Incidence Rate Of Adverse Events Research Articles

Feasibility, Safety, and Enjoyment during Wii Balance Board Exergame Training among Individuals with Sub-acute Stroke

Introduction. Nintendo® Wii is a non-immersive virtual reality platform that works integrated with the Wii Balance Board as a biofeedback system for balance rehabilitation among post-stroke patients. Objective. Primary objective was to evaluate the feasibility of employing Wii Balance Board training as a standalone treatment approach in clinical practice for sub-acute stroke patients. The secondary objective was to assess the enjoyment status during Wii Balance Board training and to calculate effect size for definitive study. Method. The study design was pilot randomized control trial. We recruited 20 sub-acute stroke patients using a block randomization technique. The participants in the experimental group received Wii Balance Board training for 12 sessions up to 2 weeks. The control group participants received standard physiotherapy treatments for standing balance for 12 sessions until 2 weeks. Outcome measures were clinical-log documentation for feasibility testing, Exergame Enjoyment Questionnaire, mini-BESTest, and FIMs. Results. The study’s enrollment and retention rate was respectively 80% (n = 20) and 70% in each group (n = 7). The incidence rate of adverse events from Wii Fit training was reported to be 40% (n = 4), along with a moderate enjoyment rate (mean±sd=50.10 ± 14.69; n = 10). The experimental intervention did not offer significant benefits over control intervention (p = 0.539, 0.622; Cohen’s d = -0.280, -0.224; 95% CI: -1.158 to 0.605, -1.101 to 0.658). Conclusion. The Wii Balance Board-based exergames training can be considered a feasible and safe balance training approach among sub-acute stroke patients. However, exergames cannot replace standard care balance rehabilitation due to poor efficacy in short term.

Toxicity profiles of immunochemotherapy for gastric or gastroesophageal junction adenocarcinoma: a systematic review and meta-analysis.

Neoadjuvant immunochemotherapy is emerging as a promising regimen for patients with locally advanced gastric and gastroesophageal junction (G/GEJ) adenocarcinoma. However, it remains unclear whether immunochemotherapy will bring more adverse events (AEs) leading to a delay or even cancellation of surgeries. We aimed to provide a comprehensive analysis of the toxicity profiles for immune checkpoint inhibitors (ICIs) combined with chemotherapy among patients with G/GEJ adenocarcinoma. Published trials up to January 2024 were identified on Web of Science, Cochrane Library, Embase, and PubMed. Single-group and controlled clinical trials with ICIs in combination with chemotherapy in patients with G/GEJ adenocarcinoma were included. Two reviewers independently extracted data including incidence rate of AEs. The primary outcomes included the proportion of patients with adverse events leading to treatment discontinuation, grade 3 or higher adverse events, and serious adverse events. This study is registered with PROSPERO (CRD42023492676). Twenty studies were included for a total of 6692 patients. In patients receiving immunochemotherapy, 17% (95% confidence interval (CI), 11-23%) had adverse events leading to treatment discontinuation, 23% (95% CI, 19-27%) had serious adverse events, and 64% (95% CI, 58-70%) had grade 3 or higher adverse events. Compared with patients receiving chemotherapy alone, patients with immunochemotherapy were associated with higher rates of adverse events leading to discontinuation (RR, 1.45; 95% CI, 1.32-1.60), serious adverse events (RR, 1.27; 95% CI, 1.04-1.57), and grade 3 or higher adverse events (RR, 1.15; 95% CI, 1.07-1.23). In conclusion, the incidence of adverse events leading to discontinuation, serious adverse events, and grade 3 or higher adverse events were higher in patients receiving immunochemotherapy compared to those with chemotherapy.

Effect of percutaneous kyphoplasty combined with percutaneous microwave ablation on pain and clinical outcome in patients with spinal metastases.

To study the effect of percutaneous kyphoplasty (PKP) combined with microwave ablation (MWA) on pain and clinical outcomes in patients with spinal metastases. Eighty-seven patients with spinal metastases were retrospectively collected and divided into the PKP group (40 cases), and PKP + MWA group (47 cases). The postoperative efficacy (Frankel grade classification) was assessed, and the height of the diseased vertebrae, pain indices [visual analogue scale (VAS) and analgesic use score (AUS)], dysfunction in daily activities [Oswestry disability index (ODI)], quality of life (quality of life scores for tumor patients), and physical status score [Eastern Cooperative Oncology Group performance status] were compared. The incidence rate of adverse events and the survival of both groups were also counted. Postoperatively, the PKP + MWA group had a higher total effective rate than the PKP group (P < 0.05). Versus the PKP group, the PKP + MWA group showed improved recovery of vertebral height, lower VAS, AUS, and ODI scores, higher QLS, and better physical status (all P < 0.05). Postoperative adverse events were not significantly different between the two groups (P > 0.05). The disease-free survival rate and overall survival rate within 1 year were higher in the PKP + MWA group than in the PKP group (P < 0.05). PKP combined with MWA elevates the height of the diseased vertebrae, alleviates the symptoms of pain and dysfunction, and promotes the quality of life and physical status in patients with spinal metastases.

