International Journal of Clinical Pharmacy最新文献

Introduction: Medication misadventure is associated with the use of polypharmacy and is highly prevalent in the older population living in the community, especially among women.

Aim: This study aimed to determine the impact of Home Medicines Reviews (HMRs) on continuous polypharmacy, the prevalence of continuous polypharmacy, and inflation-adjusted differences in costs among women who did and did not receive HMRs.

Method: The study included 9347 participants from the Australian Longitudinal Study on Women's Health who fulfilled the eligibility criteria from 77-82 years in 2003 to 91-96 years in 2017. Generalised estimating equations were used to estimate the association between HMRs and continuous polypharmacy. Out-of-pocket costs and benefits paid to government were presented as median costs for each participant from 2003 to 2017, alongside interquartile ranges.

Results: Only a small percentage of women received HMRs in 2003 (1.14%) but this percentage increased over time to 2017 (3.95%). The prevalence of continuous polypharmacy in 2017 was 39.06% amongst women who received an HMR and 28.05% amongst women who did not receive an HMR. There was evidence for an association between the use of HMRs and continuous polypharmacy in the following calendar year (OR 1.12; 95% CI 1.03, 1.21). There was an increase in out-of-pocket (OOP) medication costs in both women with and without HMRs, with the HMR group demonstrating higher OOP medication costs (AUD$26 to AUD$57) than the non-HMR group (AUD$22 to AUD$50).

Conclusion: HMRs were associated with a modest increase in the odds of continuous polypharmacy in the subsequent year. Increase in OOP medication costs over time highlights the need to further optimise cost-effective medications for individuals.

Introduction: Potentially inappropriate prescribing (PIP) increases the risk for medication-related harm amongst older adults, with those in long-term care at particular risk.

Aim: This study sought to evaluate a medicines optimisation pharmacist case management model for older adults in care homes in Northern Ireland (NI).

Method: Secondary analysis of prospective data collected during the case management model delivered to older adults (≥ 65 years) across 32 care homes in NI (N = 1,095). Medication Appropriateness Index (MAI) scores were compared at baseline and post-intervention. Variability in MAI per medication score change (ΔMAI) was examined using multiple linear regression. Multiple logistic and Poisson regressions examined potential associations between ΔMAI and secondary outcomes, including unplanned hospital admissions (all-cause); general practitioner (GP) call-outs; out-of-hours (OOH) GP call-outs; and emergency department (ED) visits.

Results: PIP was highly prevalent at baseline (83.5%; n = 914). A significant reduction in MAI (per medication) score was observed from pre to post-intervention; 82% (n = 898) of participants experienced some MAI score improvement. Overall, 3,044 clinical interventions were delivered; 2,062 medications were stopped, 141 medications were started, and 438 dosages were changed. Several unexpected significant associations were observed between ΔMAI and GP call-outs during follow-up; sensitivity analyses suggested these findings were likely due to confounding. No association was observed between ΔMAI (per medication) and likelihood for unplanned hospital admission.

Conclusion: PIP is highly prevalent in NI care homes and was significantly reduced by a medicine optimisation pharmacist case management model. Clinical pharmacist input in long-term care is warranted to lessen medication-related harm for older adults.

Introduction: Deucravacitinib is a novel, highly selective tyrosine kinase 2 allosteric inhibitor recently approved for the treatment of moderate-to-severe psoriasis in adults, though post-marketing safety data remain limited.

Aim: The purpose of this study was to perform a post-marketing safety evaluation of deucravacitinib based on the Food and Drug Administration Adverse Event Reporting System (FAERS) database.

Method: This study collected adverse event (AE) reports of deucravacitinib as primary suspected drug in the FAERS database from the third quarter of 2022 to the fourth quarter of 2024. Four main methods of the disproportionality analysis, including reporting odds ratio, proportional reporting ratio, Bayesian confidence propagation neural network, and multi-item gamma Poisson shrinker, were employed for signal detection. Potential risk signals were deemed significant only when all four algorithms simultaneously met their thresholds. The important medical event (IME) terms list was used to identify IMEs of deucravacitinib. Additionally, the Weibull distribution was used to evaluate the time-to-onset (TTO) characteristics.

