Expert Opinion on Biological Therapy最新文献

Background: For moderate-to-severe psoriasis, clinical guidelines recommend biologic treatments after failure of at least one traditional systemic therapy. Biologics target different pathways, but a common challenge is loss of efficacy, often requiring a switch. This study explores real-world therapeutic management of moderate-to-severe psoriasis, focusing on biologic treatments.

Methods: A retrospective study was conducted using health records of adult patients currently receiving biologics at Sant'Orsola Hospital in Bologna. Therapeutic sequences were investigated using state sequence analysis. Within-sequence Shannon entropy was calculated and used as the outcome in linear regression models. A directed acyclic graph informed the hierarchical regression models to identify factors influencing treatment duration.

Results: The cohort included 364 patients. Adalimumab was the most common first-line biologic (27%), followed by secukinumab (18%) and etanercept (16%). Nearly half of patients (48%) switched treatments. Increasing age was associated with lower sequence heterogeneity (β = -0.001, p = 0.002). Ustekinumab demonstrated the longest median treatment duration (1,841 days), while etanercept had the shortest (639 days). After adjusting for confounding variables, ustekinumab maintained its positive effect on treatment duration (β = 0.285, p = 0.009).

Conclusion: The treatment duration for ustekinumab was encouraging, supporting its potential role as a durable option in these patients.

Introduction: Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related death worldwide with most of patients diagnosed at advanced stage. Thus, systemic therapy remains a cornerstone of treatment. In recent years, immunotherapy has changed therapeutic scenario, being investigated also in combination with anti-vascular endothelial growth factor (VEGF) agents. This approach has demonstrated safety and efficacy in several trials, paving the way for their investigation in earlier disease stages and in different settings.

Areas covered: A structured literature review was conducted using PubMed and ClinicalTrials.gov to identify published evidence supporting safety and efficacy of anti-programmed death-1/programmed death-ligand-1(PD-1/PD-L1) and anti-VEGF agents in different therapeutic settings and identifying ongoing clinical trials and key research directions.

Expert opinion: Combination of anti-PD-1/PD-L1 and anti-VEGF agents has demonstrated safety and efficacy as a first-line treatment for advanced HCC, supported by results from phase 3 trials. These results suggest that further investigation is warranted to optimize first-line efficacy, second-line choice, and potential application in earlier disease stages. The clinical benefit of anti-PD-1/PD-L1 and anti-VEGF agents have also opened the door to a new clinical paradigm, where transitioning from systemic therapy to locoregional therapies, resection or even liver transplantation could be a feasible treatment strategy.

Background: Ustekinumab (UST) is an interleukin-12/interleukin-23 receptor antagonist approved for the treatment of Crohn's disease (CD). Although UST has demonstrated good efficacy and safety in CD, long-term real-world data in Chinese patients are relatively scarce.

Methods: A single-center, observational retrospective study was conducted in the First Affiliated Hospital of Anhui Medical University. Comprehensive baseline demographic characteristics, clinical parameters, potential predictors of clinical remission of CD patients treated with UST from January 2020 to January 2024 were collected and analyzed.

Results: A total of 348 CD patients were included. At week 52, the clinical remission rate was 70.95%, endoscopic remission 24.68%, C-Reactive Protein (CRP) normalization 54.11%, and fecal calprotectin (FCP) normalization 48.57%. Prior biologic exposure, CRP reduction at week 8, and baseline hemoglobin level were independent predictors of clinical remission. The mean survival duration with UST was 172 weeks (SE = 6, 95% CI: 160-185).

Conclusions: This study demonstrated favorable effectiveness, persistence, and safety of UST in CD patients. Prior biologic exposure, early CRP reduction and hemoglobin level were associated with clinical remission at 52 weeks.

Introduction: Metastatic colorectal cancer (mCRC) remains a leading cause of cancer mortality worldwide, with limited long-term survival despite therapeutic advances. The increasing understanding of its molecular heterogeneity has paved the way for precision medicine approaches aiming to optimize treatment efficacy and reduce unnecessary toxicity.

