Allergy最新文献

Background: Phase 3 trials have demonstrated the efficacy and safety of abrocitinib for atopic dermatitis (AD), but real-world evidence remains limited.

Methods: This study prospectively enrolled 117 moderate-to-severe AD patients at Huashan Hospital, Shanghai, China. Physician- and patient-reported outcomes were evaluated at multiple time points. Blood eosinophil counts, serum IgE, and 24 cytokines/chemokines were measured.

Results: Abrocitinib treatment led to rapid and potent improvements in disease severity. At week 12, 74.3% and 50.5% of AD patients achieved at least 75% and 90% improvement in the eczema area and severity index (EASI), respectively. Compared to dupilumab, abrocitinib showed greater improvement in Itch-NRS at week 2 and a higher proportion of EASI-75 at week 4. Adverse events occurred in 42.7% of AD patients, with gastrointestinal symptoms being the most common (17.1%). No tuberculosis (TB) reactivation was observed in patients who screened positive for TB and received isoniazid prophylaxis during the study period. Lower body mass index (BMI < 24; adjusted OR: 4.01, 95% CI: 1.36-11.73) and no prior dupilumab use (adjusted OR: 5.81, 95% CI: 1.8-18.7) were identified as predictors of a good response. By week 4, blood eosinophil counts and serum IgE significantly decreased. Reductions in Th2-, Th1-, and Treg-related cytokines/chemokines after 4 weeks of abrocitinib treatment, including IL-5, CCL17, CCL18, TNF-α, IL-6, IL-10, and CD25/IL-2Rα, were more pronounced in good responders.

Conclusion: Abrocitinib demonstrated robust efficacy and a well-tolerated safety profile in Chinese patients with moderate-to-severe AD in routine clinical practice, accompanied by normalization of elevated blood biomarkers.

Trial registration: ChiCRT Identifier: ChiCTR2200063195.

Background: Asthma exacerbations (AEs) represent the major contributor to the global asthma burden. Although genetic and environmental factors have been associated with AEs, the role of epigenetics remains uncovered.

Objective: This study aimed to identify whole blood DNA methylation (DNAm) markers associated with AEs in Europeans.

Methods: DNAm was assessed in 406 blood samples from Spanish individuals using the Infinium MethylationEPIC microarray (Illumina). An epigenome-wide association study was conducted to test the association of DNAm with AEs at differentially methylated positions, regions, and epigenetic modules. CpGs suggestively associated with AEs (false discovery rate [FDR] < 0.1) were followed up for replication in 222 European individuals, and the genome-wide significance (p < 9 × 10^-8) was declared after meta-analyzing the discovery and replication samples. Additional assessment was performed using nasal tissue DNAm data from 155 Spanish individuals. The effects of genetic variation on DNAm were assessed through cis-methylation quantitative trait loci (meQTL) analysis. Enrichment analyses of previous EWAS signals were conducted.

Results: Four CpGs were associated with AEs, and two were replicated and reached genomic significance in the meta-analysis (annotated to ZBTB16 and BAIAP2). Of those, CpG cg25345365 (ZBTB16) was cross-tissue validated in nasal epithelium (p= 0.003) and associated with five independent meQTLs (FDR < 0.05). Additionally, four differentially methylated regions and one module were significantly associated with AEs. Enrichment analyses revealed an overrepresentation of prior epigenetic associations with prenatal and environmental exposures, immune-mediated diseases, and mortality.

Conclusions: DNAm in whole blood and nasal samples may contribute to AEs in Europeans, capturing genetic and environmental risk factors.

Background: PQ Grass 27600 SU (PQ Grass) cumulative dose is a pre-seasonal, six-injection, aluminium-free, modified subcutaneous immunotherapy product under development for the treatment of allergic rhinitis (AR). A pivotal Phase III randomised double-blind, placebo-controlled clinical trial was performed to evaluate the efficacy and safety of PQ Grass in subjects with seasonal AR.

Methods: An adaptive group sequential trial PQGrass306 (G306) with one pre-defined interim analysis was designed, using 2 parallel groups applying a 1:1 active versus placebo randomisation of patients aged 18-65. The primary efficacy endpoint was the EAACI (European Academy of Allergy and Clinical Immunology) Combined Symptom and Medication Score (EAACI-CSMS_0-6) averaged over the peak grass pollen season (GPS).

Results: 858 subjects were screened and 555 subjects were randomised. Based on the results of the pre-defined interim analysis, the trial was stopped for success showing superiority in favour of PQ Grass. The primary endpoint EAACI-CSMS_0-6 (peak GPS) demonstrated a highly significant and clinically meaningful point difference of PQ Grass over placebo of -0.27 points (95% CI: -0.42 to -0.12), corresponding to a relative difference of -20.3% (p = 0.0005). Highly consistent and beneficial results were obtained for PQ Grass for all key secondary endpoints. Significant induction of blocking IgG4 and IgA antibody subclasses occurred. PQ Grass was well tolerated, and no unexpected safety signals occurred.

Conclusions: This pivotal Phase III trial demonstrated a significant and clinically meaningful effect on the primary endpoint as well as highly consistent secondary endpoint results and a supportive safety profile.