Results: Thirty-nine preferred terms were identified as potential risk signals. The most commonly reported AE were acne, mouth ulceration and folliculitis. Sixteen AEs with potential risk signals not mentioned on the label were also identified, including urticaria, oral pain, oropharyngeal pain, swelling face, lip swelling, eye swelling, cellulitis, ear pain, pharyngeal swelling, Bell's palsy, mouth swelling, cheilitis, mycobacterium tuberculosis complex test positive, facial paralysis, hepatitis A, and central nervous system (CNS) infection. Rhabdomyolysis, Bell's palsy, facial paralysis, and CNS infection were identified as the IMEs associated with deucravacitinib in this study. The Weibull distribution indicated that the TTO characteristics of deucravacitinib-associated AEs followed an early failure type.

Conclusion: This study provides new safety data for deucravacitinib in real-world settings, uncovering previously unrecognized risks and identifying several IMEs. These findings have somewhat supplemented the safety data for deucravacitinib. Given the limitations of the FAERS database, further post-marketing safety surveillance studies on deucravacitinib remain necessary in the future.

Background: Effective management of rheumatoid arthritis (RA) often requires the use of biological disease-modifying antirheumatic drugs (bDMARDs). Biosimilar drugs (biosimilars), licensed pharmaceutical products that exhibit high similarity to their reference biological products (originators), have emerged as more affordable alternatives.

Aim: To compare the real-world effectiveness and safety of biosimilars and originators of bDMARDs in the management of RA at treatment initiation.

Method: A systematic literature search was conducted using PubMed, MEDLINE, Embase, Scopus, International Pharmaceutical Abstract and CINAHL from database inception to 18th April 2025. Observational studies utilising real-world data (e.g., electronic health records, biologics registries) that compared clinical outcomes between patients initiating treatment with either a biosimilar or an originator for RA were included. Quality assessment was conducted using the Newcastle-Ottawa Scale (NOS) and a narrative synthesis was conducted to summarise key findings.

Results: A total of 13 retrospective cohort studies were included, providing data on 34,280 patients initiating treatment with bDMARDs for RA. Treatment retention was the most investigated effectiveness outcome (n = 11), and all studies found that biosimilars were associated with comparable retention profiles compared to originators. No significant differences were identified for other effectiveness outcomes (e.g., disease activity indices). For safety outcomes, adverse events (AEs) were documented in eight studies. However, seven of these studies were of poor quality in assessing safety outcomes due to inadequate control for confounding factors.

Conclusion: In real-world settings, biosimilars generally demonstrate comparable effectiveness to originators. Future investigations are warranted to examine the comparative safety profiles of biosimilars and originators.

Background: Compared with alteplase, recombinant human prourokinase (rhPro-UK)-a next-generation specific plasminogen activator-offers advantages such as weight-independent dosing and cost effectiveness. While a 35-mg dose of rhPro-UK has been recommended in previous randomized controlled trials (RCTs), its efficacy and safety profile have yet to be fully elucidated, as no relevant systematic reviews or meta-analyses have been conducted to date.

Aim: This meta-analysis aimed to evaluate the safety and efficacy of 35 mg of rhPro-UK compared with those of control treatments, including 50 mg of rhPro-UK and alteplase monotherapy, in patients with acute ischemic stroke (AIS).

Method: Two independent reviewers systematically searched the PubMed, Embase, Cochrane Library, Scopus, and ClinicalTrials.gov electronic databases up to May 24, 2025, to identify RCTs assessing the effects of 35 mg rhPro-UK versus control therapies in AIS patients. Study quality was assessed using the Cochrane RoB 2 tool. A random effects model was employed for the meta-analysis using Stata 18.0.