Efficacy and safety of mirikizumab in patients with moderately-to-severely active Crohn's disease: a phase 3, multicentre, randomised, double-blind, placebo-controlled and active-controlled, treat-through study.

Mirikizumab, a humanised monoclonal antibody that inhibits IL-23p19, is effective in moderate-to-severe ulcerative colitis. We aimed to evaluate the efficacy and safety of mirikizumab in patients with moderately-to-severely active Crohn's disease. VIVID-1 was a global phase 3, randomised, double-blind, double-dummy, placebo-controlled and active-controlled, treat-through study. The study enrolled adult patients at 324 sites (hospitals or medical centres, clinical practices, and clinical research sites) in 33 countries across Europe, Asia, North America, Central America, South America, and Australia. Adult patients with moderately-to-severely active Crohn's disease and previous inadequate response, loss of response, or intolerance to one or more approved biological therapies or conventional therapies were randomly assigned 6:3:2 to receive mirikizumab 900 mg intravenously at weeks 0, 4, and 8, then 300 mg subcutaneously every 4 weeks from weeks 12 to 52; ustekinumab about 6 mg/kg intravenously at week 0, then 90 mg subcutaneously every 8 weeks from weeks 8 to 52; or placebo. The coprimary endpoints assessing superiority of mirikizumab over placebo were composite endpoints: patient-reported outcome (PRO) clinical response at week 12 and endoscopic response at week 52 (endoscopic response-composite), and PRO clinical response at week 12 and Crohn's Disease Activity Index (CDAI) clinical remission at week 52 (CDAI clinical remission-composite). The adjusted risk differences were calculated, and the comparison was performed by the Cochran-Mantel-Haenszel test. Non-responder imputation was used. VIVID-1 was registered on ClinicalTrials.gov, NCT03926130, and is now complete. Between July 23, 2019, and Aug 23, 2023, 1150 patients were randomly assigned and received study treatment (safety population); 1065 patients were included in the efficacy population and received mirikizumab (n=579), ustekinumab (n=287), or placebo (n=199). Both coprimary endpoints were met: endoscopic response-composite was reached in 220 (38·0%) of 579 patients on mirikizumab versus 18 (9·0%) of 199 on placebo (99·5% CI 20·6-36·8; p<0·0001); CDAI clinical remission-composite was reached in 263 (45·4%) of 579 patients on mirikizumab versus 39 (19·6%) of 199 patients on placebo (99·5% CI 15·9-35·6; p<0·0001). The incidence rates of overall adverse events and discontinuations in patients treated with mirikizumab were lower compared with placebo. The most common adverse event across the three groups was COVID-19. Serious adverse events were reported in 65 (10·3%) of 630 patients on mirikizumab, 33 (10·7%) of 309 patients on ustekinumab, and 36 (17·1%) of 211 patients on placebo. There were three deaths during VIVID-1, one in the ustekinumab group, and two in the placebo group, including one in a placebo non-responder who switched to mirikizumab after week 12. None of the deaths were considered related to the study drug. The safety of mirikizumab in Crohn's disease was consistent with its known favourable profile. Mirikizumab was safe and effective as induction and maintenance treatment for patients with moderately-to-severely active Crohn's disease who had intolerance, inadequate response, or loss of response to standard therapy. Eli Lilly and Company.

Comparative Success Rate and Adverse Effects of Endoscopic Sphincterotomy Versus Endoscopic Papillary Large Balloon Dilation in Large Common Bile Duct Stones Removal. A Propensity Scores Inverse Weighting Analysis.

