INTRODUCTION: 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-...INTRODUCTION: 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. AREAS COVERED: 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. EXPERT OPINION: 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.
INTRODUCTION: 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 w...INTRODUCTION: 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. AREAS COVERED: 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. EXPERT OPINION: 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.
INTRODUCTION: Prademagene zamikeracel is an autologous, genetically corrected epidermal graft therapy designed to address the underlying molecular defect in recessive dystrophic epidermolysis bullosa (RDEB). The product...INTRODUCTION: Prademagene zamikeracel is an autologous, genetically corrected epidermal graft therapy designed to address the underlying molecular defect in recessive dystrophic epidermolysis bullosa (RDEB). The product is manufactured from a patient's own keratinocytes, which are modified ex vivo to overexpress a normal copy of COL7A1, the gene coding for type VII collagen (C7), which is essential for anchoring fibril formation and stable dermal-epidermal cohesion. In individuals with biallelic COL7A1 variants, loss of C7 results in severe skin fragility, painful and widespread wounds, debilitating scarring, and a high risk of aggressive cutaneous squamous cell carcinoma. AREAS COVERED: This review outlines the key scientific foundations, translational advances, and clinical trial outcomes that supported regulatory approval of prademagene zamikeracel for use in adult and pediatric patients with RDEB. EXPERT OPINION: The development of prademagene zamikeracel represents a significant advance in regenerative therapy for RDEB, demonstrating that durable restoration of C7 expression and long-term wound improvement can be achieved through skin grafting.
INTRODUCTION: The development of B-cell maturation antigen (BCMA)-directed therapies has been a significant advancement for the treatment of multiple myeloma. Elranatamab is a bispecific antibody (BsAb) targeting BCMA an...INTRODUCTION: The development of B-cell maturation antigen (BCMA)-directed therapies has been a significant advancement for the treatment of multiple myeloma. Elranatamab is a bispecific antibody (BsAb) targeting BCMA and CD3. It has achieved regulatory approval in several jurisdictions worldwide for the treatment of patients with relapsed/refractory multiple myeloma. Clinical trials of elranatamab in various settings are currently ongoing. AREAS COVERED: This article describes the current evidence for treating relapsed/refractory multiple myeloma with elranatamab. A search for relevant literature was conducted in PubMed, EMBASE, Cochrane Library, and hematology conference abstracts published between 2017 and 2025. Citation mining of the included studies was also conducted. EXPERT OPINION: Elranatamab monotherapy has demonstrated manageable safety and encouraging efficacy in relapsed/refractory multiple myeloma. The overall toxicity profile is comparable to other BCMA-targeting BsAbs. The low grade of cytokine release syndrome (CRS) supports the administration of elranatamab in the outpatient setting. High infection rates remain a challenge, although further refinement of anti-infection prophylaxis and adjustment of the dosing schedule may reduce the risk. Clinical trials are currently investigating elranatamab in different settings to further enhance the efficacy, including as a first-line treatment and combination regimens, although benefits need to be weighed against the increased toxicity risk.
BACKGROUND: To evaluate the clinical characteristics, and treatment patterns of difficult-to-treat (D2T) disease in children with polyarticular juvenile idiopathic arthritis (pJIA) treated with biologic disease-modifying...BACKGROUND: To evaluate the clinical characteristics, and treatment patterns of difficult-to-treat (D2T) disease in children with polyarticular juvenile idiopathic arthritis (pJIA) treated with biologic disease-modifying antirheumatic drugs (bDMARDs). RESEARCH DESIGN AND METHODS: This single-center, cross-sectional study included children with RF-positive or RF-negative pJIA who received bDMARD. D2T defined according to EULAR criteria, as inadequate response to at least two bDMARDs with different mechanisms of action. Disease activity was assessed using the JADAS-27. Treatment patterns, switches, and factors associated with D2T were analyzed. RESULTS: A total of 59 pJIA patients (79.9% female) were included, with a median follow-up of 60 months. Ten patients (16.9%) fulfilled the criteria for D2T disease after a follow-up duration of 36 months. At diagnosis, D2T patients had significantly higher inflammatory markers than non-D2T patients, with higher median CRP (45 vs. 12 mg/L, = 0.002) and ESR (77 vs. 38 mm/h, = 0.003) values. In univariate analyses, higher CRP, ESR, temporomandibular joint involvement, and higher JADAS-27 at bDMARD initiation were associated with D2T status ( < 0.05). CONCLUSIONS: D2T course was associated with temporomandibular joint involvement, elevated inflammatory markers, and higher disease activity at the initiation of the first biologic therapy.
