Expert Opinion on Pharmacotherapy最新文献

Background: Clinical trials have shown semaglutide effective in mitigating risks associated with type 2 diabetes and chronic kidney disease. However, semaglutide's real-world effectiveness and long-term outcomes are not fully established.

Research design & methods: Using 2019-2024 Kythera Labs data, an external control arm was created using criteria identified in the FLOW clinical trial. Primary outcomes were major kidney disease events (kidney failure onset and ≥ 50% reduction in estimated glomerular filtration rate from baseline). Propensity score matching and Cox regression were used to determine risk-adjusted outcomes.

Results: The control arm (n = 896,257) was compared with the clinical trial cohort (n = 1,766). After propensity score matching on age, sex, socioeconomic status, and comorbidities, semaglutide treatment was associated with a 26% reduction in primary event risk compared with the comparator group (702 vs 1,068 events; HR: 0.74; 95% CI, 0.67-0.81), consistent with the 24% risk reduction observed in the clinical trial.

Conclusion: Semaglutide treatment was linked to a significantly lower risk of clinically relevant renal outcomes. Our findings provide robust real-world evidence that supports the FLOW trial results regarding the renoprotective effects of semaglutide, highlighting its promise as an effective therapeutic option for managing renal complications.

Introduction: Hereditary angioedema (HAE) is a genetic rare condition characterized by recurrent attacks of swelling that might be potentially life-threatening. Recurrence and severity of attacks may impact psychological life, expectations and productivity. We aim to review the state-of-the-art of HAE preventive and on-demand treatment of non-biologic drugs, providing a perspective of their personalized use and development.

Areas covered: This literature analysis integrates international guidelines and clinical trial data on on-demand therapies and short-/long-term prophylaxis. Modern medications should be considered and personalized for HAE patients to provide benefits compatible with patients' lifestyles, preferences, and experiences. Accordingly, a new era toward oral formulations has begun starting from berotralstat, with a consistent number of drugs under development.

Expert opinion: All HAE patients should have an effective on-demand treatment available in case of attacks. Long-term prophylaxis (LTP) should be considered and individualized for all patients at every visit, following a shared decision-making approach to optimize disease control while limiting side effects. Parenteral administration of LTP is associated with treatment complexities and barriers. Oral treatment could address practical needs for HAE patients both in preventive and on-demand setting, avoiding injection-related side effects, reducing treatment burden, and improving quality of life. In the next future, significant advances in HAE therapeutics could result from gene therapy.

Introduction: Primary biliary cholangitis (PBC) is a chronic, cholestatic liver disease, is associated with fatigue and pruritus and can progress to cirrhosis if left untreated. Ursodeoxycholic acid (UDCA) has been the mainstay of therapy for over 40 years. However, 30-40% of PBC patients do not adequately respond to UDCA or have risk factors for disease progression and require second-line treatment.

Areas covered: Recent international cohort analyses have provided new insights that enable early identification of high-risk PBC patients and suggest that stricter treatment goals may lower mortality and reduce the need for liver transplantation. Alongside established second-line agents, several promising substances have progressed to phase 2 and 3 trials. Notably, seladelpar and elafibranor, two selective agonists of peroxisome proliferator-activated receptors, achieved high rates of biochemical response and good tolerability, leading to their recent approval for second-line treatment of PBC. Moreover, dedicated clinical trials addressed fatigue and pruritus, the two main symptoms of PBC.

Expert opinion: Personalized treatment approaches for PBC are both feasible and essential to improve biochemical response, extend transplant-free survival and alleviate symptom burden. Well-tolerated novel therapies are poised to reshape the treatment landscape in the near future.

Introduction: Lennox-Gastaut syndrome (LGS) is a severe childhood-onset developmental and epileptic encephalopathy characterized by multiple drug-resistant seizures, cognitive impairments, and distinctive EEG patterns. Given its profound impact on patients' quality of life, developing effective pharmacotherapies remains a critical clinical challenge.

Areas covered: This review examines FDA-approved medications for LGS (clonazepam, felbamate, lamotrigine, topiramate, rufinamide, clobazam, cannabidiol, and fenfluramine), commonly used off-label antiseizure medications, emerging treatments in clinical trials, and precision therapeutics targeting etiology-specific mechanisms. The literature encompasses randomized controlled trials, observational studies, and expert consensus statements on treatment approaches and challenges.

Expert opinion: Despite therapeutic advances, most patients with LGS lack individualized treatment plans with regular adjustments. Current management requires a multimodal approach integrating pharmacotherapy with other interventions. Future progress depends on improved natural history studies, standardized data collection, advanced preclinical models, innovative trial designs, and addressing healthcare inequities. While emerging precision therapies targeting genetic causes show promise, the field urgently needs better strategies to optimize existing treatments while developing disease-modifying approaches that address both seizures and non-seizure outcomes.