Endoscopic sphincterotomy (EST) is a standard treatment for common bile duct (CBD) stones. Endoscopic sphincterotomy combined with endoscopic papillary large balloon dilation (EST-EPLBD) is an effective treatment for difficult CBD stones. This study aims to evaluate and compare the effectiveness and adverse effects of EST-EPLBD and EST in treating large CBD stones. We retrospectively analyzed the data of 85 patients with large CBD stones who underwent either EST or EST-EPLBD, resulting in successful CBD stone extraction from January 2018 to June 2022. Propensity score inverse weighting was performed to reduce the possible bias in baseline characteristics between the two treatment groups. The success rate of complete stone removal in the first session, mechanical lithotripsy use, and adverse events were analyzed by multivariable risk regression analysis. The rate of complete stone removal in one session of the EST-EPLBD group was higher than that of the EST group at 28.78% (95% confidence interval [CI] 4.43, 50.1; p = 0.003). Mechanical lithotripsy use was decreased in the EST-EPLBD group by 25.81% (95% CI 42.33,9.28; p = 0.002). However, the incidence of adverse events is comparable. EST-EPLBD may be utilized in the treatment of CBD stones that exceed a diameter of 10 mm. The EST-EPLBD increased the rate of complete stone removal in a single session and reduced the need for mechanical lithotripsy. Conversely, the incidence rate of adverse events is similar.

Abstract 4122650: 1-year comparison of quadruple therapy sequencing strategies for heart failure with reduced ejection fraction using an individual-based state-transition microsimulation model

Introduction: Guidelines recommend quadruple therapy (angiotensin receptor blocker-neprilysin inhibitor [ARNI]), beta-blocker, mineralocorticoid receptor antagonist (MRA), and sodium-glucose co-transporter 2 inhibitor [SGLT2I]) as the cornerstone of heart failure (HF) with reduced ejection fraction (HFrEF) management. Yet, guidelines do not propose a specific order of initiation and titration (or “sequencing strategy”) of these agents, due to the absence of trial evidence. Aims: To model the 1-year efficacy and harms of proposed HFrEF quadruple therapy sequencing strategies using a microsimulation model. Methods: We conducted an individual-based state-transition microsimulation modeling study to compare the 1-year cumulative incidence of death, total HF hospitalization, and adverse events with 6 different HFrEF medication sequencing strategies (emulating 2 different traditional strategies, 2 two-drug combinations, a "cluster" strategy, and four-drug "simultaneous" strategy), each with two versions (weekly or biweekly medication adjustments), applied to treatment-naïve outpatients with HFrEF. We modeled death as an incidence at 1 year, and total HF hospitalization (first and recurrent events) and adverse events (bradycardia, hyperkalemia, hypotension, and renal impairment) as incidence rates per 100 patient-years. Results: At 1 year, an estimated 15.5% died without treatment compared to 6.9% with the traditional sequence adjusted biweekly, and 5.2-6.3% with other sequencing strategies. Similarly, the HF hospitalization rate decreased from 32.8 per 100 patient-years with no treatment to 11.1 per 100 patient-years traditional sequencing adjusted biweekly, and 6.9-9 per 100 patient-years with other strategies. The incidence rates of medication-related adverse events per 100 patient-years were: hypotension (5.8-6.9), renal impairment (4.6-6.0), bradycardia (2.9-3.2), and hyperkalemia (approximately 0.5). Conclusions: For treatment-naïve outpatients with HFrEF, pharmacotherapy sequencing strategies that started 2 to 4 medications on the first visit reduced the risk of death and hospitalization at 1 year compared to a traditional sequencing strategy. Weekly medication adjustments did not outperform biweekly adjustments when &gt;=2 medications were started on the initial visit. These findings can inform clinicians and policymakers in developing HFrEF medication optimization programs with sequencing strategy protocols that fit the local practical context.

Evaluating the safety of procedural sedation in emergency department settings among the pediatric population: a systematic review and meta-analysis of randomized controlled trials.

Our meta-analysis aimed to evaluate the safety of procedural sedation and analgesia in pediatric emergency department (ED) settings by investigating the incidence of cardiac, respiratory, gastrointestinal, and neurological adverse events associated with different sedation medications. In accordance with PRISMA guidelines, a comprehensive database search for randomized controlled trials was performed across ten databases from January 2005 to June 2024. Our inclusion criteria included randomized controlled trials involving children under 18years old undergoing pediatric sedation and analgesia in the ED. Data on medication types, dosages, administration routes, and adverse events were extracted and analyzed. Primary endpoints included cardiac, respiratory, gastrointestinal, and neurological adverse events. Seventeen studies met the inclusion criteria, a total of 2,302 procedural sedations. The most common adverse events were vomiting, agitation, and hypoxia, which occurred in 104.9 [95% CI = 76.9-132.9], 37.5 [95% CI = 20.6-54.4], 38.3 [95% CI = 23.9-52.6] of each 1000 sedations, respectively. Other adverse events included apnea, hypotension, and the need for bag-valve mask ventilation, which occurred in 8.6 [95% CI: 3.5-13.6], 9.3 [95% CI: -1.4 to 20.1], and 13.5 [95% CI: 3.2-23.8] of each 1,000 sedations, respectively. Severe adverse events were rare, with no reported instances of intubation and only one case of laryngospasm. Subgroup analyses revealed varying incidence rates of adverse events across different sedation protocols, with ketamine and its combinations showing higher rates of specific respiratory complications. Procedural sedation in pediatric EDs is generally safe, with a low incidence of adverse events, such as vomiting, agitation, and hypoxia. Life-threatening respiratory adverse events are extremely rare. Our findings thus support the careful selection and monitoring of sedation protocols to minimize risks.

