INTRODUCTION:Atherosclerotic cardiovascular disease (ASCVD) remains the leading global cause of morbidity and mortality, with elevated low-density lipoprotein cholesterol (LDL-C) as a major modifiable risk factor. Despite intensive statin therapy, many high-risk patients do not achieve increasingly stringent LDL-C goals, highlighting the need for additional lipid-lowering strategies. The development of proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors has significantly advanced lipid management, although currently available agents require subcutaneous administration and may be limited by adherence, accessibility, and cost. AREAS COVERED:This review discusses the pharmacological profile, clinical efficacy, safety, and potential therapeutic positioning of enlicitide decanoate, the first oral PCSK9 inhibitor. Evidence from phase 2 and phase 3 CORALreef program clinical trials evaluating enlicitide in patients with hypercholesterolemia, heterozygous familial hypercholesterolemia, and established or high risk for ASCVD is summarized. Available data on enlicitide are also compared with existing lipid-lowering therapies, including statins, ezetimibe, and approved therapies targeting PCSK9. EXPERT OPINION:Enlicitide decanoate is a promising addition to lipid-lowering therapy, potentially expanding access to PCSK9 inhibition through oral administration. However, its definitive clinical role will depend on cardiovascular outcomes data, long-term safety, adherence in real-world practice, and cost-effectiveness compared with established injectable therapies.
INTRODUCTION:Vitiligo is a chronic autoimmune condition characterized by progressive loss of melanocytes and the development of depigmented skin lesions. Increasing evidence highlights the pivotal role of dysregulated JAK-STAT signaling in disease pathogenesis. AREAS COVERED:A literature search was performed using PubMed/MEDLINE, to identify relevant studies published up to January 2026, about the contribution of JAK-STAT-dependent pathways to vitiligo progression, IFN-γ-induced chemokine production (CXCL9 and CXCL10), recruitment of cytotoxic CD8+ T lymphocytes, and the involvement of tissue-resident memory (T < sub>RM) T cells in maintaining localized immune responses. The effects of JAK inhibition across multiple cell populations, including melanocytes, keratinocytes, and immune cells were examined. Current clinical data regarding both topical and systemic JAK inhibitors in the context of targeted repigmentation strategies. EXPERT OPINION:Unlike conventional systemic immunosuppressive therapies, JAK inhibitors enable targeted modulation of specific inflammatory pathways central to vitiligo pathophysiology. Future therapeutic success will likely depend on appropriate patient selection, optimal timing of intervention, and rational combination approaches aimed at sustaining repigmentation and reducing relapse risk. Collectively, these developments support the emerging role of JAK-directed therapy as a significant advancement in the management of vitiligo.
INTRODUCTION:Advanced gastrointestinal stromal tumors (GISTs) are usually driven by KIT or PDGFRA and treated with sequential tyrosine kinase inhibitors. After imatinib, several distinct secondary KIT-resistant clones may coexist within and between lesions, limiting the coverage of any single later-line inhibitor. AREAS COVERED:This Drug Evaluation reviews the chemistry, active-state pharmacology, preclinical activity, pharmacokinetics, clinical efficacy, safety and regulatory status of bezuclastinib, with emphasis on its combination with sunitinib. PubMed, ClinicalTrials.gov, regulatory sources and major congress proceedings were searched through 13 August 2026. EXPERT OPINION:Bezuclastinib is best viewed as a combination-enabling type I KIT inhibitor that complements the type II inhibitor sunitinib. In PEAK, the combination improved median progression-free survival from 9.2 to 16.5 months and objective response rate from 25.8% to 45.6%, at the cost of more grade 3 or higher toxicity and treatment modification. Pending approval, it is likely to become a preferred second-line option for suitable patients with KIT-driven GIST. Mature survival, post-combination sequencing, resistance mechanisms, long-term patient-reported outcomes and real-world tolerability remain important evidence gaps.
