Long-term outcomes and predictors of vedolizumab persistence in ulcerative colitis.

Background: Long-term vedolizumab (VDZ) outcomes in real-world cohorts have been largely limited to 1-year follow-up, with few bio-naïve patients or objective markers of inflammation assessed. Objectives: We aimed to assess factors affecting VDZ persistence including clinical, biochemical and faecal biomarker remission at 1, 3 and 5 years. Design: We performed a retrospective, observational, cohort study. Methods: All adult inflammatory bowel disease (IBD) patients who had received VDZ induction for ulcerative colitis (UC)/IBD-unclassified (IBDU) were included. Baseline phenotype and follow-up data were collected via a review of electronic medical records. Results: We included 290 patients [UC n = 271 (93.4%), IBDU n = 19 (6.6%)] with a median time on VDZ of 27.6 months (interquartile range: 14.4-43.2). At the end of follow-up, a total of 157/290 (54.1%) patients remained on VDZ. The median time to discontinuation was 14.1 months (7.0-23.3). Previous exposure to ⩾1 advanced therapy, steroid use at baseline and disease extension (E3 and E2 versus E1) were independent predictors for worse VDZ persistence. Clinical remission (partial Mayo < 2) was 75.7% (171/226), 72.4% (157/217) and 70.2% (127/181) at years 1, 3 and 5, respectively. Steroid use during maintenance VDZ therapy occurred in 31.7% (92/290), hospitalization in 15.5% (45/290) and surgery in 3.4% (10/291). The rate of serious adverse events was 1.2 per 100 patient-years of follow-up. Conclusion: VDZ effectiveness appears enduring with favourable long-term safety profile. VDZ persistence was influenced by previous exposure to biologics/small molecules, disease distribution and steroid use at baseline in our study.

Vedolizumab long-term use in ulcerative colitis What was this study done? • Vedolizumab efficacy and safety in ulcerative colitis have been firmly established by existing evidence. • Long-term data from the GEMINI trial further corroborate the favourable safety profile over an extended duration but there is little data on long-term vedolizumab use over 1 year. What did the researches do? • We performed a retrospective, observational, cohort study. All adult IBD patients who ever received vedolizumab induction from November 2014 to December 2021 for ulcerative colitis/IBDU were included. What did the researchers find? • This real-world study demonstrates that vedolizumab persistence exceeds 80% at 1 year and remains nearly 50% at 5 years with no new safety signals. • Worse vedolizumab persistence is associated with prior exposure to biologics/small molecules, more extensive disease involvement and steroid use at vedolizumab initiation. What do the findings mean? • These findings have important implications for drug positioning and sequencing, as well as for optimizing outcomes when vedolizumab is utilized as first-line therapy. Furthermore, it also emphasizes the long-term safety profile.

Retrospective, Real Life Study on the Effectiveness and Safety of a Depigmented-Polymerized Subcutaneous Vaccine Containing a Mixture of Grasses and Olea europaea.

INTRODUCTION: Allergen immunotherapy is the only modifying treatment of the natural course of respiratory allergic diseases; however, the lack of evidence leads to little inconclusive results. Real life studies are on the rise and are becoming a valuable tool to confirm and complement findings from clinical trials. The objective of this study was to evaluate the effectiveness and safety of a depigmented-polymerized undiluted subcutaneous extract of grass and olive pollen, under routine clinical practice conditions. METHODS: This was an observational, retrospective, longitudinal, single-center study on the use of a 2-pollen (grass mix and Olea europaea) undiluted subcutaneous extract over at least 3 consecutive years. Data were collected from 76 patients (n = 44 female; median age: 12.5 years old) diagnosed with allergic rhinoconjunctivitis with/without allergic asthma due to sensitization to both grasses and O. europaea. Primary and secondary effectiveness endpoints were symptom severity, concomitant medication, and immunological profile before and after completing the immunotherapy. A 2-year follow-up of patients' symptoms and medication history after completing the subcutaneous immunotherapy (SCIT) was performed. RESULTS: There was a significant improvement of symptoms and medication consumption after 3 years of SCIT treatment, and a significant decrease in specific IgE levels for grasses and O. europaea was observed after finishing the treatment. CONCLUSION: Three years treatment of allergic patients using an undiluted mixture of two allergen extracts was shown to be safe and effective for rhinitis and asthma, with efficacy maintained for at least 2 years after finishing SCIT. These results reinforce the importance of real life clinical data in addition to those from clinical trials, helping to individualize allergic treatments.

