Drugs - Real World Outcomes最新文献

Background: Bowel urgency is a highly burdensome symptom among patients with inflammatory bowel disease (IBD).

Objectives: To assess changes in severity of bowel urgency and identify predictors of worsening or improvement among patients with Crohn's disease (CD) and ulcerative colitis (UC) at 6 months from their enrollment visit.

Methods: Data from patients in the Study of a Prospective Adult Research Cohort with IBD were analyzed. Enrolled patients with CD or UC with 6-month visits were included. Changes and predictors of bowel urgency severity over 6 months in patients with CD or UC were examined using two separate analyses: (a) "worsening" versus "no change" excluding those with moderate-to-severe bowel urgency at enrollment, and (b) "improvement" versus "no change" excluding those with no bowel urgency at enrollment. The enrollment characteristics were compared within these groups.

Results: At baseline, in both CD and UC, use of biologics and/or immunomodulators at enrollment was similar across cohorts. Among patients with CD, 206 of 582 (35.4%) reported worsening, and 195 of 457 (42.7%) reported improvement in bowel urgency. Younger age (P = 0.013) and moderate-to-severe bowel urgency (P < 0.001) were associated with improvement. Moderate bowel urgency (P = 0.026) and bowel incontinence while awake (P = 0.022) were associated with worsening. Among patients with UC, 84 of 294 (28.6%) reported worsening, and 111 of 219 (50.7%) reported improvement in bowel urgency. Higher symptomatic disease severity (P = 0.011) and more severe bowel urgency (P < 0.001) were associated with improvement.

Conclusions: Bowel urgency is an unpredictable and unstable symptom among patients with IBD. Over 50% of patients with CD or UC experienced either worsening or improvement at 6 months postenrollment.

Background: In patients with heart failure with reduced ejection fraction (HFrEF), lower discharge heart rate (HR) is known to be associated with better outcomes. However, the effect of HR control on patient outcomes, and the demographic and clinical determinants of this association, are not well documented.

Objectives: The purpose of this work was to evaluate the association between the HR control and the risk of post-discharge rehospitalization in patients hospitalized with HFrEF.

Methods: Data were collected using a retrospective medical record review in the USA. Reduction in HR between admission and discharge ("HR control") defined the primary exposure, categorized as no reduction, > 0 to < 20% reduction, and ≥ 20% reduction. Time to first rehospitalization in the post-discharge follow-up defined the study outcome and was analyzed using multivariable Cox regression modeling.

Results: A total of 1002 patients were analyzed (median age, 63 years; median follow-up duration, 24.2 months). At admission, 59.1% received beta-blockers, 57.4% received diuretics, and 47.5% received angiotensin-converting enzyme (ACE) inhibitors. Most patients (90.5%) achieved some HR control (38.4% achieved > 0 to < 20% reduction, and 52% achieved ≥ 20% reduction). Approximately 39% were rehospitalized during the follow-up (14% within 30 days). In multivariable analysis, patients with > 0 to < 20% reduction in HR had a 39% lower risk of rehospitalization [hazard ratio 0.61; 95% confidence interval (CI) 0.43-0.85]; patients with ≥ 20% reduction in HR had a 38% lower rehospitalization risk (hazard ratio 0.62; 95% CI 0.45-0.87) than those with no HR reduction.

Conclusions: Reduction in HR between admission and discharge was associated with reduced risk for rehospitalization. Findings indicate HR control as an important goal in the management of patients hospitalized for HFrEF.

Background and objective: The complex risk factors of liver injury have prevented the establishment of causal relationships. This study aimed to explore the effects of antidepressant class, cumulative days of medication exposure, presence of comorbidities, and the use of confounding drugs on the risk of antidepressant-induced liver injury.

Methods: The population-based case-control study sample included individuals registered on the Taiwan National Health Insurance Database between 2000 and 2018. Hospitalized patients with suspected drug-induced liver injury were considered as cases, while control subjects were matched 1:1 by age, gender, and index date (the first observed diagnosis of liver injury). Multivariable regression models were performed to evaluate the association between antidepressants and liver injury.

Results: The findings showed that antidepressant users exhibited a higher risk of liver injury (adjusted odds ratio [aOR] 1.16, 95% confidence interval [CI] 1.12-1.20), particularly those prescribed non-selective serotonin reuptake inhibitors (NSRIs; aOR 1.05; 95% CI 1.01-1.10), selective serotonin reuptake inhibitors (SSRIs; aOR 1.22; 95% CI 1.16-1.29), serotonin-norepinephrine reuptake inhibitors (SNRIs; aOR 1.18; 95% CI 1.13-1.24), and others (aOR 1.27; 95% CI 1.14-1.42). Moreover, cases exhibited a more significant proportion of antidepressant usage and longer durations of treatment compared with controls. The risk of liver injury was higher in the first 30 days of use across all classes of antidepressants (aOR 1.24; 95% CI 1.18-1.29).