Results: Four RCTs involving 2412 patients were included. The 35-mg dose of rhPro-UK demonstrated comparable safety and efficacy to those of the other treatments. Notably, this dose was associated with the potential advantages of increasing early neurological recovery at 24 h (SMD = - 0.29, 95% CI - 0.55 to - 0.03, P = 0.03) and reducing systemic bleeding risk at 90 days (RR = 0.59, 95% CI 0.48-0.73, P < 0.001). Subgroup analysis suggested that 35 mg of rhPro-UK might be associated with lower odds of SAEs than 50 mg of rhPro-UK (I² = 0%, P = 0.039); however, there was no significant difference in rt-PA (I² = 0%, P = 0.413) at 90 days.

Conclusion: This meta-analysis suggested that 35 mg of rhPro-UK does not significantly differ from 50 mg of rhPro-UK or alteplase in terms of clinical outcomes among AIS patients. However, the 35-mg dose of rhPro-UK has the potential advantages of enhancing early neurological recovery and reducing the risk of systemic bleeding. Subgroup analysis revealed that 35 mg of rhPro-UK might be associated with a lower risk of SAEs than 50 mg of rhPro-UK.

Introduction: IL-23p19 antagonists, selectively blocking IL-23 signaling via p19 targeting without affecting IL-12, represent a novel therapeutic class for inflammatory bowel disease (IBD). While multiple randomized controlled trials (RCTs) have evaluated their efficacy and safety in IBD, findings remain fragmented and exhibit significant heterogeneity.

Aim: This updated meta-analysis was designed to evaluate the efficacy and safety of IL-23p19 antagonists compared with placebo for induction and maintenance therapy in patients with IBD.

Method: Systematic searches of PubMed, Embase, Web of Science, Scopus, and OVID were conducted until May 13, 2025 for IBD RCTs evaluating IL-23p19 antagonists. Methodological quality was assessed using the Cochrane RoB tool. The data collected included details on study design, participant characteristics, and study outcomes. The risk ratio (RR) and corresponding 95% confidence intervals (95%CI) were calculated using the random-effects model.

Results: The review includes 14 publications involving 8,463 IBD patients. Significantly higher rates of clinical remission (RR 2.18, 95% CI 1.87-2.54), clinical response (RR 1.74, 95% CI 1.54-1.96), endoscopic remission (RR 2.94, 95% CI 2.33-3.70), and endoscopic response (RR 2.71, 95% CI 2.28-3.23) were observed in IBD patients receiving IL-23p19 inhibitors compared to placebo. Safety analyses revealed comparable overall adverse events with active therapy (RR 0.96, 95% CI 0.92-1.01); however, significant reductions occurred in serious adverse events (RR 0.51, 95% CI 0.41-0.64), treatment discontinuations due to adverse events (RR 0.36, 95% CI 0.28-0.47), and serious infections (RR 0.62, 95% CI 0.41-0.96) versus placebo.

Conclusion: This meta-analysis confirms robust therapeutic benefits and acceptable safety of IL-23p19 inhibitors in IBD patients. Subgroup analyses showed IL-23p19 inhibitors maintained comparable efficacy regardless of prior biologic use, disease duration, or baseline C-reactive protein levels, indicating consistent efficacy across these clinical subgroups. Future longitudinal investigations should evaluate durability of treatment response and extended safety outcomes.

Introduction: Ublituximab, a novel glycoengineered murine/human type Ⅰ chimeric IgG1-class monoclonal antibody targeting a unique CD20 epitope, is approved for the management of relapsing forms of multiple sclerosis in adults. While the safety and efficacy of ublituximab have been evaluated in several randomized clinical trials, real-world pharmacovigilance data remain limited.

Aim: This study aimed to evaluate the post-marketing adverse events (AEs) associated with ublituximab utilizing the FDA Adverse Event Reporting System (FAERS) database, thereby delineating the safety profile of ublituximab in the post-approval setting.