Comparison of renal prognosis between dipeptidyl peptidase-4 inhibitor users and non-users.

AIM: To evaluate the renal prognosis of dipeptidyl peptidase-4 inhibitor (DPP-4i) users and non-users using real-world Asian data. METHODS: Using databases from DeSC Healthcare, Inc., patients aged 30 years or older who used antidiabetic drugs from 2014 to 2021 were identified. Propensity score matching analyses were used to compare renal prognosis between DPP-4i users and non-users. The primary outcomes were estimated glomerular filtration rate (eGFR) decline and end-stage kidney disease (ESKD) development in the eGFR of 45 mL/min/1.73m2 or higher and eGFR of less than 45 mL/min/1.73m2 groups, respectively. RESULTS: In total, 65 375 and 9866 patients were identified in the eGFR of 45 mL/min/1.73m2 or higher and eGFR of less than 45 mL/min/1.73m2 groups, respectively. In the eGFR of 45 mL/min/1.73m2 or higher group, propensity score matching created 16 002 pairs. A significant difference was observed in the primary outcome of eGFR decline between DPP-4i users and non-users at 2 years (-2.31 vs. -2.56 mL/min/1.73m2: difference, 0.25 mL/min/1.73m2; 95% confidence interval [CI], 0.06-0.44) and 3 years (-2.75 vs. -3.41 mL/min/1.73m2: difference, 0.66 mL/min/1.73m2; 95% CI, 0.39-0.93). In the eGFR less than 45 mL/min/1.73m2 group, propensity score matching created 2086 pairs. After a mean of 2.2 years of observation, ESKD development was 1.15% and 2.30% in users and non-users, respectively, and Kaplan-Meier analysis revealed a significant difference (log rank P = .005). CONCLUSIONS: This retrospective real-world study revealed that patients using DPP-4is had a better renal prognosis than those not using DPP-4is.

Supplementing Systematic Review Findings with Healthcare System Data: Pilot Projects from the Agency for Healthcare Research and Quality Evidence-based Practice Center Program.

OBJECTIVES: The US Agency for Healthcare Research and Quality (AHRQ), through the Evidence-based Practice Center (EPC) Program, aims to provide health system decision makers with the highest-quality evidence to inform clinical decisions. However, limitations in the literature may lead to inconclusive findings in EPC systematic reviews (SRs). The EPC Program conducted pilot projects to understand the feasibility, benefits, and challenges of utilizing health system data to augment SR findings to support confidence in healthcare decision-making based on real-world experiences. STUDY DESIGN AND SETTING: Three contractors (each an EPC located at a different health system) selected a recently completed systematic review conducted by their center and identified an evidence gap that electronic health record (EHR) data might address. All pilot project topics addressed clinical questions as opposed to care delivery, care organization, or care disparities topics that are common in EPC reports. Topic areas addressed by each EPC included infantile epilepsy, migraine, and hip fracture. EPCs also tracked additional resources needed to conduct supplemental analyses. The workgroup met monthly in 2022-2023 to discuss challenges and lessons learned from the pilot projects. RESULTS: Two supplemental data analyses filled an evidence gap identified in the systematic reviews (raised certainty of evidence, improved applicability) and the third filled a health system knowledge gap. Project challenges fell under three themes: regulatory and logistical issues, data collection and analysis, and interpretation and presentation of findings. Limited ability to capture key clinical variables given inconsistent or missing data within the EHR was a major limitation. The workgroup found that conducting supplemental data analysis alongside an SR was feasible but adds considerable time and resources to the review process (estimated total hours to complete pilot projects ranged from 283-595 across EPCs), and that the increased effort and resources added limited incremental value. CONCLUSION: Supplementing existing systematic reviews with analyses of EHR data is resource intensive and requires specialized skillsets throughout the process. While using EHR data for research has immense potential to generate real-world evidence and fill knowledge gaps, these data may not yet be ready for routine use alongside systematic reviews.

From Triple- to Penta-Exposed Multiple Myeloma: A Real-World Study in a Medicare Population.

