Expert Review of Clinical Pharmacology最新文献

Introduction: Patients with cancer are frequently exposed to polypharmacy, carrying a high risk of drug-drug interactions (DDIs). Given their substantial risk for thrombosis and atrial fibrillation, anticoagulants are commonly prescribed in this population. Anticoagulants can be associated with relevant pharmacokinetic and pharmacodynamic DDIs, yet their clinical significance remains undetermined.

Areas covered: A literature search of preclinical and clinical studies was performed to identify DDIs between anticoagulation and anticancer treatment, with an emphasis on pharmacokinetic and pharmacodynamic mechanisms. This narrative review summarizes the general principles of DDIs involving anticoagulation in patients with cancer. A comprehensive review of DDIs between anticoagulants and different classes of anticancer therapies is provided, including recent outcome studies evaluating their impact on mortality, clinically relevant bleeding, and thrombosis.

Expert opinion: Based on available data, we propose a practical approach to DDI assessment and clinical interpretation to support decision-making in patients with cancer requiring anticoagulation. This includes systematic screening for DDIs, tailoring anticoagulants during both initial and long-term treatment (primarily in the context of venous thromboembolism), providing patient counseling based on available evidence, and involving the pharmacy team in complex cases.

Introduction: Janus kinase inhibitors (JAKIs) emerged as novel therapies for a wide range of autoimmune and myeloproliferative neoplasms. JAKIs have remarkable clinical effectiveness, but emerging safety concerns have sparked interest in precision dosing approaches and the role of therapeutic drug monitoring (TDM) remains largely unexplored.

Areas covered: This review summarizes the mechanisms of action, indications and adverse effects of approved JAKIs in Switzerland, namely, abrocitinib, baricitinib, momelotinib, ritlecitinib, ruxolitinib, tofacitinib, and upadacitinib. We discussed factors that impact the pharmacokinetics of JAKIs, as well as exposure-efficacy and toxicity relationships, to evaluate whether JAKIs are suitable candidates for TDM. Regulatory documents and a PubMed search using the terms 'drug monitoring,' 'pharmacokinetics,' and 'JAKIs (incl. abrocitinib, baricitinib, momelotinib, ritlecitinib, ruxolitinib, tofacitinib, and upadacitinib)' were used to compile data until March 2025.

Expert opinion: JAKIs meet the criteria for TDM as they have marked inter-individual pharmacokinetic variability, narrow therapeutic margins and exposure-response relationships. Implementing TDM in clinical practice requires to establish target concentration ranges associated with efficacy and toxicity, along with a better understanding of the pharmacokinetics of JAKIs in real-life settings.

Introduction: In the last few years, interest is growing around the topic of possible therapeutic properties of substances classified as psychedelic, especially for the treatment of mental disorders. Ayahuasca is a classic psychedelic with a complex composition, which has been used in traditional contexts for centuries.

Areas covered: In this review, we explore the current evidence and limitations around ayahuasca use for the treatment of depression, anxiety, posttraumatic stress and substance use disorders, with a focus on clinical and observation studies.

Expert opinion: Similar to what happens with other psychedelics, there is an ongoing debate on subjective experience contribution to overall therapeutic mechanisms, which can depend on the targeted conditions. There are very few evidences from controlled studies, limiting the conclusions on safety and efficacy. On top of that, ayahuasca highly variable composition posits another challenge, and studies using isolated compounds are being developed.

Metabolic dysfunction-associated steatohepatitis (MASH) with fibrosis poses a significant clinical challenge, especially given its strong association with obesity and type 2 diabetes mellitus (T2DM). Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have demonstrated impressive results in managing obesity and T2DM, prompting interest in their potential therapeutic role for MASH with fibrosis. The ESSENCE trial recently investigated the effectiveness of once-weekly semaglutide in patients with biopsy-proven MASH and moderate-to-advanced fibrosis. Interim analysis at 72 weeks demonstrated that semaglutide substantially improved liver histology, effectively resolving steatohepatitis and showing improvement in liver fibrosis, compared to placebo. Consistent with these findings, the U.S. Food and Drug Administration has granted accelerated approval to semaglutide (Wegovy) for adults with noncirrhotic MASH and stage 2 or 3 fibrosis. Those hepatic benefits were accompanied with notable improvements in body weight, insulin sensitivity and inflammatory markers. While these preliminary results are encouraging, their clinical relevance will depend on whether they translate into reduced long-term liver complications and amelioration of overall cardio-renal risk. Thus, semaglutide represents a highly promising therapeutic strategy for patients with MASH and fibrosis, addressing critical unmet needs by simultaneously targeting liver pathology and cardiometabolic health.

Introduction: Pregnancy in women with systemic lupus erythematosus presents significant clinical challenges due to heightened risks of complications for both mother and fetus. Therapeutic management must be carefully tailored to safeguard maternal health while ensuring optimal fetal development.

Areas covered: This review explores pharmacological treatments used during pregnancy in women with lupus, focusing on medication safety profiles, risk-benefit analyses of available therapeutic options, and specific challenges posed by comorbidities such as antiphospholipid syndrome and vaccination considerations.