Cancer and treatment specific incidence rates of immune-related adverse events induced by immune checkpoint inhibitors: a systematic review.

Immune-related adverse events (irAE) induced by immune checkpoint inhibitors (ICI) are a treatment-limiting barrier. There are few large-scale studies that estimate irAE prevalence. This paper presents a systematic review that reports the prevalence of irAE by cancer type and ICI. A systematic review was undertaken in MEDLINE OVID, EMBASE and Web of Science databases from 2017-2021. A total of 293 studies were identified for analysis and, of these, event rate was calculated for 272 studies, which involved 58,291 patients with irAE among 305,879 total patients on ICI. Event rate was calculated by irAE and ICI type. Mean event rate for general irAE occurrence across any grade was 40.0% (37.3-42.7%) and high grade was 19.7% (15.8-23.7%). Mean event rates for six specific types of irAE are reported. Mean event rate for ICI monotherapy was 29.7% (27.7-33.2%), 45.7% (29.6-61.7%) for ICI combination therapy, and 30.3% (27.3-35.0%) for both ICI monotherapy and combination therapy. This systematic review characterises irAE prevalence across current research that examines irAE risk factors across cancers and ICI. The findings confirms that irAE occurrence is very common in the real-world setting, both high grade and irAE across any grade.

Changes in the treatment landscape of metastatic hormone-sensitive prostate cancer following approval of upfront androgen receptor signaling inhibitors: A multicenter study.

A multicenter database was utilized to examine the current treatment landscape and clinical outcomes among patients with metastatic hormone-sensitive prostate cancer (mHSPC) following approval of upfront androgen receptor signaling inhibitors (ARSIs). We retrospectively analyzed patients with mHSPC who commenced treatment between February 2018 and June 2023. The Kaplan-Meier method was used to assess oncological outcomes, including time to castration-resistant prostate cancer (CRPC), progression-free survival 2 (PFS2, duration from initial treatment to tumor progression during second-line treatment), cancer-specific survival (CSS), and overall survival (OS). Cox regression analyses were performed to determine the impact of treatment choices on oncological outcomes. In addition, the incidence rate of adverse events was assessed. In total, 829 patients were analyzed; 42.5% received ARSIs with androgen deprivation therapy (ADT), 44.0% received combined androgen blockade (CAB), and 13.5% received ADT alone. Kaplan-Meier curves and multivariate Cox regression analyses indicated higher rates of CRPC and shorter PFS2 in patients treated with CAB versus ARSIs with ADT. By contrast, CSS and OS were not significantly different between the ARSI with ADT group and the CAB group. Grades 3-4 adverse events occurred in 1.9% of patients receiving CAB and 6.0% of those receiving ARSIs with ADT. Initial treatment with ARSIs in combination with ADT resulted in a longer time to CRPC and longer PFS2 compared to CAB. Although CAB and ADT alone were associated with fewer adverse events, ARSIs with ADT should be considered a first-line treatment option given its superior oncological outcomes.

A Retrospective Study of the Adverse Events Associated With Over-the-Counter Hearing Aids in the Manufacturer and User Facility Device Experience (MAUDE) Database.

To examine the adverse events reported in the United States Food and Drug Administration(USFDA)'s Manufacturer and User Facility Device Experience (MAUDE) database for over-the-counter (OTC) or non-prescription hearing aids. A retrospective cross-sectional study was performed using the USFDA's MAUDE database from January 2014 to August 2024. Adverse events were identified using the product codes (QUF, QUG, and QUH) and the keywords ("Hearing Aid, Air-Conduction with Wireless Technology, Over the Counter, Hearing Aid, Air-Conduction, Over the Counter, and Self-Fitting Air-Conduction Hearing Aid, Over the Counter"). Exclusion criteria included reports unrelated to OTC hearing aids and the usage of the device, or those providing insufficient information. The incidence of adverse events was estimated using data from market research reports. A total of 25 adverse events were identified, with 17 reports meeting the inclusion criteria. Medical device reports (MDRs) were available for 2022 (n=1), 2023 (n=9), and 2024 (n=7). Eighteen(60.0%) reports were related to device malfunction, six (20.0%) were regarding poor customer service, three (10.0%) referred to medical adverse events, two (6.7%) were associated withfailure to provide hearing benefits, and one (3.3%) referred to incompatibility with other medical equipment. Nine (30.0%) of the device malfunction reports were due topoor construction or the device falling apart, with eight (88.9%) of those cases resulting in foreign bodies in the ear. The incidence rate of adverse events for OTC hearing aids was calculated as 0.00132%. There is a low reported incidence of adverse events associated with OTC hearing aids. Possible poor construction of the device and its falling apart, resulting in foreign bodies in the ear, and poor customer service were commonly reported as adverse events. This information can aid providers in advising patients and managing expectations. However, more robust studies are needed to monitor adverse events associated with OTC hearing aids.