INTRODUCTION: IgG4-related disease (RD) is characterized by multiple organ inflammation and enlargement, nodular or hypertrophic lesions, significant infiltration of B cells and IgG4-positive plasma cells, and characteri...INTRODUCTION: IgG4-related disease (RD) is characterized by multiple organ inflammation and enlargement, nodular or hypertrophic lesions, significant infiltration of B cells and IgG4-positive plasma cells, and characteristic fibrosis on histology. It causes diverse organ damage, decreased quality of life, and increased mortality. AREAS COVERED: Treatment typically involves systemic glucocorticoids, which show good initial response rates. However, treatment resistance and flares upon dose reduction or discontinuation are commonly observed. Although the toxicity of glucocorticoids gathers attention, no glucocorticoid-sparing agent has been approved. The involvement of the immune system, including B cells and plasmacytes, in pathological processes has been demonstrated, and the Phase III MITIGATE trial using an anti-CD19 antibody inebilizumab met its primary endpoint, with inebilizumab recently receiving the first regulatory approval for treatment of IgG4-RD in the United States, the European Union, Japan, and others. EXPERT OPINION: This article provides an overview of advances in treatment strategies for IgG4-RD, shedding light upon the characteristics of inebilizumab and results of the clinical trials. Various targeted therapies under the development are expected to overcome limitations in safety and efficacy of glucocorticoids and to reduce risk of organ damage and fibrosis.
BACKGROUND: 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...BACKGROUND: 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. RESEARCH DESIGN AND METHODS: 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. RESULTS: 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 ( = 0.003). However, this difference was no longer significant at the 72-month follow-up ( = 0.254). At the final follow-up, 67.3% of patients continued to receive IFX treatment. Both the adherence rate to IFX ( = 0.012) and the clinical remission rate ( = 0.030) were significantly higher in patients with no surgery compared to those with surgery prior to IFX treatment. CONCLUSIONS: 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.
Prurigo nodularis (PN) is a chronic, debilitating neuro-immunological skin disease characterized by intense pruritus and hyperkeratotic nodules. Nemolizumab, a novel IL-31 receptor alpha antagonist targeting the neural i...Prurigo nodularis (PN) is a chronic, debilitating neuro-immunological skin disease characterized by intense pruritus and hyperkeratotic nodules. Nemolizumab, a novel IL-31 receptor alpha antagonist targeting the neural itch pathway, was investigated in PN. Two randomized phase 3 studies, the Olympia 1 and Olympia 2 trials, provided favorable efficacy and safety data for nemolizumab versus placebo in moderate-to-severe PN. After 16 weeks, a ≥4-point reduction in PP-NRS was achieved in 58.4% (Olympia 1) and 56.3% (Olympia 2) of nemolizumab patients compared to 16.7% and 20.9% in placebo groups, respectively (<0.001). Safety data showed no drug-related serious adverse events or organ toxicity. These trials were the first to clinically demonstrate IL-31 inhibition in PN. Nemolizumab represents a paradigm shift in PN therapy, acting as a potent "neuro-modulator" with rapid itch relief, often observed by Week 4. Future management may rely on disease endotypes to select between neural (IL-31) and immune (IL-4/13) blockade.
INTRODUCTION: 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 pract...INTRODUCTION: 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. AREAS COVERED: 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. EXPERT OPINION: 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.
da Silva AMP, de Deus O, Januário Campos Cardoso L
… +11 more, Virgilio Ribeiro F, Froelich Meldola P, Rodrigues Menezes I, Lee Han M, Quiroga DG, James Almeida K, Haddad Santos D, Perry G, Høilund-Carlsen PF, de Souza Franco E, de Sousa Maia MB
BACKGROUND: Alzheimer's disease (AD) is the most prevalent cause of dementia and has been closely linked to βSupplemental data for this article can be accessed online at ht tps://doi.org/-amyloid accumulation. However, t...BACKGROUND: Alzheimer's disease (AD) is the most prevalent cause of dementia and has been closely linked to βSupplemental data for this article can be accessed online at ht tps://doi.org/-amyloid accumulation. However, the efficacy and safety of anti-β-amyloid monoclonal antibodies remain debated. METHODS: We systematically searched PubMed, Embase, and Cochrane databases for RCTs comparing anti-β-amyloid monoclonal antibodies with placebo in early-stage AD. Eligible trials enrolled participants with biomarker-supported AD and reported global, cognitive, or safety outcomes, including the CDR-SB, ADAS-Cog 13/14, ARIA, and brain volumetric measures. RESULTS: Six RCTs including 7837 participants were analyzed. Mean age ranged from 69.8 to 75.4 years, and 57.4% were APOE ε4 carriers. Anti-β-amyloid therapy was associated with small differences in global and cognitive outcomes, best described as a modest slowing of decline on the CDR-SB and ADAS-Cog scales. Treatment was associated with increased risks of ARIA-E (RR, 9.40; 95% CI, 6.98-12.66) and ARIA-H (RR, 2.40; 95% CI, 2.08-2.78), as well as greater ventricular enlargement and hippocampal atrophy. CONCLUSION: In early AD, anti-β-amyloid monoclonal antibodies are associated with modest slowing of decline accompanied by increased ARIA risk and unfavorable structural brain changes, limiting clinical applicability. PROTOCOL REGISTRATION: www.crd.york.ac.uk/prospero identifier is CRD420251071393.
INTRODUCTION: 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 ne...INTRODUCTION: 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. AREAS COVERED: 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. EXPERT OPINION: 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.
INTRODUCTION: 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 res...INTRODUCTION: 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. AREAS COVERED: 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. EXPERT OPINION: 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.
