Expert Review of Clinical Pharmacology最新文献

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.

Introduction: To provide an up-to-date overview of current pharmacological treatments and promising emerging therapies for dry eye disease (DED), a multifactorial and increasingly prevalent ocular surface disorder.

Areas covered: A targeted literature search was conducted using PubMed, Scopus, ClinicalTrials.gov, and additional online sources to identify recent advances in the pharmacological management of DED. The review focuses on therapies approved across major regulatory bodies, as well as investigational agents in late-stage clinical development. Special attention is given to novel drug delivery platforms and innovative therapeutic mechanisms.

Expert opinion: Rapid innovation in both therapeutic targets and drug delivery technologies is transforming the treatment landscape for DED. Advanced formulations, such as nanomicelles, mucus-penetrating particles, and preservative-free emulsions, are improving ocular bioavailability, reducing adverse effects, and enhancing patient adherence. The future of DED pharmacotherapy lies in personalized, multimodal strategies that address the full spectrum of disease mechanisms, including inflammation, tear film instability, neurosensory dysfunction, and epithelial damage. The recent FDA approval of AR-15512, a TRPM8 agonist, exemplifies the trend toward mechanism-specific therapies designed to deliver both symptomatic relief and disease modification. As the therapeutic armamentarium expands globally, continued clinical trials and real-world studies will be essential to ensure durable efficacy and optimize patient outcomes.

Introduction: IgA nephropathy (IgAN) is the most common primary glomerulonephritis. For decades, the only medication treatments that were widely accepted were the use of renin-angiotensin aldosterone inhibitors and corticosteroids. The early 2020s have brought a flurry of new treatments to the once dark IgA treatment landscape. Sparsentan is a novel dual-endothelin angiotensin receptor antagonist that has been approved as an add-on therapy for the treatment of IgAN.

Areas covered: We discuss the treatment landscape and the unmet needs for treating IgA nephropathy. Multiple clinical trials showing the efficacy of sparsentan including DUET, PROTECT, SPARTACUS, and SPARTAN will be described. Additionally, we will preview the future options for IgA patients.

Expert opinion: Sparsentan is a major step forward in improving outcomes for patients with IgAN. This once-a-day agent, in addition to other standards of care, limits proteinuria and progression to ESKD and kidney transplantation. The ability to lower proteinuria without weakening the immune system is a substantial gain for patients. As an agent that impacts the glomeruli directly, sparsentan is able to limit damage in mechanisms that previous RASi and steroids have not. Including sparsentan in the combination treatment for IgAN must be considered for adequate kidney protection.

Introduction: Drug-resistant epilepsy (DRE) affects 30% of epilepsy patients and represents a major therapeutic challenge. Understanding its genetic determinants is crucial for the development of effective precision medicine strategies.

Areas covered: This review comprehensively evaluates genetic factors in DRE, including polymorphisms in pharmacokinetic (e.g. ABCB1) and pharmacodynamic (e.g. SCN1A), findings from genome-wide association studies (GWAS) that recently identified a significant locus at 1q42.11-q42.12 (CNIH3/WDR26) for focal DRE, the critical role of rare variants (e.g. in SCN1A, KCNQ2) and copy number variations (CNVs) in severe epileptic encephalopathies, and the emerging fields of epigenetics and polygenic risk scores (PRS).

Expert opinion: Methodological limitations, including modest sample sizes and phenotypic heterogeneity, hamper genetic research on DRE. While common variants show little impact, rare variants, including CNVs, and epigenetic alterations offer promising opportunities. Future priorities include functional studies to clarify the impact of gene variants, the integration of multi-omics data and the development of advanced analytical techniques, such as machine learning and network approaches, to translate genetic discoveries into clinically actionable precision medicine and ultimately improve outcomes for DRE patients.