INTRODUCTION: Chronic obstructive pulmonary disease (COPD) is characterized by various inflammation patterns, with type 1 and type 3 being the most prevalent. Type 2, which is similar to that found in asthma and is orche...INTRODUCTION: Chronic obstructive pulmonary disease (COPD) is characterized by various inflammation patterns, with type 1 and type 3 being the most prevalent. Type 2, which is similar to that found in asthma and is orchestrated by interleukins such as IL-4, IL-5, IL-13, and IL-33, is not common, but is associated with a higher disease burden, including loss of lung volume and higher exacerbations rates. AREAS COVERED: IL-33 has recently been found to play a pathogenic role in COPD development and progression; therefore, its blockade with antibodies such as itepekimab may have therapeutic potential. This review summarizes the scientific rationale for the potential use of itepekimab in COPD and reviews the available clinical data. EXPERT OPINION: Based on existing clinical data, itepekimab may be a potential therapy for COPD that can be easily administered at home, with dosing tailored to the disease phase (every 2 weeks during exacerbation and every 4 weeks during stable state).
INTRODUCTION: Systemic lupus erythematosus is a heterogeneous autoimmune disease in which lupus nephritis represents one of the most severe and prognostically relevant manifestations, accounting for substantial morbidity...INTRODUCTION: Systemic lupus erythematosus is a heterogeneous autoimmune disease in which lupus nephritis represents one of the most severe and prognostically relevant manifestations, accounting for substantial morbidity and mortality. Despite therapeutic advances, long-term renal outcomes remain suboptimal, prompting the need to reassess current management strategies. AREAS COVERED: This review discusses recent advances in the classification and treatment of lupus nephritis, with particular emphasis on evolving conceptual frameworks and emerging therapies. We summarize updates in international guidelines, including the 2025 EULAR recommendations, which incorporate biologic and targeted agents such as obinutuzumab and voclosporin into standard treatment regimens and promote combination strategies to improve efficacy while limiting cumulative toxicity. In addition, we review data from recent clinical trials evaluating novel agents, including telitacicept, baricitinib, and dapirulizumab, as well as early-stage and experimental approaches such as CAR T-cell therapies. The review is based on a narrative analysis of recent clinical trials and guideline updates. EXPERT OPINION: The therapeutic landscape of lupus nephritis is rapidly evolving, with promising new agents expanding available options; however, high costs, limited access, and insufficient long-term data currently restrict their widespread first-line use. Future head-to-head trials and real-world studies are essential to refine treatment algorithms and improve durable renal outcomes.
INTRODUCTION: Colorectal cancer (CRC) employs immune evasion strategies, particularly through the expression of immune checkpoint ligands, including PD-L1. These ligands interact with inhibitory receptors, including prog...INTRODUCTION: Colorectal cancer (CRC) employs immune evasion strategies, particularly through the expression of immune checkpoint ligands, including PD-L1. These ligands interact with inhibitory receptors, including programmed cell death protein 1 (PD-1) and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), which reduces the immune system's antitumor T-cell response. Modulation of these mechanisms has revolutionized the treatment paradigm, particularly for biologically distinct subsets of CRC. AREAS COVERED: This article examines the background and clinical development of immune checkpoint inhibitors (ICIs) in CRC, with particular attention to MSI-H/dMMR tumors with high mutational burden and immunogenicity. It discusses the major trials of nivolumab, pembrolizumab, and ipilimumab, including combinations from the CheckMate-142 and CheckMate-8HW trials. It also mentions new findings on tumor-intrinsic PD-1 signaling, MAPK pathway activation, and chemotherapy resistance. A thorough literature review of key trials and recent peer-reviewed publications provides a perspective on current evidence. PubMed/MEDLINE, Embase, Scopus, and the Cochrane Library (2015-2026) were searched. EXPERT OPINION: The combination of PD-1 and CTLA-4 inhibitors in MSI-H/dMMR metastatic colorectal cancer has demonstrated long-term clinical efficacy and a genuine survival benefit. However, in MSS metastatic colorectal cancer, there has been limited response, emphasizing the importance of innovative combination therapies to address both primary and secondary resistance.