INTRODUCTION: Treatment of multiple myeloma (MM) has been transformed by novel therapies, including CD38 monoclonal antibodies (mAbs), immunomodulatory drugs (IMiDs), and proteasome inhibitors (PIs), resulting in increasing numbers of patients who are triple-class exposed (TCE; exposed to ≥ 1 drug in each class). Many patients are penta-exposed (PE; ≥ 2 IMiDs, ≥ 2 PIs, and a CD38 mAb), some are triple-class refractory (TCR), and some are PE and TCR (PE-TCR). Data on real-world outcomes in elderly patients with MM across this spectrum of exposure are limited. METHODS: Data from the Medicare Chronic Conditions Warehouse Database from November 2006-December 2020 were used to examine cohorts of TCE, TCR, PE, and PE-TCR patients. Outcomes were assessed from the start of the index line of therapy (LOT), defined as the first LOT after becoming TCE or PE. RESULTS: A total of 2830 TCE, 1371 TCR, 1121 PE, and 774 PE-TCR patients were identified. Pomalidomide was the most frequently used medication for the index LOT in all cohorts (32.6% [PE-TCR] to 43.3% [TCR]). The most frequently used regimens for the index LOT were pomalidomide plus daratumumab for TCE (17.2%) and PE (7.0%), pomalidomide plus carfilzomib for TCR (10.3%), and pomalidomide plus elotuzumab for PE-TCR (7.4%). Median time to discontinuation (TTD) ranged from 4.2 (PE-TCR) to 6.9 (TCE) months, and overall survival (OS) ranged from 13.0 (TCR) to 15.9 (PE) months. Healthcare resource utilization (HRU) was lowest for TCE and highest for PE-TCR patients. Mean monthly healthcare costs (HCC) ranged from $23,091 (TCE) to $24,412 (PE-TCR). MM medications represented 66.2% (PE-TCR) to 72.8% (TCE) of costs. CONCLUSIONS: In this study across a spectrum of Medicare TCE patients, there was heterogeneity in treatment regimens, suggesting no standard of care. TTD and OS were short, and HRU and HCC were high. These results underscore the potential for new therapies in this population.

Palbociclib in HR-Positive, HER2-Negative Advanced/Metastatic Breast Cancer: A Systematic Scoping Review of Real-World Evidence from Countries Outside of Western Regions that Are Underrepresented in Clinical Trials.

INTRODUCTION: Limited awareness exists regarding real-world data (RWD) for palbociclib in patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced/metastatic breast cancer in populations from certain countries outside of Western regions. METHODS: A systematic scoping review was conducted using PubMed and Embase to evaluate RWD for palbociclib from countries outside of Western regions that are underrepresented in clinical trials. Search criteria were aligned with our research question for relevant English-language publications, without restrictions on publication date, followed by Phase 1 (title and abstract) and Phase 2 (full-text) screening of retrieved citations as per Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Data analyses of eligible studies were done separately for abstracts and full-text publications to enhance the precision and reliability of the results. RESULTS: Database search yielded 1485 non-duplicate records, 46 qualified for inclusion, of which 47.8% were published as full text. The analysis of outcomes, based exclusively on full-text publications that collectively included 2048 patients treated with palbociclib, revealed the median progression-free survival (PFS) of 20.2-36.7 months, overall survival (OS) of 39.9 months (reported in one publication) and objective response rate (ORR) of 45.3-80.0% with first-line treatment. In ≥ second line, the median PFS, OS and ORR ranged from 7.0 to 24.2 months, 11 to 19.6 months, and 13.9% to 47.9%, respectively. The safety profile of palbociclib was similar to that reported in pivotal clinical studies, and no new safety concerns were identified. CONCLUSIONS: A comprehensive volume of evidence demonstrates that palbociclib's effectiveness and safety profile in real-world settings align with those observed in clinical trials, offering valuable insights for clinical decision-making in countries outside of Western regions underrepresented in clinical trials.

Next-generation sequencing in oncology: challenges in economic evaluations.

INTRODUCTION: Next-generation sequencing (NGS) identifies genetic variants to inform personalized treatment plans. Insufficient evidence of cost-effectiveness impedes integration of NGS into routine cancer care. The complexity of personalized treatment challenges conventional economic evaluation. Clearly delineating challenges informs future cost-effectiveness analyses to better value and contextualize health, preference-, and equity-based outcomes. AREAS COVERED: We conducted a scoping review to characterize the applied methods and outcomes of economic evaluations of NGS in oncology and identify existing challenges. We included 27 articles published since 2016 from a search of PubMed, Embase, and Web of Science. Identified challenges included defining the evaluative scope, managing evidentiary limitations including lack of causal evidence, incorporating preference-based utility, and assessing distributional and equity-based impacts. These challenges reflect the difficulty of generating high-quality clinical effectiveness and real-world evidence (RWE) for NGS-guided interventions. EXPERT OPINION: Adapting methodological approaches and developing life-cycle health technology assessment (HTA) guidance using RWE is crucial for implementing NGS in oncology. Healthcare systems, decision-makers, and HTA organizations are facing a pivotal opportunity to adapt to an evolving clinical paradigm and create innovative regulatory and reimbursement processes that will enable more sustainable, equitable, and patient-oriented healthcare.

