Expert Opinion on Pharmacotherapy最新文献

Introduction: This review provides an updated overview of the evolving pharmacologic landscape of human epidermal growth factor receptor 2 (HER2)-targeted therapies in breast cancer, highlighting key clinical trial data, recent indication expansions, resistance mechanisms, and emerging therapeutic agents in development.

Areas covered: This review draws on a comprehensive literature search of published studies and major oncology conference proceedings, focusing primarily on data from key phase III clinical trials of HER2-targeted therapies. Studies published within the past decade that have influenced current standards of care were prioritized.

Expert opinion: The treatment paradigm for HER2-expressing breast cancer is evolving rapidly. Trastuzumab deruxtecan has redefined management for both HER2-positive and the newly recognized HER2-low subgroups, while tucatinib offers a critical systemic option for central nervous system metastases. Optimal sequencing and resistance management remain critical challenges in this dynamic field. Nonetheless, HER2-targeted pharmacotherapy continues to advance rapidly, driven by innovative drug designs and strategic clinical developments.

Introduction: Endometriosis is a chronic inflammatory condition affecting ~10% of reproductive-age individuals and contributing significantly to infertility, pain, and reduced quality of life. Since our 2020 review, new pharmacologic strategies, updated guidelines, and advances in clinical trial evidence have reshaped the therapeutic landscape. Effective, patient-centered management is essential to lessen the burden of disease.

Areas covered: This review synthesizes current evidence-based pharmacotherapy for endometriosis, integrating 2022 European Society of Human Reproduction and Embryology recommendations and including a literature review of PubMed, with an emphasis on articles published after 2020. First-line therapies, including NSAIDs, combined oral contraceptives, and progestins such as dienogest, remain central, while GnRH agonists/antagonists and aromatase inhibitors are considered in refractory cases. Recent data highlight add-back therapy to reduce hypoestrogenic side effects. We also review postoperative regimens, fertility-preserving strategies, management in post-hysterectomy and postmenopausal populations, and therapies under investigation - including anti-inflammatory, antifibrotic, angiogenesis-modulating, and microbiome-targeting approaches.

Expert opinion: Hormonal suppression remains the cornerstone of treatment, but novel nonhormonal strategies and advances in precision medicine hold promise for more durable and individualized care. Ongoing clinical trials, artificial intelligence - assisted diagnostics, and fertility-focused pharmacotherapies represent exciting frontiers. Multimodal, patient-tailored approaches will be key to optimizing long-term outcomes in endometriosis management.

Introduction: Psoriatic arthritis (PsA) is a systemic inflammatory disease affecting joints, entheses, skin, nails, and spine, often accompanied by comorbidities such as obesity, metabolic syndrome, and cardiovascular disease. Despite therapeutic advances, progressive joint damage, functional impairment, and reduced quality of life remain major concerns.

Areas covered: This review highlights recent and emerging therapies in PsA, including newer biologic DMARDs (risankizumab and bimekizumab), tyrosine kinase 2 (TYK2) inhibitors, dual Janus Kinase (JAK) 1/TYK2 inhibitors, interleukin-23 receptor (IL-23 R)-targeted peptides, Affibody® molecules, and IL-17A/IL-17F-inhibiting nanobodies. Metabolic-targeted approaches, particularly glucagon-like peptide-1 receptor agonists (GLP-1RAs), offer potential benefits in obesity-driven disease. Evidence from randomized controlled trials (RCTs) and observational studies is summarized, encompassing efficacy across disease domains, safety profiles, and durability of response. Dual-pathway targeting for refractory cases is also discussed.

Expert opinion: Advances in mechanism-based and metabolic-targeted therapies enable more individualized PsA management, improving the likelihood of achieving treatment targets. Ongoing challenges include early recognition, treatment of refractory disease, and long-term safety assessment. Progress in patient-centered therapy selection and precision medicine is expected to enhance outcomes, reduce disease burden, and optimize healthcare resources. Emerging pharmacotherapies continue to expand the treatment landscape, supporting a shift toward more effective, durable, and personalized management strategies.

Background: The optimal long-term antithrombotic strategy for patients with stable coronary artery disease (CAD) requiring oral anticoagulation (OAC) remains debated. Therefore, we conducted this meta-analysis to compare OAC monotherapy versus combination therapy (OAC plus a single antiplatelet agent) in this population.

Methods: A comprehensive literature search was conducted across major electronic databases for randomized controlled trials (RCTs) through December 2025. Pooled risk ratios (RRs) with 95% confidence intervals (CIs) were calculated using a random-effects model.

Results: Six RCTs (N = 5,924 patients) were included. OAC monotherapy significantly reduced the risk of major bleeding (RR, 0.49; 95% CI, 0.36-0.67), net adverse clinical events (RR, 0.63; 95% CI, 0.50-0.79), and cardiovascular death (RR, 0.72; 95% CI, 0.54-0.96) compared to combination therapy. While the overall incidence of major adverse cardiovascular events (MACE) was comparable (RR 0.83; 95% CI, 0.69-1.01), a pre-specified subgroup analysis by OAC type revealed a significant interaction (p-interaction = 0.01), showing MACE was significantly reduced with direct OAC (DOAC)-based monotherapy (RR 0.74; 95% CI, 0.61-0.89).