PURPOSE: To evaluate the early real-world efficacy of intravitreal aflibercept 2 mg biosimilar (aflibercept-ayyh, Pavblu, Amgen, USA.) across common retinal vascular diseases in treatment-naïve eyes. METHODS: This retros...PURPOSE: To evaluate the early real-world efficacy of intravitreal aflibercept 2 mg biosimilar (aflibercept-ayyh, Pavblu, Amgen, USA.) across common retinal vascular diseases in treatment-naïve eyes. METHODS: This retrospective, observational study was conducted at The Retina Service of Wills Eye Hospital (Mid Atlantic Retina, Philadelphia, PA, USA.) and included treatment-naïve eyes with retinal vascular diseases treated with aflibercept-ayyh in a real-world clinical setting. Functional and anatomical changes from baseline to last follow-up were analyzed using paired t-tests and Wilcoxon signed-rank tests. RESULTS: A total of 707 eyes (1,912 injections) were analyzed over a mean follow-up of 8.5 ± 6.5 weeks (2.7 ± 1.4 injections). Mean BCVA improved from 0.68 to 0.60 logMAR (+3.8 ETDRS letters, < 0.001), and mean CFT decreased from 331.9 µm to 232.6 µm (-99.3 µm, < 0.001). IRF decreased from 50.1% to 23.5%, SRF from 26.3% to 6.2%, and sub-RPE/PED fluid from 39.5% to 31.3%. CRVO and BRVO showed the greatest improvements. No intraocular inflammation, vascular occlusion, endophthalmitis, or systemic adverse events occurred; cataract progression was observed in 0.7% of eyes. CONCLUSION: Aflibercept-ayyh demonstrated significant early visual and anatomical improvements across major retinal vascular diseases with a favorable short-term safety profile.
INTRODUCTION: Tildrakizumab, a selective interleukin (IL)-23 p19 inhibitor, is an established treatment for moderate-to-severe plaque psoriasis. However, clinical trials are characterized by strict eligibility criteria,...INTRODUCTION: Tildrakizumab, a selective interleukin (IL)-23 p19 inhibitor, is an established treatment for moderate-to-severe plaque psoriasis. However, clinical trials are characterized by strict eligibility criteria, which often prevent the recruitment of patients with complex real-world conditions. This review summarizes Italian real-world experience providing critical information for optimizing the use of tildrakizumab in clinical practice, ultimately improving patient outcomes. AREAS COVERED: A literature search was performed in PubMed for real-world studies of tildrakizumab conducted in Italy and published between May 2020 and January 2025. The selected articles reported here provide an overview of the safety and effectiveness of tildrakizumab in real-world in clinically challenging subgroups, including patients with comorbidities, high‑impact area involvement, prior biologic exposure, obesity, and advanced age. EXPERT OPINION: Real‑world evidence from Italy consistently confirms that tildrakizumab provides durable effectiveness and a favorable safety profile across a broad spectrum of patients, often matching or exceeding outcomes reported in pivotal trials. The availability of two approved dosing options may support personalized treatment approaches, although current evidence remains observational and further long-term studies are required to define the full clinical implications.
INTRODUCTION: Severe asthma and chronic rhinosinusitis with nasal polyps (CRSwNP) are frequent comorbidities driven by common Type 2 inflammatory pathways. While biologics target both conditions, a standardized definitio...INTRODUCTION: Severe asthma and chronic rhinosinusitis with nasal polyps (CRSwNP) are frequent comorbidities driven by common Type 2 inflammatory pathways. While biologics target both conditions, a standardized definition for 'dual clinical remission' is lacking. This review evaluates the comparative efficacy of current biologics to propose a unified treatment strategy. AREAS COVERED: We reviewed pivotal phase 3 and 4 trials (including SINUS-52, SYNAPSE, OSTRO, WAYPOINT, and the head-to-head EVEREST trial) evaluating dupilumab, mepolizumab, benralizumab, omalizumab, and tezepelumab. We analyzed outcomes regarding asthma control, nasal polyp reduction, and olfactory recovery. A new composite definition for dual remission - combining zero exacerbations/oral corticosteroids use with clinically meaningful sinonasal improvement - is proposed. EXPERT OPINION: Achieving dual remission requires a biomarker-guided hierarchy. Dupilumab demonstrates superior efficacy in the 'sinonasal-dominant' phenotype, particularly for olfactory restoration, while anti-IL-5 agents are preferable for the 'exacerbation-dominant' eosinophilic phenotype. Emerging data from the WAYPOINT trial suggests tezepelumab (anti-TSLP) as a potent option for broad epithelial blockade. We advocate moving beyond isolated disease control toward a stratified 'United Airway' remission target guided by fractional exhaled nitric oxide, blood eosinophils, and immunoglobulin E levels.
