Expert Opinion on Pharmacotherapy最新文献

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.

Introduction: Sleep dysfunction occurs in various forms and is a bothersome and intrusive non-motor symptom of Parkinson's disease (PD). Frequently undiagnosed, their poor management can have a great impact on the quality of life of PD patients and their caregivers.

Areas covered: This article covers the safety and efficacy of pharmacological strategies for the management of the most frequent sleep disturbances in Parkinson's disease. Non-pharmacological aspects are also discussed, but these are not the main focus. Literature searches using electronic databases (Medline, Cochrane Library) and systematic checking of references from review articles/other reports were performed.

Expert opinion: Melatonin and clonazepam are the most commonly used therapies for the management of REM sleep behavior disorder (RBD). The most used pharmacological wake-promoting agents in the treatment of excessive daytime sleepiness (EDS) are modafinil and caffeine. Poor nocturnal sleep quality is usually linked to EDS, thus proper sleep hygiene is recommended. As nocturnal motor symptoms are commonly associated with sleep fragmentation and early morning off, optimization of dopaminergic treatment during nighttime is highly recommended for the proper management of insomnia. Further interventions include eszopiclone and melatonin for the management of insomnia. Therapeutic options for restless legs syndrome (RLS) include calcium channel alpha-2-delta ligands and low-dose dopamine agonists (DA). Further confirmatory evidence is needed before the general recommendation of these treatments.

Introduction: Infertility related to polycystic ovary syndrome (PCOS) represents a significant challenge for women of reproductive age. Over the last few years, evidence-based medicine has driven new approaches for treating infertility in patients with PCOS, changing rapidly and deeply the clinical practice.

Areas covered: The authors provide an in-depth examination of recent developments in drug treatment strategies that have impacted the clinical practice and changed the previous approach to infertility in patients with PCOS.

Expert opinion: The authors identify four primary areas of interest that have impacted clinical practice in the last few years. Specifically, they discuss the current role of metformin administration in women with PCOS and infertility, the choice for using clomiphene citrate or letrozole as first-line treatment for ovulation induction, the use of new gonadotropin formulations for in vitro fertilization (IVF) program, and the elective embryo transfer in IVF cycles as golden standard treatment for patients with PCOS at high-risk for ovarian hyperstimulation syndrome.

Introduction: Acne vulgaris is a chronic inflammatory disease of the pilosebaceous unit that affects approximately 9.4% of the global population. Current treatment strategies aim to target as many pathogenic factors involved in the appearance of acne lesions and are centered on a systematic treatment escalation based on disease severity, extension, and treatment response, starting with topical treatments for mild cases and progressing over to systemic therapies in more severe cases. A literature search, which included clinical guidelines, clinical studies, and review articles on acne treatment and maintenance, was conducted to review the pharmacological approaches currently available to treat this disease.

Areas covered: Topical therapies such as topical retinoids, benzoyl peroxide, azelaic acid, salicylic acid, topical antibiotics, and clascoterone, as well as systemic treatments such as oral antibiotics and isotretinoin are discussed in detail. Combined oral contraceptives and spironolactone will not be discussed in this article.

Expert opinion: There is a need for a blockbuster acne drug that simultaneously targets the four main pathogenic factors involved in the appearance of acne lesions while presenting with minimal side effects. Until such a drug exists, combination therapy will remain the standard of treatment for most acne patients.

Introduction: Heterotopic ossification (HO), acquired or hereditary, is a diverse pathological condition defined by the production of extraskeletal bone in muscles, soft tissues, and connective tissues. Acquired HO is relatively prevalent and develops mostly in response to trauma, although its etiology is unknown. Genetic forms provide insight into the pathobiological mechanisms of this disorder. Fibrodysplasia ossificans progressiva (FOP) is a rare hereditary form of HO that can have a significant impact on affected individuals. FOP steadily weakens affected subjects and increases their risk of death.

Areas covered: The U.S. Food and Drug Administration has recently approved the retinoid palovarotene as the first compound to treat heterotopic ossification in patients with FOP. This review provides a comprehensive overview of current and potential future pharmacotherapeutic options and their modes of action. The online databases PubMed, Cochrane Library, Web of Science, and ClinicalTrials.gov were searched using the terms 'heterotopic ossification' and 'fibrodysplasia ossificans progressiva' or synonyms, with a special focus over the last 5 years of publications.

Expert opinion: Approval of palovarotene, as the first retinoid indicated for reduction in the volume of new HO, may revolutionize the therapeutic landscape. However, long-term safety and efficacy data for palovarotene are currently lacking.

Introduction: Heart failure (HF) is a global health challenge that requires a multidisciplinary approach. Despite recent advances in pharmacological and interventional therapy, morbidity and mortality in these patients remain high. For this reason, and because of its interplay with other cardiovascular and non-cardiovascular diseases, HF represents a major area of research, with new trials being published every year and international guidelines constantly updated.

Areas covered: The authors review the current status and possible future developments in HF pharmacotherapy.

Expert opinion: The treatment of HF has made significant advances in recent years, and the current recommendations are based on large outcome trials. This has led to significant reductions in both mortality and morbidity, but the death rate remains unacceptably high. In this context, a patient-centered approach that considers comorbidities and specific clinical scenarios when dosing HF medication is essential. Prevention of hospital admissions for cardiac decompensation is of utmost importance in patients with HF as is the enablement of activities of daily living, an endpoint which has only recently been incorporated into major HF trials.