Areas covered: This review provides an in-depth analysis of the current and emerging molecular targets in mCRC, including RAS, BRAF, HER2, and microsatellite instability. We discuss the clinical relevance of tumor sidedness, hyperselection panels, EGFR ligand expression, and rare alterations such as NTRK, RET, and ALK fusions. The review also explores the evolving role of KRAS G12C inhibitors, HER2-targeted therapies, and the application of liquid biopsy - particularly circulating tumor DNA (ctDNA) - in treatment monitoring, rechallenge strategies, and resistance detection. Literature was selected through a comprehensive review of recent clinical trials, consensus guidelines, and translational studies.

Expert opinion: Personalized treatment is now an attainable goal in mCRC. While promising, broader implementation of molecular-driven strategies requires overcoming challenges such as resistance mechanisms, assay standardization, and equitable access. The integration of innovative agents with real-time molecular monitoring holds the key to a more dynamic and effective management of mCRC.

Objectives: Uveitis is a prevalent complication of juvenile idiopathic arthritis (JIA), leading to ocular morbidity. This study aimed to evaluate uveitis frequency in JIA patients on biologics and explore the impact of biologic selection on its occurrence.

Methods: Among 2,385 JIA patients reviewed, 101 patients who developed uveitis were analyzed. This patients were categorized based on their uveitis development: under methotrexate, after discontinuation of methotrexate, and under biologics.

Results: Uveitis frequency among all reviewed JIA patients was 6.3%. Among those who developed uveitis while receiving biologics, 30 were on etanercept and one on infliximab at the time of onset. When the entire cohort of JIA patients treated with biologics for joint symptoms was evaluated, it was observed that out of 365 patients using etanercept, uveitis developed in 30 individuals, in one out of 39 patients using infliximab, while no cases of uveitis were observed among 285 patients using adalimumab.

Conclusion: In this study we observed a larger frequency of new onset uveitis in JIA patients treated with TNF receptor fusion proteins than those treated with anti-TNF monoclonal antibodies. Monoclonal anti-TNF-α agents may remain the preferred options. This study highlights the necessity of integrating uveitis risk assessment into JIA treatment strategies.

Introduction: Zanidatamab is a humanized biparatopic IgG antibody that selectively inhibits HER2 signaling pathway by targeting two distinct epitopes in the extracellular domains II and IV of HER2. Zanidatamab received accelerated approval from the United States Food and Drug Administration for the treatment of HER2-positive (immunohistochemistry [IHC] 3+) biliary tract cancer (BTC) in November 2024. Additionally, zanidatamab received approval for the treatment of HER2 IHC 3+ BTC from the European Medicines Agency in June 2025, and from National Medical Products Administration of China in May 2025.

Areas covered: We review the currently available advanced BTC treatments from the perspective of targeted therapy, discuss the implications of HER2 as a therapeutic target in BTC, and discuss the available clinical trial data for zanidatamab for BTC treatment. We then comment on how zanidatamab can fit into the current standard of care for advanced BTC treatment, and the directions of future development strategies.

Expert opinion: Zanidatamab appears to be effective for controlling disease progression and maintaining a durable response in patients with previously-treated unresectable or metastatic HER2-positive BTC, with acceptable safety profiles. Based on these favorable data, further investigations using zanidatamab as an earlier line of therapy for BTC are ongoing.

Introduction: Allergen immunotherapy (AIT) is the only disease-modifying treatment for allergic rhinitis and asthma. Sublingual immunotherapy (SLIT) is commonly used in clinical practice. Although its effectiveness has been proven in randomized controlled trials and real-world studies, poor or no responses may occur in some cases.

Areas covered: The present review aims to summarize the main possible factors involved in ineffective SLIT treatment, including immunological mechanisms, molecular and diagnostic errors, non-purified extracts, inadequate dosage, and patients' intrinsic and extrinsic characteristics. Possible remedies are also reported to predict and overcome poor patient response to guarantee optimal treatment efficacy.

Expert opinion: Identifying the reason for SLIT ineffectiveness is clinically relevant. Allergologists should carefully investigate the possible cause of poor or no response to SLIT. Identification is important as the potential removal of the interfering problems might allow SLIT to continue. The most common causes of poor SLIT efficacy include diagnostic errors, incorrect allergen dosage and schedule, poor quality extract, comorbidity, impaired immune system function, and inadequate adherence.