A New Validated Approach for Identifying Childhood Immunizations in Electronic Health Records in the United Kingdom.

BACKGROUND: Routinely collected electronic health records (EHR) offer a valuable opportunity to carry out research on immunization uptake, effectiveness, and safety, using large and representative samples of the population. In contrast to other drugs, vaccines do not require electronic prescription in many settings, which may lead to ambiguous coding of vaccination status and timing. METHODOLOGY: We propose a comprehensive algorithm to identifying childhood immunizations in routinely collected EHR. In order to deal with ambiguous coding, over-recording, and backdating in EHR, we suggest an approach combining a wide range of medical codes in combination to identify vaccination events and using appropriate wash-out periods and quality checks. We illustrate this approach on a cohort of children born between 2006 and 2014 followed up to the age of five in the Clinical Practice Research Datalink (CPRD) Aurum, a UK primary care dataset of EHR, and validate the results against national estimates of vaccine coverage by NHS Digital and Public Health England. RESULTS: Our algorithm reproduced estimates of vaccination coverage, which are comparable to official national estimates and allows to approximate the age at vaccination. Electronic prescription data only do not cover vaccination events sufficiently. CONCLUSION: Our new proposed method could be used to provide a more accurate estimation of vaccination coverage and timing of vaccination for researchers and policymakers using EHR. As with all observational research using real-world data, it is important that researchers understand the context of the used dataset used and the clinical practice of recording.

Ceftolozane/Tazobactam for the Treatment of Adults With Cystic Fibrosis: Results From a French Prospective Cohort Study.

Background: People with cystic fibrosis (pwCF) are particularly susceptible to respiratory infections, including those caused by multidrug-resistant (MDR) pathogens. Ceftolozane/tazobactam (C/T) is an antibacterial agent combination active against MDR gram-negative bacteria that has shown promising results in isolates from pwCF. This subanalysis is the first extensive observation of real-world C/T use in pwCF. Methods: The multicenter observational CONDUCT study included consecutive patients, some with cystic fibrosis, who received ≥1 dose of C/T at 28 centers throughout France. Patients were treated according to hospital standards and followed up until the end of C/T treatment (EOT). Results: Among 260 patients who had received ≥1 dose of C/T, 63 were pwCF, including 12 with previous lung transplant. The median age was 34 years and 55.6% of patients were female. Pseudomonas aeruginosa was the most frequently isolated pathogen (n = 40/41 [97.6%]). Most tested P aeruginosa strains (n = 65/73 [91.5%]) and all other isolated strains (Escherichia coli, Citrobacter koseri, Proteus mirabilis, and Serratia marcescens) were susceptible to C/T. Most patients completed the treatment duration, including those with historical ß-lactam hypersensitivity. Reasons for stopping treatment were planned EOT and improvement in condition; overall, 88.9% of patients (n = 56/63) experienced improvement in condition. No new safety signals were identified. Mean forced expiratory volume in 1 second improved from 1.33 L to 1.47 L before and after C/T treatment, respectively (n = 52; P = .057). Conclusions: C/T treatment was well tolerated and effective in pwCF, including those with previous ß-lactam hypersensitivity.

Sodium-glucose cotransporter 2 inhibitors reduce the risk of incident type 2 diabetes in people with heart failure without diabetes: An analysis of real-world, cohort data.

