Expert Opinion on Pharmacotherapy

Introduction: The global rise of multidrug-resistant (MDR) Gram-negative bacteria (GNB) has intensified the threat of chronic and hard-to-treat infections, many of which are associated with biofilm formation. These biofilms confer enhanced resistance to antimicrobials and immune responses, posing a major clinical challenge. Areas covered: This review summarizes the biological mechanisms of biofilm formation in GNB and explores both traditional and novel strategies for their prevention and eradication. The literature search covered peer-reviewed articles from major databases, focusing on therapeutic approaches such as quorum sensing inhibitors, EPS matrix disruptors, phage therapy, nanotechnology, and synergistic drug combinations. The novelty of this review lies in its effort to understand biofilm biology to identify key intervention points and organize therapeutic strategies according to their biological, chemical or physical nature. Emphasis is also placed on combined approaches that simultaneously target multiple components of the biofilm structure. Expert opinion: Despite significant in vitro progress, most antibiofilm strategies remain experimental. Translating these findings into clinical applications requires standardization, in vivo validation, and regulatory alignment. A multidisciplinary approach integrating different agents and targeted drug delivery systems holds promise for improving patient outcomes.

Introduction: Eosinophilic esophagitis (EoE) is an immune-mediated disease characterized by esophageal dysfunction and eosinophil rich inflammatory infiltrate. Its incidence is rising globally due to increased awareness, improved diagnostics, and environmental and genetic factors. EoE is driven by a Th2-mediated immune response to food and environmental allergens, leading to chronic inflammation, epithelial barrier dysfunction and progressive esophageal remodeling. Areas covered: This review explores pediatric EoE, focusing on epidemiology, pathogenesis, clinical presentation, diagnosis, and both standard and new treatment strategies. Symptoms vary by age, from feeding difficulties in infants to dysphagia and food impaction in older children. Diagnosis relies on clinical symptoms, endoscopic findings and histologic assessment. Standard treatments include dietary elimination, proton pump inhibitors and topical corticosteroids, while biologic therapies such as dupilumab offer targeted alternatives for refractory cases. Expert opinion: Future research focuses on optimizing treatment sequencing (step-up and step-down approach), exploring non-eosinophil-mediated inflammation, and enhancing noninvasive test to predict disease severity and phenotypes for better long-term management.

Introduction Tuberculosis (TB) remains a major infectious threat to global health, while type 2 diabetes mellitus (diabetes) has reached epidemic proportions in many regions of the world. In low-and-middle income countries (LMIC) and among indigenous and minority communities in high-income settings (HIC), these diseases also increasingly overlap posing new clinical and therapeutic challenges. Areas covered We searched PubMed/CINAHL/Web of Science/Scopus, Google Scholar up to 30 November 2024. While the Immuno-metabolic parallels between TB and Diabetes are underappreciated. Improved understanding of mechanisms may pave the way for novel therapeutic strategies, for example, using antidiabetic medications as adjuvant host-directed therapies (HDT) in active TB. We review the epidemiology of TB, diabetes and their combined comorbidity, their immune and metabolic mechanisms and clinical relevance as well as potential opportunities for general and targeted therapeutic intervention. Expert opinion Immunometabolic interaction between diabetes and tuberculosis is bidirectional. Underlying this interaction are shared inflammatory mechanisms. It follows that treatments for diabetes and its complication may be beneficial in tuberculosis and that the treatment of both active and latent tuberculosis may improve glycemic control. These interactions are amenable to investigation in experimental models, in human experimental medicine studies and in clinical trials. KEYWORDS: TB, diabetes mellitus, insulin resistance, inflammation, host-directed therapy