Conclusion: In patients with stable CAD requiring OAC, OAC monotherapy significantly reduces bleeding and improves net clinical benefit without increasing ischemic risk. These findings support OAC monotherapy, particularly with DOACs, as the preferred long-term strategy, especially in East Asian populations.

Introduction: Cholangiocarcinoma (CCA) is a rare, highly lethal biliary malignancy comprising intrahepatic (iCCA), perihilar (pCCA), and distal (dCCA) subtypes, with a rising global incidence. Surgery is the only curative option, yet most patients present with advanced disease, making systemic therapy the mainstay. Molecular profiling has revealed marked heterogeneity, and fibroblast growth factor receptor 2 (FGFR2) fusions in iCCA represent one of the most actionable targets.

Areas covered: An extensive literature search was performed in PubMed/MEDLINE, Embase, and ClinicalTrials.gov to identify preclinical studies, clinical research, and clinical trials evaluating FGFR inhibitor therapy in CCA. This review summarizes FGFR signaling biology, the prevalence and diagnostic challenges of FGFR2 fusions, and clinical evidence for FGFR inhibitors. Resistance mechanisms, diagnostic strategies, toxicity profiles, and ongoing trials are also reviewed.

Expert opinion: FGFR inhibitors are transitioning from experimental to established targeted options, underscoring the need for routine molecular profiling and optimized fusion detection. Key challenges include overcoming resistance, refining patient selection, and defining the role of FGFR inhibition in combination strategies and earlier-line or perioperative settings. Further evidence is needed to clarify long-term clinical benefit in FGFR2-altered CCA.

Introduction: Pediatric obsessive-compulsive disorder is a chronic and often under-diagnosed condition with onset in childhood or adolescence, leading to marked functional impairment. While current first-line treatments, cognitive-behavioral therapy and selective serotonin reuptake inhibitors, are effective in many cases, a substantial proportion of patients remain refractory, especially those with early onset.

Areas covered: This review explores the emerging etiopathogenetic models of pediatric OCD, emphasizing neurodevelopmental, glutamatergic, and immune-inflammatory mechanisms. A literature search was conducted using PubMed and ClinicalTrials.gov, focusing on controlled and observational studies on pediatric OCD, including novel therapeutic targets. Special attention is given to the PANDAS/PANS subgroup, which has helped shift the paradigm beyond monoaminergic dysfunction. New pharmacological strategies, such as glutamate modulators and anti-inflammatory agents, are critically examined alongside established psychotherapeutic approaches.

Expert opinion: OCD remains the only psychiatric disorder in which a childhood syndrome, PANDAS, has led to immune-based hypotheses that influenced adult research and treatment. Despite promising signals from small trials and case studies, robust pediatric data are scarce. Future efforts should prioritize large-scale, age-specific trials, early stratification based on immune profiles, and mechanistically guided interventions to advance personalized care in pediatric OCD.

Introduction: Gout is the most common inflammatory arthritis in adults in the U.S. and worldwide. Men are affected more than women, and cardiometabolic diseases frequently accompany this condition.

Areas covered: In this review, we focus on evidence related to the risk of cardiovascular disease (CVD) and cardiovascular mortality in people with gout. We examine the role of treatments for gout in reducing CV risk.

Expert opinion: Gout, as a prototype of systemic inflammatory conditions, is associated with joint and systemic inflammation. Gout is an independent risk factor for coronary artery disease, myocardial infarction (AMI), and atrial fibrillation (AF), among other CVD, and death. Urate lowering therapy (ULT), in particular, allopurinol, is associated with a lower risk of AMI, AF, and other CV outcomes in people with gout. Colchicine use is associated with reduced acute CV events both in general population with CAD and in gout. Treat-to-target (T2T) serum urate approach entails titrating ULT by monitoring serum urate levels and gout flares. Allopurinol, the most commonly used and inexpensive ULT, in approved daily doses of 300-800 mg can achieve target serum urate of less than 6 mg/dl or 5 mg/dl using a T2T apporach.

Introduction: Lipoprotein(a) [Lp(a)] is established as an independent risk factor for atheromatous cardiovascular disease and aortic valve stenosis. Currently available lipid-lowering pharmacotherapies have limited effects on elevated levels of Lp(a), and several new therapies are in development to lower Lp(a).

Areas covered: This article reviews the novel therapies in development to reduce Lp(a) in patients with elevated levels. These were identified by a PubMed search and mainly focus on the drugs that are at an advanced stage of development.

Expert opinion: The N-acetylgalactosamine (GalNAc)-conjugated antisense oligonucleotide (ASO) pelacarsen and the small-interfering RNA (siRNA) agents olpasiran, lepodisiran, and zerlasiran have all been shown to be safe and effective in lowering Lp(a) levels between 80% and almost 100%. Pelacarsen, olpasiran, and lepodisiran are being tested in phase 3 cardiovascular outcome studies, and the first results may be available in 2026. Muvalaplin is a small molecule given orally once daily and reduces Lp(a) by up to 65%. It is also being assessed in a cardiovascular outcome study. It will be essential to identify what baseline level of Lp(a) is needed, and what degree of Lp(a) lowering is required to produce a cardiovascular benefit and whether aggressive lowering of Lp(a) has any adverse effects.