SQ-standardized house dust mite immunotherapy as an immunomodulatory treatment in patients with asthma

Abstract

Background: Specific immunotherapy is the only treatment with the potential to prevent progression of the allergic disease and the potential to cure patients. The immunomodulatory ability of SQ-standardized house dust mite (HDM) subcutaneous immunotherapy (SCIT) was investigated in patients with allergic asthma.

Methods: Fifty-four adults with HDM-allergic asthma were randomized 1:1 to receive SQ-standardized HDM SCIT (ALK) or placebo for 3 years. At baseline, and after 1, 2 and 3 years of treatment, the lowest possible inhaled corticosteroid dose required to maintain asthma control was determined, followed by determinations of nonspecific and HDM-allergen-specific bronchial hyperresponsiveness, late asthmatic reaction (LAR), immediate and late-phase skin reactions, and immunological response.

Results: SQ-standardized HDM SCIT provided a statistically significantly higher HDM-allergen tolerance (P<0.05 vs placebo) in terms of a 1.6-fold increase in PD(20) (HDM-allergen inhalation challenge), a 60-fold increase in skin test histamine equivalent HDM-allergen concentrations, reduced immediate- and reduced or abolished late-phase skin reactions, as well as fewer patients with LAR. PD(20) (methacholine inhalation challenge) increased initially and was similar between groups. House dust mite SCIT induced an initial increase in serum HDM-allergen-specific IgE (P=0.028 vs placebo), which then declined to baseline value. House dust mite SCIT induced an increase in components blocking IgE binding to allergen [ΔIgE-blocking factor: 0.31; 95% CI of (0.26; 0.37)] after 1 year that remained constant after 2 and 3 years (P < 0.0001 vs placebo).

Conclusion: SQ-standardized HDM SCIT induced a consistent immunomodulatory effect in adults with HDM-allergic asthma; the humoral immune response was changed and the HDM-allergen tolerance in lung and skin increased.

© 2010 John Wiley & Sons A/S.

Figures

Figure 1

(A) The nonspecific bronchial hyperresponsiveness (BHR) in terms of change from baseline in log10(PD20); estimate and 95% confidence intervals with P-values for the difference between treatment groups. PD20 is the methacholine dose (μg) causing a 20% decline in FEV1. Test: anova with change from baseline as response variable, treatment as fixed effect and baseline as covariate. (B) The house dust mite (HDM)-allergen-specific BHR in terms of change from baseline in log10(PD20); estimate and 95% confidence intervals with P-values for the difference between treatment groups. PD20 is the HDM-allergen dose (SQ-U) causing a 20% decline in FEV1. Test: anova with change from baseline as response variable, treatment as fixed effect and baseline as covariate.

Figure 2

The percentage (%) of patients experiencing a late asthmatic reaction in terms of use of beta-2 agonist in each treatment group with P-values for the difference between treatment groups (Fischer’s exact test). NS, no statistical significance.

Figure 3

In the skin prick test titration, the house dust mite-allergen dose (in HEP) and skin reactions (weal area in cm2) were ln-transformed. A statistical parallel line regression model was applied. The histamine equivalent Dermatophagoides pteronyssinus allergen concentrations at baseline and after 1, 2, and 3 years of active treatment (A) and placebo treatment (B) are plotted. HEP, Histamine Equivalent in Prick.

Figure 4

(A) Median areas (in cm2) of the immediate-phase skin reactions for each treatment group at baseline and after 1, 2 and 3 years of treatment with P-values for the difference between treatment groups (Wilcoxon Rank Sum Test). (B) Median areas (in cm2) of the late-phase skin reactions for each treatment group at baseline and after 1, 2 and 3 years of treatment with P-values for the difference between treatment groups (Wilcoxon Rank Sum Test). (C) The percentage (%) of patients without a late-phase skin reaction (weal area <1 cm2), the percentage of patients that experienced intermediate reactions (weal area 1–20 cm2) and the percentage of patients that experienced a severe reaction (weal area >20 cm2) are illustrated at baseline, and after 1, 2 and 3 years of treatment for both house dust mite (HDM) subcutaneous immunotherapy (SCIT) and placebo treatment groups.

Figure 5

Change from baseline in IgE-blocking factor (Dermatophagoides pteronyssinus); estimate and 95% confidence intervals after 1, 2 and 3 years of treatment with P-values for the difference between treatment groups. IgE-blocking factor is a measure of the inhibitory capacity of competing components to specific IgE-allergen binding. Test: anova with change from baseline as response variable, treatment as fixed effect and baseline as covariate.