Expert Opinion on Pharmacotherapy最新文献

Introduction: Myelofibrosis (MF) is a clonal hematological disorder characterized by bone marrow fibrosis, splenomegaly, and inflammatory cytokine dysregulation. While the role of steroids in MF is not fully defined, their anti-inflammatory properties may offer therapeutic benefits, particularly in managing anemia and other cytopenias. Steroids exert their effects by suppressing pro-inflammatory cytokines such as IL1, IL6, and TNF, and by enhancing anti-inflammatory cytokines like IL4 and IL10. Elevated levels of IL6 and other cytokines in MF are associated with anemia and poor prognosis, suggesting that steroid therapy could mitigate these effects.

Areas covered: In this manuscript, we review clinical studies which evaluated the safety and efficacy of steroids in MF patients. Moreover, we examine clinical data of the combination of steroids with immunomodulatory agents and JAK inhibitors. Our literature search consisted of an extensive review of PubMed and clinicaltrials.gov.

Expert opinion: The role of steroids in the management of MF remains poorly defined, though emerging evidence suggests a potential therapeutic benefit, particularly in managing anemia and other cytopenias. The combination with IMIDs has also yielded positive outcomes as demonstrated in several studies. Steroids may also play a crucial role in managing cytopenias in MF patients receiving JAKi.

Introduction: Rheumatoid arthritis (RA) poses significant healthcare challenges in Latin America (LA) due to its high prevalence and unique healthcare dynamics. Despite global advancements, LA faces specific hurdles in effectively managing RA.

Areas covered: This review examines RA epidemiology, treatment strategies, and clinical challenges in LA. RA prevalence varies, with higher rates among indigenous populations. While conventional disease-modifying antirheumatic drugs (csDMARDs) are recommended as first-line therapy, access remains inconsistent. Biologics and targeted synthetic DMARDs are available, but biosimilars have limited accessibility, with drug prices varying significantly. Key barriers include supply interruptions, diagnosis delays, and high non-adherence rates driven by socioeconomic factors. A severe shortage of rheumatologists, particularly in rural areas, affects patient care. Cardiovascular events, comorbidities, and endemic infections further complicate RA management.

Expert opinion: Although RA care in LA has improved through better use of csDMARDs and advanced treatments, major challenges persist, such as a shortage of specialists, limited medical education, and fragmented healthcare systems. Expanding training programs, enhancing telemedicine, and ensuring drug supply continuity are essential. Strengthening clinical research, improving access to affordable treatments, and developing comprehensive, region-specific strategies are crucial to closing the gap between LA and more developed regions in RA care..

Introduction: Pimavanserin is an efficacious, atypical neuroleptic. It ameliorates the frequency and severity of hallucinations and delusions in patients with Parkinson's disease with psychosis. Most antipsychotic drugs directly block dopamine receptors and thus worsen motor behavior. In contrast, pimavanserin reduces the activity of excitatory serotonin receptor subtypes. They stimulate dopaminergic pathways in the mesolimbic system. As a result, onset of psychosis may occur particularly in patients on a chronic dopamine-substituting treatment regimen, like in Parkinson's disease.

Areas covered: This narrative drug evaluation describes the properties and effects of pimavanserin. It is approved for the treatment of psychosis in Parkinson's disease. A literature search was performed using the terms dopamine, levodopa, psychosis, and Parkinson's disease without standardized selection of cited references.

Expert opinion: An essential advantage of pimavanserin is the focus in the pivotal trials on the treatment of psychosis in patients with Parkinson's disease. Main competitors for the use in clinical practice are the atypical neuroleptic compounds quetiapine and clozapine. Both share considerable structural and pharmacological similarities, i.e. certain anticholinergic properties. They are recommended in guidelines. Once pimavanserin will become available as a generic drug, its use will probably increase worldwide.

Introduction: A substantial majority of patients diagnosed with metastatic breast cancer consists of individuals 65-year-old or above. Emerging treatment approaches, which utilize genomics-guided therapy and innovative biomarkers, are currently in development. Given the numerous choices in the metastatic context, it is necessary to adopt a personalized approach to decision-making for these patients.