INTRODUCTION: Giant cell arteritis (GCA) is the most common systemic vasculitis in individuals over 50 years of age. Aortic involvement is frequent, often clinically silent, and significantly increases the risk of thorac...INTRODUCTION: Giant cell arteritis (GCA) is the most common systemic vasculitis in individuals over 50 years of age. Aortic involvement is frequent, often clinically silent, and significantly increases the risk of thoracic aortic aneurysm, underscoring the need for early detection and optimal management. AREAS COVERED: This review summarizes current knowledge on the pathophysiology, diagnosis, and management of GCA-related aortitis, with emphasis on Th17- and Th1-driven immune pathways and their therapeutic implications. A structured literature search was conducted in major medical databases, including PubMed/MEDLINE, focusing on studies addressing aortic involvement in GCA, imaging modalities for disease assessment, and therapeutic strategies such as glucocorticoids, conventional synthetic disease-modifying antirheumatic drugs, biologic agents, and Janus kinase inhibitors. EXPERT OPINION: Management should follow a treat-to-target strategy aimed at achieving clinical and, when feasible, imaging remission. Although glucocorticoids remain the cornerstone of treatment, steroid-sparing approaches, particularly with tocilizumab, and emerging targeted biotherapies may improve long-term vascular outcomes and prognosis in selected patients.
OBJECTIVES: HER2-positive breast cancer is an aggressive subtype. High-cost originator trastuzumab limits treatment access, making biosimilars like HLX02 a valuable alternative. METHODS: This retrospective real-world stu...OBJECTIVES: HER2-positive breast cancer is an aggressive subtype. High-cost originator trastuzumab limits treatment access, making biosimilars like HLX02 a valuable alternative. METHODS: This retrospective real-world study compared HLX02 ( = 42) with originator trastuzumab ( = 237) within the neoadjuvant THP-EC regimen for early HER2-positive breast cancer. The primary endpoint was total pathological complete response (tpCR). RESULTS: Before propensity score matching (PSM), the tpCR rate was higher with HLX02 (73.81% vs. 43.04%, < 0.001). After PSM, tpCR rates were comparable (HLX02: 73.81% vs. originator: 72.27%; = 0.448), with no significant subgroup differences. Safety profiles, including cardiac toxicity, were similar between groups. CONCLUSION: HLX02 demonstrated equivalent efficacy and safety to the originator trastuzumab in this setting, representing a cost-effective treatment alternative.
INTRODUCTION: Pancreatic cancer is highly aggressive with poor prognosis and limited therapies. Extracellular RNAs (exRNAs), including microRNAs (miRNAs), long noncoding RNAs (lncRNAs), and circular RNAs (circRNAs), play...INTRODUCTION: Pancreatic cancer is highly aggressive with poor prognosis and limited therapies. Extracellular RNAs (exRNAs), including microRNAs (miRNAs), long noncoding RNAs (lncRNAs), and circular RNAs (circRNAs), play key roles in its progression. Transported through vesicles or freely circulating, they regulate proliferation, epithelial-mesenchymal transition, angiogenesis, immune evasion, and metastasis. exRNAs contribute to chemoresistance, immune suppression, tumor growth, and intercellular communication, shaping pancreatic cancer's aggressive phenotype and overall tumor microenvironment. AREAS COVERED: Recent research highlights exRNAs as prognostic biomarkers and therapeutic targets. Modulating exRNA expression or inhibiting their function may offer new strategies to overcome resistance to existing therapies. This review summarizes current knowledge on the relevance of exRNAs and their potential applications in understanding pathogenesis and improving treatment. A deeper insight into exRNA-mediated signaling networks may help develop innovative therapeutic approaches for more effective pancreatic cancer management in the future. EXPERT OPINION: Pancreatic cancer, especially pancreatic ductal adenocarcinoma, has poor prognosis due to late diagnosis, aggressiveness, and treatment resistance. exRNAs, including circRNAs, miRNAs, and lncRNAs, regulate tumor progression and are promising biomarkers and therapeutic targets. Despite challenges with stability, delivery, and patient variability, exRNAs show considerable potential for early detection, personalized therapy, genome-editing strategies, and combination treatments with chemotherapy or immunotherapy.
