The availability of monoclonal antibody therapies impacting on the basic pathways of bone formation; (romosozumab) and bone resorption (denosumab) has contributed greatly to our ability to manage patients with osteoporosis and fracture risk. Monoclonal antibodies offer the potential to optimize therapeutic efficacy with minimal adverse effects. This review discusses aspects of registration clinical trials as well as experience gained from the clinical use of monoclonal antibodies for osteoporosis. The registration clinical trials prove anti-fracture efficacy with subsequent trials investigating bone mineral density, bone turnover markers, and high-resolution bone imaging. Many of these trials indicate superiority of monoclonal antibody therapy for osteoporosis compared with traditional antiresorbers such as bisphosphonates. There remain significant care gaps in the management of patients at high risk of fragility fracture. Many patients at very high risk remain undiagnosed and therefore untreated. Monoclonal antibody antiresorptive therapy such as denosumab with high specificity and romosozumab with the ability to rapidly stimulate new bone formation are significant advances. Future therapies may direct 'maintenance' therapies to avoid reversal of beneficial effects on monoclonal antibody treatment discontinuation. Other novel therapies being investigated may provide benefits not only to osteoporosis but other diseases associated with aging.
Advanced non-squamous non-small cell lung cancer (NSCLC) remains associated with substantial mortality despite major advances in targeted therapy and immuno-oncology. c-Met protein overexpression represents a biologically relevant and relatively prevalent phenotype that may define a therapeutically vulnerable population lacking canonical genomic drivers. This review examines the scientific rationale for targeting c-Met protein overexpression and critically evaluates telisotuzumab vedotin (Teliso-V), a c-Met-directed antibody-drug conjugate (ADC) delivering the cytotoxic microtubule polymerization inhibitor MMAE. The structure, mechanism of action, dose optimization strategy, and exposure-toxicity relationships are discussed alongside emerging efficacy data from early-phase studies and the phase II LUMINOSITY trial. The evolving role of biomarker-driven ADC therapy in previously treated EGFR-wildtype non-squamous NSCLC, companion diagnostics, and regulatory considerations are also addressed. Teliso-V represents an important extension of the ADC paradigm into a protein-expression-defined NSCLC population, demonstrating clinically meaningful activity with a predictable and manageable safety profile dominated by cumulative risk for peripheral neuropathy. While accelerated approval underscores its therapeutic promise, long-term positioning will depend on confirmatory trials, refinement of biomarker testing, and optimization of patient selection. If validated, this strategy may redefine later-line treatment expectations by aligning cytotoxic payload delivery with biologically enriched disease subsets.
Hereditary angioedema (HAE) is a rare, potentially life-threatening, unpredictable disease characterized by recurrent subcutaneous and/or submucosal edema (HAE attacks). HAE imposes a significant biopsychosocial burden on patients and their families owing to the erratic nature and variable severity of HAE attacks. Current guidelines appoint sustained disease control as one of the main treatment goals, achievable through the initiation of long-term prophylaxis (LTP). This review focuses on the evaluation of three monoclonal antibodies developed for LTP of HAE, namely lanadelumab (Takhzyro®), garadacimab (Andembry®), and navenibart, in this order. Lanadelumab inhibits plasma kallikrein and has been an approved LTP option since 2018. Garadacimab inhibits activated factor XII (FXIIa) and has been approved for LTP in 2025. Navenibart, a drug currently under development, inhibits plasma kallikrein and has been modified to extend its circulating half-life. The transition from older non-targeted LTP options to the use of monoclonal antibody-based therapies has fundamentally changed the treatment landscape by offering a safe, effective, and highly targeted solution. Although having different pharmacological characteristics, these LTP options share the same objective: to achieve complete disease control. Hereditary angioedema is a rare disease where the main symptoms are unpredictable swellings of the skin or mucous membranes. These swellings may lead to disfigurement and can even be life-threatening when affecting the mucous membranes of the upper airways. The unpredictability of the swellings leads to a high psychological, economic, and social burden for the patients. To alleviate these burdens, physicians aim to prevent the occurrence of swellings and advise their patients to take preventive medications regularly. Monoclonal antibodies are a group of medications that are being used in more and more fields of medicine because they provide us with the opportunity to target specific molecules in the body. Three different monoclonal antibodies are used or being developed for the long-term prevention of swellings in hereditary angioedema, lanadelumab, garadacimab, and navenibart. In this article, the authors summarize the information available in the literature about these three drugs. However, these medications do not offer 100% protection against swelling attacks; therefore, it is important that patients always keep acute treatment with them, even if they receive preventive medications and/or are symptom-free.
