Expert Opinion on Pharmacotherapy最新文献

Introduction: Endometriosis affects 5% to 10% of reproductive age women and may be associated with severely painful and debilitating symptoms as well as infertility. Endometriosis involves hormonal fluctuations, angiogenesis, neurogenesis, vascular changes and neuroinflammatory processes. The neuroinflammatory component of endometriosis makes it a systemic disorder, similar to other chronic epithelial inflammatory conditions.

Areas covered: Inflammatory mediators, mast cells, macrophages, and glial cells play a role in endometriosis which can result in peripheral sensitization and central sensitization. There is overlap between chronic pelvic pain and endometriosis, but the two conditions are distinct. Effective treatment is based on a personalized approach using a variety of pharmacologic and other treatment options.

Expert opinion: Hormonal therapies are a first-line approach, but endometriosis is a challenging condition to manage. 'Add-back' hormonal therapy has been effective. Painful symptoms are likely caused by the interplay of multiple factors and there may be a neuropathic component. Analgesics and anticonvulsants may be appropriate. A holistic approach and multimodal treatments are likely to be most effective. In addition to pharmacologic treatment, there are surgical and alternative medicine options. Endometriosis may also have a psychological component.

Introduction: The concept that children are therapeutic orphans emerged in the 1960s, triggering eventually worldwide legislation to facilitate pediatric studies, called 'Pediatric Drug Development (PDD).' However, PDD's true aim is not better medicines for children but labels in minors; minors are not another species.

Areas covered: Absorption, distribution, metabolism, and excretion (ADME) differ in preterm newborns, but babies mature. With the exception of neonatology, the justifications for clinical, pharmacokinetic, and safety studies were and are exaggerated.

Expert opinion: PDD reflects an artificial regulatory challenge, reflecting mankind's transition into a world of effective new drugs compared to previous millennia when only materials taken from nature were available. Minors need dose assessment and proof of safety; there is a tendency to exaggerate the scope of pharmacokinetic and safety studies before and after the eighteenth birthday, potentially motivated not by industry's greed, but by researchers' desire for funding and regulatory authorities' desire for recognition, specifically as since 2007 the European Medicines Agency (EMA) augmented and expanded PDD: a new type of conflict of interest in medicines' administration and mainstream medical science.

Introduction: Pneumonia remains a significant global health challenge due to its high prevalence and mortality rate, and challenging treatment. This review explores the best strategies to optimize the antibiotic therapy for pneumonia in critically ill patients, focusing on pharmacokinetics, pharmacodynamics, and therapeutic data.

Areas covered: A review of scientific publications on severe pneumonia highlights the challenges of optimizing antibiotic use to improve lung diffusion, bacterial killing, and achieving PK/PD targets, emphasizing the need to understand microbiological epidemiology and MIC breakpoints. Key strategies like nebulization, therapeutic drug monitoring, and emerging technologies such as ELF TDM and nanomaterial-based drug delivery systems are essential for optimizing PK/PD outcomes and addressing antimicrobial resistance.

Expert opinion: Improving our understanding of pulmonary pharmacokinetics and optimizing their tissue diffusion are instrumental for achieving precision antibiotic therapy for severe pneumonia. By addressing current limitations and embracing interdisciplinary collaboration, we can pave the way for more efficient personalized approaches in infectious disease management.

Introduction: Androgen deprivation therapy consists of the cornerstone of prostate cancer medical treatment. Until recently, castration of hypothalamus-hypophysis-gonadal axial was based on injectable medical agents. A few years ago, a novel per os administered GnRH antagonist was approved leading testosterone to castration level. Relugolix was approved by FDA in 2020, and it is the first per os administered GnRH antagonist. The present study is a literature review of the efficacy, safety and clinical perspectives of relugolix.

Areas covered: A literature narrative review was conducted using PubMed/MEDLINE, Scopus, and the Cochrane library. Studies written in English language, considering efficacy, safety and cost-effectiveness of relugolix compared with other androgen deprivation therapies were included in the review.

Expert opinion: Recent studies have examined efficacy of relugolix revealing a testosterone suppression percentage of 78.4% after 48 weeks from treatment initiation. Moreover, relugolix has been associated with less major cardiovascular events as well as better rate of testosterone recovery after treatment completion compared with the GnRH agonists. However, there is no head-to-head trial comparing relugolix with injectable GnRH antagonists, so far. As a result, a trial comparing the methods of antagonists' administration should be performed in the future.

Introduction: Gastroesophageal reflux disease (GERD) is a common debilitating chronic disease presenting in two main forms based on esophageal mucosal appearance, the erosive reflux disease (ERD) and the non-erosive reflux disease (NERD). Acid secretion is a key factor in the disease pathogenesis and management. Potent acid-suppressant drugs have been manufactured since the mid of 1970s, initially with histamine-H₂-receptors antagonists, and later, inhibitors of the proton pump (H⁺-K⁺-ATPase).More recently, potassium-competitive acid blockers (p-CABs), particularlyVonoprazan, have been introduced. Vonoprazan has shown high efficacy and safety profiles and exhibits several advantages that allow to overcome shortcomings of proton pump inhibitors (PPIs).

Areas covered: In this review, we provide an updated summary of Vonoprazan pharmacodynamics and its role in clinical practice for the management of erosive esophagitis and GERD-related heartburn. Moreover, we discuss characteristics of Vonoprazan that allow to bypass some limitations of the older PPIs.