INTRODUCTION:HIV treatment is evolving toward simplified regimens with fewer agents, improved tolerability, and activity against resistant virus. This review evaluates the potential clinical role of lenacapavir (LEN), a capsid inhibitor, combined with bictegravir (BIC), an integrase strand transfer inhibitor, as a single-tablet regimen (STR) for HIV treatment. AREAS COVERED:This review summarizes the pharmacology, pharmacokinetics, clinical efficacy, safety, resistance profile, and comparative therapeutic landscape of LEN and BIC, and discusses their potential integration into future HIV treatment strategies. EXPERT OPINION:Current HIV therapy is dominated by highly effective and well-tolerated STRs with high barriers to resistance. However, unmet needs remain for individuals with resistant virus, intolerance to injectables, or preference for regimens with fewer agents. The LEN/BIC combination represents a potentially potent and well-tolerated STR with activity against multidrug-resistant HIV. BIC provides a high genetic barrier to resistance, while LEN's prolonged half-life may offer pharmacologic forgiveness. Nevertheless, important challenges remain, with limited data, clinically significant drug-drug interactions related to LEN metabolism and its potential for resistance emergence. Future HIV therapy will evolve toward increasingly personalized treatment integrating daily oral, extended-interval oral, and long-acting injectables. Within this evolving paradigm, LEN/BIC will expand therapeutic options and advance patient-centered HIV care.
INTRODUCTION:Chronic migraine (CM) is a disabling neurological disorder with evolving diagnostic criteria that have influenced how we interpret the evidence base for preventive treatment. Affecting 1-2% of the population, CM imposes substantial individual and societal burden. AREAS COVERED:This narrative review summarizes the evidence for CM prevention. Literature was identified through PubMed and Google Scholar through April 2026. We review traditional oral preventives, onabotulinumtoxinA, calcitonin gene-related peptide (CGRP)-targeted monoclonal antibodies, gepants, and emerging therapeutic targets, emphasizing CM-specific efficacy, safety, and outcomes in patients with medication overuse and prior treatment failures. EXPERT OPINION:Although traditional oral preventives remain widely used in CM, most lack CM-specific trial data under current diagnostic criteria and their use largely reflects extrapolation from episodic migraine. Therapies targeting migraine pathophysiology, including CGRP-targeted agents and onabotulinumtoxinA, offer more robust CM-specific evidence, although effect sizes are modest and comparative efficacy data against established oral preventives remain limited. Despite guidelines endorsing CGRP-targeting therapies as first-line, access barriers limit real-world implementation. Incomplete response and the lack of predictive biomarkers, reflecting disease heterogeneity, pose major challenges in CM management. Future progress may lie in strengthening the evidence for combination therapy, expanding therapeutic targets, and developing clinically actionable biomarkers for individualized care.
INTRODUCTION:Iron supplementation, erythropoiesis-stimulating agents (ESAs), and hypoxia-inducible factor-prolyl hydroxylase inhibitors (HIF-PHIs) are currently the main therapeutic options for anemia associated with chronic kidney disease (CKD). In 2026, KDIGO published an updated clinical practice guideline for anemia management in CKD. AREAS COVERED:This review summarizes the recent advances in the pharmacological management of CKD-associated anemia, focusing on iron supplementation, ESAs, and HIF-PHIs. EXPERT OPINION:The 2026 KDIGO Clinical Practice Guideline for the Management of Anemia in Chronic Kidney Disease advocates a more proactive approach to iron supplementation in patients with CKD, based on emerging evidence, and provides guidance on HIF-PHIs, which are increasingly used in clinical practice. Robust evidence regarding the optimal thresholds for initiating iron therapy and target values for iron parameters remains lacking, highlighting the need for treatment strategies tailored to patient and regional characteristics. Although HIF-PHIs have demonstrated efficacy comparable to that of ESAs, concerns remain regarding potential increases in the risks of cardiovascular and thromboembolic events in some patient populations, additionally, their long-term safety regarding malignancy has not been fully established. Further studies are needed to establish individualized treatment strategies and clarify the long-term safety and optimal therapeutic targets for anemia management in patients with CKD.