Introduction: Hypertensive left ventricular hypertrophy (HTN LVH) is a highly prevalent high-risk condition, and the recommendations for HTN LVH treatment are essentially unchanged for several decades. Areas covered: The current therapeutic approach to HTN LVH is to choose antihypertensive drugs according to their ability to reverse left ventricular (LV) remodeling. On the other hand, for the majority arterial hypertension (HTN) patients we should start treatment with a combination of different antihypertensive drugs. Therefore, the goal of antihypertensive treatment of HTN LVH should be adapted to the current recommendation in other parts of guidelines. The recommendation we need is not only which individual drug, but rather which combination of two antihypertensive agents is optimal for reversed LV remodeling. Expert opinion: In this paper, we pointed out that treatment recommendation for HTN LVH can be updated in a similar way as therapy for the whole HTN population - by recommending a combination of two or three antihypertensives in a single pill. Clinicians should be directly advised what is the first- and what the second-line combination of antihypertensives for HTN LVH in evidence-based medicine. Therefore, we suggest that combination treatment should be studied, compared and then recommended also for very prevalent higher-risk HTN LVH patients.

Introduction: Opioid use disorder (OUD) is recognized as a chronic, relapsing disorder with a high mortality and psychiatric and somatic comorbidity. Areas covered: Existing guidelines and meta-analyses on pharmacotherapy of opioid use disorder were reviewed. Opioid maintenance treatment (OMT) is the generally accepted first line treatment in OUD with oral methadone and buprenorphine being the gold standard. In recent years a number of novel opioids have been introduced into clinical practice including depot formulations of buprenorphine, retarded morphine and heroin (diacetylmorphine). The review refers to the different drugs available and gives an overview on clinical use, side effects, and efficacy in certain subgroups. Expert opinion: OMT is a success story with emerging new pharmacological options available. While oral methadone or buprenorphine still are the most suitable medications for many patients, depot formulations of buprenorphine may improve adherence and facilitate clinical management of many patients. Diacetylmorphine and retarded morphine are second line medications for treatment refractory patients. Future research may focus on responder characteristics for certain medications and efficacy in special subgroups as well as interaction of psychosocial and pharmacological treatments.

Introduction: A critical challenge in providing effective medical care for individuals in opioid agonist treatment (OAT) for opioid use disorder is the effective management of acute and chronic pain. While pain commonly co-occurs with opioid use disorder, there is limited research to guide effective management of pain in this population. Areas covered: We first provide an overview of the etiology and treatment of acute and chronic pain, highlighting areas of complexity for patients receiving OAT. We then describe the search strategy, which involved a date-inclusive search for relevant terms in PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials. After summarizing the results of this search on the evidence for pharmacological and behavioral treatments of acute and chronic pain for individuals on OAT, we conclude with a discussion of these findings and a summarized expert opinion on the state of the evidence. Expert opinion: The evidence suggests that while research on effective treatment of acute and chronic pain in individuals in OAT is limited, promising work is ongoing to translate existing treatments, particularly behavioral treatments for chronic pain, to support this population. However, further research is warranted, particularly regarding pharmacological options.

Introduction: Cardiometabolic diseases, particularly type 2 diabetes (T2D) and cardiovascular disease (CVD), represent leading global health challenges with rising incidence and prevalence. Despite strong evidence supporting the benefits of sodium-glucose cotransporter inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP-1 RA) in managing CVD risk in T2D, these therapies remain underutilized. Areas covered: This review discusses the present state of SGLT2i and GLP-1 RA usage, emphasizing barriers to their adoption, including clinical inertia, high costs, and misconceptions about injectable therapies. The literature search was conducted using PubMed, UpToDate, major society journals, and clinical guidelines. Information was gathered from cohort studies, survey reports, randomized controlled trials, and meta-analyses that examine the effectiveness and challenges surrounding these treatments. Expert opinion: Addressing the underuse of SGLT2i and GLP-1 RA requires a multifaceted approach. Key strategies include improving prescriber awareness, reducing out-of-pocket costs, fostering interdisciplinary collaboration, and leveraging digital health tools. Implementation science has shown promise in enhancing therapy uptake. Future efforts must integrate these therapies into value-based care models to ensure timely, equitable access, ultimately reducing cardiovascular (CV) morbidity and mortality in high-risk T2D populations.