AIM: Sodium-glucose cotransporter 2 inhibitors (SGLT2is), used as a glucose-lowering therapy in people with type 2 diabetes (T2D), have significant cardiorenal benefits, reducing hospitalization for heart failure (HF) and cardiovascular mortality in patients with and without T2D. Recent clinical trial evidence suggests their potential utility in preventing incident T2D among the high-risk HF populations. Therefore, we aimed to assess whether this finding was reproducible in a real-world setting. METHODS: We performed a retrospective cohort analysis of 484 643 patients with HF, without baseline diabetes, prescribed either angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers with/without SGLT2is (treatment, n = 42 018; reference, n = 442 625) across 95 global health care organizations, using a large real-world ecosystem. Propensity score matching balanced arms 1:1 for confounders (n = 39 168 each arm). Subgroup analysis further evaluated the impact on patients with prediabetes and the efficacy of dapagliflozin/empagliflozin, specifically, on incident T2D and secondary outcomes, including all-cause mortality, acute pulmonary oedema and hospitalization. RESULTS: Treatment with SGLT2is significantly reduced incident T2D {hazard ratio (HR) 0.71 [95% confidence interval (CI) 0.63, 0.75]} in patients with HF. The analysis of patients with prediabetes found that SGLT2is further reduced incident T2D [HR 0.62 (95% CI 0.45, 0.80)]. The magnitude of reduction in incident T2D was higher in patients prescribed dapagliflozin [HR 0.47 (95% CI 0.39, 0.56)] versus empagliflozin [HR 0.81 (95% CI 0.70, 0.93)]. CONCLUSION: Treatment with SGLT2is in patients with HF was associated with a reduced risk of incident T2D, most strikingly in people with prediabetes.

Efficacy, adherence and persistence of various glucagon-like peptide-1 agonists: nationwide real-life data.

AIM: The management of type 2 diabetes mellitus has advanced in the last two decades since the introduction of glucagon-like peptide-1 receptor agonists (GLP-1RAs). However, multiple factors may interfere with achieving better glycaemic control. This study evaluated the differences between various GLP-1RAs in efficacy, adherence and persistence. MATERIALS AND METHODS: We conducted a retrospective cohort study using the electronic medical database from Clalit Health Services. Adults with type 2 diabetes mellitus who purchased any GLP-1RA between 2009 and 2021 were included. The Index Date was defined as the date of the first purchase of any GLP-1RA. We evaluated the adherence, persistence and glycaemic control after GLP-1RAs initiation. Baseline glycaemic and post-treatment glycaemic controls were analysed. RESULTS: In total, 70 654 patients were included. The mean age was 11.7 ± 60.4, and 51% were females. A significant reduction in glycated haemoglobin (HbA1c) was observed in all patients who received GLP-1RAs. However, the percentage of changes in the HbA1c was higher among weekly GLP-1RA than daily initiators (14.6% vs. 10.2%, p < 0.001). The proportion of subjects with any decrease in HbA1c was higher among the once-weekly compared with the daily dose (82.4% vs. 74.7%) and mainly patients initiated semaglutide or dulaglutide, with 16.0% and 14.7% reduction. The frequency of good adherence (the proportion of days covered ≥80%) was significantly higher among the weekly group odds ratio = 1.25 (95% confidence interval 1.21-1.28). Good adherence was reported in older age, female gender, Jewish ethnicity and high socio-economic status (p < 0.001). CONCLUSIONS: Weekly GLP-1RAs initiators were more adherent, persistent to therapy and achieved better glycaemic control. Epidemiological variables might play a role in achieving this goal.

Comparing the effectiveness of molnupiravir and nirmatrelvir-ritonavir in non-hospitalized and hospitalized COVID-19 patients with type 2 diabetes: A target trial emulation study.

AIMS: To compare the effectiveness of molnupiravir and nirmatrelvir-ritonavir for non-hospitalized and hospitalized COVID-19 patients with type 2 diabetes (T2DM). MATERIALS AND METHODS: Territory-wide electronic health records in Hong Kong were used to perform target trial emulation using a sequential trial approach. Patients (1) aged ≥18 years, (2) with T2DM, (3) with COVID-19 infection, and (4) who received molnupiravir or nirmatrelvir-ritonavir within 5 days of infection between 16 March 2022 and 31 December 2022 in non-hospital and hospital settings were included. Molnupiravir and nirmatrelvir-ritonavir initiators were matched using one-to-one propensity-score matching and followed for 28 days. Risk of outcomes was compared between groups by Cox regression adjusted for baseline characteristics. Subgroup analyses were performed on age (<70 years, ≥70 years), sex, Charlson comorbidity index (<4, ≥4), and number of COVID-19 vaccine doses (<2 doses, ≥2 doses). RESULTS: Totals of 17 974 non-hospitalized (8987 in each group) and 3678 hospitalized (1839 in each group) patients were identified. Non-hospitalized nirmatrelvir-ritonavir initiators had lower risk of all-cause mortality (absolute risk reduction [ARR] at 28 days 0.80%, 95% confidence interval [CI] 0.56-1.04; hazard ratio [HR] 0.47, 95% CI 0.30-0.73) and hospitalization (ARR at 28 days 4.01%, 95% CI 3.19-4.83; HR 0.73, 95% CI 0.66-0.82) as compared with molnupiravir initiators. Hospitalized nirmatrelvir-ritonavir initiators had reduced risk of all-cause mortality (ARR at 28 days 2.94%, 95% CI 1.65-4.23; HR 0.56, 95% CI 0.40-0.80) as compared with molnupiravir initiators. Consistent findings were found across all subgroups. CONCLUSIONS: The use of nirmatrelvir-ritonavir may be preferred to molnupiravir for COVID-19 patients with T2DM and without contraindication to either treatment.

