Expert Opinion on Biological Therapy最新文献

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.

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: 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.

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.

Introduction: Inherited epidermolysis bullosa (EB) is a family of rare-inherited dermatoses that result in mucocutaneous fragility and blister formation inducible by minor trauma. Clinically, EB mainly presents as increased skin fragility with trauma-induced blisters and erosions, combined with extracutaneous manifestations and their complications in other epithelialized organs. No cure for inherited EB is currently available. Treatment of inherited EB is mainly supportive, aiming to reduce patients' pain and itching.

Areas covered: Some advances in the treatment of inherited epidermolysis bullosa have recently been achieved, including topical drug treatment, systemic drug treatment, gene-based therapy, and cell-based therapy. This review focuses on the treatment progress of inherited epidermolysis bullosa. PubMed was searched up to February 2025 to identify relevant studies on inherited EB.

Expert opinion: Emerging advances of therapies in gene-based therapy and cell-based therapy can partially address the symptoms of EB and provide hope for the patients.

Introduction: The successful clinical trials of the type I interferon (IFN) receptor monoclonal antibody, anifrolumab, have proven the benefit of IFN blockade in systemic lupus erythematosus (SLE), and paved the way for novel therapies targeting this pathway.

Areas covered: This review will cover the updated evidence regarding the efficacy and safety of anifrolumab since its positive phase III trial in 2020. In addition, indications of the clinical benefit of emerging IFN-targeting therapies, such as monoclonal antibodies targeting IFN-producing cells and small-molecule inhibitors of IFN signaling, currently in phase II/III clinical trials will be discussed.

Expert opinion: Evidence from clinical trials and real-world studies have revealed the potential for IFN blockade to reduce disease activity and flares, improve glucocorticoid (GC) tapering and increase the attainment of treat-to-target goals in SLE, including in refractory patients. The efficacy of IFN blockade across different SLE disease manifestations and patient subgroups remains under investigation, as well as the ability of such treatments to reduce end organ damage. Regardless, it is clear that IFN blockade has earned a place as part of the standard of care in SLE. Future studies are needed to define whether IFN blockade moves toward being a first-line treatment.

Introduction: Until recently, the biological treatment options for hidradenitis suppurativa (HS) were largely restricted to adalimumab and secukinumab. In 2024, bimekizumab, an IL-17A and IL-17F antibody was introduced to the clinical practice.

Areas covered: Bimekizumab offers a new therapeutic approach for managing HS. It was approved by the U.S Food and Drug Administration (FDA) and European Medicines Agency (EMA) in 2024. The available biologic therapies in HS treatment are described. The data from phase II and phase III clinical trials were analyzed to evaluate the bimekizumab effectiveness in HS treatment. Data from those trials and latest summaries of product characteristics (SmPC) were retrieved to investigate its safety profile. The current preliminary data regarding its long-term effectiveness from BE HEARD EXT (NCT04901195) trial were presented.

Expert opinion: The common side effects of bimekizumab were upper respiratory infections, candida infections and eczematous reactions across all indications. The favorable side effects profile and strong clinical effectiveness proved in clinical trials gave the bimekizumab potential to become the first-choice drug in HS treatment.

Introduction: Osteoporosis is a significant public health issue due to its associated morbidity, mortality, and economic burden. Despite available effective treatments, a treatment gap persists, characterized by delayed diagnosis, undertreatment, and poor adherence. Biosimilars, such as biosimilars for denosumab, offer an opportunity to improve treatment accessibility and affordability for osteoporosis and cancer-related bone loss.

Areas covered: This review explores the current treatment challenges in osteoporosis, the potential of denosumab biosimilars in improving access and outcomes, and the necessity of a multidisciplinary, patient-centered approach.

Expert opinion: The emergence of biosimilars for denosumab offers an opportunity to enhance accessibility and affordability of osteoporosis treatment, as biosimilars provide effective and economic versions of reference biologic therapies. A multidisciplinary approach is vital in managing osteoporosis, central to which is the patient, whose preferences, values, and lifestyle must guide the treatment plan. Healthcare providers play a crucial role in educating patients, promoting adherence to prescribed treatments, and involving patients in their own care to improve health outcomes.