While clinical trials have demonstrated that approximately 50% of patients with Crohn's disease (CD) maintain clinical remission at 1 year with infliximab (IFX), the outcomes of long-term IFX treatment in CD are still under scrutiny. This retrospective cohort study analyzed 113 patients with CD from September 2010 to July 2025 to evaluate adherence and clinical remission rates, as well as to identify factors associated with treatment adherence. The median duration of IFX treatment was 61.7 months. At the 72-month follow-up (M72), patients were categorized into M72-remission (44.2%) and M72-non-remission (55.8%) groups. The M72-remission group had a significantly higher baseline Crohn's disease activity index score than the M72-non-remission group (p = 0.003). However, this difference was no longer significant at the 72-month follow-up (p = 0.254). At the final follow-up, 67.3% of patients continued to receive IFX treatment. Both the adherence rate to IFX (p = 0.012) and the clinical remission rate (p = 0.030) were significantly higher in patients with no surgery compared to those with surgery prior to IFX treatment. Early clinical remission was not associated with the adherence to IFX treatment. Previous surgery may be an independent risk factor for long-term IFX treatment failure. Infliximab (IFX), a first-line treatment for patients with Crohn’s disease, showed moderate effectiveness in achieving clinical and endoscopic remission in previous induction and maintenance trials. This study shows that 67.3% of patients continued IFX therapy and 70.8% maintained clinical remission at the end of follow-up, including one patient who received IFX for more than 175 months. These findings indicate that clinical remission, IFX trough levels, and levels of antibodies to infliximab during induction treatment were not associated with adherence to long-term IFX treatment. However, prior surgery, including intestinal or perianal surgery, may be an independent risk factor for long-term IFX treatment failure.
Chronic graft-versus-host disease remains a major cause of late morbidity and mortality after allogeneic hematopoietic stem cell transplantation. Conventional prevention and management strategies, heavily reliant on prolonged immunosuppression, are limited by suboptimal efficacy, substantial toxicity, and a failure to address disease heterogeneity. This review synthesizes recent advances in the biological understanding of cGVHD, particularly the immune dysregulation and fibrotic progression that underpin its diverse clinical manifestations. We discuss a paradigm shift from uniform immunosuppression toward a structured framework encompassing four sequential phases: comprehensive assessment, risk-adapted prevention, mechanism-driven treatment, and holistic long-term survivorship care. Key innovations highlighted include the use of predictive biomarkers for early intervention, the use of steroid-sparing targeted therapies (such as JAK/ROCK2 inhibitors), and the integration of patient-reported outcomes and functional measures into routine evaluation. The field is poised for transformative change. We advocate for the routine implementation of risk-stratified prevention, preemptive antifibrotic strategies, and organ-specific multidisciplinary management. Crucially, therapeutic success should be redefined around patient-centered goals: safe steroid discontinuation, symptom control, functional recovery, and preserved quality of life. Embedding lifestyle support and longitudinal follow-up into standard care is essential to reduce the overall burden of cGVHD and improve long-term survival.
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. 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. 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.
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. 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. 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.
Biologic agents have significantly improved psoriasis treatment, but patient responses exhibit considerable heterogeneity, highlighting the urgent need for practical predictive biomarkers of therapeutic efficacy. This prospective cohort study enrolled 422 psoriasis patients and 150 healthy controls. Sixteen CPD parameters were measured using a hematology analyzer. We analyzed associations between baseline CPD and disease severity as well as inflammatory markers, assessed their predictive value for treatment response over 48 weeks of biologic therapy, and monitored early dynamic changes in CPD and their relationship with treatment response in 169 patients. All CPD parameters were significantly elevated in psoriasis patients compared to healthy controls (all p < 0.001). Baseline mean lymphocyte volume (MN-V-LY) demonstrated sustained negative correlations with PASI improvement rates from weeks 4 to 48 (ρ = -0.278 to -0.449, all p < 0.001). Early reduction in monocyte volume heterogeneity (SD-V-MO) was significantly associated with long-term efficacy (ρ = -0.355 to -0.546, all p < 0.001). As simple, standardized hematological parameters, CPD show potential for clinical application in predicting biologic therapy response in psoriasis.