Areas covered: The authors provide a comprehensive analysis of the existing literature on the use of systemic anticancer treatments in older women, specifically those aged 65 and above, who have metastatic breast cancer, focusing on the reported effectiveness and adverse effects of these treatments in this population.

Expert opinion: The evidence to treat older patients with metastatic breast cancer primarily relies on subgroup analyses, whose interpretation should be approached with caution. In several clinical trials subgroup analysis, it has been observed that this population seem to have comparable benefits and toxicities to younger patients, but real-world data have showed older women exhibit worse rates of survival compared to younger women. Multiple factors are likely involved in this, but we postulate this is related to lower rates of guideline concordant, and factors such as comorbidity, lack of social supports, malnutrition, and geriatric factors like frailty and/or vulnerability. This underscores the importance of a broader assessment for patients with a geriatric perspective and involvement of multi-disciplinary team.

Introduction: In primary biliary cholangitis (PBC), approximately 40% of the patients respond incompletely to first-line treatment with ursodeoxycholic acid (UDCA), resulting in a poorer prognosis. Although obeticholic acid (OCA) is approved as a second-line therapy, it is not well-tolerated by patients with significant itching or advanced cirrhosis. Peroxisome proliferator-activated receptor (PPAR) agonists, including fibrates traditionally known as antihyperlipidemic agents, have emerged as potent alternatives for treating PBC patients with an incomplete response to UDCA.

Areas covered: This article provides a detailed overview of the mechanisms of PPAR agonists and evaluates their efficacy and adverse events, focusing on findings from recent phase III clinical trials.

Expert opinion: PPAR agonists are significant alternatives in the treatment of PBC, showing the potential to enhance biochemical responses, reduce mortality, and alleviate pruritus. Long-term outcomes for PBC patients, particularly those with advanced disease, and longitudinal data on the antipruritic effects of PPAR agonists require further investigation. Combining PPAR agonists with other treatments and advancing personalized approaches may enhance therapeutic efficacy and patient outcomes. This study provides future perspectives on the roles of PPAR agonists in PBC management.

Introduction: Primary sclerosing cholangitis (PSC) is the most specific hepatobiliary extraintestinal manifestation in inflammatory bowel disease (IBD). PSC ultimately has a poor prognosis, with disease progression resulting in liver cirrhosis and subsequent liver failure. While there is current data for the medical management of IBD, the optimal approach for concurrent PSC-IBD is unclear.

Areas covered: This review focuses on the current literature of pharmacotherapy in the PSC-IBD population including anti-tumor necrosis factor agents, vedolizumab, JAK inhibitors, IL-12/23 inhibitors, and thiopurines. Regarding PSC-IBD, it focuses on effectiveness of IBD therapies on liver biochemistry and IBD activity as well as the advent of clinically relevant liver outcomes and safety. The authors also address the need for further advances in research.

Expert opinion: The longer-term data for pharmacological management for IBD is well established. In the concomitant PSC-IBD population there is no drug to date that has effectively reduced disease related morbidity and mortality outcomes. There are limitations in the current, mostly retrospective data on IBD drugs in PSC-IBD with respect to samples sizes, heterogenous outcomes, and lack of a high-quality surrogate endpoint in PSC. However, current data for adalimumab offers encouraging results which require further exploration with larger prospective studies.

Introduction: Chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL), characterized by its monoclonal lymphoproliferative nature, is an indolent but incurable malignancy. The treatment landscape of CLL/SLL has drastically transformed in the last decade since the introduction of targeted therapy and immune-effector T-cell therapy. The paradigm shift from chemoimmunotherapy to targeted and cellular therapies was largely driven by improved efficacy and safety. With the success of targeted therapies, novel agents and combinations are rapidly emerging on the horizon.

Areas covered: In this review, we will summarize clinical evidence supporting current and emerging therapies with emphasis on investigational therapies and novel combinations of commercial agents. Clinical trials were identified via clinicaltrials.gov, and a PubMed literature search was last performed in June 2024.

Expert opinion: With the availability of more effective and better-tolerated treatments for CLL/SLL, the role of early intervention should be further investigated due to its potential to alter disease course, delay progression, and improve overall survival rates. With many highly effective agents and combinations expected to become commercially available, attention to safety profiles and careful selection of patients for each treatment will be critical, with consideration of comorbidities, logistical issues, and financial burden of treatment.