Genetic and T2 biomarkers linked to the efficacy of HDM sublingual immunotherapy in asthma.

Abstract

BACKGROUND:

Hypersensitivity to house dust mite (HDM) allergens is a common cause of allergic asthma symptoms and can be effectively treated with allergy immunotherapy (AIT).

OBJECTIVE:

To investigate whether genetic and type 2 (T2) inflammatory biomarkers correlate with disease severity in subjects with allergic asthma, and whether this can be modified by AIT.

METHODS:

MITRA (NCT01433523) was a phase III, randomised, double-blind, placebo-controlled trial of HDM sublingual immunotherapy (SLIT)-tablets in adults with HDM allergic asthma. Post hoc analyses of the study population (N=742) evaluated associations between T2 inflammatory (blood eosinophils, eosinophil cationic protein (ECP), total IgE and tryptase) and genetic (single-nucleotide polymorphisms, SNP) biomarkers (n=582) for the primary study endpoint (time to first moderate/severe asthma exacerbation). SNP associations were verified in HDM-positive subgroup from an independent 3-year Severe Asthma Research Programme (SARP3) subject cohort.

RESULTS:

An increased asthma exacerbation risk in subjects homozygous for SNP rs7216389 (chromosomal locus 17q12-21) was reduced (p=0.037) by treatment with HDM SLIT (HR=0.37 (95% CI 0.22 to 0.64), p<0.001). The associations between exacerbation risk and 17q12-21 SNPs were replicated in the SARP3 HDM-positive subgroup. High levels of T2 biomarkers were associated with increased risk of asthma exacerbations in the placebo group. HDM SLIT-tablet treatment reduced this risk (blood eosinophils: HR=0.50 (95% CI 0.30 to 0.85); ECP: HR=0.45 (95% CI 0.29 to 0.87); tryptase: HR=0.45 (95% CI 0.25 to 0.80)). The treatment effect was higher (p=0.006) for subjects with a higher number of elevated T2 biomarkers.

CONCLUSIONS:

HDM SLIT-tablet AIT is efficacious in HDM-sensitised asthma subjects with a genetic asthma predisposition and/or an underlying T2 endotype.

TRIAL REGISTRATION NUMBER:

NCT01433523.

• Authors: Ilka Hoof, Klaus Bønnelykke, Thomas Stranzl, Stephanie Brand, Xingnan Li, Mohamed H Shamji, Deborah A Meyers, Eric D Bateman, Eugene Bleecker, Peter Sejer Andersen
• Journal: Thorax (Thorax) Vol. 79 Issue 4 Pg. 332-339 (Mar 15 2024) ISSN: 1468-3296 [Electronic] England
• PMID: 38160049 (Publication Type: Randomized Controlled Trial, Clinical Trial, Phase III, Journal Article)
• Copyright: © Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.

Chemical References

• Tryptases
• Antigens, Dermatophagoides
• Tablets
• Biomarkers
• Allergens

Topics

• Adult
• Animals
• Humans
• Sublingual Immunotherapy (adverse effects)
• Tryptases (therapeutic use)
• Pyroglyphidae
• Treatment Outcome
• Hypersensitivity
• Asthma (therapy, drug therapy)
• Antigens, Dermatophagoides (therapeutic use)
• Tablets (therapeutic use)
• Biomarkers
• Allergens