Method: The AE reports of ublituximab as the primary suspected drug from Q4 2022 to Q4 2024 were collected from the FAERS database. Disproportionality analysis, including the Reporting Odds Ratio, the Proportional Reporting Ratio, the Bayesian Confidence Propagation Neural Network, and the Multi-Item Gamma Poisson Shrinker, was performed to identify potential safety signals associated with ublituximab. Complementary analyses, comprising subgroup analysis, Weibull distribution, and sensitivity assessment, were conducted to characterize the ublituximab-associated AEs.

Results: A total of 1,190 reports encompassing 448 distinct AEs were collected. Known AEs that are consistent with the FDA label, such as infusion-related reactions (n = 591, ROR = 271.35, 95% CI 246.57-298.61) and infections (urinary tract infection: n = 28, ROR = 4.31, 95% CI 2.97-6.27; Respiratory tract infection: n = 8, ROR = 7.39, 95% CI 3.69-14.8), were reaffirmed, along with unexpected AEs like alopecia (n = 12, ROR = 2.06, 95% CI 1.17-3.64) and headache (n = 50, ROR = 2.55, 95% CI 1.93-3.38). The Weibull distribution characteristic of AEs is an early failure type, which indicates that vigilant monitoring in the initial treatment cycle is critical. Subgroup analyses revealed variations in the distribution across age and gender subgroups. Sensitivity analysis confirmed the consistency and robustness of the data.

Conclusion: This study provided preliminary insights into the post-marketing safety profile of ublituximab by confirming its known AEs and investigating unexpected AEs. These findings contribute to evidence-based risk minimization strategies and pharmacovigilance activities for ublituximab in clinical practice.

Introduction: Aplastic anemia is a rare but life-threatening disorder often triggered by drug exposure. Given its low incidence, identifying drug-associated risks requires large-scale real-world data. The FDA Adverse Event Reporting System (FAERS) is a valuable pharmacovigilance resource for detecting rare and serious drug reactions.

Aim: This study aimed to evaluate the association between a broad range of medications and the risk of drug-induced aplastic anemia using FAERS data obtained through disproportionality analysis, regression modeling, time-to-onset analysis, and predictive modeling.

Method: A retrospective pharmacovigilance study was conducted using FAERS reports from January 1, 2004, to December 31, 2024. Aplastic anemia cases were identified using five Preferred Terms from the Medical Dictionary for Regulatory Activities. Signal detection was performed using ROR, PRR, BCPNN, and MGPS. Logistic regression analyses with weighted LASSO variable selection identified the independent risk factors. A predictive model was developed and validated using receiver operating characteristic (ROC) curve analysis. Time-to-onset (TTO) and pharmacological classification were also conducted.

Results: A total of 4493 drug-related aplastic anemia cases were identified. Disproportionality analysis revealed 593 significant drugs, of which 16 met stringent inclusion criteria for multivariate analysis. Temozolomide was most frequent (n = 148), followed by methotrexate (n = 126), busulfan (n = 100), and linezolid (n = 90). Other common drugs included ribavirin, nivolumab, pembrolizumab, fludarabine, carboplatin, etoposide, and cyclophosphamide. Male sex was a significant risk factor (OR = 1.63), while older age (> 42 years) and higher weight (> 60 kg) were protective. The predictive model showed good discrimination (AUC = 0.777). Median TTO was 299 days, with most cases occurring within six months. The 16 implicated drugs fell into categories including antineoplastics, antibacterials, antivirals, antiepileptics, and antigout agents.

Conclusion: This study identified key drugs and patient factors associated with aplastic anemia, providing a data-driven framework for pharmacovigilance. These findings support early detection and informed clinical and regulatory decision making, but prospective studies are required to confirm causality and refine individualized risk predictions.

Introduction: Approximately one-third of patients with minor ischemic stroke (MIS) and transient ischemic attack (TIA) fail to achieve functional independence due to stroke progression or recurrent stroke. Identifying effective secondary prevention strategies is crucial to reduce morbidity, mortality, and disability.