Economic burden of respiratory syncytial virus in adults in Germany - a health claims analysis between 2015 and 2018.

AIMS: Respiratory syncytial virus (RSV) causes severe lower respiratory tract infections (LRTI) in infants and adults. While the clinical burden was recently estimated in adults in Germany, little is known about the economic burden yet. To fill this gap, we aimed to assess hospital and outpatient healthcare resource utilization (HRU) and costs of RSV infections in adults in Germany. METHODS: In this retrospective, observational study on nationwide, representative, anonymized claims data (2015-2018), we identified patients ≥18 years with ICD-10-GM-codes specific to RSV ('RSV-specific'). To increase sensitivity, patients with unspecified LRTIs (including unspecified bronchitis, bronchiolitis, bronchopneumonia, and pneumonia) during RSV seasons were also included as cases potentially caused by RSV ('RSV-possible'). RSV-related HRU (hospital days, ICU and ventilation treatment, drug dispensation) and direct costs were estimated per episode. Excess costs per episode and for follow-up periods were compared to a matched control cohort. All outcomes were reported per healthcare sector and stratified by age and risk groups as well as disease severity (ICU admission/ventilation). RESULTS: Direct inpatient and outpatient mean episode costs were 3,473€and 82€, respectively, with substantially higher costs for severe cases requiring intensive care and/or ventilation (10,801€). Direct costs for RSV-specific cases were higher than for RSV-possible cases (inpatients: 6,247€vs. 3,450€; outpatients: 127€vs. 82€). Moreover, costs were significantly higher for RSV patients than for controls and increased over time (inpatients: 5,140€per episode vs 10,093€per year; outpatients: 46€per quarter vs 114€per year). LIMITATIONS: While the number of RSV-specific cases was low, inclusion of seasonal LRTI cases likely increased the sensitivity to detect RSV cases and allowed a better estimation total costs of RSV. CONCLUSIONS: The economic burden of RSV-LRTI in adults in Germany is substantial, persists long-term and is particularly high in the elderly. This highlights the need for cost-effective prevention measures.

crossnma: An R package to synthesize cross-design evidence and cross-format data using network meta-analysis and network meta-regression.

BACKGROUND: Although aggregate data (AD) from randomised clinical trials (RCTs) are used in the majority of network meta-analyses (NMAs), other study designs (e.g., cohort studies and other non-randomised studies, NRS) can be informative about relative treatment effects. The individual participant data (IPD) of the study, when available, are preferred to AD for adjusting for important participant characteristics and to better handle heterogeneity and inconsistency in the network. RESULTS: We developed the R package crossnma to perform cross-format (IPD and AD) and cross-design (RCT and NRS) NMA and network meta-regression (NMR). The models are implemented as Bayesian three-level hierarchical models using Just Another Gibbs Sampler (JAGS) software within the R environment. The R package crossnma includes functions to automatically create the JAGS model, reformat the data (based on user input), assess convergence and summarize the results. We demonstrate the workflow within crossnma by using a network of six trials comparing four treatments. CONCLUSIONS: The R package crossnma enables the user to perform NMA and NMR with different data types in a Bayesian framework and facilitates the inclusion of all types of evidence recognising differences in risk of bias.

Patient-reported symptoms and burden of eosinophilic esophagitis: evidence from real-world clinical practice.