INTRODUCTION: Chronic graft-versus-host disease (cGVHD), a frequent, debilitating autoimmune-like syndrome affecting allogeneic transplant recipients begins with inflammatory response to per-transplant tissue injury whic...INTRODUCTION: Chronic graft-versus-host disease (cGVHD), a frequent, debilitating autoimmune-like syndrome affecting allogeneic transplant recipients begins with inflammatory response to per-transplant tissue injury which evolves into chronic inflammation, T- and B-cell dysregulation, and aberrant tissue repair and fibrotic reaction. Monocytes and macrophages contribute to multiorgan inflammation and fibrosis that are hallmarks of cGVHD. AREAS COVERED: Axatilimab is a high-affinity anti-CSF-1 R humanized immunoglobulin G4 monoclonal antibody that blocks ligand binding to CSF-1 R and downregulates development and differentiation of pathogenic monocyte-derived macrophages. A phase 1/2 study, and subsequently a phase 2 randomized trial that evaluated axatilimab in patient with refractory cGVHD, reported an ORR of 50-74%. Toxicity was dose-dependent. Based on the Phase 2 results, the lowest dosage, 0.3 mg/kg every 2 weeks, was identified as appropriate for the indication. Here, we examine clinical development of axatilimab leading up to its approval by the Food and Drug Administration for treatment of cGVHD after failure of at least two prior therapies. EXPERT OPINION: Axatilimab has demonstrated safety, tolerability, and efficacy in clinical trials; however, many questions remain unanswered including long-term safety data, efficacy when compared to other cGVHD therapies, risks and benefits of axatilimab in combination, and role in earlier lines of cGVHD treatment.
Liu Y, Lee JH, Mo CC
… +11 more, Salman TJ, Hossain S, Midha S, Nadeem O, Nicholson T, Croteau J, Kazierad N, Mouhieddine TH, Theprungsirikul P, Laubach JP, Richardson PG
INTRODUCTION: Monoclonal antibodies (mAbs) and antibody-drug conjugates (ADCs) are among the backbones of treatment for relapsed/refractory multiple myeloma (RRMM). Beyond current standard-of-care regimens, the roles of...INTRODUCTION: Monoclonal antibodies (mAbs) and antibody-drug conjugates (ADCs) are among the backbones of treatment for relapsed/refractory multiple myeloma (RRMM). Beyond current standard-of-care regimens, the roles of mAbs/ADCs are evolving associated with advances in first-line therapy, emerging data on additional regimens, and developments with immunotherapies and other novel agents. AREAS COVERED: We review mechanisms of action, efficacy, real-world effectiveness, and key aspects of the safety profiles of daratumumab, isatuximab, elotuzumab, and belantamab mafodotin in RRMM. We consider efficacy in patient subgroups and the challenges of treatment sequencing and highlight new antigen targets and mAb/ADC therapies under investigation. We searched the published literature with PubMed and congress abstracts using drug names or classes and 'myeloma.' EXPERT OPINION: The widespread use of daratumumab and isatuximab in first-line therapy and evolving roles of CAR T-cell therapies and bispecific antibodies are reshaping RRMM treatment. mAb/ADC-based regimens remain key options in this setting, offering practical, effective, and tolerable approaches for real-world practice. Ongoing research will inform individualized treatment choices and rational sequencing of therapies, with a need for immune-based biomarkers and biologic profiling to enable optimal, integrated use of mAbs, ADCs, CAR T-cell therapies, and bispecific antibodies to further improve outcomes for patients with RRMM.
INTRODUCTION: Hepatocellular carcinoma (HCC) remains a leading cause of cancer-related mortality worldwide, largely arising in the setting of chronic liver disease and cirrhosis. Given the immunosuppressive hepatic tumor...INTRODUCTION: Hepatocellular carcinoma (HCC) remains a leading cause of cancer-related mortality worldwide, largely arising in the setting of chronic liver disease and cirrhosis. Given the immunosuppressive hepatic tumor microenvironment, optimizing immunotherapeutic strategies is critical to improve patient outcomes. AREAS COVERED: This review examines the biological rationale and clinical evidence supporting dual immune checkpoint inhibition with nivolumab plus ipilimumab in advanced HCC. We discuss mechanisms of immune tolerance in cirrhosis and tumor progression, including regulatory T cells, myeloid-derived suppressor cells, hypoxia, metabolic reprogramming, and T-cell exhaustion. Key clinical data from early-phase studies, such as CheckMate 040 and the phase III CheckMate 9DW, are analyzed, focusing on overall survival, response rates, and durability of response compared with tyrosine kinase inhibitors. A structured literature search of PubMed, Embase, and major oncology congress proceedings was conducted to identify relevant preclinical and clinical studies. EXPERT OPINION: Dual checkpoint blockade represents an effective first-line option for selected patients with advanced HCC, offering meaningful survival benefit at the cost of increased immune-related toxicity. Future progress depends on improved patient selection, biomarker development, and rational combination strategies.