Expert Opinion on Pharmacotherapy最新文献

Introduction: The annual incidence of Philadelphia chromosome-positive chronic myeloid leukemia (CML) is 1 per 100,000 pregnancies. The management of CML during pregnancy poses challenges due to the teratogenicity risk associated with the BCR:ABL1 tyrosine kinase inhibitors (TKIs).

Areas covered: In this review, we discuss the possible fetotoxicity of CML therapies during pregnancy including TKIs and non TKI-based regimens, and the treatment strategies for pregnant patients. A literature search was conducted using PubMed/MEDLINE, Embase, and Web of Science for studies published from January 2000 through December 2025. Articles addressing the management of CML during pregnancy, including maternal and fetal outcomes, TKI exposure, and therapeutic strategies, were reviewed.

Expert opinion: The diagnosis of CML during pregnancy is rare, and evidence guiding optimal management remains limited. Current recommendations categorize treatments into TKIs and non TKI-based therapies. All TKIs are not recommended during the first trimester due to their risk of teratogenesis, but imatinib and nilotinib may be cautiously used from Weeks 16-18 onward. Non-TKI therapies, such as hydroxyurea and interferon-α, are considered safe throughout pregnancy. Data on ponatinib and asciminib remain insufficient to allow the safe use of these agents during pregnancy. Future research should aim to improve treatment-free remission rates through novel agents and combination strategies to allow a higher proportion of younger patients to discontinue therapy. Clinicians should always counsel women on pregnancy risks during therapy while reassuring male patients of TKI safety when fathering children.

Introduction: The growing spread of resistance development among Gram-negative pathogens currently represents a worrisome issue for public health. Adopting proper corrective actions aimed at increasing the likelihood of preserving the efficacy of these novel agents by minimizing the propensity risk of resistance development is a compelling need for overcoming this issue.

Areas covered: This review provides an updated critical reappraisal focused on preclinical and clinical evidence supporting the usefulness of an aggressive beta-lactams pharmacokinetic/pharmacodynamic (PK/PD) target for overcoming resistance occurrence in Gram-negative infections. A literature search was carried out on PubMed-MEDLINE from January 2015 to December 2025.

Expert opinion: Identifying proper strategies allowing to minimize the risk of resistance emergence among Gram-negative pathogens represents a compelling unmet clinical need. From a pharmacological perspective, optimizing the use of novel beta-lactams and beta-lactam/beta-lactamase inhibitor combinations based on PK/PD principles may represent a valuable approach for overcoming antimicrobial resistance. Both preclinical and clinical evidence suggested that attaining an aggressive PK/PD target may allow to prevent resistance emergence to beta-lactams. Delivering beta-lactams by prolonged or continuous infusion and optimizing plasma exposure by means of a therapeutic drug monitoring-guided approach could be helpful tools for maximizing the likelihood of attaining aggressive PK/PD targets with beta-lactams.

Introduction: Hyperhidrosis is a functional disorder characterized by excessive sweat production beyond physiological needs for thermoregulation, significantly impairing quality of life, affecting physical comfort, psychological well-being, social interactions, and work productivity.

Areas covered: This review focuses on evidence-based therapeutic options for hyperhidrosis. Topical treatments (glycopyrronium bromide, glycopyrronium tosylate, aluminum salts), systemic therapy (oral oxybutynin), injectable approaches (botulinum toxin), iontophoresis, and surgical interventions (local excision, sympathectomy) are discussed in detail. Clinical studies demonstrate that topical and systemic agents are effective for localized and multisite forms, respectively, while botulinum toxin offers strong efficacy for focal hyperhidrosis. The review also addresses combination strategies, treatment tolerability, cost-effectiveness, and patient-centered approaches.

Expert opinion: Managing hyperhidrosis requires a nuanced, individualized strategy that balances symptom control, safety, patient preferences, and quality of life. Combination therapies and flexible treatment sequencing can reduce early reliance on invasive procedures. Despite therapeutic advances, widespread adoption is limited by heterogeneous guidelines, off-label use, and under-recognition of psychosocial impact. Future research should focus on prospective, large-cohort studies, standardized outcome measures, and development of selective, well-tolerated therapies. While a universal cure is unlikely, sustained symptom control and meaningful improvement in quality of life represent realistic objectives.

Introduction: Myelodysplastic syndromes/neoplasms (MDS) comprise a heterogeneous group of clonal myeloid malignancies characterized by ineffective hematopoiesis and a variably increased risk of progression to acute myeloid leukemia (AML). Higher-risk MDS, as defined by the revised- and molecular International Prognostic Scoring System, remains largely incurable except through allogeneic hematopoietic stem cell transplantation. Management continues to rely primarily on hypomethylating agents, which were approved nearly two decades ago and remain the cornerstone of therapy despite their modest efficacy.

Areas covered: Advances in molecular profiling and next-generation sequencing have greatly improved disease classification and prognostication tools. However, with the exception of IDH1 inhibitor ivosidenib, targeted therapies in higher-risk MDS remain the exception to the rule. Although numerous early-phase clinical trials have yielded promising signals, phase III trials have repeatedly failed to replicate these findings. This largely reflects the intrinsic biological complexity and heterogeneity of MDS, as well as logistical challenges in trial design and execution.

Expert opinion: Examining the history and evolution of investigational pharmacotherapy in higher-risk MDS may help identify where efforts to translate early phase successes into successful phase III trials have faltered. The expanding biological knowledge base and the design of better therapies will hopefully pave the way for future therapeutic breakthroughs.

Background: Evidence for low-dose oral minoxidil (LDOM) and topical minoxidil in male and female pattern hair loss (MPHL and FPHL), particularly around hair transplant surgery, lack standardization. This study developed consensus-based guidance for their use in these patients.