Expert opinion: Long-term safety and efficacy of Vonoprazan have already been demonstrated for the induction and maintenance of ERD, preventing nocturnal acid breakthrough, reducing reflux symptoms in non-responder to standard therapy. Ongoing and future studies are expected to further elucidate its long-term benefits and potential applications in other acid-related disorders.

Introduction: Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) has been introduced as a superior term to describe steatosis on a background of metabolic dysregulation and is slated to become the leading cause of HCC worldwide, as the incidence of metabolic comorbidities is increasing. As such, MASLD has evolved into an important public health issue, potentially leading to higher rates of liver mortality and end-stage liver disease. To this end, understanding the association between MASLD and HCC may allow for the identification of better interventions and novel therapeutic strategies.

Areas covered: The authors provide a review of current knowledge on HCC development among patients with MASLD, with insights into molecular pathways and current and future therapeutic strategies.

Expert opinion: MASLD has a strong association with the risk of HCC development, as metabolic comorbidities induce dysregulation in molecular pathways, leading to insulin-resistance, oxidative stress, and chronic inflammation, thus causing progression to cirrhosis and eventually to HCC. Therapeutic strategies focused on reducing diabetes-associated complications, as well as the prevalence of obesity and smoking can improve patient outcomes and reduce HCC incidence. Future studies on the molecular background of metabolic alterations may help devise new therapeutic approaches aiming to improve the current management of MASLD-HCC.

Introduction: Standard-of-care first-line treatments for paroxysmal nocturnal hemoglobinuria (PNH) include the anti-C5 therapies eculizumab and ravulizumab. However, persistent anemia, likely due to extravascular hemolysis, and reduced quality of life (QoL) due to frequent infusions remain concerns. Iptacopan is a first-in-class oral proximal complement inhibitor that targets factor B in the alternative pathway (upstream of C5), limiting intravascular and extravascular hemolysis.

Areas covered: In patients previously treated with anti-C5 therapies or naive to complement inhibitors, iptacopan 200 mg twice daily resulted in clinically meaningful results in the pivotal phase 3 APPLY-PNH (NCT04558918) and APPOINT-PNH (NCT04820530) trials. Treatment with iptacopan was safe, and no treatment-related adverse events led to discontinuation.

Expert opinion: APPLY-PNH and APPOINT-PNH reported clinically meaningful improvements in hemoglobin, bilirubin, and lactate dehydrogenase levels; transfusion avoidance; reticulocyte count; and fatigue. Iptacopan's safety profile was comparable to other complement inhibitors. Oral iptacopan therapy allows patients to avoid infusions, limit clinical visits, decrease medical costs, improve anemia that persists with other complement inhibitors, and improve QoL. Long-term follow-up will further assess infections, thrombosis, and breakthrough hemolysis. Before treatment, physicians need to discuss current therapeutic options with patients for shared decision-making. Guidelines are being created to assist healthcare professionals in this advancing field.

Introduction: Recent data question the use of aspirin as a bedrock of antiplatelet therapy in patients with arterial diseases. There are controversies regarding the efficacy of aspirin therapy with respect to specific demographic characteristics, dose and formulations, benefit in primary prevention, and duration in secondary prevention. Importantly, to balance the ischemic benefits and the risk of excessive bleeding following a coronary event, recent studies have investigated strategies to discontinue aspirin therapy and continue with P2Y₁₂ receptor inhibitor monotherapy. However, the precise time when to discontinue aspirin is still unresolved.

Areas covered: Evidence from recent studies evaluating the role of aspirin in primary and secondary prevention studies was collected from a selective literature search. In this review, the authors discuss current recommendations, large-scale studies of aspirin therapy, controversies, and potential future opportunities for aspirin therapy.

Expert opinion: With the new evidence showing lower bleeding risk with aspirin-free strategies in both primary and secondary prevention studies, the role of aspirin is being revaluated with P2Y₁₂ receptor inhibitor monotherapy. The potential benefits of novel aspirin formulations and alternative delivery methods, such as inhaled aspirin, are undergoing much-needed investigation with the goal of optimizing care for a wide range of patients.

Introduction: Desmoid tumor (DT) is a rare, locally aggressive, mesenchymal neoplasm that can arise at any site in the body. Medical therapies play a major role for DT's patients requiring treatment. A novel systemic approach has recently emerged with Nirogacestat, a γ-secretase inhibitor targeting the NOTCH signaling pathway.

Areas covered: Nirogacestat is the first drug in its class to receive approval from the Food and Drug Administration (FDA) and is the first FDA-approved treatment specifically for DTs. We reviewed the data leading to its discovery, including its mechanism of action, pharmacological properties, clinical efficacy, and its positioning within the current treatment armamentarium for DTs.

Expert opinion: High-quality evidence for systemic therapies in the management of DTs remains an unmet need. Nirogacestat now joins sorafenib as the only drugs with efficacy in DTs demonstrated by randomized phase 3 studies. Currently, there are no comparative trials of the available systemic therapies. Therefore, physicians should consider factors such as drug accessibility, cost, toxicity profile, comorbidities, and patient preferences when selecting treatment. Long-term efficacy and safety data will be essential for evaluating the duration of treatment response and monitoring late-onset side effects of Nirogacestat.