Expert Opinion on Pharmacotherapy最新文献

Introduction: Cannabis use disorder (CUD) is a growing global health concern, with limited pharmacological treatments currently available despite increasing prevalence and legalization trends.

Areas covered: This review explores the landscape of pharmacotherapies for CUD, including both repurposed agents and emerging investigational compounds. We summarize findings from recent systematic reviews and meta-analyses, with attention to mechanisms of action and clinical relevance. Agents discussed include gabapentin, N-acetylcysteine, synthetic cannabinoids, fatty acid amide hydrolase (FAAH) inhibitors, orexin receptor antagonists, and psychedelics. A narrative approach was used, informed by targeted searches of PubMed, Google Scholar, and clinical trial registries from 2000 to 2025, focusing on human studies, randomized trials, and meta-analyses relevant to pharmacologic management of CUD.

Expert opinion: The pharmacologic treatment of CUD is in its early stages, with no approved agents and modest efficacy demonstrated to date. Novel compounds targeting endocannabinoid tone and motivational circuits show promise, but significant research is still needed. Future progress depends on better integration with behavioral care, trial stratification by clinical phenotype, and increased investment in translational research to move beyond withdrawal symptom management toward sustained recovery.

Introduction: There have been recent major advances in the management and treatment of mantle cell lymphoma (MCL). This uncommon subtype of mature B-cell lymphoma has a heterogeneous clinical course, including a spectrum of indolent and aggressive disease. While historically regarded as an incurable disease with a poor long-term prognosis, recent developments have improved outcomes.

Areas covered: The incorporation of targeted treatments, such as covalent Bruton's tyrosine kinase inhibitors (cBTKi), with or without chemo-immunotherapy in the upfront treatment setting is supported by recent clinical trials indicating encouraging efficacy and safety. Measurable residual disease (MRD) testing is emerging as a potent tool in guiding treatment decision and improving outcomes while minimizing toxicities. Therapies utilized in relapsed/refractory disease, such as BCL2 inhibitors as well as immune-leveraging therapies, including T-cell engaging antibodies and chimeric antigen receptor (CAR) T-cells therapy, are being evaluated in upfront settings.

Expert opinion: This review will discuss recent advances in the upfront management of this challenging disease as well as a suggested treatment algorithm considering both availability and unavailability of first-line cBTKi. The incorporation of cBTKi to chemo-immunotherapy regimens appears effective and safe. However, patients with high-risk disease may require novel therapeutic approaches due to suboptimal outcomes with chemo-immunotherapy.

Background: PCOS is an endocrine disorder affecting women of reproductive-aged group. It has multiple manifestations, including metabolic, reproductive, and psychological domains. Among PCOS patients, pharmaceutical management remains a primary approach to its treatment, particularly when lifestyle changes do not yield improvements.

Objective: This study aims to highlight trends in global research concerning PCOS and its pharmacological treatment within the last decade using bibliometric analysis.

Methods: A bibliometric analysis was conducted for the 2015-2024 timeframe using Web of Science database. Search queries were designed for PCOS as well as its pharmacological treatment options. Data analysis was performed through visualization of collaborations, research trends, etc. in VOS viewer.

Results: 2607 publications qualified for inclusion criteria. The most frequently treated topics were combined oral contraceptives, metformin, letrozole, and inositols. China is the leading contributor toward publication volume, while the U.S.A. was the most cited and had the strongest links. Influence appeared to stem from Monash University, and Legro RS was the most influential the most impactful author.

Conclusion: The study reveals global trends in PCOS pharmacotherapy, with a growing focus on metabolic and molecular aspects. Key contributors and emerging therapies highlight the expanding scope and future potential of PCOS treatment research.

Introduction: Homozygous familial hypercholesterolemia (HoFH) is a rare, inherited disorder characterized by severe LDL-hypercholesterolemia and accelerated atherosclerotic cardiovascular disease. It typically presents in childhood or adolescence, and if untreated, may be fatal in the first decades of life. The microsomal triglyceride transfer protein (MTP) is essential for the assembly and secretion of apolipoprotein (apo)B-containing lipoproteins. MTP inhibition with lomitapide effectively lowers plasma LDL-cholesterol as an adjunct therapy in adults with HoFH.

Areas covered: We discuss the role of MTP as a therapeutic target for HoFH, describe the pharmacodynamics, pharmacokinetics, and metabolism of lomitapide, and report on the findings of the phase III APH-19 trial in pediatric HoFH.

Expert opinion: Lomitapide is an oral small molecule inhibitor of MTP, which reduces LDL-cholesterol by 53.5% in pediatric patients with HoFH on maximal standard lipid-lowering therapy, including lipoprotein apheresis. Moreover, small case series have shown that pediatric HoFH patients on lomitapide were able to cease or reduce the frequency of lipoprotein apheresis. Safety and tolerability studies are consistent with the known mechanism of lomitapide on the gastrointestinal and hepatic systems, and are generally mild and manageable in pediatric HoFH patients. The results of longer-term safety data are awaited.

Introduction: The newly approved use of pitolisant in pediatric narcolepsy marks a significant advancement for patients and clinicians, given the scarcity of medications for this age group that are both safe and effective in reducing narcolepsy symptoms and improving quality of life.

Areas covered: This article covers the use of pitolisant for treating narcolepsy type 1 (NT1) and 2 (NT2) in pediatric patients considering drug's pharmacokinetics and pharmacodynamics. By integrating recent literature and real-world data, the safety, the tolerability and the efficacy of this drug have been analyzed, also including evidence drawn from studies involving patients with Prader-Willi Syndrome.