Chimeric antigen receptor (CAR) T-cell therapies have rapidly become an integral part of the treatment landscape for relapsed or refractory lymphomas. While early clinical trials demonstrated impressive response rates in patients with multiply relapsed disease and improved outcomes in those with disease refractory to first-line treatments, subsequent longer follow-up has revealed the occurrence of both early and late relapses, as well as the emergence of delayed toxicities. Ten years after the initiation of the pivotal phase I/II trials that led to the approval of CD19-directed CAR T-cell therapies for large B-cell lymphoma (LBCL), extended follow-up data is now available. This review focuses on the long-term outcomes and toxicities of these therapies, as well as challenges to durable responses and future directions. Long-term follow-up has confirmed the curative potential of CAR T-cell therapy in relapsed or refractory LBCL. Toxicities are generally manageable, and although infections remain an important cause of non-relapse mortality, standardized prophylactic approaches can mitigate risk. Advances in CAR T-cell engineering and administration are likely to enhance treatment effectiveness, expand indications, and improve patient outcomes.
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. 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. 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.
Natural killer (NK) cells are innate immune effectors that can eliminate malignant cells without prior sensitization. By recognizing cellular stress signals and releasing inflammatory mediators, they contribute to immune surveillance and regulation. Their therapeutic potential lies in their ability to act across donor barriers with a reduced risk of graft-related complications; however, clinical translation remains challenging due to tumor immune evasion and limited persistence in suppressive environments. This review summarizes the biological roles of NK cells in cancer immunity and examines recent therapeutic approaches that harness their cytotoxic and regulatory properties. We discuss barriers to clinical application, including immune suppression, antigen loss, and manufacturing limitations. In addition, we highlight emerging strategies, such as gene editing, rational combination therapies, and standardized clinical trial designs, aimed at improving therapeutic efficacy. NK cell-based therapies represent a promising avenue in cancer immunotherapy but require carefully designed solutions to overcome their inherent limitations. Advances in biomarker-guided patient selection, integration with existing treatment modalities, and international collaboration will be critical for translating NK cell biology into effective and durable clinical outcomes.
Antibody-mediated rejection (AMR) is a major obstacle after heart transplantation. Although its pathophysiology is now clearer than a decade ago, clinical management is still fragmented and poorly evidence-based. Recent work reframes the classic paradigm of donor-specific antibodies (DSA) dependent complement activation as only one axis of injury. Converging data place natural killer (NK) cells at the center of vascular damage: they execute DSA-driven antibody-dependent cellular cytotoxicity (ADCC) via Fcγ receptors and, through 'missing-self' recognition, trigger DSA-negative endothelial injury. These insights have seeded new therapeutic strategies, yet clinical data remain sparse and heterogeneous. We now have many new insights and therapeutic possibilities, but progress hinges on robust data from well-conceived, adequately powered trials. To make this feasible, the field needs a refined, activity-based, heart-specific AMR classification aligned with Banff and validated noninvasive biomarkers (e.g. dd-cfDNA, endothelial-injury markers, NK-activity signatures) to enable early detection, monitoring, and rigorous trial enrollment. Emerging biology positions NK-cell targeting as a leading therapeutic direction. Clinical adoption will depend on reproducible assays, multicenter validation, and standardized reporting.
Melanomas cause the vast majority of skin-cancer related deaths, despite accounting for only around 2% of skin cancer cases. Moreover, due to genetic and environmental factors, the melanomas that predominate in East Asian populations, generally acral and mucosal melanomas, are extremely rare in Caucasian populations. These melanomas differ from other cutaneous melanomas in clinicopathological features and mutational landscapes, including a lower prevalence of commonly targetable mutations such as BRAF V600, and are usually diagnosed at a more advanced stage with a poor prognosis. The advent of immunotherapies therefore represents a great stride forward in the treatment of melanoma, including in East Asian countries, with immune checkpoint blockade now available as first-line treatment in China. This review briefly outlines the epidemiology and unique clinical characteristics of melanoma in East Asian patients; summarizes existing immunotherapy approvals, treatment landscape, and unmet needs; and aims to enable clinicians to make more informed treatment decisions for patients. Further research is urgently needed into novel immunotherapeutic combinations, and biomarkers of response, to fully unlock the potential of immunotherapy for East Asian AM and MM and guide future therapeutic strategies.