INTRODUCTION:The rising prevalence of MDR Gram-negative infections, particularly ESBL-producing Enterobacterales, has created a critical oral treatment gap, necessitating prolonged intravenous therapy. Oral carbapenems/penems offer a long-awaited opportunity to bridge this gap. AREAS COVERED:This review examines the chemistry, pharmacokinetics/pharmacodynamics, and phase 3 trial evidence for tebipenem and sulopenem, recently FDA-approved for urinary tract infections (UTI). We analyze the regulatory landscape pearls and pitfalls of these agents, and their management through an outpatient antimicrobial stewardship (AMS) perspective. Literature was searched in PubMed, Scopus, ClinicalTrials.gov, and regulatory databases through June 2026. EXPERT OPINION:Oral carbapenems/penems evoke enthusiasm over closing a long-standing oral treatment gap for MDR Gram-negative infections, alongside apprehension regarding resistance risks. With both agents now approved in the United States, this promise is now a reality, marking the start of a new era in oral therapy. However, global regulatory fragmentation and evidence limited to UTIs remain key barriers to broader clinical use. Crucially, growing use may shift carbapenem selection pressure from hospitals into the community. This risk requires strict resistance surveillance and formulary restriction to confirmed MDR infections lacking oral alternatives. Their clinical trajectory will depend less on intrinsic activity than on the rigor of AMS frameworks governing their use.
INTRODUCTION:Chronic spontaneous urticaria (CSU) results from multiple interacting pathogenic mechanisms. Despite available treatments, a proportion of patients remain inadequately controlled, supporting the need for therapeutic options. AREAS COVERED:This review examines the role of Bruton's tyrosine kinase (BTK) in CSU and summarizes the development of BTK inhibitors. Data on fenebrutinib, remibrutinib, rilzabrutinib, TAS5315, and other emerging agents are reviewed, focusing on mechanisms of action, efficacy, safety, and their potential place in practice. TAS5315 remains at an earlier stage of development, with CSU findings available from conference abstracts and registry data. The literature search included PubMed-indexed articles, clinical trial reports, regulatory documents, and congress presentations relevant to BTK inhibition in CSU. EXPERT OPINION:BTK inhibitors act on intracellular pathways involved in mast-cell activation, basophil signaling, and B-cell mediated immune responses. Studies have shown reductions in disease activity across multiple BTK inhibitors, with benefit observed early after treatment initiation in several studies. Remibrutinib is the first BTK inhibitor approved for CSU and has the most extensive phase 3 evidence. Oral administration may provide a treatment option for patients. Defining the place of BTK inhibitors within treatment algorithms and identifying patients most likely to benefit from this approach remain areas for future research.
INTRODUCTION:Atopic dermatitis (AD) is a chronic, relapsing inflammatory skin disease associated with recurrent flares, impaired quality of life, and significant psychological burden. Despite therapeutic progress, important unmet needs remain, particularly for steroid-sparing treatments that are safe for long-term use, suitable for sensitive areas, and applicable in pediatric patients. Phosphodiesterase-4 (PDE4) inhibitors represent a targeted anti-inflammatory approach through modulation of intracellular cAMP signaling. AREAS COVERED:This narrative review summarizes current evidence on topical and systemic PDE4 inhibitors in AD. A literature search was performed using PubMed/MEDLINE and ClinicalTrials.gov for studies published up to March 2026. Approved agents such as crisaborole, roflumilast, and difamilast demonstrate moderate efficacy and favorable safety, mainly in mild-to-moderate AD. Emerging therapies, including apremilast, orismilast, and lotamilast, show variable results and remain under investigation. EXPERT OPINION:PDE4 inhibitors have a stable but limited role in AD management. Their main advantages include good tolerability, long-term safety, and suitability for proactive treatment and sensitive skin areas. However, their efficacy is generally lower than that of biologics and JAK inhibitors. Their future role will likely depend on use as adjunctive or personalized therapies rather than replacement of high-efficacy systemic treatments.