Adverse events associated with herbal medicine products reported in the Korea Adverse Event Reporting System from 2012 to 2021.

Systematic collection of diverse adverse events during herbal medicine administration is crucial. The Korea Adverse Event Reporting System (KAERS) compiles spontaneously reported adverse event data for medicinal products including herbal medicines. This study focused on extracting and analyzing adverse event data specifically related to herbal medicine products from the KAERS database. Individual case safety reports (ICSRs) encompassing 84 types of herbal medicine products, identified by item codes from 2012 to 2021, were extracted from the KAERS database. Descriptive statistics were employed to analyze the characteristics of the extracted reports, and adverse event information was systematically categorized and analyzed based on the MedDRA System Organ Class and preferred term classification. In total, 1,054 ICSRs were extracted, with some documenting multiple adverse events in a single ICSR, resulting in 1,629 extracted adverse events. When categorized by the MedDRA System Organ Class, gastrointestinal disorders were the most prevalent (28.7%), followed by skin and subcutaneous tissue disorders (20.1%). Based on the preferred terms, the most frequently reported adverse events were diarrhea (5.8%), urticaria (5.3%), pruritus (4.7%), rash (4.4%), and abdominal discomfort (4.2%). The most frequently reported herbal medicines were Bangpungtongseong-san (297 cases), Kyeongok-go (144 cases), and Eunkyo-san (108 cases). Spontaneously reported adverse events associated with herbal medicine products were systematically documented using the KAERS database. This study, which focused on voluntarily reported adverse reactions, underscores the need for additional research to estimate the incidence rate of adverse events and assess causality.

Real-world Study of the Safety and Efficacy of Pembrolizumab in the Treatment of Advanced Non-small Cell Lung Cancer

Pembrolizumab (PEM) has been shown to be effective in clinical trials for the treatment of advanced non-small cell lung cancer (NSCLC), but clinical trials were based on cohorts of patients selected on specific criteria, and whether the findings are consistent with real-world patients is debatable. The aim of this study is to evaluate the efficacy and safety of PEM in the treatment of advanced NSCLC based on real-world data. A retrospective collection of real-world data from patients with advanced NSCLC receiving PEM was conducted. Propensity score matching was used to eliminate inter-group differences and assess the efficacy and safety of PEM compared to chemotherapy. Among 450 matched patients, the incidence rates of any-grade adverse events were 79.87% in the PEM group and 86.71% in the chemotherapy group, while the incidence rates of grade ≥3 adverse events were 4.03% and 7.31%, respectively. The objective response rates were 48.63% for PEM and 36.00% for chemotherapy (P=0.011). The median progression-free survival was 15.5 months for PEM and 8.8 months for chemotherapy (P<0.001), and the median overall survival was not reached for PEM and 26.2 months for chemotherapy (P<0.001). PEM treatment for advanced NSCLC demonstrates favorable survival outcomes and acceptable safety in real-world clinical practice.

Application effect of task-oriented multi-dimensional nursing intervention in patients with coronary atherosclerotic heart disease and concurrent hypertension

Background: The purpose of this study was to explore the application effect of task-oriented multi-dimensional nursing interventionin patients with coronary atherosclerotic heart disease (CAD) and concurrent hypertension. Methodology: The clinical data of 196 patients with CAD and concurrent hypertension in our hospital between January 2019 and January 2022 were retrospectively analysed. The patients receiving task-oriented multi-dimensional nursing were set as study group (n=98), while those given routine nursing as control group (n=98). The two groups were compared in the Hamilton Anxiety Scale (HAMA) scores, left ventricular end-diastolic diameter (LVEDD), 36-Item Short Form Health Survey (SF-36) scores, left ventricular ejection fraction (LVEF), Hamilton Depression Scale (HAMD) scores, systolic blood pressure (SBP), treatment compliance and incidence rates of adverse events. Results: After intervention, study group showed lower HAMA and HAMD scores, SBP and LVEDD, but higher SF-36 scores and LVEF than control group (P&lt;0.05). The treatment compliance rate was higher in control group than that in study group (92.86% vs. 80.61%), while an opposite result was detected in the total incidence rate 5.10% vs. 13.27%, P&lt;0.05). Conclusion: Multidimensional nursing benefits CAD patients with hypertension, improving emotions, compliance, and quality of life, reducing adverse events, and promoting recovery. Recommended for clinical use. Keywords: Coronary atherosclerotic heart disease; task-oriented theory; multi-dimensional nursing care; clinical nursing.

