Expert Opinion on Pharmacotherapy最新文献

Introduction: This study evaluated the impact of anti-inflammatory and analgesic agents on managing pain and sensitivity related to dental bleaching.

Methods: A PROSPERO-registered systematic review (CRD42024528788) searched PubMed, Scopus, Web of Science, LILACS, EBSCOhost, LIVIVO, Embase, and Grey literature (Google Scholar) up to March 2024. From 3,185 articles screened, 16 placebo-controlled RCTs involving 823 patients were included. NSAIDs were the most commonly used drugs, with some studies incorporating corticosteroids. Risk of Bias (RoB) was assessed using Rob-2, and a meta-analysis evaluated mean differences and relative risks across subgroups. GRADE-pro assessed evidence certainty.

Results: Findings revealed no significant improvement in pain or sensitivity scores (VAS: p = 0.770; NRS: p = 0.980) or tooth sensitivity incidence (p = 0.750) compared to placebo. However, one hour post-bleaching, the intervention group showed a slight VAS score reduction (mean difference: -0.49, CI95% = -0.83 to -0.16; p = 0.004). Whitening results (ΔE: p = 0.140) and NSGU perception showed no differences, but the VITA scale slightly favored the placebo (p = 0.030). Ibuprofen or paracetamol-plus-codeine were the only that showed any clinical benefit.

Conclusions: anti-inflammatory or analgesic agents provided minimal benefit for controlling post-bleaching pain/sensitivity reducing 0.49-VAS-scores (clinically insignificant). There is need of optimize pain management in dental bleaching especially focusing on COX-2 selective NSAIDs.

Introduction: The aim of treatment in very low-, low- and intermediate-1-risk myelodysplastic syndrome (MDS) is mainly to relieve symptoms due to cytopenias. Only a few therapeutic drugs are currently available, but novel drugs are under clinical investigations. In this setting, imetelstat, a telomerase inhibitor, is a promising new agent.

Areas covered: This review summarizes promising emerging strategies using imetelstat for the treatment of lower-risk MDS.

Expert opinion: Favorable results were demonstrated in the IMerge phase 3 clinical trial using imetelstat in transfusion-dependent patients with lower-risk MDS relapsed or refractory to erythropoiesis-stimulating agents (ESAs). This study led to imetelstat approval by the United States Food and Drug Administration (FDA) in June 2024.

Introduction: Systemic sclerosis (SSc) represents a complex, multisystem rheumatologic disorder characterized by immune dysregulation, vascular dysfunction, and multi-organ fibrosis. This review discusses the efficacy of the available therapeutic options and the significance of developing effective strategies against its varied manifestations, pivotal to improving patient outcomes.

Areas covered: The review elaborates on the pharmacological treatments available for managing key manifestations of SSc, including skin and lung involvement, and vascular complications, as well as the most recent findings in the field. We evaluated recent literature and clinical trials from the past decade, as well as most recent guidelines from entities like EULAR and the ACR, to provide a comprehensive overview of current management strategies.

Expert opinion: Despite advancements in therapeutic options, SSc remains a challenging disease to manage due to its complexity, our relatively limited understanding of disease pathogenesis, and its severe impact on quality of life. The development of targeted therapies and the refinement of existing treatment protocols offer hope for better management. Future research should focus on personalized medicine approaches and refining treatment algorithms to optimize outcomes for patients.

Introduction: The use of hormonal treatment for the vasomotor symptoms (VSM) associated with the menopause is back in favor, as the adverse effects reported in the early 2000s have been dispelled. However, many women are still reluctant to use, or have contraindications to, hormonal therapy. Elinzanetant is a combined neurokinin (NK)-1 and -3 receptor antagonist, being trialed for menopausal symptoms.

Area covered: A combination of OASIS 1 and 2 in the menopause showed that elinzanetant caused a reduction in the frequency and intensity of VSM and may also independently reduce sleep disturbances. Adverse effects were low with elinzanetant.

Expert opinion: Further study is needed to clarify whether elinzanetant reduces sleep disturbance and whether this is due to antagonism at NK-1 receptors. If further studies support OASIS 1 and 2, elinzanetant maybe considered for use in hot flashes associated with the menopause, in subjects where hormonal therapy is contraindicated or not accepted. Fezolinetant, an NK-3 receptor antagonist, has recently been registered for VSM associated with the menopause. Fezolinetant does not have a clear-cut effect on sleep disturbances independent of VMS. Only, if elinzanetant can be shown to independently reduce sleep disturbances, it may have an advantage over fezolinetant.