INTRODUCTION:Crohn's-like disease of the pouch (CLDP) is an important long-term complication following ileal pouch-anal anastomosis (IPAA) for ulcerative colitis, associated with significant morbidity, impaired quality of life, and increased risk of pouch failure. Diagnosis remains challenging, in part due to heterogeneity in diagnostic criteria, and management is largely phenotype-driven and requires a multidisciplinary approach integrating medical, endoscopic, radiologic, dietary, and surgical therapies. AREAS COVERED:This narrative review is based on a literature search of PubMed and Scopus up to May 2026. The review summarizes the current evidence regarding pharmacological management of CLDP, including antibiotics, corticosteroids, immunomodulators, biologic therapies, and small molecules, alongside emerging data regarding dietary, endoscopic, and surgical interventions. Observational evidence suggests anti-TNF and interleukin-directed therapies demonstrate the strongest effectiveness signals, particularly in penetrating and fibrostenotic phenotypes, while vedolizumab may be most efficacious in inflammatory-predominant disease. However, interpretation remains limited by the absence of randomized controlled trials, inconsistent diagnostic criteria, heterogeneous phenotype composition, and the lack of phenotype-specific outcome reporting. EXPERT OPINION:Future progress in the field will depend on development of standardized diagnostic criteria, routine phenotype-specific outcome reporting, phenotype-based treatment algorithms, and prospective multicenter studies to better define optimal therapeutic sequencing and long-term pouch outcomes.
INTRODUCTION:Severe juvenile acne vulgaris is a chronic inflammatory disorder that can impair quality of life and lead to permanent scarring during adolescence. Advances in understanding acne pathophysiology have shifted treatment toward early intervention, antimicrobial stewardship, and individualized systemic strategies. AREAS COVERED:This narrative review summarizes current evidence on pharmacotherapy for severe juvenile acne, focusing on systemic treatments. PubMed, Embase, Google Scholar, Cochrane Library, and ClinicalTrials.gov database were searchede from inception to March 2026. Key pathogenic mechanisms,, including sebaceous hyperactivity, follicular hyperkeratinization, Cutibacterium acnes, dysbiosis, immune-inflammatory activation, and hormonal influences, are reviewed. EXPERT OPINION:Severe juvenile acne should not be dismissed as a physiologic feature of adolescence, because delayed or inadequate treatment may cause major physical and psychological sequelae. Oral isotretinoin remains the gold standard for severe nodulocystic, scarring, or treatment-resistant acne. Timely specialist assessment is essential to avoid unnecessary delay when licensed criteria are met, while ensuring compliance with product information, regulatory requirements, and risk-minimization measures. Prolonged systemic antibiotic use should be limited through benzoyl peroxide combinations and shorter courses. Future strategies will likely become more individualized, microbiome-conscious, and inflammation-targeted, aiming to prevent scarring and psychosocial burden as well as achieve lesion clearance.
INTRODUCTION:Psoriasis is a chronic inflammatory disease with a significant physical and psychosocial burden. Although biologic therapies targeting IL-17 and IL-23 are highly effective, their cost, injection burden, and variable response highlight the need for convenient oral alternatives. TYK2, a key mediator of the IL-23/IL-17 axis, represents a promising therapeutic target. Our objective is to evaluate the pharmacology, clinical efficacy, safety, and potential role of zasocitinib in plaque psoriasis. AREAS COVERED:This review evaluates preclinical and clinical studies of zasocitinib, focusing on early-phase trials and comparisons with existing therapies. Zasocitinib is a highly selective oral TYK2 inhibitor that modulates IL-12, IL-23, and interferon signaling. Adverse events were generally mild to moderate, with no major safety signals or laboratory abnormalities. EXPERT OPINION:Psoriasis varies widely, but management is generally guided by disease severity and treatment response. Although better treatment options are still needed, especially for mild disease, new drugs like zasocitinib may have a role but will likely face competition from highly effective, established therapies.