Safety and efficacy assessment of the Inno-Xmart venous stent system in managing symptomatic iliofemoral venous obstruction: a 12-month outcome analysis.

This study aims to evaluate the safety and efficacy of the dedicated Inno-Xmart braided venous stent system (Suzhou Innomed Medical Device Co., Ltd., Jiangsu, China) in treating symptomatic iliofemoral venous obstruction. This clinical study followed a prospective, multicentre, single-arm design with the application of an objective performance goal. Patients diagnosed with symptomatic iliofemoral venous obstruction who met the eligibility criteria of this study were enrolled and treated with the Inno-Xmart venous stent system. The safety endpoints included the assessment of stent fracture, satisfaction of delivery system and 12-month incidence rate of major adverse events (MAEs). The primary efficacy endpoint focused on evaluating the 12-month primary patency rate through venography as determined by core laboratory. Secondary efficacy endpoints included surgical success rate, 6-month primary patency rate and the changes in quality of life from baseline to 6- and 12-month follow-up intervals. Between September 18, 2019, and April 26, 2021, 193 patients were successfully enrolled across 18 research institutions. The surgical success rate was 95.3% (184/193), the 12-month MAE rate was 5.1% (9/178) with no stent fractures or migrations. The 12-month primary patency rate for the participants was 96.1%, significantly surpassing the literature-derived objective performance of 80% (95% confidence interval [CI], 92.1-98.4; P < 0.0001). In addition, the mean venous clinical severity score (VCSS) and Chronic Venous Disease Quality of Life Questionnaire (CIVIQ) scores at the 6- and 12-month follow-ups were significantly lower than the preoperative scores (P < 0.001). The innovative, dedicated braided venous stent designed to address symptomatic iliofemoral venous obstruction demonstrates a high technical success rate, low complication rates, and impressive mid-term (12-month) patency. It effectively enhanced the quality of life for patients and holds promising prospects for a wide range of applications. The clinical study was officially registered in the "Chinese Clinical Trial Registry" (Registration number: ChiCTR2000040216, date of registration: November 25th, 2020).

Geographical Differences in the Safety and Efficacy of Tofacitinib Versus TNFi: APost Hoc Analysis of ORAL Surveillance.

In ORAL Surveillance, incidence rates (IRs) of major adverse cardiovascular events (MACE) and malignancies (excluding non-melanoma skin cancer [NMSC]) in cardiovascular (CV)-risk-enriched patients with rheumatoid arthritis (RA) were numerically greater with tofacitinib in North America versus the rest of the world, due to underlying risk factors. Here, we evaluated the safety and efficacy of tofacitinib versus tumor necrosis factor inhibitors (TNFi) among patients with RA across geographical regions. Patients with RA in ORAL Surveillance (NCT02092467), who were aged ≥ 50years with ≥ 1additional CV risk factor, received tofacitinib 5 or 10mg twice daily or TNFi; 45.9% were from either Poland or North America. This post hoc analysis stratified patients by region (Poland, North America, Other countries). Efficacy endpoints included Clinical Disease Activity Index, Disease Activity Score in 28 joints, with C-reactive protein (DAS28-4[CRP]), and Health Assessment Questionnaire-Disability Index (HAQ-DI). IRs and hazard ratios for adverse events were reported. Of 4362 patients (Poland, N = 759; North America, N = 1243; Other countries, N = 2360), more patients from North America versus Poland/Other countries had CV risk factors such as body mass index ≥ 30kg/m2 and history of diabetes/hypertension; however, more patients from Poland versus other regions were ever smokers and more patients from Poland/North America versus Other countries had history of coronary artery disease. MACE IRs were similar in North America and Poland, and numerically higher versus Other countries. IRs for malignancies (excluding NMSC) were numerically higher in NorthAmerica versus Poland/Other countries with tofacitinib. Serious infections IRs werenumerically higher in North America versus Poland across treatments. Venousthromboembolism/all-cause mortality IRs were generally comparable across regions. DAS28-4(CRP)/HAQ-DI improvements were generally lowest in North America. Differences in safety outcomes were driven by the presence of baseline risk factors; North America and Poland demonstrated a higher proportion of patients with some baseline CV risk factors/comorbidities versus Other countries. NCT02092467 (ClinicalTrials.gov).

