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

Ilka Hoof, Klaus Bønnelykke, Thomas Stranzl, Stephanie Brand, Xingnan Li, Mohamed H. Shamji, Deborah A. Meyers, Eric D. Bateman, Eugene Bleecker, Peter Sejer Andersen

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)332-339
Number of pages8
JournalThorax
Volume79
Issue number4
DOIs
StatePublished - Dec 30 2023

Keywords

  • allergic lung disease
  • asthma
  • asthma genetics
  • asthma mechanisms

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine

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