INTRODUCTION: The rapid development and approval of biosimilars in the US offer a critical opportunity to improve the affordability and accessibility of biologic therapies. AREAS COVERED: This targeted literature review...INTRODUCTION: The rapid development and approval of biosimilars in the US offer a critical opportunity to improve the affordability and accessibility of biologic therapies. AREAS COVERED: 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. EXPERT OPINION: 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.
INTRODUCTION: Zolbetuximab, the first monoclonal antibody targeting claudin 18.2 (CLDN18.2), is approved as first-line treatment for patients with HER2-negative and CLDN18.2-positive gastric or gastroesophageal junction...INTRODUCTION: Zolbetuximab, the first monoclonal antibody targeting claudin 18.2 (CLDN18.2), is approved as first-line treatment for patients with HER2-negative and CLDN18.2-positive gastric or gastroesophageal junction cancers, offering new hope to patients who previously derived limited benefit from molecular targeted therapies or immune checkpoint inhibitors. AREAS COVERED: This review presents clinical insights not fully captured in pivotal phase III trials, examining the clinicopathological characteristics of zolbetuximab-induced gastritis and the dynamics of CLDN18.2 expression during treatment. It further explores key clinical challenges - including standardized patient selection, management of gastrointestinal toxicities, and optimization of treatment sequencing - while providing an overview of recent advances in next-generation CLDN18.2-targeted strategies such as antibody - drug conjugates, bispecific antibodies, and CAR-T cell therapies. EXPERT OPINION: CLDN18.2-targeted therapy has demonstrated the therapeutic feasibility of targeting non-oncogenic drivers, representing a paradigm shift in gastric cancer treatment. Next-generation modalities such as ADCs, bispecific antibodies, and CAR-T cell therapies have shown efficacy even in patients with lower CLDN18.2 expression, suggesting potential to expand treatment eligibility. Moving forward, deeper understanding of gastrointestinal toxicities associated with CLDN-targeted therapies, elucidation of resistance mechanisms, and development of rational combination strategies will be essential to maximize therapeutic benefit in patients with CLDN18.2-positive gastric cancer.
INTRODUCTION: Oncolytic virus (OV) therapy represents a promising approach currently undergoing (pre)-clinical testing for several cancers. Until recently, it was thought that the tropism of oncolytic viruses was restric...INTRODUCTION: Oncolytic virus (OV) therapy represents a promising approach currently undergoing (pre)-clinical testing for several cancers. Until recently, it was thought that the tropism of oncolytic viruses was restricted to epithelial cancer cells unless they were modified to target additional cell types. It has now become evident that some OVs possess a natural ability to target cancer-associated fibroblasts (CAFs). CAFs are strongly highlighted in supporting cancer progression and impeding anti-cancer therapeutics. Therefore, targeting CAFs in addition to tumor cells could enhance therapy efficacy. AREAS COVERED: To date, the molecular determinants of tumor cell permissiveness to OV therapy have been thoroughly investigated. The recent notion that CAFs could also be a target for OVs highlights the importance of a comparable understanding of what makes CAFs permissive to OVs. This review explores the various molecular pathways and molecules that may affect the susceptibility of CAFs to OV infection and lysis. We discuss the potential impact of virus entry receptors, microRNAs, Ras and PI3K/AKT signaling, p53 status and type I interferon signaling. EXPERT OPINION: Further scrutinizing the factors that influence sensitivity of CAFs to OVs can help to identify targets for therapy optimization, especially in tumors with a high abundance of CAFs.
Kougkas N, Skouvaklidou E, Deligeorgakis D
… +8 more, Tsafis K, Mpitouli A, Dimitriadou V, Skepastianos V, Boutel M, Avgerou P, Adamichou C, Dimitroulas T
BACKGROUND: Axial spondyloarthritis (axSpA) leads to significant impairments in quality of life (QoL) and work productivity. While infliximab is effective in treating axSpA, its impact in patients with concomitant extra-...BACKGROUND: Axial spondyloarthritis (axSpA) leads to significant impairments in quality of life (QoL) and work productivity. While infliximab is effective in treating axSpA, its impact in patients with concomitant extra-skeletal manifestations is limited, particularly in the Greek population. AIMS: To evaluate intravenous infliximab's impact on disease activity, QoL, and work productivity in Greek patients with axSpA, and to compare treatment effects in subgroups with and without concomitant psoriasis and inflammatory bowel disease. METHODS: Thirty-nine patients with axSpA participated in a prospective, observational study and assessed at baseline, 6 and 12 months. Disease activity was measured using ASDAS and BASDAI, QoL was assessed via EQ VAS and HAQ, and work productivity was evaluated with WPAI. RESULTS: Infliximab resulted in significant reductions in ASDAS and BASDAI. QoL improved (HAQ decreased and EQ VAS increased). Work productivity also significantly improved, with decreases in absenteeism, presenteeism, activity impairment, and work productivity loss. Importantly, no significant differences were observed between subgroups. CONCLUSION: This study provides real-world evidence that infliximab improved disease activity, quality of life, and work productivity in all patient groups. Although subgroup differences were not statistically significant, these findings suggest consistent therapeutic benefits across diverse clinical presentations of axSpA.