Expert Opinion on Pharmacotherapy最新文献

Introduction: Dravet Syndrome (DS) is a devastating developmental and epileptic encephalopathy marked by early refractory seizures and pervasive symptoms impacting cognition, behavior, motor function, sleep, and autonomic control. This review appraises established and emerging therapeutics, tracing the field's shift from broad antiseizure medications to gene-modifying strategies. Sustained progress hinges on targeting defined nodes in DS pathophysiology to improve the whole patient, not just seizure control.

Areas covered: We searched PubMed and ClinicalTrials.gov for 'Dravet syndrome' OR 'DS' AND 'pharmacotherapy' AND 'treatments' OR "therapeutics. We prioritized DS-specific randomized controlled trials, open-label extensions, structured reviews, network meta-analyses, and natural-history cohorts to assess clinical use, efficacy, and safety, and integrated preclinical in vitro/in vivo models to map mechanisms of action.

Expert opinion: DS therapeutics are converging on disease modification: gene-regulatory approaches lead, and targeted small molecules extend, mechanism-based care. We outline a practical precision ecosystem with four pillars: (i) early genetic screening with genotype-informed prediction, (ii) pharmacogenomic-guided prescribing, (iii) patient-specific variant modeling to clarify mechanism and optimize drug selection, and (iv) targeted restorative gene-modifying therapies that address causation. Together, these elements shift DS care toward individualized, mechanism-matched treatment providing seizure control as well as measurable gains in communication, learning, mobility, sleep, and autonomic stability.

Introduction: Metabolic dysfunction-associated steatotic liver disease (MASLD) has become a major public health concern. Recently, the development of liver-targeted pharmacologic therapies has gained momentum, culminating in the conditional approval of resmetirom which has generated renewed optimism for the management of MASLD. In addition, several other investigational agents have shown promising results in clinical trials.

Areas covered: In this review, we summarize the data on recent pharmacologic developments in the treatment of MASLD, with a particular focus on agents targeting the more progressive form - at-risk metabolic dysfunction-associated steatohepatitis (MASH). These therapies act through a variety of direct and indirect pathways within the liver.

Expert opinion: The approval of liver-targeted therapies for MASH marks the beginning of a new era in disease management, offering promising outcomes even for advanced stages such as cirrhosis. The rising prevalence of obesity and T2DM suggests that new treatment options that can treat multiple comorbidities - including GLP1 receptor agonists, dual, and multi-agonists - are likely to play a significant role in the management of MASH. The availability of effective pharmacologic treatment options highlights the need for effective screening strategies in high-risk populations and call for the engagement of policymakers to develop coordinated plans at a global level.

Introduction: The spread of multidrug-resistant (MDR) Gram-negative bacteria, such as carbapenem-resistant Enterobacterales and Pseudomonas aeruginosa, has led to a pressing need for novel treatment options. Cefepime/taniborbactam is a new β-lactam/β-lactamase inhibitor combination showing activity against a broad spectrum of β-lactamases, also including carbapenemases of different classes.

Areas covered: In this narrative review, we discuss the preclinical and clinical evidence on cefepime/taniborbactam, including in vitro activity, pharmacokinetic/pharmacodynamic studies, and efficacy and safety data from randomized controlled trials.

Expert opinion: Cefepime/taniborbactam demonstrates promising in vitro activity against a broad range of β-lactamase-producing bacteria, such as carbapenemase-producing Enterobacterales, including those producing metallo-β-lactamases, and difficult-to-treat Pseudomonas aeruginosa. Its efficacy and safety profile in complicated urinary tract infections suggest that it could represent a valuable therapeutic option, particularly in settings with high prevalence of difficult-to-treat pathogens.

Introduction: Cytomegalovirus (CMV) is one of the most common infections after solid organ or hematopoietic stem cell transplantation. Typically, ganciclovir or valganciclovir have been used for first-line therapy, with foscarnet and cidofovir being used for resistant or refractory infections. Maribavir was recently approved as a novel CMV therapeutic for transplant recipients.

Areas covered: We examine published studies of maribavir for posttransplant cytomegalovirus infection and summarize the current understanding of its pharmacology, clinical efficacy, toxicity, and risk of treatment-emergent resistance.

