Effect of CRTH2 antagonism on the response to experimental rhinovirus infection in asthma : a pilot randomised controlled trial
© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY. Published by BMJ..
BACKGROUND AND AIMS: The chemoattractant receptor-homologous molecule expressed on T helper type 2 cells (CRTH2) antagonist timapiprant improved lung function and asthma control in a phase 2 study, with evidence suggesting reduced exacerbations. We aimed to assess whether timapiprant attenuated or prevented asthma exacerbations induced by experimental rhinovirus (RV) infection. We furthermore hypothesised that timapiprant would dampen RV-induced type 2 inflammation and consequently improve antiviral immune responses.
METHODS: Atopic patients with partially controlled asthma on maintenance inhaled corticosteroids were randomised to timapiprant (n=22) or placebo (n=22) and challenged with RV-A16 3 weeks later. The primary endpoint was the cumulative lower respiratory symptom score over the 14 days post infection. Upper respiratory symptoms, spirometry, airway hyperresponsiveness, exhaled nitric oxide, RV-A16 virus load and soluble mediators in upper and lower airways samples, and CRTH2 staining in bronchial biopsies were additionally assessed before and during RV-A16 infection.
RESULTS: Six subjects discontinued the study and eight were not infected; outcomes were assessed in 16 timapiprant-treated and 14 placebo-treated, successfully infected subjects. There were no differences between treatment groups in clinical exacerbation severity including cumulative lower respiratory symptom score day 0-14 (difference 3.0 (95% CI -29.0 to 17.0), p=0.78), virus load, antiviral immune responses, or RV-A16-induced airway inflammation other than in the bronchial biopsies, where CRTH2 staining was increased during RV-A16 infection in the placebo-treated but not the timapiprant-treated group. Timapiprant had a favourable safety profile, with no deaths, serious adverse events or drug-related withdrawals.
CONCLUSION: Timapiprant treatment had little impact on the clinicopathological changes induced by RV-A16 infection in partially controlled asthma.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2022 |
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| Erschienen: |
2022 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:77 |
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| Enthalten in: |
Thorax - 77(2022), 10 vom: 02. Okt., Seite 950-959 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Farne, Hugo [VerfasserIn] |
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| Links: |
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| Themen: |
Adrenal Cortex Hormones |
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| Anmerkungen: |
Date Completed 18.05.2023 Date Revised 24.05.2023 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1136/thoraxjnl-2021-217429 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM332545768 |
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| 100 | 1 | |a Farne, Hugo |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Effect of CRTH2 antagonism on the response to experimental rhinovirus infection in asthma |b a pilot randomised controlled trial |
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| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY. Published by BMJ. | ||
| 520 | |a BACKGROUND AND AIMS: The chemoattractant receptor-homologous molecule expressed on T helper type 2 cells (CRTH2) antagonist timapiprant improved lung function and asthma control in a phase 2 study, with evidence suggesting reduced exacerbations. We aimed to assess whether timapiprant attenuated or prevented asthma exacerbations induced by experimental rhinovirus (RV) infection. We furthermore hypothesised that timapiprant would dampen RV-induced type 2 inflammation and consequently improve antiviral immune responses | ||
| 520 | |a METHODS: Atopic patients with partially controlled asthma on maintenance inhaled corticosteroids were randomised to timapiprant (n=22) or placebo (n=22) and challenged with RV-A16 3 weeks later. The primary endpoint was the cumulative lower respiratory symptom score over the 14 days post infection. Upper respiratory symptoms, spirometry, airway hyperresponsiveness, exhaled nitric oxide, RV-A16 virus load and soluble mediators in upper and lower airways samples, and CRTH2 staining in bronchial biopsies were additionally assessed before and during RV-A16 infection | ||
| 520 | |a RESULTS: Six subjects discontinued the study and eight were not infected; outcomes were assessed in 16 timapiprant-treated and 14 placebo-treated, successfully infected subjects. There were no differences between treatment groups in clinical exacerbation severity including cumulative lower respiratory symptom score day 0-14 (difference 3.0 (95% CI -29.0 to 17.0), p=0.78), virus load, antiviral immune responses, or RV-A16-induced airway inflammation other than in the bronchial biopsies, where CRTH2 staining was increased during RV-A16 infection in the placebo-treated but not the timapiprant-treated group. Timapiprant had a favourable safety profile, with no deaths, serious adverse events or drug-related withdrawals | ||
| 520 | |a CONCLUSION: Timapiprant treatment had little impact on the clinicopathological changes induced by RV-A16 infection in partially controlled asthma | ||
| 650 | 4 | |a Randomized Controlled Trial | |
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a asthma | |
| 650 | 4 | |a viral infection | |
| 650 | 7 | |a Adrenal Cortex Hormones |2 NLM | |
| 700 | 1 | |a Glanville, Nicholas |e verfasserin |4 aut | |
| 700 | 1 | |a Johnson, Nicholas |e verfasserin |4 aut | |
| 700 | 1 | |a Kebadze, Tata |e verfasserin |4 aut | |
| 700 | 1 | |a Aniscenko, Julia |e verfasserin |4 aut | |
| 700 | 1 | |a Regis, Eteri |e verfasserin |4 aut | |
| 700 | 1 | |a Zhu, Jie |e verfasserin |4 aut | |
| 700 | 1 | |a Trujillo-Torralbo, Maria-Belen |e verfasserin |4 aut | |
| 700 | 1 | |a Kon, Onn Min |e verfasserin |4 aut | |
| 700 | 1 | |a Mallia, Patrick |e verfasserin |4 aut | |
| 700 | 1 | |a Prevost, A Toby |e verfasserin |4 aut | |
| 700 | 1 | |a Edwards, Michael R |e verfasserin |4 aut | |
| 700 | 1 | |a Johnston, Sebastian L |e verfasserin |4 aut | |
| 700 | 1 | |a Singanayagam, Aran |e verfasserin |4 aut | |
| 700 | 1 | |a Jackson, David J |e verfasserin |4 aut | |
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