trastuzumab (BP 02 / BP02)

Clarifying corticosteroid balance in comparisons of asthma biologics.

Xiao Hua H, Bai Bin B

Bronchial Thermoplasty in Severe Asthma: Bridging Randomised and Real-World Evidence: A Systematic Review and Meta-Analysis.

Lúcio Maria João MJ, Pereira Maria Luiza ML, Barata Catarina C, Lopes Carlos C et al.

Introduction: Bronchial thermoplasty (BT) reduces airway smooth muscle and may benefit severe asthma, but its role alongside biologics remains unclear. We assessed randomised and real-world evidence on efficacy and safety. Methods: We searched PubMed, Scopus, and Cochrane Library for RCTs and observational studies of BT in adults with severe uncontrolled asthma, analysing them separately. Results: Twenty studies were included (five RCTs, 15 observational). In RCTs, BT improved asthma-related quality of life (AQLQ;MD, 0.69; 95% CI 0.30-1.09), asthma control (ACQ; MD,-0.64; 95%CI, -1.10 to -0.19), and morning peak expiratory flow (MD, 20.62 L/min; 95% CI, 4.92-36.32), but did not improve rescue medication use or symptom-free-days. BT increased the risk of hospitalisation during the treatment period (RR, 3.50; 95%CI, 1.26-9.68), with no significant excess thereafter. Real-world studies showed improvements in AQLQ (MD,1.38; 95%CI, 0.97-1.80), ACQ (MD,-1.24; 95%CI, -1.86 to -0.62), and annualised exacerbation rates (MD, -3.79 exacerbations/patient-year; 95%CI, -6.98 to -0.61). Evidence suggested a possible, inconsistent corticosteroid-sparing effect; data on biologics and long-term safety were limited. Conclusions: BT improved asthma-related quality of life and control, mainly in trials without sham controls, but increased short-term hospitalisation risk. Real-world findings were similar but came from uncontrolled studies. BT is not an established alternative to biologics, but may suit carefully selected patients with severe asthma who cannot use or do not respond to them.

Complement in HER2-Positive Breast Cancer: A Conditionally Protective Mechanism Under Attack.

Petkova Dobromira D, Kuleva Ivaila I, Stoyanova Zhasmin Z, Ilcheva Boryana B et al.

The therapeutic efficacy of anti-HER2 monoclonal antibodies in breast cancer has traditionally been attributed to direct inhibition of signaling and antibody-dependent cellular cytotoxicity (ADCC). Recent evidence, however, has established complement activation through the classical pathway as a possible adjunct mechanism underlying the synergistic activity of the trastuzumab and pertuzumab combination. This synergy is mediated by complement-dependent cytotoxicity (CDC) and complement-dependent cellular phagocytosis (CDCP), and is lost upon C1q deletion in preclinical models. Tumor cells evade complement-mediated killing through overexpression of membrane-bound complement regulatory proteins (mCRPs), particularly CD55 and CD59, which correlate with shorter disease-free survival in patients treated with trastuzumab. C1q itself plays a dual, context-dependent role: it acts as a complement-independent tumor suppressor in HER2-positive breast cancer while promoting tumor progression in most other malignancies. Emerging therapeutic strategies, including biparatopic antibodies such as zanidatamab, complement-redirecting immunoconjugates, and mCRP-targeting approaches, aim to overcome complement resistance and enhance antitumor immunity. On this basis, we propose that HER2-positive breast cancer represents a conditionally complement-protective tumor, in which the balance between antibody-directed complement activation and mCRP-mediated evasion determines treatment outcome. This review evaluates the current evidence linking complement to anti-HER2 therapy and highlights future directions for successful treatment.

Prevalence of Atopic Dermatitis in the United States, 2019-2023: National, State, and County-Level Estimates from Administrative Claims Data.

Abuabara Katrina K, Capozza Korey K, Muthuri Stella S, Florea Ana A et al.

The prevalence of diagnosed atopic dermatitis (AD) and associated patient and treatment characteristics have not been comprehensively investigated in the United States of America (USA), especially at the state and county levels. Evaluating geographic distribution, treatment utilization, and disease characteristics at a more granular level can enhance the understanding of disease burden and aid in the identification of areas with unmet needs. The aims of the study were to describe the prevalence of AD, the associated medical conditions, and filled prescription medications for patients with diagnosed AD in the USA at the national, state, and county levels. Using the open-claims IQVIA® Longitudinal Access and Adjudicated Data database, individuals with ≥ 1 ICD-10-CM AD diagnosis code between 1 January 2019 and 31 December 2023 (index period) were identified. Age- and sex-standardized prevalences were calculated at national, state, and county levels. Geographic location was inferred from the healthcare provider's zip code. Demographics and treatments were assessed during the 365-day baseline period. A total of 5,573,454 patients were identified with an AD diagnosis during the index period. Median age of patients with diagnosed AD was 18 years (interquartile range, 6-49); 57.1% of patients were female, 38.3% were children (0-11 years old), 11.4% were adolescents (12-17 years old), and 50.2% were adults (≥ 18 years old). Nationally, the prevalence of diagnosed AD was 2.4%; age-standardized prevalence was 2.2% in males and 2.6% in females. Prevalence was highest in children (7.2%), followed by adolescents (3.6%) and adults (1.4%). State-level prevalence ranged from 1.3% (Missouri) to 4.5% (Washington, DC). At the county level, AD prevalence ranged from 0 to 19.6%. Prescriptions filled during the baseline period included topical (56.3%) and oral (22.6%) corticosteroids, biologics (2.8%), and oral JAKis (0.2%). During the 6-month postindex period, topical (27.6%) and oral (11.6%) corticosteroids remained the most frequently filled prescriptions; biologics (2.8%) and oral JAKis (0.2%) were less frequently filled. Using a large open-claims database, distinct variations in AD prevalence between age groups and geographies were identified. Differences in the low use of biologics and oral JAKis with high corticosteroid use were observed nationally.