Introduction: Major global guidelines currently recommend sodium-glucose co-transporter-2 inhibitors (SGLT-2i) as the first-line agent in people with type 2 diabetes (T2D) who have either established cardiovascular disease (eCVD), heart failure (HF), or chronic kidney disease (CKD), regardless of baseline glycated hemoglobin (HbA1c). Moreover, SGLT-2i are currently included in guideline-directed medical therapy as one of the pillars for people with HF and CKD, regardless of T2D. These recommendations are based on positive cardio-renal outcomes from several randomized controlled trials (RCTs).

Areas covered: Following an extensive search in electronic databases of PubMed, Google Scholar, and clinicaltrials.gov, we critically analyzed the RCTs that assessed cardio-renal outcome trials of SGLT-2i and put a perspective on how SGLT-2i delivered an emphatic win for people with HF and CKD, with or without T2D.

Expert opinion: From thirteen high-quality RCTs, including five cardiovascular outcome trials, five HF outcome trials, three renal outcome trials, and a pooled meta-analysis, it is evident that SGLT-2i has delivered an emphatic win in people with HF and CKD, with or without T2D, with an acceptable safety profile. Ongoing RCTs shall further enlighten whether SGLT-2i will be effective in polycystic kidney disease, lupus nephritis, vasculitis, end-stage CKD with or without hemodialysis, and renal transplant.

Introduction: Oral mucosal toxicities are serious complications associated with conventional cytotoxic radiation and drug-based cancer regimens, and novel treatments such as immunotherapy and targeted agents. These toxicities, including oral mucositis, mammalian target of rapamycin inhibitor-associated stomatitis, oral immune-related adverse events, oral lichenoid lesions secondary to rituximab or imatinib, and geographic tongue associated with bevacizumab, sorafenib, sunitinib, or axitinib, can lead to significant morbidity, potentially compromising cancer treatment outcomes by necessitating treatment dose reductions, interruptions, or discontinuation.

Areas covered: This review discusses the epidemiology, clinical presentation, pathobiology, and current management strategies for these oral mucosal toxicities.

Expert opinion: With the evolution of novel cancer therapies, including immunotherapy and targeted agents, oral mucosal toxicities have become more prevalent, presenting significant management challenges. Advances in understanding the pathobiology of these complications have led to the development of promising therapeutic strategies. However, variability in patient responses underscores the need for precision medicine approaches that tailor treatments to individual molecular and immunological profiles. While the standardization of clinical trials has improved the comparability of interventions, therapies must be rigorously tested to ensure they do not interfere with the oncologic efficacy of cancer treatments. Ongoing research is essential to refine preventive and therapeutic approaches.

Introduction: Atopic dermatitis (AD) is a chronic inflammatory skin condition, rising in prevalence and significantly impacting quality of life. Janus kinase (JAK) inhibitors are small molecules targeting the JAK-STAT signaling pathway, responsible for immune response and cell proliferation. Therapy with topical JAK inhibitors (JAKinibs) improves AD itch and skin lesions and is well tolerated with no major side effects, making it an interesting novel therapy for AD.

Areas covered: This review provides a comprehensive look at the available research on topical JAK inhibitors, primarily for atopic dermatitis, based on clinical trial outcomes.

Expert opinion: In this review, we summarize research on topical JAKinibs, including ruxolitinib, tofacitinib, delgocitinib, cerdulatinib, and bredocitinib, which target multiple cytokine pathways and have been shown to reduce the itch and inflammation. Their low bioavailability contributes to infrequent and mild side effects. The main limitation of predominantly short-term studies is that the long-term effects of JAK inhibitor therapy are not yet fully known. The body of research is growing, and more information about their effectiveness and safety is being added each year.

Introduction: Worldwide, 15-40% of advanced-stage non-small cell lung cancers (NSCLCs) have an activating EGFR mutation, treatable with tyrosine-kinase inhibitors (TKIs) such as osimertinib, recommended as front-line therapy. Despite the efficacy of first-line osimertinib, most patients will experience disease progression. Therefore, combining it with chemotherapy has become an area of interest.

Areas covered: Osimertinib is a third-generation EGFR-TKI that has extended survival in NSCLC patients with EGFR mutation. However, resistance eventually leads to treatment failure. This has driven the advancement of strategies to overcome resistance to osimertinib. In this setting, the FLAURA2 trial yielded positive results by combining osimertinib with chemotherapy. Additionally, a range of other approaches, including the use of bispecific antibodies and antibody-drug conjugates alongside third-generation EGFR-TKIs or chemotherapy, support the development of novel therapeutic combinations, some of which have already been approved for EGFR-mutated advanced NSCLC.

Expert opinion: Next to osimertinib monotherapy, expanded upfront treatment options for patients with EGFR-mutated advanced NSCLC require patient selection considering disease extent, toxicity and tolerability, dosing schedule and what the patient can expect through shared decision-making. Further studies are needed to identify the patients who will benefit the most from combination therapies and to sequence the new drugs into the treatment algorithm.