Clinical efficacy of the ALK house dust mite allergy immunotherapy tablet corralates with immunological endpoints

Authors: Pastorello, E¹; Scadding, G²; Ipsen, H³; Ljorring, C³; Bufe, A

¹Niguarda Ca` Granda Hospital, Unit of Allergy and Immunolog, Milano, Italy; ²Royal National Throat, Nose and Ear Hospital, London, United Kingdom; ³ALK, Research & Development, Hørsholm, Danmark; Ruhr-Universität Bochum, Experimentelle Pneumologie, Bochum, Germany4

Source: Journal Compilation©2010Blackwell Publishing Ltd. Allergy 65 (Suppl. 92):174-175

Background: The immunological effect of immunotherapy includes stimulation of the allergen-specific Th1 response. The hypothesis was that allergen-specific (s) IgG4 and sIgE-blocking factor  (serum components blocking IgE-allergen binding), would correlate with the clinical response to immunotherapy with the ALK house dust mite (HDM) allergy immunotherapy tablet (AIT) (ALK, Hørsholm, Denmark). The tablet is a fast-dissolving lyophilisate containing a 1:1 mixture of allergens from Dermatophagoides pteronyssinus (Der p) and farinae (Der f).

Methods: A one-year, double-blind, placebo-controlled trail with HDM AIT was conducted in 604 subjects, aged ≥ 14 years, with mild to moderate HDM allergic asthma. Subjects were randomised to active treatment (1, 3 or 6DU) or placebo once daily. The Primary efficacy endpoint was the reduction in inhaled corticosteroid (ICS) use after one year. At baseline and after one year treatment, sIgE-blocking factor and sIgG4 levels were measured in a subset of the subjects (N = 161). For statistical analysis, delta-ICS and delta-sIgE-blocking factor or delta-log10(sIgG4) were correlated and a Spearman correlation coefficient and P-value for each correlation was calculated.

Results: The trail showed a statistically significant difference in reduction of ICS use between the 6 DU and placebo group (P = 0,0036). Dose-dependent and significant inductions of sIgG4 and sIgE-blocking factor were observed from baseline to the end of treatment. In the 6 DU group, log10(Der f sIgG4) increased 0,47 units from baseline, while the placebo group did not show any changes in sIgG4. The corresponding increase in log10(Der f sIgG4) was 0,37 units. Der f sIgE-blocking factor increased 0,22 units and Der p sIgE-blocking factor 0,17 units in the 6 DU group, while the lower dose groups showed smaller increases and  the placebo group no change. The ICS reduction and the immunological changes were significantly correlated (Der p sIgE-blocking factor: r = -0,25, P = 0,002; Der f sIgE-blocking factor: r = -0,18, P = 0,028: Der p sIgG4: r = - 0,17, P = 0,030; Der f sIgG4: r = -0,17, P = 0,030).

Conclusion: The induction of sIgE-blocking factor and sIgG4 was dose-dependent and correlated with clinical efficacy in terms of reduction in ICS use. This is the first time such correlation has been documented. Further evaluations are necessary to determine whether the immunological parameters may be used as predictive biomarkers of clinical response to ALK HDM AIT in individual patients.