Expert Opinion on Biological Therapy最新文献

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: Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is an ultra-rare disease that arises from malignant precursor dendritic cells. Historically, there was no uniform standard-of-care chemotherapy. In this setting, outcomes were substandard, especially for patients not eligible for intensive chemotherapy, clinical trials, and/or hematopoietic stem cell transplantation, which constituted the majority of patients. The development of targeted therapy, namely the anti-CD123 agent tagraxofusp, marked the beginning of a new era in the treatment of BPDCN.

Areas covered: This review summarizes current targeted therapies in BPDCN, highlights recent therapeutic strategies and emerging approaches with the potential to improve patient outcomes. We also discuss key barriers to clinical implementation, including adverse events associated with anti-CD123-directed therapies and limitations related to treatment cost and accessibility.

Expert opinion: The approval of tagraxofusp established a foundation for targeted therapy in BPDCN and demonstrated high response rates, leading to the development of additional antibody - drug conjugates and cellular therapies targeting CD123. Other promising investigational targeted approaches may include BCL2 inhibitors, proteasome inhibitors, and therapies directed against surface antigens such as CD38 and CD303, as well as bromodomain and extraterminal (BET) inhibitors. Collectively, these strategies represent important advances that may significantly improve the historically poor outcomes associated with BPDCN.

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, p = 0.002) and ESR (77 vs. 38 mm/h, p = 0.003) values. In univariate analyses, higher CRP, ESR, temporomandibular joint involvement, and higher JADAS-27 at bDMARD initiation were associated with D2T status (p < 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.

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.

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.

Introduction: Rapid and equitable access to antiviral biologics in outbreaks is constrained by bespoke manufacturing, lengthy trials, and uneven procurement. Biosimilar antivirals could change responsiveness from single-source supply to multi-manufacturer preparedness if regulatory and chemistry, manufacturing, and controls (CMC) platforms are leveraged.

Areas covered: Evidence on antiviral biologic classes, orthogonal analytics, critical quality attributes, pharmacokinetic/pharmacodynamic (PK/PD) biomarkers, regulatory convergence, value assessment, and manufacturing scale-up is summarized. Platform CMC and tech-transfer enablers (e.g. single-use, modular/distributed facilities) are described alongside integration of dynamic transmission models with distributional cost-effectiveness analysis to address equity. The review evaluates how high-resolution analytical similarity, combined with comparative clinical pharmacology, can reduce the need for comparative clinical efficacy studies in selected programs. paradigm. Databases and regulatory/health technology assessment portals were searched from January 2010 to 10 October 2025. Predetermined criteria with structured extraction and consensus resolution were utilized for dual screening.

Expert opinion: The field is moving toward PK/PD-anchored, analytics-first pathways that, with thorough mapping of structure - function relationships, may limit the need for Phase III trials. Pre-specified PD/analytic packages are provided for each modality/virus, along with reference product batch libraries, bridging plans, reliance agreements, and standing commission regulations to operationalize this approach in an emergency.

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: 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.