Expert Review of Clinical Pharmacology最新文献

Introduction: Several clinical trials have demonstrated that chemotherapy contributes to prolonged survival in patients with previously treated advanced gastric cancer (AGC).

Areas covered: Currently, cytotoxic agents with established efficacy for previously treated AGC include paclitaxel (PTX), irinotecan (IRI), and trifluridine/tipiracil (FTD/TPI), while the anti-vascular endothelial growth factor(VEGF) agent ramucirumab (RAM) has also shown efficacy. Pembrolizumab is indicated for AGC with microsatellite instability-high (MSI-H) or high tumor mutational burden (TMB). For human epidermal growth factor receptor 2 (HER2)-positive previously treated AGC, trastuzumab deruxtecan (T-DXd) has emerged as the first molecular targeted therapy. Additionally, claudin-18 isoform 2 (CLDN18.2)-targeting antibody therapy has been established as a first-line treatment, with numerous ongoing clinical trials in later-line settings. Other promising molecular targets include trophoblast cell surface antigen 2 (TROP2), cytoplasmic activation/proliferation-associated protein 1(CAPRIN-1), and KRAS. Furthermore, innovative therapeutic approaches such as antibody-drug conjugates (ADCs), bispecific antibodies (BsAbs), and chimeric antigen receptor T-cell (CAR-T) therapy are being developed. This review summarizes the historical and established evidence from clinical trials on previously treated AGC and discusses ongoing clinical trials and future perspectives in treatment development, with a focus on targeted therapies.

Expert opinion: Biomarker-driven treatment is expected to become the mainstream approach in the future.

Introduction: Every year more than 50 million people in the world experience a traumatic brain injury (TBI). In its more severe form the mortality is high, and survivors can be very disabled. Nevertheless, there are currently no approved pharmacological treatments that definitely improve the prognosis in humans, and given the consistently disappointing results, pharmaceutical companies are reluctant to invest further.

Areas covered: We reviewed relevant PubMed-indexed studies on pharmacological trials conducted during the acute phase of TBI. The potential reasons for the observed lack of efficacy are discussed, including the vast heterogeneity within the TBI population, the limitations of randomization in balancing prognostic factors, and challenges posed by current clinical endpoints used to assess treatment outcomes.

Expert opinion: The search for new pharmacological treatments of TBI patients must continue, but a change of paradigm should be accepted by scientists and regulatory authorities. In the unique context of TBI patients, randomization and patients stratification are not sufficient to create homogeneous and comparable groups. Current clinical outcomes are too influenced by variables and too 'hard.' Alternative endpoints, i.e. relevant pathophysiological variables (e.g. ICP, biomarkers, MRI), if accepted could encourage pharmaceutical companies to develop drugs in TBI.

Introduction: Overlap weighting has emerged as a valuable method for addressing confounding in observational studies, particularly in real-world data settings characterized by imbalanced covariates and limited overlap between treatment groups. Its ability to produce stable, interpretable estimates makes it an attractive alternative to inverse probability of treatment weighting (IPTW), which can suffer from extreme weights and instability.

Areas covered: This report outlines the methodological basis of overlap weighting and contrasts it with IPTW. The limitations of IPTW are illustrated through a clinical example comparing clopidogrel and prasugrel, where substantial baseline differences lead to poor propensity score (PS) overlap. Overlap weighting is discussed as a solution that emphasizes individuals in clinical equipoise (i.e. PS near 0.5), minimizes the influence of outliers, and achieves exact covariate balance.

Expert opinion: Overlap weighting is well-suited for observational studies with moderate to poor overlap and can be considered a preferred approach in many real-world contexts. Presenting results from multiple PS methods, including standardized mortality ratio (SMR) weighting, IPTW, PS adjustment, and overlap weighting, can help assess robustness and enhance the credibility of causal inferences.

Introduction: Anticholinergic burden (AChB), the cumulative impact of medications with anticholinergic properties, is a modifiable risk factor linked to cognitive impairment, falls, and functional decline in older adults. Yet despite the availability of multiple AChB assessment tools, no consensus gold standard exists, and commonly used scales often rely on static, expert-derived drug rankings.

Areas covered: This narrative review synthesizes recent advances in AChB measurement and deprescribing. It critically evaluates established tools like the Anticholinergic Cognitive Burden (ACB) scale and Drug Burden Index (DBI), alongside emerging machine learning - based models such as the ML-AB scale. The review also explores the role of digital health innovations such as clinical decision support systems and wearable technologies in enhancing risk stratification and deprescribing interventions.