Conclusion: SSRIs or SNRIs are commonly used to treat depression and other psychological disorders, and consideration of their potential effects on the liver is essential.

Background: Opicapone is a third-generation catechol-O-methyl-transferase inhibitor currently used for the treatment of motor fluctuations in Parkinson's disease. Its benefit and safety have been established by clinical trials; however, data about its use in a real-life context, and particularly in an Italian population of patients with Parkinson's disease, are missing.

Objectives: We aimed to gather data about the real-life tolerability/safety of opicapone when used for the treatment of Parkinson's disease-related motor fluctuations.

Methods: We enrolled 152 consecutive patients with Parkinson's disease and followed them for 2 years after opicapone introduction. We obtained baseline clinical and demographical information, including disease duration, stage, phenotype, as well as axial and non-motor symptoms. We collected the reasons for any treatment interruption and adverse events emerging after opicapone introduction.

Results: Eighty-nine (58%) patients reported adverse events and 46 (30%) patients discontinued the treatment. Adverse events occurred less frequently in "earlier" patients accordingly to the disease course and L-Dopa treatment pathway; a motor fluctuation duration ≥12 months and Hoehn and Yahr scale score ≥2.5 were the main predictors of therapy withdrawal.

Conclusions: This study confirms the good tolerability/safety profile of opicapone in a real-life setting and provides country-specific data for Italian patients with Parkinson's disease.

Aims: Protein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) are novel lipid-lowering agents used in patients with cardiovascular disease. Despite reassuring safety data from pivotal trials, increasing evidence from real-world studies suggests that PCSK9i increase the risk of bacterial and viral infections. Therefore, this study aimed to identify signals of infection-related adverse events (AEs) associated with PCSK9i.

Methods: We performed an observational pharmacovigilance study using the World Health Organization's VigiBase, recorded up to December 2022. We included individual case safety reports (ICSRs) of PCSK9 inhibitors, alirocumab and evolocumab, and compared them with those of other drugs. Infection-related ICSRs were retrieved from the Medical Dictionary for Regulatory Activities System Organ Class 'infections and infestations.'

Results: Among 114,293 reports (258,099 drug-AE pairs) related to PCSK9 inhibitors, 54% included female patients, 41% included patients aged ≥65 years, and 82% included patients who received evolocumab. Additionally, beyond AEs recognized by regulatory authorities, organ infections such as influenza (reporting odds ratio [ROR] 2.89, 95% confidence interval [CI] 2.74-3.05), gastric infections (ROR 2.47, 95% CI 1.63-3.75), and kidney infections (ROR 1.36, 95% CI 1.06-1.73) were observed. Sensitivity analysis indicated a heightened risk of infection-related AEs associated with PCSK9i regardless of the specific drug type.

Conclusions: In addition to the labelled respiratory infections, six infection-related symptoms in the gastrointestinal, urinary, and renal organs were identified. Our findings support the need for systematic surveillance of infections among PCSK9i users.

Background: Treatment for haemophilia A has expanded from plasma-derived factor VIII (pdFVIII) and standard half-life (SHL) recombinant FVIII (rFVIII) to extended half-life (EHL) rFVIII and non-factor products that mimic FVIII activity.

Objective: To determine amounts of clotting factor concentrates (CFCs) and emicizumab dispensed and associated healthcare expenditures in Japanese patients with haemophilia A.

Methods: This retrospective, non-interventional, observational study analysed data from 2016 to 2020 from a large-scale, hospital-based administrative database. Patients had haemophilia A without inhibitors and ≥ 2 prescriptions of the same CFC or emicizumab.

Results: In total, 974 patients with haemophilia A (median age, 30.0 years; median follow-up, 3.7 years) were included. Outpatient use of EHL rFVIII and emicizumab increased, although pdFVIII/SHL rFVIII were still used over the study. Median annual total healthcare expenditures/patient increased from ¥9,200,230 in 2016 to ¥19,748,221 in 2020. Overall, the median annual drug expenditure/patient increased from ¥8,723,120 in 2016 to ¥18,051,689 in 2020. Drug expenditure was highest with emicizumab, with an increase in median annual expenditure/patient from 2018 (n = 4, ¥26,030,206) to 2020 (n = 107, ¥45,430,408). Overall, 233 patients (23.9%) switched from an SHL to an EHL product. Although amounts of FVIII prescribed increased in the 3 months after switching, overall, there was no noticeable difference before and after switching. Median total healthcare and FVIII product expenditures increased following switching.

Conclusions: Prescribing of EHL products increased over the study and healthcare expenditures increased for patients who switched from SHL to EHL rFVIII products.