Expert opinion: Pitolisant represents a groundbreaking treatment for pediatric narcolepsy, addressing the paucity of safe and effective options for this age group. Its unique mechanism as a histamine H3 receptor antagonist reduces excessive daytime sleepiness and cataplexy while offering cognitive benefits. With a favorable safety profile and good tolerability, pitolisant efficiently outperforms traditional therapies, which often have distressing side effects. Its use is particularly critical in childhood, a developmental stage where factors like growth, school performance, and socialization must be carefully considered, making it a transformative option for pediatric care.

Introduction: Oncogenic activation of KRAS is a common driver of solid tumor malignancies and has been considered 'undruggable' for several decades. Oral small molecule inhibitors, including sotorasib and adagrasib, have demonstrated moderate efficacy in targeting KRAS G12C in NSCLC. More potent inhibitors are needed, and the landscape is rapidly evolving.

Areas covered: Opnurasib (JDQ-443) is an irreversible covalent inhibitor of GDP-bound KRAS G12C that has been under investigation in patients with KRAS G12C-mutated solid tumors, including NSCLC. Here, we review its mechanism of action, pharmacologic properties, clinical efficacy, role within the NSCLC landscape prior to its withdrawal from the market, as well as the regulatory and market-driven dynamics that may result in the abandonment of aspiring drugs.

Expert opinion: JDQ-443's unique binding within the Switch II pocket of KRAS G12C allows for novel interactions and helps define its characteristic profile of anti-tumor activity, tolerability, and resistance. JDQ-443 has demonstrated promising early clinical activity in KRAS G12C-mutated NSCLC. More data is necessary to allow comparison of available agents and combination strategies. In the face of an expanding market, development of JDQ-443 has been halted despite promising safety and efficacy outcomes and ongoing innovative trials, highlighting critical challenges in the drug development process. The existing body of work characterizing JDQ-443 remains extremely informative.

Introduction: As the global population ages, understanding immune checkpoint inhibitor (ICI) efficacy and safety in the older cancer patients is critical. ICIs represent a major advance, but their effectiveness relative to age-related immune changes warrants investigation.

Areas covered: This review synthesizes current clinical and preclinical evidence examining how aging influences ICIs response. We discuss age-related immunological changes (immunosenescence), alterations in the tumor microenvironment, mechanistic insights from preclinical aging models, and clinical trial/real-world data on ICIs efficacy and safety including immune-related adverse events (irAEs) across various cancers in older patient, referencing meta-analyses and specific trial outcomes.

Expert opinion: Extensive clinical data suggest ICIs often provide significant survival benefits and are generally well-tolerated in appropriately selected older patients, with outcomes frequently comparable to younger cohorts, although efficacy can vary by tumor type, performance status (PS), and biomarkers. While irAEs require careful management considering comorbidities and frailty, overall incidence is not consistently higher in older adults. Treatment decisions should be individualized, integrating biological age indicators, PS, and comorbidities, rather than relying solely on chronological age. Future research should focus on identifying robust biomarkers and tailored strategies to optimize ICIs use in this demographic.

Introduction: There has been a lack of novel medication classes approved for reducing blood pressure (BP) in hypertensive patients. Endothelins, powerful vasoconstricting peptides, have been at the forefront of experimental hypertension research since they were discovered in 1988. The recent PRECISION trial demonstrated the efficacy of aprocitentan, a novel endothelin receptor antagonist, in lowering blood pressure in patients with resistant hypertension (RH). This trial was the driving force behind the approval of aprocitentan in 2024 for the treatment of resistant hypertension.

Areas covered: This clinical trial review will cover the literature leading to the approval of aprocitentan and argue for its use on top of current treatments of hypertension. We argue for the need of novel anti-hypertensive medication classes and provide a brief overview of endothelin receptor antagonists. Finally, we will describe the PRECISION trial and highlight the key benefits of aprocitentan that it elucidated.

Expert opinion: The PRECISION trial demonstrated numerous key benefits of aprocitentan, including efficacy in reducing BP and proteinuria, minimal adverse side effects, and efficacy in patients with advanced chronic kidney disease (CKD) without development of hyperkalemia. However, a lack of long-term data necessitates future investigation regarding safety. Aprocitentan may represent a novel therapeutic alternative to treat patients with RH and CKD.

Introduction: Despite investigating the various effects of dopamine agonists (DA) on cardiometabolic-related factors, there are conflicting findings in this field. This study aimed to investigate the effect of DA on changes in various factors related to cardiometabolic diseases.

Methods: Comprehensive search was performed across five databases using predefined keywords to identify randomized controlled trials investigating the impact of DA on cardiometabolic factors. The combined weighted mean difference (WMD) and 95% confidence intervals (CI) were analyzed using a random-effects model.

Results: Findings from 22 studies demonstrated significant reductions in fasting blood sugar (FBS) (WMD: -16.95 mg/dl; 95% CI: -23.59, -10.31), insulin (WMD: -2.02 µU/ml; 95% CI: -3.63 to -0.40), HOMA-IR (WMD: -0.82; 95% CI: -1.51 to -0.13), and HbA1c (WMD: -0.73; 95% CI: -0.96 to -0.49) as well as Systolic (SBP) (WMD: -3.75 mg/Hg; 95% CI: -6.25, -1.25) and diastolic blood pressure (DBP) (WMD: -3.45 mg/Hg; 95% CI: -5.55, -1.36) levels following intervention with DA compared to the control group. Subgroup analyses provided additional insights, revealing that bromocriptine had a more pronounced effect on glucose metabolism markers than other DA.

Conclusions: It appears that DA, along with other lifestyle factors, can lead to significant improvements in some factors associated with cardiometabolic.