BACKGROUND: Eosinophilic esophagitis is a chronic inflammatory disorder of the esophagus. This real-world study used patient and physician surveys to describe the clinical characteristics and disease burden of eosinophilic esophagitis-overall and in a subgroup of patients with dysphagia despite treatment. METHODS: Data analyzed in this study were collected in 2020 from US and EU patients with eosinophilic esophagitis. Eligible patients were aged ≥ 12 years with a diagnosis of eosinophilic esophagitis, had an esophageal count of ≥ 15 eosinophils/high-power field at diagnosis, and were currently prescribed treatment for eosinophilic esophagitis. RESULTS: Overall, 1001 patients were included, of whom 356 (36%) had dysphagia despite treatment. Demographics and clinical characteristics were similar in both populations. The severity of eosinophilic esophagitis was mild in more patients overall (69%) versus those with dysphagia despite treatment (48%). Patient disease history was similar in both populations, with some exceptions: common patient-reported symptoms were dysphagia (70% and 86%) and heartburn/acid reflux (55% and 49%), and common physician-reported symptoms were dysphagia (75% and 91%) and food impaction (46% and 52%). Treatment history was similar in both populations; overall, the most common treatments were proton pump inhibitors (83%) and topical corticosteroids (51%). Patients reported slightly more days with symptoms, higher impacts on activities of daily living, and slightly higher anxiety or depression in the dysphagia-despite-treatment population versus the overall population. CONCLUSIONS: Eosinophilic esophagitis presents severe symptoms and comorbidities that substantially impact patients' well-being and quality of life. Greater awareness of and novel treatments for eosinophilic esophagitis are needed.

Real-world Treatment Sequencing and Outcomes With Cabozantinib After First-line Immune Checkpoint Inhibitor-based Combination Therapy For Patients With Advanced Renal Cell Carcinoma: CARINA Study Results.

INTRODUCTION: Real-world data are limited on treatment sequencing and outcomes after first-line (1L) immune checkpoint inhibitor (CPI)-based combination treatment of advanced renal cell carcinoma (aRCC). PATIENTS AND METHODS: In this real-world, UK-based, retrospective study (CARINA; NCT04957160), data were obtained from hospital and electronic prescribing records. Patients were aged ≥ 18 years at aRCC diagnosis and had received 1L CPI-CPI or tyrosine kinase inhibitor (TKI)-CPI combination therapy before second-line (2L) therapy including cabozantinib. We describe treatment outcomes including 1L and 2L durations of treatment (DoT) and overall survival (OS). RESULTS: Data from April 2015 to June 2022 were collected on 281 patients from nine UK centres. Median 1L DoT was 2.3 months for CPI-CPI therapy (n = 171) and 5.0 months for TKI-CPI therapy (n = 58). After 1L CPI-CPI or TKI-CPI therapy, median 2L DoT was 5.8 versus 4.2 months, respectively, for cabozantinib (n = 163), and 3.8 versus 2.4 months for other therapies (n = 118); median 2L OS was 15.2 and 15.3 months, respectively, for cabozantinib, and 14.6 and 24.2 months for other therapies. CONCLUSION: DoT for 2L treatment was numerically better for cabozantinib than for other therapies, and after 1L CPI-CPI therapy than after 1L TKI-CPI therapy. Median OS was similar for 2L cabozantinib and other 2L therapies, and median OS for 2L cabozantinib was similar after both 1L therapy types. These results demonstrate the antitumour effect of 2L therapies, including cabozantinib, after 1L CPI-based combination treatment, regardless of whether 1L CPI-CPI or TKI-CPI therapy is used.

Efficacy and Safety of Escalating the Dose of Oral Semaglutide from 7 to 14 mg: A Single-Center, Retrospective Observational Study.

INTRODUCTION: The efficacy and safety of oral semaglutide, the first glucagon-like peptide 1 receptor agonist available in tablet form for the treatment of type 2 diabetes, were established in the phase 3a PIONEER program. However, evidence regarding the titration of oral semaglutide in real-world clinical settings remains insufficient. This study aimed to elucidate the therapeutic advantages of escalating the dose of oral semaglutide from 7 to 14 mg through clinical data analysis. METHODS: This retrospective observational study was conducted at a single center in Japan, focusing on adults with type 2 diabetes who were initiated on 14 mg oral semaglutide. The primary endpoint was the alteration in HbA1c levels 24 weeks after the initial prescription of 14 mg oral semaglutide. Secondary endpoints included changes in metabolic parameters and the incidence of adverse events. RESULTS: Data from 66 patients who met the inclusion criteria were analyzed. The mean change in HbA1c levels from baseline to 24 weeks following dose escalation was - 0.5 ± 0.8% [from 7.4 ± 1.0% at baseline to 7.0 ± 0.9% at 24 weeks (p < 0.01)]. Moreover, a significant reduction in body weight of - 2.0 ± 4.4 kg was observed at 24 weeks [from 90.0 ± 20.5 kg at baseline to 88.2 ± 21.4 kg at 24 weeks (p < 0.01)], with 41% of patients achieving at least a 3% reduction compared to baseline. Gastrointestinal disorders emerged as the most prevalent adverse event (10.6%), particularly nausea (7.6%), although predominantly of mild or moderate severity, with no instances of serious adverse events necessitating drug discontinuation. CONCLUSION: Escalating the dose of oral semaglutide to 14 mg could be an effective approach for enhancing glycemic control and managing body weight in individuals with type 2 diabetes.

