Sublingual immunotherapy (SLIT) represents a safer, more comfortable and more convenient allergen immunotherapy than its subcutaneous counterpart. There is an increasing body of evidence showing that SLIT for house dust mites (HDM), grass, ragweed and/or tree pollen improves allergic symptoms and asthma control.1 It is unclear whether SLIT consistently reduces the occurrence of asthma attacks.1–3

Published in 2016, the MITRA trial was arguably the most robust randomised controlled trial assessing the effect of SLIT (specifically HDM-SLIT) on the prevention of asthma attacks in mild-to-moderate allergic asthma.2 Briefly, the MITRA trial was conducted in 834 people with uncontrolled mild-to-moderate allergic asthma and positive HDM allergen-specific immunoglobulin E (IgE) (≥0.7 kU/L or >3 mm on skin prick—usual cutoffs). After randomisation to HDM-SLIT or placebo, participants were monitored on stable background inhaled corticosteroid (ICS) therapy for 7–12 months, thereafter, reducing their ICS dosing up to complete withdrawal within the next 6 months. This ALK-Abelló-sponsored investigation showed a statistically—and just about clinically significant4—decrease in the risk of moderate-to-severe exacerbation in the intervention arms, no matter the dose of HDM-SLIT.

In the original MITRA publication,2 only a few prespecified subgroup ‘responder’ analyses were reported on the trial population (age, sex, allergen sensitisation type and cosensitisation). Unfortunately, no ‘SLIT-responder group’ was identified. The absence of theragnostic markers left clinicians to randomly select who they propose SLIT to, and guidelines to softly suggest HDM-SLIT to be considered as an alternative add-on for uncontrolled mild-to-moderate allergic asthma.3

In this issue of Thorax, Hoof et al from a group of researchers from the pharmaceutical company and academic centres take a …