Expert Opinion on Pharmacotherapy最新文献

Introduction: Alcohol use disorder (AUD) is present in the majority of patients with alcohol-associated liver disease (ALD), which leads to about 50% of cirrhosis-related hospitalizations and over 25% of deaths worldwide. Patients with ALD often present at an advanced stage, like cirrhosis with its complications and alcohol-associated hepatitis (AH), which has high short-term mortality. Current treatments are limited, with the limited benefit of glucocorticoids only in the short-term among patients with AH, highlighting an urgent need for novel therapies.

Areas covered: This review applies the PIRO (Predisposition, Injury, Response, Organ dysfunction) concept to ALD, understanding an ongoing process of liver damage, and opportunities to address and halt the progression. We also highlight the significance of treating AUD to improve long-term outcomes in ALD.

Expert opinion: Personalized therapies targeting specific genetic profiles and multiple pathogenic pathways are crucial in managing ALD. Emerging therapies like gut-liver-brain axis modulators like fecal microbiota transplant and probiotics, interleukin-22, granulocyte-colony stimulating factor (G-CSF) and stem cells, epigenetic regulators of inflammation and regeneration are encouraging with the potential of efficacy in patients with ALD. Liver transplantation (LT) is a definitive therapy for advanced cirrhosis with increasing impetus on early LT select patients with active alcohol use.

Introduction: Persistent genital arousal disorder/genitopelvic dysesthesia (PGAD/GPD) is a rare, yet debilitating disease, which has been included in ICD-11. Pharmacotherapy in PGAD/GPD is a mixed blessing - drugs may either alleviate symptoms or worsen/induce them. Therefore, we aim at offering both an overview of pharmacological approaches to treat this disorder, including treatment failures, and to highlight drugs that may induce or worsen symptoms. We include all available data published so far as well as data from an own registry.

Areas covered: The international registries have not recorded any completed or ongoing trials on pharmacotherapy of PGAD/GPD. We refer to case reports, case series, online surveys, and data from our own registry that includes 90 subjects with PGAD/GPD.

Expert opinion: There is weak evidence (level 4) that some drugs such as SSRIs, SNRIs, cannabinoids, and anticonvulsants (pregabalin and gapabentin) may alleviate symptoms in PGAD/GPD. However, serotonergic drugs may also induce or worsen PGAD/GPD during administration or termination, as observed in 28% of cases. In conclusion, the pharmacotherapy of PGAD/GPD is still in its infancy just like the etiopathological understanding of the disease. Clinicians should be aware of PGAD/GPD, conduct careful diagnostics, and discuss an individual treatment plan with the patient.

Introduction: Studies have shown the relative cardiovascular safety of hormone replacement therapy (HRT) for women in the general population. Evidence on women with diabetes remains scarce. We aimed to investigate the risk of cardiovascular disease (CVD) in menopausal women with diabetes who use HRT compared to non-users.

Methods: Search across Medline, Embase, Web of Sciences, and Cochrane databases up to November 2023 was conducted. We combined keywords of menopause, diabetes, HRT, and various CVD outcomes. Non-English studies, observational studies other than cohort and case-control, reviews, and conference abstracts were excluded. Bias was checked using validated risk-of-bias tools. Random-effects model was used to calculate pooled relative risks (RR) for similar outcomes.

Results: Out of 7625 identified articles, 19 (6 clinical trials and 13 observational studies) were included, primarily from Europe and the U.S.A. Most studies had moderate risk of bias. Meta-analysis of myocardial infarction (MI) risk from nine observational studies (n =  ~34,626) showed a pooled RR of 0.83 (95% CI 0.62-1.12). Limited data precluded meta-analysis for the clinical trials and other outcomes from observational studies.

Conclusions: Observational studies do not suggest an increased risk of MI in menopausal women with diabetes prescribed HRT. Further research with a more robust method is warranted to validate this finding.

Prospero registration number: CRD42023479335.

Introduction: Apolipoprotein (apo)C-III, a key regulator of plasma triglyceride (TG) levels, is a prime candidate for the treatment of hypertriglyceridemia (HTG), prevention of acute pancreatitis, and reduction of future atherosclerotic cardiovascular disease (ASCVD) events.

Areas covered: We discuss the role of apoC-III as a therapeutic target for HTG, describe the pharmacodynamics, pharmacokinetics, and metabolism of olezarsen, as well as report on the findings of recent clinical trials with this liver-directed APOC3 antisense oligonucleotide (ASO).

