Premium
OX 40L blockade and allergen‐induced airway responses in subjects with mild asthma
Author(s) -
Gauvreau G. M.,
Boulet L.P.,
Cockcroft D. W.,
FitzGerald J. M.,
Mayers I.,
Carlsten C.,
Laviolette M.,
Killian K. J.,
Davis B. E.,
Larché M.,
Kipling C.,
Dua B.,
Mosesova S.,
Putnam W.,
Zheng Y.,
Scheerens H.,
McClintock D.,
Matthews J. G.,
O'Byrne P. M.
Publication year - 2014
Publication title -
clinical and experimental allergy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.462
H-Index - 154
eISSN - 1365-2222
pISSN - 0954-7894
DOI - 10.1111/cea.12235
Subject(s) - medicine , placebo , asthma , immunology , sputum , tolerability , chills , adverse effect , pathology , tuberculosis , alternative medicine
Summary Background The OX 40/ OX 40L 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. Objective We tested whether treatment with an anti‐ OX 40L monoclonal antibody ( MA b) would inhibit allergen‐induced responses in subjects with asthma. Methods Twenty‐eight mild, atopic asthmatic subjects were recruited for a double‐blind, randomized, placebo‐controlled, parallel‐group trial (ClinicalTrials.gov identifier NCT 00983658) to compare blockade of OX 40L using a humanized anti‐ OX 40L MA b 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. Results Treatment with anti‐ OX 40L MA b did not attenuate the early‐ or late‐phase asthmatic responses at days 56 or 113 compared with placebo. In the anti‐ OX 40L MA b 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‐ OX 40L MA b on airway hyperresponsiveness or blood eosinophils. The frequency of AE s was similar in both groups. Conclusion and Clinical Relevance Pharmacological activity of anti‐ OX 40L MA b 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.