Introduction: Eosinophilic esophagitis (EoE) is an immune-mediated disease characterized by esophageal dysfunction and eosinophil rich inflammatory infiltrate. Its incidence is rising globally due to increased awareness, improved diagnostics, and environmental and genetic factors. EoE is driven by a Th2-mediated immune response to food and environmental allergens, leading to chronic inflammation, epithelial barrier dysfunction and progressive esophageal remodeling.

Areas covered: This review explores pediatric EoE, focusing on epidemiology, pathogenesis, clinical presentation, diagnosis, and both standard and new treatment strategies. Symptoms vary by age, from feeding difficulties in infants to dysphagia and food impaction in older children. Diagnosis relies on clinical symptoms, endoscopic findings and histologic assessment. Standard treatments include dietary elimination, proton pump inhibitors and topical corticosteroids, while biologic therapies such as dupilumab offer targeted alternatives for refractory cases.

Expert opinion: Future research focuses on optimizing treatment sequencing (step-up and step-down approach), exploring non-eosinophil-mediated inflammation, and enhancing noninvasive test to predict disease severity and phenotypes for better long-term management.

Background: Ischemic stroke is a major cause of morbidity and mortality worldwide. Although reperfusion therapy enhances patient outcomes, the ideal antiplatelet regimen post-treatment remains unclear. This study investigates the efficacy and safety of dual antiplatelet therapy (DAPT) versus triple antiplatelet therapy (TAT) in ischemic stroke patients after reperfusion.

Research design and methods: A retrospective observational analysis was conducted on 730 patients treated at a single institution from January 2018 to December 2023. Patients were divided into two groups: DAPT (aspirin and clopidogrel) or TAT (aspirin, clopidogrel, and tirofiban). Outcomes included neurological improvement via NIHSS scores, functional recovery using mRS, and bleeding complications.

Results: TAT demonstrated significantly better neurological recovery, with more patients achieving NIHSS ≤ 3 (p < 0.001). All TAT patients had mRS ≤ 2 at 30 days. However, TAT was associated with higher bleeding rates (37.4% vs. 18.8%, p < 0.05). Intravenous thrombolysis increased bleeding risk (OR = 3.95, 95% CI: 1.26-12.44, p = 0.02).

Conclusion: TAT may enhance neurological recovery but increases bleeding risk. Patient selection and monitoring are crucial, and long-term studies are needed to fully evaluate its risk-benefit profile.

Introduction: The global rise of multidrug-resistant (MDR) Gram-negative bacteria (GNB) has intensified the threat of chronic and hard-to-treat infections, many of which are associated with biofilm formation. These biofilms confer enhanced resistance to antimicrobials and immune responses, posing a major clinical challenge.

Areas covered: This review summarizes the biological mechanisms of biofilm formation in GNB and explores both traditional and novel strategies for their prevention and eradication. The literature search covered peer-reviewed articles from major databases, focusing on therapeutic approaches such as quorum sensing inhibitors, EPS matrix disruptors, phage therapy, nanotechnology, and synergistic drug combinations. The novelty of this review lies in its effort to understand biofilm biology to identify key intervention points and organize therapeutic strategies according to their biological, chemical or physical nature. Emphasis is also placed on combined approaches that simultaneously target multiple components of the biofilm structure.

Expert opinion: Despite significant in vitro progress, most antibiofilm strategies remain experimental. Translating these findings into clinical applications requires standardization, in vivo validation, and regulatory alignment. A multidisciplinary approach integrating different agents and targeted drug delivery systems holds promise for improving patient outcomes.

Introduction: A critical challenge in providing effective medical care for individuals in opioid agonist treatment (OAT) for opioid use disorder is the effective management of acute and chronic pain. While pain commonly co-occurs with opioid use disorder, there is limited research to guide effective management of pain in this population.

Areas covered: We first provide an overview of the etiology and treatment of acute and chronic pain, highlighting areas of complexity for patients receiving OAT. We then describe the search strategy, which involved a date-inclusive search for relevant terms in PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials. After summarizing the results of this search on the evidence for pharmacological and behavioral treatments of acute and chronic pain for individuals on OAT, we conclude with a discussion of these findings and a summarized expert opinion on the state of the evidence.

Expert opinion: The evidence suggests that while research on effective treatment of acute and chronic pain in individuals in OAT is limited, promising work is ongoing to translate existing treatments, particularly behavioral treatments for chronic pain, to support this population. However, further research is warranted, particularly regarding pharmacological options.