Aim: This systematic review and network meta-analysis aimed to evaluate the effectiveness and safety of various antiplatelet therapies using network meta-analysis and to identify the optimal treatment option for patients with MIS or high-risk TIA.

Method: Studies were retrieved from PubMed, Embase, Web of Science, and Cochrane Library from inception to August 29, 2024. Randomized controlled trials (RCTs) and observational studies comparing antiplatelet treatments for MIS or high-risk TIA were included through consensus. The primary outcome was recurrent strokes. The secondary outcomes included recurrent ischemic strokes and a composite outcome combining ischemic stroke, myocardial infarction, and vascular death. The safety outcomes included intracerebral hemorrhage (ICH), any bleeding events, and all-cause mortality. Treatments were ranked based on the surface under the cumulative rank curve (SUCRA).

Results: Nineteen studies, including 12 RCTs and seven observational studies with 90,483 patients, were analyzed. Compared with aspirin or other mono antiplatelet therapies, both dual antiplatelet therapies of clopidogrel plus aspirin and ticagrelor plus aspirin reduced the risk of recurrent strokes, recurrent ischemic strokes, and the composite outcome without increasing the risk of ICH or all-cause mortality. However, ticagrelor plus aspirin significantly increased the risk of any bleeding. This treatment had the highest SUCRA score (0.97) for the primary outcome and the lowest (0.01) for any bleeding.

Conclusion: Based on the combined results of effectiveness and safety, clopidogrel plus aspirin may be the optimal choice. However, for patients with a low bleeding risk, ticagrelor plus aspirin serves as an appropriate alternative.

Introduction: Antimicrobial stewardship (AMS) education plays a vital role in addressing antimicrobial resistance (AMR), yet its long-term impact on behavior and clinical outcomes remains underexplored. Educational interventions are often assessed through knowledge-based outcomes, with limited evaluation of sustained practice changes or patient-level results, and standardized higher-level outcome measures across diverse healthcare settings.

Aim: This scoping review aimed to map pre-post AMS healthcare educational interventions using the Kirkpatrick Model, evaluating their effectiveness across its four levels: reaction, learning, behavior, and results. The goal was to identify trends, highlight gaps, and provide insight into reported outcomes, delivery methods, and evaluation tools, supporting future research and strengthening the evidence base for AMS education.

Method: This review followed the Joanna Briggs Institute framework. A literature search of nine databases identified studies from 2010 to 2024. Eligible studies included pre-post AMS educational interventions targeting undergraduate students and healthcare professionals (HCPs) and reporting outcomes which were subsequently mapped by the reviewers to the Kirkpatrick Model. Data were categorized by target population, delivery format, and evaluation tools. Narrative synthesis was used to describe trends and relationships.

Results: Studies targeted HCPs such as physicians, pharmacists, nurses, and dental professionals, and undergraduate students in pharmacy, medicine, nursing, and dentistry. Sixty-three studies were included. Outcomes were distributed across Level 1 (Reaction) (n = 46, 24%), Level 2 (Learning) (n = 51, 27%), Level 3 (Behavior) (n = 50, 26%), and Level 4 (Results) (n = 45, 23%). While n = 24 (38%) assessed all four levels, another n = 24 (38%) reported mixed or partial levels. Face-to-face or online-only formats achieved Levels 1 and 2. Whereas blended or workplace-integrated interventions more often demonstrated behavior change and clinical outcomes (Levels 3 and 4). Longitudinal follow-up and mixed evaluation tools (e.g., surveys, chart reviews, interviews) supported higher-level impacts. Pharmacy-led, interdisciplinary, and contextually tailored interventions mapped to all levels.

Conclusion: AMS education often leads to short-term learning gains, but fewer interventions achieve sustained behavior change or measurable clinical outcomes. Blended and practice-integrated formats, paired with long-term evaluation, are key to realizing the full potential of AMS education. Embedding such approaches in undergraduate and professional programs can better prepare the future HCPs to address AMR effectively.