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@article{Silkoff:2018:10.1016/j.jaci.2017.06.027,
author = {Silkoff, PE and Flavin, S and Gordon, R and Loza, MJ and Sterk, PJ and Lutter, R and Diamant, Z and Turner, RB and Lipworth, BJ and Proud, D and Singh, D and Eich, A and Backer, V and Gern, JE and Herzmann, C and Halperin, SA and Mensinga, TT and Del, Vecchio AM and Branigan, P and San, Mateo L and Baribaud, F and Barnathan, ES and Johnston, SL},
doi = {10.1016/j.jaci.2017.06.027},
journal = {Journal of Allergy and Clinical Immunology},
pages = {1220--1230},
title = {Toll-like receptor 3 blockade in rhinovirus-induced experimental asthma exacerbations: a randomized controlled study},
url = {http://dx.doi.org/10.1016/j.jaci.2017.06.027},
volume = {141},
year = {2018}
}

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TY  - JOUR
AB  - BACKGROUND: Human rhinoviruses (HRVs) commonly precipitate asthma exacerbations. Toll-like receptor 3, an innate pattern recognition receptor, is triggered by HRV, driving inflammation that can worsen asthma. OBJECTIVE: We sought to evaluate an inhibitory mAb to Toll-like receptor 3, CNTO3157, on experimental HRV-16 inoculation in healthy subjects and asthmatic patients. METHODS: In this double-blind, multicenter, randomized, parallel-group study in North America and Europe, healthy subjects and patients with mild-to-moderate stable asthma received single or multiple doses of CNTO3157 or placebo, respectively, and were then inoculated with HRV-16 within 72 hours. All subjects were monitored for respiratory symptoms, lung function, and nasal viral load. The primary end point was maximal decrease in FEV1 during 10 days after inoculation. RESULTS: In asthmatic patients (n = 63) CNTO3157 provided no protection against FEV1 decrease (least squares mean: CNTO3157 [n = 30] = -7.08% [SE, 8.15%]; placebo [n = 25] = -5.98% [SE, 8.56%]) or symptoms after inoculation. In healthy subjects (n = 12) CNTO3157 versus placebo significantly attenuated upper (P = .03) and lower (P = .02) airway symptom scores, with area-under-the-curve increases of 9.1 (15.1) versus 34.9 (17.6) and 13.0 (18.4) versus 50.4 (25.9) for the CNTO3157 (n = 8) and placebo (n = 4) groups, respectively, after inoculation. All of the severe and 4 of the nonserious asthma exacerbations occurred while receiving CNTO3157. CONCLUSION: In summary, CNTO3157 was ineffective in attenuating the effect of HRV-16 challenge on lung function, asthma control, and symptoms in asthmatic patients but suppressed cold symptoms in healthy subjects. Other approaches, including blockade of multiple pathways or antiviral agents, need to be sought for this high unmet medical need.
AU  - Silkoff,PE
AU  - Flavin,S
AU  - Gordon,R
AU  - Loza,MJ
AU  - Sterk,PJ
AU  - Lutter,R
AU  - Diamant,Z
AU  - Turner,RB
AU  - Lipworth,BJ
AU  - Proud,D
AU  - Singh,D
AU  - Eich,A
AU  - Backer,V
AU  - Gern,JE
AU  - Herzmann,C
AU  - Halperin,SA
AU  - Mensinga,TT
AU  - Del,Vecchio AM
AU  - Branigan,P
AU  - San,Mateo L
AU  - Baribaud,F
AU  - Barnathan,ES
AU  - Johnston,SL
DO  - 10.1016/j.jaci.2017.06.027
EP  - 1230
PY  - 2018///
SN  - 0091-6749
SP  - 1220
TI  - Toll-like receptor 3 blockade in rhinovirus-induced experimental asthma exacerbations: a randomized controlled study
T2  - Journal of Allergy and Clinical Immunology
UR  - http://dx.doi.org/10.1016/j.jaci.2017.06.027
UR  - http://hdl.handle.net/10044/1/51680
VL  - 141
ER  -

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