Hereditary α-tryptasemia is associated with response to omalizumab in severe allergic asthma

Higher basal serum tryptase (BST) levels have been associated with increased asthma severity that correlated with active tryptase allele number and was linked to poor clinical responses to anti-IgE treatment (omalizumab). However, the commonest cause of elevated BST is hereditary α-tryptasemia (HαT) caused by increased α-tryptase-encoding Tryptase alpha/beta 1 (TPSAB1) copy number, and its relationship to omalizumab response in asthma remains unclear.

Our aim was to assess the relative contribution of tryptase genotype and HαT to the clinical efficacy of omalizumab treatment in patients with severe allergic asthma.

A cohort (N=181) of severe allergic asthma patients treated with omalizumab from 2 tertiary referral centres in Slovenia and the UK underwent tryptase genotyping, and clinical features were subsequently compared between groups with and without HαT.

Limited benefit from omalizumab therapy was demonstrated in 22.7% of patients. Overall, HαT was identified in 8.3% of patients with severe allergic asthma treated with omalizumab. HαT was found in 20% of individuals with poor clinical responses to omalizumab, compared to 5% of those with positive responses (OR = 4.6 [95% CI 1.5-12.3]; P = .0068). In multivariable analysis, adjusted for study site and other covariates, HαT remained independently associated with poor response to omalizumab (OR = 4.56; [95% CI, 1.24-16.74]; P = .022). Among patients with HαT, 4 of 15 had BST below 8 ng/mL.

HαT is associated with poorer clinical response to anti-IgE treatment in patients with severe allergic asthma.