The approval in 2011 of belimumab, the first biologic approved for systemic lupus erythematosus (SLE), paved the way for testing additional biologic agents to expand treatment options for SLE. We discuss new biologic therapies that show promising results and discuss some of the barriers that must be considered in SLE clinical trials. This review focuses on established and novel biologics targeting the BAFF/APRIL, type-I IFN, CD20, and CD40/CD40 ligand pathways and on CAR-T therapy. We review the relevant clinical trials, focusing on safety and efficacy. A literature search was conducted in PubMed/MEDLINE. Keywords used were "Lupus Erythematosus, Systemic' OR (("Lupus* AND ("Biological Products' OR Biologics*)). These search results were filtered to include only clinical trials. In addition, literature from the authors' personal collections were considered. Several novel therapies have shown promising results. The treatment approach for SLE is shifting toward a balanced and targeted immunosuppression tailored to key drivers of SLE pathophysiology and diverse phenotypes. Given the number of agents already or soon-to-be approved, the appropriate therapy for a given patient must be a shared patient-physician decision.
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. 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.' 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.
Predicting drug - drug interactions (DDIs) is essential for safe, effective medication therapy, yet conventional in vitro assays and in silico models are not completely reliable in their assessments. Multi-organ-on-a-chip (MOC) platforms provide a more physiologically relevant approach that may improve in vitro DDI predictions, particularly for complex DDIs. We outline current DDI workflows, their strengths and limitations, and how single-organ chips can produce quantitative absorption, distribution, metabolism, and excretion (ADME) and toxicity parameters relevant for DDI analysis. We then discuss the need for emerging MOC platforms and the unique advantages that they offer, highlighting case studies that capture more complex DDI scenarios, as well as body-on-a-chip prototypes integrated with mechanistic modeling. MOC systems are currently poised to complement, not replace, established in vitro and modeling approaches for DDI predictions. Near-term value lies in fit-for-purpose contexts of use, supplying physiologically grounded parameters and mechanistic insight to physiologically based pharmacokinetic (PBPK) modeling. With continued progress in addressing key challenges (e.g. physiological scaling, sorptive materials, microscale analytics, variability, throughput, and standardization), MOCs should mature into reliable tools to assist in DDI prediction, and potentially even qualified assays as part of regulatory DDI risk assessment frameworks.
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. 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. 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).
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. 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. 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.
Biosimilar stewardship includes safety, appropriate use, and value. However, it faces challenges due to shortages in disproportionality methods. Artificial intelligence (AI) tools have been emerged as practical 'intelligence augmentation' strategies that strengthen, rather than replace, traditional pharmacovigilance (PV) signal management. We conducted a narrative review with evidence mapping (Jan 2010-Nov 2025) across PubMed/MEDLINE, Embase, Scopus, Web of Science, Cochrane, citation-chasing, and targeted grey/first-party sources (regulators/HTA portals, PV centers, NHS dashboards, technical documentation). We prioritized biosimilar-specific pharmacovigilance, switching/implementation, and value-tracking evidence; general PV/AI literature was used primarily to describe analytic methods and governance where it directly informs biosimilar-specific problems A study-selection summary is provided for transparency. To improve interpretability for readers, we also include brief 'deployment vignettes' describing how key AI-enabled functions are operationally implemented in routine pharmacovigilance workflows. Medium-term priorities include federated, KPI-linked analytics and better external validation and transportability; near-term 'assist' deployments - such as narrative NLP, normalization, de-duplication, and multi-feature ranking under human-in-the-loop governance - can quantifiably improve case completeness, traceability, and triage. To achieve reliable production use, persistent bottlenecks (class imbalance, vocabulary mapping) require clear monitoring and standard assessment procedures.
The rapid development and approval of biosimilars in the US offer a critical opportunity to improve the affordability and accessibility of biologic therapies. This targeted literature review was conducted using PubMed to examine the broad impact of biosimilars on the US health system, focusing on payers, healthcare professionals, and patients within oncology and inflammatory disease settings. Literature published between 1 January 2016, and 1 December 2024, was analyzed. Existing research primarily addresses clinical equivalence to reference biologics and safety of switching, with a paucity in data demonstrating broader patient population benefits of biosimilars. Cost savings from biosimilars are described, but there is a lack of evidence that these savings translate into improved access or earlier use of biologics, or whether budgetary reallocations enable access to other innovative treatments. While biosimilars are expected to reduce spending and expand treatment options, data on their extended stability and real-world outcomes are scarce. In conclusion, biosimilars offer potential to reduce healthcare costs and improve access to biologic therapies. Further research is needed to fully establish their holistic benefits across patient populations. This would enable a better understanding of how biosimilar adoption influences real-world treatment access, clinical and system-wide outcomes.