Background: Third-generation antiseizure medications, such as brivaracetam, are recognized for their superior safety, tolerability, and pharmacokinetic profiles. However, their potential benefits are often limited in low-income populations because of challenges related to availability and affordability.

Objective: We aimed to evaluate the effectiveness and safety of brivaracetam for treating epilepsy in a low-income population, within a real-world setting.

Methods: This retrospective cohort study included individuals with epilepsy from a low-income population in Bogotá, Colombia, who were treated with brivaracetam between January 2020 and July 2023. Effectiveness (mean seizure reduction and ≥ 50% seizure reduction) and safety (retention rate and adverse events) were evaluated.

Results: A total of 106 individuals were included, with a median age of 33 years (interquartile range: 24-44). Most had focal epilepsy with a median disease duration of 25.4 years (standard deviation: 13.6). The baseline seizure frequency was 4 seizures per month (interquartile range: 2-15) and individuals had previously received a mean of 4.4 (standard deviation: 1.8) antiseizure medications. The mean percentage seizure reduction at 3, 6, and 12 months was 55.3%, 66.9%, and 63.8%, respectively. Additionally, 60%, 63.8%, and 65.9% of individuals achieved a ≥ 50% seizure reduction at 3, 6, and 12 months, respectively. Retention rate at 3 months was 89% (n = 95) and 18.7% (n = 20) reported adverse effects.

Conclusions: In a real-world setting, brivaracetam has been shown to be safe and effective for the treatment of epilepsy in individuals from a low-income population. This study suggests that people with epilepsy living in this context can significantly benefit from the use of third-generation antiseizure medications.

Background and objective: Dual human epidermal growth factor receptor 2 (HER2) blockade with trastuzumab and pertuzumab combined with taxane-based chemotherapy (Cht) has been the standard first-line treatment for HER2-positive metastatic breast cancer (mBC) for years, due to the impressive results of the CLEOPATRA study. Real-world (RW) studies have become critical for assessing treatment effectiveness and safety in real-life circumstances. The aim of this study was to analyze the treatment outcomes of first-line therapy for HER2-positive mBC in RW clinical practice, specifically focusing on the use of maintenance endocrine therapy (ET) in hormone receptor positive (HR-positive) patients.

Methods: This retrospective analysis included 106 HER2-positive mBC patients treated with trastuzumab and pertuzumab combined with taxane-based Cht from October 2015 to December 2020 at the University Hospital Centre Zagreb.

Results: At a median follow-up of 30 months, median progression-free survival (PFS) was 25 months for the total population (95% confidence interval [CI] 16 - not analyzed). Patients with de novo mBC had longer median PFS than patients with recurrent disease (not reached vs. 18 months; hazard ratio 1.99; 95% CI 0.69-3.64, p<0.022). Age, hormone receptor positivity, visceral involvement, number of Cht cycles and previous adjuvant trastuzumab did not impact PFS. Most HR-positive patients (N=55, 88.7%) received maintenance ET after induction Cht.

Conclusion: This retrospective study provides additional data on patient characteristics, treatment and outcomes of RW HER2-positive mBC patients treated with pertuzumab and trastuzumab as first-line therapy. In our institution, maintenance ET after induction Cht has become standard clinical practice.

Background: Although Janus kinase (JAK) inhibitors have expanding indications, deep vein thrombosis (DVT) and pulmonary embolism (PE) are serious adverse events associated with their use. Moreover, their analysis using the Japanese database of spontaneous adverse drug reaction reports has not yet been conducted.

Objective: The objective of this study was to analyze the Japanese Adverse Drug Event Report database (JADER) to evaluate the association between JAK inhibitors and DVT and PE.

Methods: JADER reports from April 2004 to October 2023 were analyzed. A classification of reports for the period covered was performed by drug, and an imbalance analysis was performed with oral JAK inhibitors as the target drug and DVT, PE, and "embolic and thrombotic events, venous" (Standardised MedDRA Query; SMQ) as the target adverse events. Reported odds ratios (ROR) and information components (IC) were calculated for signal detection.

Results: Overall, 6631 JAK inhibitor-related adverse events were reported, including 60 and 41 cases of DVT and PE, respectively. The ROR and IC of the JAK inhibitors for DVT were 2.52 (1.95-3.25) and 1.27 (0.41-2.13), while those of baricitinib for DVT were 4.37 (2.83-6.73) and 1.90 (0.47-3.33), respectively. ROR signals were detected for JAK inhibitors for PE and "embolic and thrombotic events, venous (SMQ)," overall and for several JAK inhibitors but none for IC.

Conclusions: Several JAK inhibitors are under postmarketing phase vigilance, and the number of reported adverse events is low. However, when administering these drugs, care should be taken to avoid the development of thromboembolism, considering the patient's background.