Expert opinion: While traditional tools remain useful, they suffer from limitations in adaptability and integration into routine workflows. Newer AI and data-driven approaches show promise in improving predictive accuracy and scalability. A paradigm shift is emerging, with future deprescribing efforts likely to depend on hybrid systems that combine mechanistic understanding with empirical robustness. For optimal impact, these tools must be validated, implemented thoughtfully, and aligned with patient-centered outcomes in diverse care settings.

Introduction: The management of severe asthma in older adults is an increasingly important clinical challenge. Aging-associated structural, functional, and immunological changes contribute to a distinct geriatric asthma phenotype, often marked by mixed inflammation, comorbidities, and reduced treatment responsiveness.

Areas covered: This review provides an overview of current biologic therapies approved for severe asthma and examines existing clinical evidence regarding efficacy, safety, and real-world outcomes in geriatric patients. Clinical challenges include the heterogeneity of asthma phenotypes in this age group, and the impact of multimorbidity and polypharmacy on treatment outcomes.

Expert opinion: A geriatric-centered approach to severe asthma is essential, emphasizing early initiation of biologic therapies, individualized risk-benefit analysis, and improved inclusion in research. The modulation of systemic inflammation, while carefully monitored, may bring also systemic benefits that may go beyond respiratory system. Achieving asthma remission in older adults is now a feasible goal, contingent upon proactive, tailored treatment strategies supported by more inclusive evidence.

Introduction: Rosacea is a chronic skin condition classified into four subtypes: erythematotelangiectatic, papulopustular, phymatous, and ocular involvement. The physical symptoms and recurrent nature can impact patient quality of life. Effective treatment requires a phenotype-directed strategy that addresses both clinical features and patient concerns.

Areas covered: This review summarizes current treatment guidelines and therapeutic options for rosacea, categorized into topical agents, oral medications, procedural interventions, and lifestyle modifications. A literature search was conducted using PubMed, Google Scholar, and ClinicalTrials.gov to identify relevant studies.

Expert opinion: Rosacea management is most effective when treatment is individualized based on phenotype. Topical medications such as metronidazole, azelaic acid, ivermectin, and minocycline are used as first-line treatment for mild to moderate rosacea. Oral medications, including doxycycline and minocycline, are efficacious in treating mild to moderate forms of rosacea. Oral medications can be prescribed in combination with topical therapy. Pulse dye lasers, intense pulsed light, and other laser therapies can be used for severe rosacea. Procedural interventions such as electrosurgery, dermabrasion, and surgical resurfacing may be necessary in cases with severe phymatous changes. Alongside these medical treatments, lifestyle modifications, such as avoiding known triggers and implementing sun protection, are essential for managing rosacea flare-ups and preventing exacerbations.

Introduction: There has been a significant change in the treatment paradigm of biliary tract cancers (BTCs) in recent years with the introduction of chemoimmunotherapy and the development of targeted agents. In the present review, we describe the current landscape of systemic therapy for BTC and discuss forthcoming novel therapeutics.

Areas covered: We completed a narrative review using pertinent clinical trials discussing systemic therapy for BTC listed on PubMed, as well as ongoing trials included on clinicaltrials.gov. We discuss evidence for use of systemic therapy in the adjuvant setting and review first- and second-line systemic therapy, including targeted agents, for treatment of advanced BTC.

Expert opinion: Despite advances in systemic therapy for BTC, there is a high incidence of recurrence for resected diseases and the prognosis for metastatic diseases remains poor. Development and assessment of novel therapeutics will be essential going forward, as will research regarding means to overcome resistance mechanisms that limit efficacy of targeted agents.

Introduction: Managing epilepsy in patients with end-stage kidney disease presents unique challenges due to altered pharmacokinetics of anti-seizure medications (ASMs) and the effects of dialysis treatments. Dialysis can significantly affect ASM clearance, requiring careful dosing adjustments to maintain therapeutic efficacy while avoiding toxicity. This review aims to provide an up-to-date overview of the current knowledge and to offer practical clinical guidance on the use of ASMs in patients undergoing hemodialysis and peritoneal dialysis.

Areas covered: Relevant literature on ASMs in dialysis patients was searched in MEDLINE and Google Scholar. Additional information was retrieved from the summary of product characteristics for each ASM.

Expert opinion: Evidence on the management of ASMs in patients receiving dialysis is still limited, mainly based on small observational studies and case reports. Currently, no official guidelines are available. Effective treatment strategies require individualized approaches. ASMs with low protein binding and predominant renal elimination generally require post-dialysis dose adjustments. Therapeutic drug monitoring may be indicated in some cases. Data regarding the impact of different dialysis filter types on ASM clearance are sparse. The paucity of data, especially for newer ASMs, underscores the urgent need for further research to establish comprehensive, evidence-based recommendations for this vulnerable patient population.