First real-world study on the effectiveness and tolerability of rimegepant for acute migraine therapy in Chinese patients

BackgroundRimegepant, a small molecule calcitonin gene-related peptide (CGRP) receptor antagonist, is indicated for acute and preventive migraine treatment in the United States and other countries. However, there is a lack of prospective real-world evidence for the use of rimegepant in Chinese migraine patients.MethodsThis was a single-arm, prospective, real-world study. While taking rimegepant to treat migraine attacks as needed, eligible participants were asked to record their pain intensity, functional ability, and accompanying symptoms for a single attack at predose and 0.5, 1, 2, 24, and 48 h postdose via a digital platform. Adverse events (AEs) during the rimegepant treatment period were recorded and analysed. The percentages of participants who experienced moderate to severe pain at predose and 0.5, 1, 2, 24, and 48 h postdose were assessed. Additionally, the percentages of participants who reported better/good outcomes in terms of pain intensity, functional ability, and accompanying symptoms at 0.5, 1, 2, 24, and 48 h postdose were analysed. In addition, the total cohort (full population, FP) was stratified into a prior nonresponder (PNR) group to observe the effectiveness and safety of rimegepant for relatively refractory migraine and a rimegepant and eptinezumab (RE) group to observe the effectiveness and safety of the combination of these drugs.ResultsBy November 24th, 2023, 133 participants (FP, n = 133; PNR group, n = 40; RE group, n = 28) were enrolled, and 99 participants (FP, n = 99; PNR group, n = 30; RE group, n = 23) were included in the analysis. Rimegepant was effective in treating migraine in the FP and both subgroups, with a significant decreasing trend in the percentages of participants experiencing moderate to severe pain postdose (p < 0.05) and a marked increase in the percentages of participants who reported better/good outcomes in terms of pain intensity, functional ability, and accompanying symptoms at 0.5, 1, 2, 24, and 48 h postdose compared with predose. AEs were reported by 6% of participants in the FP, and all AEs were mild.ConclusionsIn the real world, rimegepant is effective in the acute treatment of migraine patients in China. The low incidence rate of AEs highlighted the favourable tolerability profile of rimegepant.Trial registrationClinicaltrials.gov NCT05709106. Retrospectively registered on 2023-02-01.Graphical

Assessment of prolonged safety and tolerability of erenumab in migraine patients in a long-term open-label study (APOLLON)

BackgroundEfficacy and safety of human monoclonal antibody erenumab used for migraine prophylaxis have been shown in clinical studies. APOLLON is an open-label, multi-center, single arm study, which permits dose adjustments of erenumab and includes an option for a drug holiday. The findings contribute to the accumulating long-term evidence regarding erenumab’s tolerability and safety profile in individuals experiencing episodic and chronic migraines.MethodsThe study population consisted of adult patients with episodic or chronic migraine, who had successfully completed the HER-MES study (NCT03828539). Patients were treated with erenumab for 128 weeks at a flexible dose of either 70 mg or 140 mg. Treatment discontinuation attempts were allowed as voluntary single treatment interruption (‘drug holiday’) of up to 24 weeks.Results701 patients were enrolled in APOLLON. The exposure associated incidence rate (EAIR) of adverse events (AEs) (N = 601) per 100 subject years was 101.71 (95% CI [92.28; 111.14]) meaning a patient could expect having about one adverse event per each year of treatment. EAIR was higher in females (n = 524, EAIR: 104.40, 95% CI [93.93; 114.86]) than in males (n = 77, EAIR: 86.55, 95% CI [65.39; 107.71]) and increased with initial monthly migraine days (MMD) and prior prophylactic treatment failures. A total of 155 patients discontinued erenumab treatment during open-label treatment phase. Of these, 29 were due to AEs (4.1% of total cohort) and out of these 65.5% (N = 19) were considered treatment-related. Safety parameters were in line with HER-MES data and did not reveal new safety signals. Drug holidays were realized by 108 patients (15.4%), of which 64.8% (N = 70) returned to treatment. The mean number of monthly headache days (MHDs), MMDs, and days with acute headache medication significantly increased during drug holiday. After resumption of erenumab treatment, a rapid reduction of the migraine parameters was observed.ConclusionsAPOLLON provides long-term safety and tolerability data confirming the beneficial safety profile of erenumab over a period of 128 weeks. In addition, reversibility of migraine deterioration during drug holiday was shown and most patients returned to their treatment with similar response rates compared to initial treatment.Trial registrationClinicalTrials.gov ID: NCT04084314 (https://clinicaltrials.gov/study/NCT04084314), First submitted: 2019-09-06.