Methods: An international panel involving hair transplant surgeons used a three-round modified Delphi process (consensus ≥ 70%) to rate 47 items on baseline assessment, dosing, monitoring, peri-operative use, safety, and topical minoxidil.

Results: Panelists agreed that body weight and blood pressure should be checked before initiating LDOM, with additional individualized testing. Recommended adult starting doses were 1.25-2.5 mg/day for MPHL and 0.625-1.25 mg/day for FPHL, with maximum daily doses of 5 mg and 2.5 mg, respectively. Clinical response is expected within 4-6 months. Therapy maybe continued long-term if effective and well tolerated. After hair-transplant surgery, LDOM can generally be taken 1-3 days post-procedure. Topical minoxidil can be applied to the grafted area at 7-14 days post-transplant. Topical minoxidil 5% is effective at the frontal scalp and vertex. Minoxidil should be avoided during pregnancy/breastfeeding.

Conclusions: These consensus statements provide recommendations and a treatment algorithm for integrating LDOM and topical minoxidil into care of hair-transplant patients with pattern hair loss.

Introduction: Moderate-to-severe plaque psoriasis in the pediatric population represents a complex therapeutic challenge. Although the advent of biologic drugs (anti-TNF, anti-IL17) has revolutionized efficacy standards, there remains an unmet need for oral, safe therapeutic options that do not require regular monitoring. Apremilast, an oral phosphodiesterase 4 (PDE4) inhibitor, has recently been evaluated in this population.

Areas covered: This review analyzes the 16-week and 52-week results of the phase 3 SPROUT trials which evaluated the efficacy and safety of apremilast in children and adolescents (aged 6-17 years) with moderate-to-severe plaque psoriasis. Data show that apremilast offers significant improvement compared to placebo at Week 16, with a response profile maintained through Week 52.

Expert opinion: Although the efficacy of apremilast is lower compared to modern biologics (e.g. secukinumab, ixekizumab), the drug offers unique practical advantages: oral administration, absence of pre-treatment screening for tuberculosis and chronic hepatitis, and no requirement for laboratory monitoring. With patent expiration and the arrival of generics, apremilast may represent a potential cost-effective 'first-line systemic' option for pediatric patients who are not candidates for or are reluctant to accept injectable therapies.

Introduction: Direct oral anticoagulants (DOACs) are preferred as the first line oral anticoagulation therapy for atrial fibrillation and venous thromboembolism, given their superior efficacy and safety profile over vitamin K antagonists (VKAs). However, it can be challenging to select the optimal agent, dose or strategy in many clinical situations.

Areas covered: This narrative review summarizes the current recommendations for optimization of DOAC therapy and attempts to shed light from recent evidence where there is clinical uncertainty. Particular focus is given to patients with renal impairment or supranormal renal function, those at extremes of body weight and those with high bleeding risk. Also discussed is the conundrum of timing of anticoagulant reinitiation after major hemorrhage or ischemic stroke.

Expert opinion: DOAC use has expanded substantially since their introduction almost two decades ago. This is partially due to increased clinician familiarity with their use. However, simultaneous evidence has grown supporting their effectiveness in a wider range of patients, including patients with very high or very low body weight, as well as patients on regular hemodialysis. A greater awareness of these developments will allow more patients to benefit from the advantages of DOACs over other agents.

Introduction: Antibody-drug conjugates (ADCs) have revolutionized oncology, yet tumor microenvironment (TME) heterogeneity remains a major barrier. TME-targeted ADCs offer a paradigm shift by specifically modulating immunosuppressive cellular crosstalk and stromal components to overcome tumor evasion.

Areas covered: This review summarizes design strategies and clinical progress of TME-targeted ADCs. Literature was searched via PubMed and Embase (2015-2025), focusing on early-phase trials, safety profiles, and translational challenges in advanced solid tumors.

Expert opinion: The next decade will transition from broad TME disruption to precision engineering. AI-driven spatial omics will refine biomarker-led selection, identifying 'TME phenotypes' for tailored therapy. Emerging multi-immune-axis platforms, such as immunostimulatory antibody conjugates (ISACs) and bispecific ADCs, will transcend single-target limitations. We anticipate regulatory approvals of TME-targeted ADCs for 'cold' tumors within five years, serving as priming agents for immunotherapy. Within ten years, TME-targeted ADCs should migrate to neoadjuvant settings to 'normalize' the tumor ecosystem before surgery. This evolution from treatment in advanced settings to foundational curative therapy, using personalized ADC combinations tailored to individual immune landscapes, will be essential to overcome adaptive resistance and achieve long-term remission.

Introduction: Low-density lipoprotein cholesterol (LDL-C) is the major lipid target to reduce the risk of atherosclerotic cardiovascular disease (ASCVD) in patients with hypercholesterolemia and in those with mixed dyslipidemia. Lifestyle and diet modification should always be the first approach to management, but pharmacological intervention is often required.

Areas covered: This article discusses the current therapies to reduce LDL-C and introduces some of the new drugs in late-stage development. The articles reviewed were identified by a PubMed search up to the current time.

Expert opinion: Statins remain the primary therapy to reduce LDL-C, but statins are often insufficient to achieve the more aggressive LDL-C targets. Ezetimibe is the next recommended therapy to add, and bempedoic acid provides another oral drug that can be added or substituted for the statins. The injectable proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors are the most effective drugs in reducing LDL-C, but their uptake has not met expectations because of issues of cost and patients' reluctance to take injection therapy. The oral PCSK9 inhibitors in development and obicetrapib appear safe and very effective and if approved they should provide useful alternatives for reaching LDL-C goals but the problem of long-term adherence to therapy will remain.