Expert opinion: Olezarsen, a GalNac-conjugated ASO targeting apoC-III, can reduce TG levels by ~ 50% in patients with extreme HTG due to familial chylomicronemia syndrome, as well as in patients with moderate HTG. Attention is now focused on whether olezarsen reduces ASCVD risk in patients with moderate and severe HTG. While olezarsen does cause elevations in liver enzymes, these changes are not clinically meaningful, and are not associated with thrombocytopenia, an issue with its predecessor, volanesorsen. The need for 4-weekly administration puts olezarsen at a disadvantage to competing injectables. Results from the CORE, CORE2, and ESSENCE phase III clinical trials in patients with severe HTG, expected in the second half of 2025, will help determine the requirement for a larger cardiovascular outcomes trial.

Introduction: Chronic obstructive pulmonary disease (COPD) is a common syndrome associated with smoking and environmental exposures coupled with genetic susceptibility. Recent major advancements in the treatment of COPD patients have become available.

Areas covered: New data on the role of classic bronchodilators, including short-acting and long-acting beta2-agonists and anti-muscarinic antagonists, in the treatment of COPD patients are discussed. Data promoting a more targeted approach to inhaled and systemic corticosteroid use in COPD are reviewed. Phosphodiesterase (PDE) inhibitors, including the recently approved PDE 3/4 inhibitor inhaled ensifentrine, are noted. Selective use of antibiotics can play a role in complex COPD patients. COPD patients with evidence of asthma-COPD overlap syndrome and type-two lymphocytic inflammatory-mediated airway constriction appear to respond to biologics, particularly the anti-IL-4/IL-3 antagonist monoclonal antibody, dupilumab.

Expert opinion: New therapeutic options have made the approach and treatment of the COPD patient much more complicated. These options tend to be very expensive. Attention to identifying the endotype and phenotype will help direct the pharmacotherapy.

Introduction: Onychomycosis is an infection of the nail bed and the nail plate. While oral antifungals are first-line for moderate-to-severe onychomycosis, topical efinaconazole 10% solution (JUBLIA®; Clenafin®) is effective and safe for mild-to-moderate severity onychomycosis. It is FDA-approved for patients aged 6 years and above.

Areas covered: This literature review includes pharmacokinetics, microbiology, efficacy, safety, and post-marketing surveillance. It demonstrates consistent safety and efficacy across diverse patient demographics and comorbidities, including pediatric, diabetic and the elderly populations, without systemic side effects or drug interactions.

Expert opinion: Efinaconazole 10% solution is an important addition to the armamentarium of therapies available to treat onychomycosis. Certain subgroups respond particularly well: females versus males, children versus adults, early onset onychomycosis (<1-year disease), those with mild onychomycosis (≤25% nail involvement), absence of tinea pedis, and thin nail plates at baseline (<1 mm thickness). Efinaconazole 10% solution is effective in diabetics and has demonstrated efficacy against dermatophytomas. Efinaconazole may be a consideration when terbinafine resistance is a concern, due to its different target of action.

Introduction: Updated guidelines for heart failure with reduced ejection fraction (HFrEF) and acute decompensation have improved outcomes, but ongoing efforts are focused on uncovering new evidence and developing novel therapies. This review examines the limitations of current treatments and the potential impact of emerging therapies.

Areas covered: A literature search focused on studies investigating drugs for HFrEF. We review recent clinical trials and emerging therapies to assess evidence strength, explore guideline updates, and identify strategies to optimize patient outcomes.

Expert opinion: The HFrEF treatment landscape is rapidly evolving, with advances in therapies like sodium/glucose cotransporter inhibitors and sacubitril-valsartan. Though managing acute decompensated heart failure remains challenging, recent trials suggest improvements in diuretic strategies and anti-inflammatory treatments. Ongoing research is essential for validating these therapies and incorporating them into standard practice.

Introduction: Antidepressants and menopause are risk factors which are independently associated with an increased risk of fractures. This review aims to investigate the risk of fragility fractures in women aged 40 and older and prescribed antidepressants.

Methods: A literature search was conducted using PubMed, Ovid Embase, Ovid PsychINFO, Web of Science, and Scopus from inception to 1 June 2024. Relevant citations were identified and screened against our inclusion/exclusion criteria. The study population comprised women over 40 years. The risk of fragility fractures was compared between users and non-users of antidepressants. Risk of bias assessment was carried out using the ROBINS-I tool. A meta-analysis of cohort studies was performed to assess fracture risk associated with prescribing of any antidepressant agents, and SSRIs specifically.

Results: Of the 3,676 articles retrieved, five observational studies were found eligible for inclusion (n = 1,240,354). In a meta-analysis of 4 studies, an increased risk of fractures in women was associated with the prescribing of antidepressants (HR = 1.62, 95% CI: 1.15-2.28; I² = 96.50%) and SSRIs in particular (HR = 1.36, 95% CI: 1.20-1.55; I² = 40.32%).

Conclusions: Findings from this review suggest that prescribing of antidepressants is associated with an increased risk of fractures in women aged 40 and older. Substantial heterogeneity between studies may have affected the results of the meta-analysis.