PURPOSE: The early asthmatic (EAR) and late asthmatic responses (LAR) to allergen challenge (AC) have been used to assess the effectiveness of newly developed asthma medications. The selection of the allergen used for AC may influence the results. Differences in tolerance and severity of asthma have been described between house dust mite (HDM) and cat allergens. We evaluated the effect of HDM versus cat allergens on EAR and LAR during a clinical trial of MEDI-528, a humanized, anti- IL-9 monoclonal antibody for the treatment of atopic asthma.
METHODS: Study subjects were participants in a randomized, placebo-controlled, double-blind trial to evaluate the effectiveness of MEDI-528 on the LAR in atopic asthma. AC was performed during a screening challenge which delivered a dose of allergen to generate EAR of a >20% fall in FEV1. Subjects with LAR were randomized to treatment and challenged with allergen at weeks 1, 4, and 8. Methacholine challenge (MC) was performed on the day before and the day following AC. In a post-hoc analysis, subjects were stratified by the two principal allergens used for the allergen challenge. The effect of this stratification on LAR, EAR, and MC was assessed.
RESULTS: HDM was the primary allergen used in 13 subjects and cat allergen was the primary allergen in 15 patients. The maximum mean decrease in FEV1 during both EAR and LAR for subjects who received HDM was greater than the decline for subjects who received cat allergen at all study points (Table). HDM produced a greater fall in methacholine PC20 FEV1 from pre- to post-AC at screening (mean 1.899 vs. 0.343; p<0.002), week 1 (1.394 vs. 0.148; p<0.002), and week 4 (1.196 vs. −0.248; p<0.02).
CONCLUSION: Airway responses after inhalation of cat allergens were not equivalent to those after inhalation of HDM allergens with respect to EAR, LAR, and MC.
CLINICAL IMPLICATIONS: Consideration should be given to the type of allergen employed when using either early or late asthmatic response to assess treatment effects of novel asthma medications.
DISCLOSURE: Joseph Parker, Employee Joseph Parker, Nestor Molfino, Barbara White, and Suha Suri are employees of MedImmune LLC.; Consultant fee, speaker bureau, advisory committee, etc. Gail Gauvreau and Paul O'Byrne are consultants to MedImmune and investigators on MedImmune sponsored clinical trials. Louis-Phillippe Boulet is an investigator on MedImmune sponsored clinical trials.; Product/procedure/technique that is considered research and is NOT yet approved for any purpose. MEDI-528 is an investigational product for the treatment of asthma.