Expert Opinion on Pharmacotherapy最新文献

Background: Opioids are a treatment for cancer pain, but may be less effective for neuropathic than nociceptive pain. However, evidence supporting opioid - neuropathic drug combinations for neuropathic cancer pain (NCP) remains limited.

Research design and methods: This randomized, open-label, parallel-group study, conducted across Japan, evaluated the efficacy and safety of mirogabalin + opioids (M+O) versus opioid monotherapy (O) in patients with NCP. Change in the numerical rating scale (NRS) pain score from baseline at Week 4 was the primary endpoint.

Results: Of 142 patients, 141 were randomized (M+O, n = 71; O, n = 70). The M+O group achieved a greater reduction in NRS pain scores from baseline at Week 4 than the O group (intergroup difference in least squares mean changes: -1.5, 95% confidence interval: -2.4, -0.6; P = 0.0017) and higher NRS responder (≥30% reduction) rates (72.3% vs. 42.0%; P = 0.0039). Treatment-emergent adverse event incidences were 60.9% (42/69) and 27.1% (19/70) in the M+O and O groups, respectively. Somnolence (20.3%) and dizziness (8.7%) were the most common adverse drug events for mirogabalin.

Conclusions: Mirogabalin, as an opioid add-on, improved neuropathic pain vs opioid monotherapy in patients with NCP. Concomitant use of mirogabalin could be a novel treatment option for NCP.

Clinical trial registration: Japan Registry of Clinical Trials (https://jrct.mhlw.go.jp/) identifier is jRCTs031220569.

Introduction: Tourette syndrome is a neurodevelopmental disorder characterized by chronic motor and vocal tics. Both tic severity and co-morbid psychiatric disorders can affect patients' health-related quality of life to an extent that warrants active treatment interventions. Different decisional approaches can be implemented to determine the need for pharmacotherapy.

Areas covered: A critical appraisal of the existing literature on the clinical scenarios where pharmacotherapy for Tourette syndrome is deemed necessary has highlighted three indications: (1) physical discomfort - e.g. pain or injury; (2) emotional or social problems - e.g. depression or isolation; or (3) functional interference - e.g. impairment of academic achievements.

Expert opinion: Pharmacotherapy for tic disorders aims to reduce tic severity enough to improve daily functioning and health-related quality of life rather than to eliminate symptoms. Expert consensus emphasizes patient-centered decision-making that integrates disease-specific quality of life measures with objective tic severity scales. Medications may be prioritized when tics cause significant impairment, pose medical risks, require rapid control, or coexist with treatable co-morbidities. Current guidelines rely largely on limited trials and expert opinion, with dopamine-modulating agents and alpha-2 agonists being most commonly used. Further research should focus on open questions about real-world effectiveness and generalizability of individual pharmacological agents.

Introduction: Several studies have identified Hypoxia-Inducible Factor 2-alpha (HIF-2α) as a key oncogenic driver in clear cell renal cell carcinoma (ccRCC). In this context, belzutifan emerges as an oral inhibitor of HIF-2α, that acts by blocking the heterodimerization of HIF-2α with HIF-1β, thereby preventing the transcription of hypoxia-target genes and reducing VEGF-mediated tumor growth. The LITESPARK series of studies recently defined the emerging role of belzutifan in the therapeutic landscape of RCC, and further studies are ongoing.

Areas covered: In the current review, we discuss the role of belzutifan as an innovative and promising therapeutic strategy for targeting a key biological mechanism in ccRCC.

Expert opinion: According to available evidence and data, belzutifan has generally been well tolerated, though anemia is a frequent on-target side effect and, along with hypoxia, necessitates monitoring throughout treatment. As reported, ongoing phase III clinical trials are set to yield potentially practice-changing results, investigating innovative combinatorial strategies including belzutifan. Ongoing advancement of predictive biomarkers and understanding of resistance mechanisms could improve patient selection and identify new drug targets, thereby increasing the clinical efficacy of belzutifan.

Introduction: Antimalarial agents, particularly hydroxychloroquine and chloroquine, are widely used in systemic autoimmune diseases. While ocular toxicity is well established, the extent and clinical relevance of potential auditory toxicity remain unclear. We conducted a systematic review to evaluate the available evidence on auditory adverse effects associated with antimalarial use in systemic autoimmune diseases.

