjusted indirect comparisons were used to compare annualised bleeding rates (ABRs) for any, treated, joint, and spontaneous bleeds between efanesoctocog alfa and comparators. The estimates from respective comparisons were pooled using random-effect meta-analyses to evaluate the overall difference between efanesoctocog alfa and comparator therapies.

Results: Four EHL therapies (rurioctocog alfa pegol, efmoroctocog alfa, turoctocog alfa pegol, damoctocog alfa pegol) and two octocog alfa SHL therapies were included. In meta-analyses, efanesoctocog alfa was associated with significantly lower ABRs for any [mean difference (95% CI) - 2.24 ( - 3.24; - 1.25)], spontaneous [ - 1.52 ( - 2.33; - 0.72)], and joint bleeds [ - 1.60 ( - 2.32; - 0.88)] versus EHL therapies, and with significantly lower ABRs for any [ - 3.61 ( - 4.43; - 2.79)], treated [ - 1.55 ( - 1.89; - 1.20)], spontaneous [ - 2.52 ( - 3.31; - 1.72)], and joint bleeds [ - 3.42 ( - 4.77; - 2.08)] versus SHL therapies.

Conclusion: Efanesoctocog alfa was associated with significantly lower ABRs (any, spontaneous and joint) compared with EHL or SHL prophylaxis therapies. Patients had, on average, 2.2 and 3.6 fewer bleeds per year versus EHL and SHL therapies, respectively.

Introduction: There is no information on the incidence of severe hypoglycemia in real-world patients with diabetes receiving ultra-rapid lispro (URLi). This post-marketing, observational, safety study assessed the incidence proportion and incidence rate of the first severe hypoglycemia event requiring a hospital visit in URLi-treated patients. It also compared the risk of severe hypoglycemia between patients treated with URLi or other rapid-acting insulin analogs (RAIAs).

Methods: Claims data were obtained from a nationwide hospital-based administrative database in Japan (Medical Data Vision). Adults with diabetes who initiated URLi or other RAIA on/after June 01, 2020, were followed up through May 31, 2023. Severe hypoglycemia was identified using a validated algorithm. Incidence proportion and incidence rate of the first severe hypoglycemia event requiring a hospital visit was described in URLi-treated patients (descriptive analysis). These outcomes were also compared against propensity score (PS)-matched other RAIA-treated patients (comparator; comparative analysis). Hazard ratio (HR) and 95% confidence interval (CI) was estimated with a Cox proportional hazards model.

Results: The descriptive analysis' URLi-treated cohort included 17,838 patients [mean (standard deviation, SD) age 65.9 (15.7) years; 58.3% male]. The majority had type 2 diabetes (75.7%). The incidence proportion of the first severe hypoglycemia event requiring a hospital visit was 0.6% (95% CI 0.5, 0.8) and the incidence rate was 1.7 per 100 person-years (95% CI 0.7, 4.3). The comparative analysis included 10,592 URLi-treated and 52,917 comparator-treated patients. The incidence rate of severe hypoglycemia did not significantly differ between these cohorts (HR 0.8; 95% CI 0.5, 1.1; p = 0.132;.

Conclusion: This study did not show a statistically significant increase in the incidence and risk of the first severe hypoglycemia event requiring a hospital visit in real-world URLi-treated patients in Japan, compared with a PS-matched cohort of other RAIA-treated patients.

Introduction: Real-world studies in the USA report that 41-56% of patients with multiple sclerosis (MS) are ≥ 50 years old, yet data on their response to disease-modifying therapies (DMTs) is limited. Dimethyl fumarate (DMF) is an oral DMT approved for treating relapsing MS. This analysis evaluated the safety, efficacy, and immunophenotype changes of DMF in patients ≥ 50 years compared with patients < 50 years.

Methods: ESTEEM, a 5-year, real-world, observational phase 4 study, assessed the safety and effectiveness of DMF, including treatment-emergent serious adverse events (SAEs) and adverse events (AEs) leading to treatment discontinuation. Absolute lymphocyte counts (ALCs) were recorded from a subset of patients. The PROCLAIM study, a phase 3b interventional study, reported safety outcomes and lymphocyte subset changes in patients with relapsing-remitting MS (RRMS) treated with DMF. The study evaluated safety outcomes by analyzing the incidence of SAEs and detailed changes in CD4⁺ and CD8⁺ T cell compartments over 96 weeks of DMF treatment.

Results: ESTEEM included 4020 patients aged < 50 years and 1069 aged ≥ 50 years. AEs leading to discontinuation were reported by 19.6% patients < 50 years and 29.6% of patients ≥ 50 years, with gastrointestinal disorders being the most common. SAEs were reported by 5.2% of patients < 50 years and 8.9% those ≥ 50 years. In PROCLAIM, SAEs were reported in 13% of patients < 50 years and 10% of those ≥ 50 years. Median ALC decreased by 35% in patients < 50 years and 50% in those ≥ 50 years in ESTEEM, with similar patterns observed in PROCLAIM.

Conclusions: ESTEEM found no unexpected safety signals in older patients and annualized relapse rates (ARRs) were significantly reduced in both age groups. Both studies indicated that DMF is efficacious and has a favorable safety profile in patients with RRMS aged ≥ 50 years.

Clinical trial registration: ESTEEM (NCT02047097), PROCLAIM (NCT02525874).

Introduction: Oral corticosteroids (OCS) are used to manage chronic obstructive pulmonary disease (COPD) exacerbations but are associated with adverse outcomes that may increase healthcare resource utilization and costs. We compared attendance/costs associated with OCS-related adverse outcomes in patients who ever used OCS versus those who never used OCS and examined associations between cumulative OCS exposure and attendance/costs.

Methods: This direct matched observational cohort study used the UK Clinical Practice Research Datalink GOLD database (data range 1987-2019). Patients with a COPD diagnosis on/after April 1, 2003, and Hospital Episode Statistics linkage were included. Emergency room, specialist or primary care outpatient, and inpatient attendance were analyzed. Costs, estimated using Health and Social Care 2019 and National Health Service Reference Costs 2019-2020 reports, were adjusted for sex, age, exacerbation number, and inhaler type used in the 12 months before index date.

Results: The OCS cohort had higher annualized disease-specific (excluding respiratory) total attendance/costs versus the non-OCS cohort (adjusted incidence rate ratio [aIRR] with 95% confidence intervals [CIs]) ranging from 37% (1.37 [1.31, 1.43]) for emergency room attendances to 149% (2.49 [2.36, 2.63]) for specialist consultations. Disease-specific (excluding respiratory) attendance/costs increased in a positive dose-response relationship for most attendance categories versus the < 0.5 g reference dose. For the 0.5 to < 1.0 g cumulative dose category, the greatest increases in disease-specific (excluding respiratory) attendance/costs occurred for primary care consultations (aIRR [95% CI] 1.38 [1.32, 1.44]). For the ≥ 10 g cumulative dose category, the greatest increases were observed for primary care consultations (aIRR [95% CI] 2.83 [2.66, 3.00]), non-elective long stays (≥ 2 days; 2.54 [2.15, 2.99]), and non-elective short stays (≤ 1 day; 2.51 [2.12, 2.98]). Similar findings were observed for all-cause attendance/costs.

Conclusion: Among patients with COPD, OCS-related adverse outcomes were associated with higher attendance and costs, with a positive dose-response relationship. A graphical abstract is available with this article.