Expert opinion: Although significant advances have been made in managing lupus during pregnancy, many treatments, particularly biologic therapies, still lack sufficient evidence for unrestricted use. This underscores the necessity for vigilant monitoring and individualized treatment protocols. Preconception consultation remains crucial for optimizing therapeutic strategies, ensuring appropriate medication adjustments prior to conception. A coordinated multidisciplinary approach is essential to navigate these complexities and achieve favorable outcomes for both mother and child.

Introduction: Vasomotor symptoms (VMS) and decreased libido are common menopausal symptoms. Patients with breast cancer receiving endocrine therapy experience new or worsening menopausal symptoms. Pharmacologic therapy for VMS has been centered on selective serotonin reuptake inhibitors and serotonin norepinephrine reuptake inhibitors, gabapentin, and clonidine. These therapeutic options fall short in obtaining adequate symptom relief, illustrating a therapeutic gap in efficacious treatment modalities. There are no historical systemic treatment options for low libido.

Areas covered: This review summarizes the current pharmacologic therapy for VMS, focusing on the practical considerations for use of the novel VMS (fezolinetant, elinzanetant) and libido agents (flibanserin, bremelanotide). Literature search was completed with PUBMED, Cochrane Library, and Web of Science. Fezolinetant is a novel neurokinin 3 receptor antagonist that has demonstrated clinical benefit in patients without a history of breast cancer. For libido management, flibanserin and bremelanotide act as serotonin/dopaminergic modulators and melanocortin receptor agonists, respectively.

Expert opinion: These novel agents are eagerly awaited therapeutic options; however, clinical trials excluded breast cancer patients. This review provides clinicians with relevant considerations to assess when recommending these therapies for patients with breast cancer, while awaiting ongoing research to give additional insights for best tailoring therapy for this patient population.

Introduction: Naxitamab (previously named hu3F8) is a humanized monoclonal antibody (mAb) targeting disialoganglioside GD2, a ganglioside homogeneously and abundantly expressed on neuroblastoma and other neuroectodermal tumors. Anti-GD2 mAbs are an integral part of the standard therapeutic paradigm for high-risk neuroblastoma. Naxitamab, in combination with granulocyte-macrophage colony-stimulating factor (GM-CSF), is approved by regulatory authorities for patients with relapsed or refractory neuroblastoma in the bone and/or bone marrow.

Areas covered: This review provides a comprehensive overview of the preclinical development, clinical efficacy, and safety profile of naxitamab. It summarizes and discusses the key clinical trials, real-world experiences, and adverse events management.

Expert opinion: Naxitamab has shown a favorable toxicity profile and meaningful therapeutic efficacy in relapsed or refractory diseases and as consolidation therapy in high-risk neuroblastoma. Ongoing clinical studies and expanded global use continue to evaluate its safety and efficacy, to optimize its integration with standard care, and to fully exploit its therapeutic potential. Advances in protein engineering can further extend the utility of anti-GD2 mAbs, enabling the creation of radioimmunoconjugates, novel bispecific antibodies, and pre-targeting strategies, offering potent tumor selectivity while mitigating off-target toxicity.

Introduction: Long-acting growth hormone (LAGH) preparations have been developed to reduce the burden of daily injections and improve compliance in children and adults with growth hormone deficiency (GHD). Somapacitan is the only LAGH approved for both pediatric and adult GHD that has been in the market for nearly 2 years for these indications. It has now up to 4 years of follow up data from pediatric clinical trials.

Areas covered: In this article, we will review the rationale for developing somapacitan and other LAGH, the pharmacologic characteristics, pharmacokinetics, and pharmacodynamics of somapacitan. We will summarize the clinical trial results of safety, efficacy, and adherence of somapacitan in comparison to daily growth hormone (GH) in both adults and children. We will also provide practical recommendations on the initiation and monitoring of somapacitan, and discuss potential future uses of this LAGH.

Expert opinion: Continued somapacitan therapy in clinical trials in children with GHD has shown ongoing catch-up growth while having a similar safety profile to daily growth hormone. However, it will be important to capture real world data demonstrating ongoing safety, efficacy, and adherence in children and adults receiving somapacitan and other LAGH therapies.

Introduction: Breast cancer is the most common cancer in women. As global populations age, the number of older adults with breast cancer is expected to increase significantly. Recently, progress has been made across all subtypes of breast cancer with the development of new targeted therapeutics and the success of novel combinations. However, treating older adults remains challenging due to the limited representation of this population in clinical trials, resulting in a lack of robust data on treatment efficacy and tolerability.

Areas covered: We reviewed FDA-approved therapies for breast cancer since 2020. We analyzed pivotal clinical trials leading to registration, as well as subanalyses of older populations and real-world studies for each approved therapy, with a focus on their impact in older adults.

Expert opinion: Breast cancer is a quickly changing field with many new therapeutics and novel combinations on the horizon. With each new approval, it is critical to assess expected side effects and approach each patient with an individualized plan. Many clinical trials enroll a small number of older adults, making it difficult to extrapolate data to geriatric populations. Future trials should incorporate broader eligibility criteria and include geriatric-specific endpoints to better inform treatment decisions for older adults with breast cancer.