Methods: A systematic search was performed in PubMed, Scopus, and the Cochrane Library from inception to January 2025. Observational and interventional studies reporting audiological outcomes in patients exposed to antimalarials were included, excluding malaria-related treatments. Risk of bias was assessed according to study design. Due to substantial clinical and methodological heterogeneity, results were synthesized descriptively without meta-analysis.

Results: Sixteen studies encompassing heterogeneous autoimmune populations and audiological methods were included. The reported prevalence of hearing abnormalities varied widely across studies and diagnostic techniques. Associations with antimalarial exposure, dose, or duration were inconsistent. Some studies described subclinical cochlear or brainstem alterations, while others found no significant differences compared with non-exposed patients.

Conclusions: Available evidence is limited and heterogeneous, precluding causal inferences regarding antimalarial-related auditory toxicity. Increased clinical awareness of auditory symptoms may be reasonable, but standardized monitoring is not supported. Prospective controlled studies with standardized audiological assessments are needed.

Introduction: Tenosynovial giant cell tumors (TGCTs) are locally aggressive mesenchymal neoplasms that can cause chronic disability. Surgery is a mainstay of treatment but can carry a high risk of morbidity or can confer limited benefit. As such, effective alternative treatment options are needed, including systemic agents. Improved understanding of the pathophysiology of TGCTs has led to such drug development.

Areas covered: Vimseltinib is a switch-control tyrosine kinase inhibitor designed to selectively inhibit CSF1R, which, along with CSF1, is responsible for the synovial inflammation that characterizes TGCTs. In this drug evaluation, we review the mechanism of action, pharmacologic properties, clinical efficacy and current role within the TGCT treatment landscape of vimseltinib.

Expert opinion: Vimseltinib demonstrated a significant response rate as well as meaningful symptomatic improvement in patients with TGCTs. Furthermore, there is an absence of severe toxicities that have arisen with other agents in the TGCT treatment space, specifically liver failure. Vimseltinib is a favorable option for patients with TGCTs and further efforts to determine its place in the sequence of overall management are needed.

Introduction: Despite the fact that IgA nephropathy (IgAN) is the most common chronic glomerulonephritis across the age spectrum worldwide, there is a lack of evidence-based treatment recommendations for pediatric patients. Moreover, current treatment options in children are very limited. This review aims to provide a comprehensive overview of current therapeutic strategies for managing IgAN, with a particular focus on new drugs recently evaluated in adult cohorts, as well as novel treatments reported in pediatric case studies.

Areas covered: A literature search was conducted using Pubmed and Scopus, covering the period from January 2013 to June 2025. Studies relevant to topic were included. Currently, there are numerous adult trials studying medications that target fundamental IgAN pathogenetic pathways, with very promising results in terms of proteinuria reduction and stabilization of kidney function.

Expert opinion: The higher disease activity and longer life expectancy in pediatric patients create a critical need for the evaluation of modern therapies in children with IgAN. Thus, it is crucial to prioritize pediatric clinical trials and to focus on removing the barriers that limit their implementation.

Introduction: Functional dyspepsia (FD) is a highly prevalent disorder of gut - brain interaction, characterized by heterogeneous symptoms, overlapping pathophysiology, and limited treatment efficacy. Iberogast®, a multi-herbal phytomedicine available for more than five decades, has emerged as a promising therapeutic option by addressing multiple mechanisms simultaneously.

Areas covered: This narrative review summarizes the pharmacological rationale, mechanisms of action, and clinical evidence supporting Iberogast's role in FD and related conditions. Literature was identified through searches of PubMed, Scopus, and Web of Science, complemented by reference screening, with the last update on 19 August 2025. Particular attention is given to the original nine-component formulation (STW 5) and the refined six-component version (STW 5-II). Evidence from randomized controlled trials, meta-analyses, mechanistic studies, and real-world data is synthesized to provide an integrated appraisal of efficacy, safety, and therapeutic positioning.

Expert opinion: Iberogast remains an evidence-based phytomedicine with a favorable safety profile, filling therapeutic gaps in FD by targeting motility, hypersensitivity, inflammation, and barrier function. Future research should include trials comparing Iberogast with established drugs, evaluating cyclic therapy in real-world settings, and exploring new indications such as irritable bowel syndrome, inflammatory bowel disease, use in pediatrics, and overlapping dyspepsia - reflux phenotypes.