Complications of Oral Corticosteroid Use in Otolaryngology.

Oral corticosteroids (OCS) are frequently prescribed by otolaryngologists. However, there are limited quantitative data on OCS-related adverse events (AEs) in otolaryngology. We sought to quantify OCS-related AEs in otolaryngology. All outpatient otolaryngology encounters in our healthcare system (2018-2023) at which an OCS was prescribed were identified via the electronic medical record. The diagnoses indicating OCS were categorized as sinonasal, otologic, pharyngo-laryngeal, and other. The medical record was subsequently examined to assess for OCS AEs during the 21-day period following the prescription. OCS AEs were grouped into (1) gastrointestinal, (2) metabolic, (3) bone/muscle, (4) ophthalmologic, and/or (5) psychiatric complications. The frequency and types of OCS related AEs were determined. A total of 20 746 otolaryngology encounters with OCS prescribed were examined. Seventy OCS courses had 1 or more AEs, implying a number needed to harm of 296.4 (240.2-386.8). There were 83 total OCS-related AEs, yielding an AE incidence rate of 4.0:1000 (95% CI, 3.0-5.0:1000) OCS prescriptions. The mean age of subjects with AEs (61.5 years) was significantly higher than those without (50.3 years; P < .001). Forty-seven (56.6%) of the complications were metabolic, with hyperglycemia and hypokalemia the most common, followed by gastrointestinal (26.5%), ophthalmologic (3.6%), psychiatric (2.4%), and musculoskeletal (2.4%). AEs related to OCS prescribed by otolaryngologists occur at a rate of once per 296 courses of treatment and older populations may be at increased risk for AEs. Otolaryngologists should balance AE rates against anticipated benefits of steroid therapy. 3.

Robust safety monitoring and signal detection using alternatives to the standard poisson distribution

ABSTRACT Proper and timely characterization of the safety profile of a pharmaceutical product under development is imperative for assessing the overall benefit-risk relationship of the product and for making key development decisions. For ongoing clinical development, a comprehensive and robust safety monitoring and safety signal detection program which is based upon quantitative statistical reasoning is critical. Methods presented here can be applied to safety signal detection and periodic safety monitoring. Various statistical properties, distributions, and models, all utilizing a Bayesian framework are considered and further examined in order to identify robust methods applicable to a broad set of scenarios and situations. Methods developed for incidence counts (including those with under-dispersed distributions) with variable time-at-risk and with underlying constant or non-constant hazard rates, are proposed and compared to traditional methods designed to assess adverse event incidence rates or binomial incidence proportions (which assume an underlying constant hazard rate and subsequent Poisson distribution for modeling event counts).

Efficacy and Safety of Durvalumab/Tremelimumab in Unresectable Hepatocellular Carcinoma as Immune Checkpoint Inhibitor Rechallenge Following Atezolizumab/Bevacizumab Treatment.

While guidelines recommend immune checkpoint inhibitor (ICI) rechallenge as second-line therapy for unresectable hepatocellular carcinoma (HCC), data supporting this remain limited, particularly regarding a standard regimen for first- and second-line treatments. Tremelimumab/durvalumab was recently approved but data on ICI rechallenge are lacking. The purpose of this study was to evaluate the early efficacy and safety of tremelimumab/durvalumab for HCC as an ICI rechallenge following initial ICI therapy with atezolizumab/bevacizumab. This multicenter retrospective study included patients with HCC who underwent treatment with tremelimumab/durvalumab, with relevant available clinical information. We evaluated the safety and efficacy of tremelimumab/durvalumab as ICI rechallenge following initial treatment with atezolizumab/bevacizumab. We analyzed the outcomes in patients who underwent tremelimumab/durvalumab as an ICI rechallenge and those who received tremelimumab/durvalumab as their initial ICI therapy RESULT: A total of 45 patients treated with tremelimumab/durvalumab were included, with 55.6% (25/45) undergoing ICI rechallenge. The objective-response and disease-control rates in patients who underwent ICI rechallenge were 14.3% (3/21) and 47.6% (10/21), respectively, similar to those in patients initially treated with tremelimumab/durvalumab. All patients (n = 3) who experienced the best response to progressive disease (PD) with initial atezolizumab/bevacizumab experienced PD during ICI rechallenge. The incidence rates of adverse events were similar between patient groups treated with tremelimumab/durvalumab as ICI rechallenge and initial ICI. Among patients experiencing immune-related adverse events (irAEs) with atezolizumab/bevacizumab, 75% (3/4) encountered similar irAEs during ICI rechallenge. Early safety and efficacy profiles of durvalumab/tremelimumab as ICI rechallenge are satisfactory.