INTRODUCTION:Carbapenem-resistant Acinetobacter baumannii (CRAB) infections pose a global health threat due to high mortality, rising resistance, and limited treatment options. AREAS COVERED:Worldwide, OXA-type carbapenemases are the predominant mechanism of resistance; other mechanisms, including efflux pumps, porin mutations, and, rarely, metallo-β-lactamases, may contribute to resistance in resistant isolates, complicating management. Despite the different publication dates, both the Infectious Diseases Society of America (IDSA) and the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) guidance support the use of a combination of at least 2 agents for severe infections, despite a lack of high-quality randomized trial data. Sulbactam/durlobactam is prioritized as the core of treatment in the IDSA guidelines, whereas the ESCMID does not state a preference. Cefiderocol is also a novel cephalosporin suggested for refractory or resistant infections or for those with prior treatment failure, although randomized trial data are inconsistent regarding mortality. Old treatment choices such as carbapenems, polymyxins, and tetracyclines maintain their role as components of a combination treatment in difficult-to-treat infections from CRAB. EXPERT OPINION:There is a need to reinforce infection prevention and control measures, conduct further research on novel antibiotics and rapid, accurate diagnostic tests, and obtain high-quality data to support current practice.
INTRODUCTION:Alopecia areata (AA) has entered a new therapeutic era, but the future of pharmaceutical management in Asia will be determined not only by drug efficacy but also by how targeted therapies are selected, monitored, sequenced, and financed across heterogeneous health systems. AREAS COVERED:This narrative review examines the evolving pharmacologic management of AA in Asia, with emphasis on Asian clinical practice guidelines as well as pivotal randomized trials, long-term extension studies, and recent Asian real-world evidence. This review highlights regional differences in disease burden, access to therapy, infection-aware safety monitoring, outcome assessment, and implementation challenges that distinguish Asian practice from Western treatment models. EXPERT OPINION:The next major advance in Asia will not be the simple expansion of Janus kinase inhibitor availability. Rather, it will be the development of implementation-ready, precision-oriented care pathways that integrate disease trajectory, patient-reported burden, special-population needs, and pharmacoequity. Future progress will depend on better evidence for early intervention, maintenance and discontinuation strategies, multidimensional outcome measures beyond scalp regrowth alone, and regional registries capable of supporting long-term comparative effectiveness and pharmacovigilance.
INTRODUCTION:The discovery of epidermal growth factor receptor (EGFR) mutations has deeply reshaped the treatment of non-small cell lung cancer (NSCLC). Throughout the last years, third-generation tyrosine kinase inhibitor (TKI) osimertinib in monotherapy has been the standard of care; however, resistance limits durable responses, necessitating novel combinations and sequencing strategies. AREAS COVERED:This review discusses recent advances in EGFR-targeted therapies within the molecular landscape of classical and uncommon EGFR mutations, focusing on frontline intensification strategies in metastatic disease-specifically TKI combinations with chemotherapy (FLAURA2) or bispecific antibodies (MARIPOSA)-and emerging post-progression strategies to overcome acquired resistance mechanisms. A comprehensive literature search (January 2021-March 2026) was conducted via PubMed, and recent major oncology conference proceedings (ASCO, ESMO, WCLC, ELCC) and clinical trial registries for ongoing studies. EXPERT OPINION:The therapeutic landscape is shifting from a uniform frontline TKI monotherapy approach toward biomarker-driven, risk-stratified, intensification. High-risk patients (e.g. TP53 co-mutations, L858R) derive significant benefit from combination regimens, whereas mono-TKI remains appropriate for favorable prognostic subgroups. Future progress relies on validating predictive biomarkers-particularly circulating tumor DNA (ctDNA) dynamics-to guide adaptive treatment strategies, balancing efficacy gains against toxicity and costs, while ensuring equitable global access to novel therapies.