Background: Optimal medical therapy plays a critical role in improving the prognosis of patients with coronary artery disease (CAD), particularly through the management of dyslipidaemia. This study investigated treatment practices for patients with dyslipidaemia-complicated CAD (DL-CAD) in Japan, focusing on cases considered refractory to standard management. Research design and methods: A web-based survey was conducted from 10 November 2023 to 1 December 2023 among cardiologists. Responses from 202 participants were analysed and divided into two groups based on the proportion of patients with refractory DL-CAD: <10% (n = 102) and ≥ 10% (n = 100). Results: There was no significant difference in the use of maximally tolerated statins between groups. However, ezetimibe, EPA, and omega-3-acid ethyl esters were used more frequently in the group with a higher proportion of refractory patients. Logistic regression analysis revealed that the use of ezetimibe was the only factor affecting the proportion of patients with refractory DL-CAD (odds ratio: 1.26, p = 0.0499). Conclusions: Japanese cardiologists tend to prescribe ezetimibe in addition to maximally tolerated statin for patients with refractory DL-CAD. Furthermore, they are increasingly targeting elevated triglycerides using polyunsaturated fatty acids as a strategy to reduce residual cardiovascular risk when LDL-C targets are unmet.

Introduction: Ensifentrine, recently approved by the FDA for chronic obstructive pulmonary disease (COPD) maintenance treatment, is a novel inhaled therapy with a dual mechanism of action targeting phosphodiesterase (PDE)3 and PDE4. While long-acting bronchodilators and inhaled corticosteroids remain initial guideline-based COPD treatments, persistent symptoms and disease exacerbations highlight an existing unmet need. Ensifentrine offers both bronchodilator and anti-inflammatory benefits, offering the potential to address this treatment gap. Areas covered: This article reviews the mechanism of action of ensifentrine, details supporting preclinical evidence, and summarizes key clinical studies. It further explores ensifentrine's potential impact on the COPD treatment landscape and its potential applicability in other pulmonary diseases. Expert opinion: Ensifentrine's dual bronchodilator and anti-inflammatory action offer a promising adjunct to standard COPD treatments, particularly for patients with persistent symptoms despite conventional therapy. It improves lung function, meaningfully reduces exacerbation frequency, reduces symptoms, and enhances quality of life. Its inhaled delivery minimizes systemic exposure and side effects commonly observed with oral PDE inhibitors. Furthermore, its anti-inflammatory properties suggest potential applications in other chronic respiratory diseases, such as asthma and non-cystic fibrosis bronchiectasis.

Introduction: Intravitreal injections remain the standard for treating common retinal diseases including age-related macular degeneration (AMD), diabetic macular edema (DME) and diabetic retinopathy. However, frequent administration creates significant treatment burden due to limited drug half-life and the chronic nature of these conditions. Areas covered: This review summarizes emerging drug delivery techniques and therapies for retinal disease that have achieved FDA approval within the past five years or have advanced to Phase 3 development, including intravitreal sustained-release platforms and alternative delivery routes (suprachoroidal, subretinal, topical, and subcutaneous). Specific innovations discussed include the ranibizumab port delivery system, EYP-1901 (Duravyu, vorolanib implant), KSI-301 (tarcocimab tedromer), KSI-501, OTX-TKI (Axpaxli, axitinib implant), 4D-150, revakinagene taroretcel-lwey (Encelto, NT-501, encapsulated cell therapy), Xipere (triamcinolone acetonide injectable suspension), AU-011 (belzupacap sarotalocan targeted delivery), ABBV-RGX-314, elamipretide, and OCS-01 (high concentration dexamethasone). Expert opinion: Promising innovations include sustained-release intravitreal implants, topical and subcutaneous delivery systems, and targeted methods like suprachoroidal and subretinal injections, each with unique advantages and limitations. Challenges include overcoming the blood-retinal barrier, surgical complications with implantable devices, and ensuring patient adherence. Advances in smart delivery systems, drug formulations, and predictive models, alongside interdisciplinary collaboration, will be crucial in achieving personalized, effective, and sustainable retinal therapies.