Expert opinion: Maribavir is generally the preferred therapy for CMV infection that is resistant or refractory to valganciclovir/ganciclovir treatment or transplant recipients who are intolerant of first-line treatment. It is well-tolerated overall without significant myelosuppression or nephrotoxicity, a stark difference from traditional CMV antivirals. However, there are high rates of treatment-emergent maribavir resistance, particularly among patients with high baseline CMV viral loads. Some UL97 mutations impart resistance to both maribavir and ganciclovir, though high-grade cross-resistance is rare. Transplant recipients who receive maribavir require close monitoring as resistance can develop even after an initial therapeutic response. Maribavir is an effective and well-tolerated addition to the CMV armamentarium, though it has important caveats that require consideration by infectious disease and transplant practitioners.

Introduction: The prevalence of invasive fungal infections (IFI) is increasing globally, with approximately 6,500,000 cases of IFI per year and 3,800,000 deaths. Most IFI deaths are attributable to opportunistic mycoses, such as Aspergillus and Candida. However, changes in climate and travel are leading to rising rates of endemic mycoses. Compounding this burden is the rise of antifungal drug resistance, requiring the development of new agents.

Areas covered: Data were identified using PubMed searches for the terms 'antifungal,' 'olorofim,' 'SUBA-itraconazole,' 'ibrexafungerp,' 'rezafungin,' 'fosmanogepix,' and 'encochleated amphotericin B.' Approved agents include ibrexafungerp, an oral triterpenoid inhibitor of 1,3-β-D-glucan synthase; rezafungin, a long-acting echinocandin with weekly dosing; and SUBA-itraconazole, a reformulation of itraconazole with more consistent absorption. Other investigational agents include: olorofim, an inhibitor of dihydroorotate dehydrogenase with activity against invasive molds and Coccidioides; fosmanogepix, an inhibitor of mannoprotein cell wall attachment, with broad activity against yeasts and molds; encochleated amphotericin B, an oral formulation of the long-established intravenous agent; and nikkomycin Z, a chitin synthase inhibitor under development since 1992.

Expert opinion: Despite improvements, gaps remain in treatments for severe IFI, particularly given increasing resistance. These agents represent significant advances, but further research is needed to define their use in patient management.

Introduction: Immune thrombocytopenia (ITP) is an acquired autoimmune hematologic disorder characterized by autoantibody-mediated platelet destruction and impaired platelet production, resulting in thrombocytopenia and an increased risk of bleeding complications. Many patients will require additional treatment beyond first-line corticosteroids. In 2025, the US FDA approved rilzabrutinib, a Bruton tyrosine kinase inhibitor, for the treatment of adult patients with persistent or chronic ITP who have had an insufficient response to a previous treatment.

Areas covered: This review summarizes the pharmacology, efficacy, and safety of rilzabrutinib for the treatment of persistent or chronic ITP, followed by an expert opinion of the authors. PubMed was searched for relevant literature up to September 2025.

Expert opinion: The approval of rilzabrutinib represents an important advancement in the treatment of ITP and adds to the therapeutic armamentarium for this patient population. While rilzabrutinib has demonstrated efficacy compared to placebo in previously treated ITP patients, there is a lack of direct comparisons with other treatment options. The safety profile of rilzabrutinib differs from other BTK inhibitors approved for B-cell malignancies. Rilzabrutinib is subject to numerous drug-drug interactions, and careful selection of this agent and review of concomitant medications will be important to ensure its safe and effective use.

Introduction: Stimulant medications, such as methylphenidate and amphetamine derivatives, and non-stimulant medications, such as atomoxetine, guanfacine, clonidine, and viloxazine, are considered the cornerstones of pharmacological treatment for attention-deficit/hyperactivity disorder (ADHD). However, a significant number of individuals respond partially to these treatments or are concerned about side effects. This creates a need for new treatment strategies that target alternative neurobiological mechanisms and offer improved tolerability and efficacy profiles.

Area covered: This review examines pharmacological agents currently in phase III clinical development or recently completed trials for the treatment of ADHD. We highlight four promising candidates: centanafadine, solriamfetol, CTx-1301, and NRCT-101SR. We discuss their pharmacological mechanisms, clinical efficacy, safety profiles, and regulatory status, with an emphasis on how these agents may address existing therapeutic gaps and the potential clinical implications. A literature search was conducted using PubMed and ClinicalTrials.gov databases for articles published between January 2018-July 2025.

Expert opinion: Recent advances in ADHD pharmacotherapy suggest that approaches targeting monoaminergic systems beyond dopamine and noradrenaline reuptake inhibition may provide therapeutic benefits. Additionally, multi-phase extended-release formulations may improve adherence and enhance symptom control throughout the day. As phase III data become available, these agents have the potential to redefine ADHD treatment paradigms.