A new paradigm in the management of scalp pruritus: findings from the SCALP-PR trial.

PURPOSE: The "Impact of scalp pruritus in dermatological consultations in Spain: The SCALP-PR trial" was initiated to address the common yet often insufficiently examined issue of scalp pruritus in dermatology. This condition leads to an uncontrollable urge to scratch, affecting the patients' quality of life and potentially causing scalp damage. This study aimed to explore the prevalence, patient profile, underlying conditios, and therapeutic approaches for scalp pruritus in Spain, and to assess the safety and efficacy profile, as well as the tolerability of a non-pharmacologic treatment. METHODS: From 2021 through 2022, 75 dermatologists enrolled a total of 359 patients in a study on scalp pruritus, approved by the Bellvitge University Hospital Research Ethics Committee, Barcelona, Spain. This evidence-based research combined a meta-analysis with observational study techniques focused on real-world evidence to examine the therapeutic impact on quality of life (QoL). Utilizing the Dermatology Life Quality Index (DLQI) for QoL assessments, the study evaluated the effectiveness of the topical product over 15 days. Data collection was conducted via an eCRF and analyzed with statistical methods to provide reliable insights into the management of scalp pruritus. RESULTS: The prevalence of scalp pruritus in Spain was found to be 6.9%, predominantly among women with a mean age of 52.5 years. The leading causes identified were seborrheic dermatitis and pruritus of undetermined etiology or sensitive scalp. Stress was noted as a key factor, with corticosteroids and hygienic measures being common therapies. The topical product demonstrated significant reductions in pruritus and scratching in more than 90% of patients after 15 days. Improvements were also seen in dermatological quality of life, with 87.1% of patients showing enhancements in DLQI scores. The product was well-received thanksto its cosmetic properties, with high ratings in texture, ease of application, and fragrance. CONCLUSION: The topical product studied is a safe, effective, and cosmetically appealing treatment, improving scalp pruritus in various etiologies for most patients. The results highlight the need for patient-center treatments in dermatology, providing important insights for clinical practice and future research.

[CAR T-cell therapy for malignant lymphoma].

Advances in understanding of the pathogenesis of B-cell lymphoma have led to development of various novel targeted therapies. Among them, CD19-targeted chimeric antigen receptor (CAR) T-cell therapies for relapsed and refractory B-cell lymphomas have shown remarkable efficacy in clinical trials, and three CAR T-cell products are now available in Japan. Real-world evidence (RWE) has shown that these products can provide comparable efficacy to clinical trials in clinical practice, where CAR T-cells were administered in patients with wider range of backgrounds. This finding will certainly broaden the role of CAR T-cell therapies in the treatment of B-cell lymphoma. However, since about half of the patients treated with CAR T-cell therapy progress thereafter, there is an urgent need for risk stratification and optimized management of refractory cases. Here, we review the results of clinical trials and RWE of CAR T-cell therapy in B-cell lymphoma.

The CARMEN-France registry of adult patients with immune thrombocytopenia and autoimmune hemolytic anemia in France.

The CARMEN-France registry is a prospective, multicenter registry in France including adult patients with a new diagnosis of immune thrombocytopenia or of autoimmune immune hemolytic anemia (2402 patients included in December 31, 2023). The recording of clinical, biological and treatment data allows detailed epidemiological and pharmacoepidemiological real-world studies. This review summarizes the CARMEN-France registry protocol, gives examples of studies conducted in the registry, and indicates future directions such as inclusion of patient reported outcomes, linkage with the French national health insurance database and linkage with other registries in Europe.