Background: STELLAR-2 assessed the equivalent efficacy of the ustekinumab biosimilar, Bmab 1200, versus reference ustekinumab in patients with moderate-to-severe chronic plaque psoriasis. Safety, immunogenicity, and pharmacokinetics (PK) were also evaluated.

Research design and methods: In this double-blind, parallel-group, Phase 3 study, patients were randomized 1:1 to Bmab 1200 or reference ustekinumab in Treatment Period (TP)1, and at Week 16, those who responded to reference ustekinumab (improvement in Psoriasis Area and Severity Index [PASI] score ≥ 50%) were re-randomized (1:1) to continue reference ustekinumab or switch to Bmab 1200 in TP2. The primary endpoint was the change in PASI from baseline to Week 12. Equivalent efficacy was established if 90% and 95% confidence intervals (CIs) for the treatment difference were within predefined equivalence margins of ± 10% and ± 13%, respectively.

Results: Overall, 384 patients were randomized (Bmab 1200: N = 191; reference ustekinumab: N = 193) in TP1. At Week 12, the least squares mean treatment difference (0.6800%; 90% CI: -1.27, 2.63; 95% CI: -1.64, 3.00) was within the predefined equivalence margins for 90% and 95% CIs. Safety, immunogenicity, and PK were comparable between treatment groups.

Conclusions: Bmab 1200 and reference ustekinumab had similar efficacy, safety, immunogenicity, and PK in patients with moderate-to-severe plaque psoriasis.

Trial registration: www.clinicaltrialsregister.eu identifier is 2021-006668-25; www.clinicaltrials.gov identifier is NCT05335356.

Introduction: This review aims to summarize real-world evidence on the use of biologic therapies in juvenile idiopathic arthritis (JIA), including systemic and non-systemic subtypes, and to explore treatment strategies.

Areas covered: The evolving therapeutic landscape of JIA, emphasizing the differential efficacy and safety profiles of biologic agents such as IL-1 and IL-6 inhibitors, TNF inhibitors, secukinumab and abatacept across JIA subtypes. Special attention is given to real-world registry data, observational studies, and cohort analyses evaluating treatment responses, disease remission rates, flare risk after biologic discontinuation, and the effectiveness of biosimilars. Evidence regarding biologic switching strategies and the challenges of treating difficult-to-manage subtypes such as systemic JIA and enthesitis-related arthritis are also addressed.

Expert opinion: Earlier use of biologic agents may become more widely accepted, particularly in high-risk JIA subtypes. This shift has the potential to promote earlier remission, reduce long-term joint damage and corticosteroid dependency, and minimize hospitalization and complications. However, this approach must be carefully balanced against increased treatment costs and potential long-term dependence on biologics.

Introduction: Ulcerative colitis (UC) is a chronic inflammatory bowel disease characterized by a relapsing-remitting colonic inflammation. Despite advances in understanding UC pathogenesis, a definitive cure remains elusive. Current therapies aim to promote symptom resolution, mucosal healing, and ideally histologic remission. Moderate-to-severe UC patients may require advanced therapies, including biologics and small molecules, targeting pathways that have been implicated in the UC pathogenesis.

Areas covered: This review provides an in-depth analysis of current and emerging therapies targeting the interleukin (IL)-23 pathway in moderate-to-severe UC. It discusses both ustekinumab, a nonselective IL-12/23p40 blocker, and selective IL-23p19 inhibitors (i.e. mirikizumab, guselkumab, and risankizumab), covering their mechanisms of action, clinical efficacy, and safety profiles from registrative and post-marketing studies. The review also explores promising oral therapies under investigation, including IL-23 receptor (IL-23 R) antagonists and TYK2 inhibitors, highlighting their early-phase results.

Expert opinion: IL-23p19 inhibitors have shown significant efficacy in inducing and maintaining remission in UC, with favorable safety profiles. Oral agents represent an exciting frontier, potentially improving patient adherence and accessibility. Direct comparative trials are needed to refine therapeutic positioning in personalized treatment algorithms.