OX40L blockade and allergen‐induced airway responses in subjects with mild asthma
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SummaryBackgroundThe OX40/OX40L interaction contributes to an optimal T cell response following allergic stimuli and plays an important role in the maintenance and reactivation of memory T effector cells.ObjectiveWe tested whether treatment with an anti‐OX40L monoclonal antibody (MAb) would inhibit allergen‐induced responses in subjects with asthma.MethodsTwenty‐eight mild, atopic asthmatic subjects were recruited for a double‐blind, randomized, placebo‐controlled, parallel‐group trial (ClinicalTrials.gov identifier NCT00983658) to compare blockade of OX40L using a humanized anti‐OX40L MAb to placebo‐administered intravenously in 4 doses over 3 months. Allergen inhalation challenges were carried out 56 and 113 days after the first dose of study drug. The primary outcome variable was the late‐phase asthmatic response. Other outcomes included the early‐phase asthmatic response, airway hyperresponsiveness, serum IgE levels, blood and sputum eosinophils, safety and tolerability.ResultsTreatment with anti‐OX40L MAb did not attenuate the early‐ or late‐phase asthmatic responses at days 56 or 113 compared with placebo. In the anti‐OX40L MAb treatment group, total IgE was reduced 17% from pre‐dosing levels, and sputum eosinophils decreased 75% by day 113 (both P =0.04). There was no effect of anti‐OX40L MAb on airway hyperresponsiveness or blood eosinophils. The frequency of AEs was similar in both groups.Conclusion and Clinical RelevancePharmacological activity of anti‐OX40L MAb was observed by decreases in serum total IgE and airway eosinophils at 16 weeks post‐dosing, but there was no effect on allergen‐induced airway responses. It is possible that the treatment duration or dose of antibody was insufficient to impact the airway responses.
