PMID- 31223480
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220408
IS  - 2050-0068 (Print)
IS  - 2050-0068 (Electronic)
IS  - 2050-0068 (Linking)
VI  - 8
IP  - 6
DP  - 2019
TI  - Effects of interleukin-6 receptor blockade on allergen-induced airway responses 
      in mild asthmatics.
PG  - e1044
LID - 10.1002/cti2.1044 [doi]
LID - e1044
AB  - BACKGROUND: Interleukin (IL)-6 signalling has been implicated in allergic asthma 
      by animal, genetic association and clinical studies. In this study, we tested the 
      hypothesis that tocilizumab (TCZ), a human monoclonal antibody that blocks IL-6 
      signalling, can prevent the development of allergen-induced bronchoconstriction 
      in humans. METHODS: We performed a randomised, double-blind, placebo-controlled 
      study, with eligible participants completing two allergen inhalation challenge 
      tests, conducted before and after treatment with a single dose of TCZ or placebo. 
      The primary efficacy endpoint was the magnitude of the late asthmatic response 
      recorded between 3 and 7 after allergen challenge. The secondary efficacy 
      endpoint was the early asthmatic response, measured 20 min to 2 h after allergen 
      challenge. RESULTS: A total of 66 patients enrolled between September 2014 and 
      August 2017, when the trial was stopped for futility based on results from an 
      interim analysis. Eleven patients fulfilled all eligibility criteria assessed at 
      baseline and were subsequently randomised to the TCZ (n = 6) or placebo (n = 5) 
      groups. Both the primary and secondary efficacy endpoints were not significantly 
      different between the two groups. Five patients reported adverse events (AEs), 
      three in the TCZ group (11 AEs) and two in the placebo group (four AEs). Only one 
      AE was TCZ-related (mild neutropenia), and there were no serious AEs. Significant 
      treatment effects were observed for serum levels of C-reactive protein, IL-6 and 
      soluble IL-6R levels. CONCLUSION: In a small proof-of-concept clinical trial, we 
      found no evidence that a single dose of tocilizumab was able to prevent 
      allergen-induced bronchoconstriction. (Trial registered in the Australian New 
      Zealand Clinical Trials Registry, number ACTRN12614000123640).
FAU - Revez, Joana A
AU  - Revez JA
AUID- ORCID: 0000-0003-3204-5396
AD  - QIMR Berghofer Medical Research Institute Brisbane QLD Australia.
FAU - Bain, Lisa M
AU  - Bain LM
AD  - QIMR Berghofer Medical Research Institute Brisbane QLD Australia.
FAU - Watson, Rick M
AU  - Watson RM
AD  - Division of Respirology Department of Medicine McMaster University Hamilton ON 
      Canada.
FAU - Towers, Michelle
AU  - Towers M
AD  - Diamantina Institute University of Queensland Brisbane QLD Australia.
FAU - Collins, Tina
AU  - Collins T
AD  - Diamantina Institute University of Queensland Brisbane QLD Australia.
FAU - Killian, Kieran J
AU  - Killian KJ
AD  - Division of Respirology Department of Medicine McMaster University Hamilton ON 
      Canada.
FAU - O'Byrne, Paul M
AU  - O'Byrne PM
AD  - Division of Respirology Department of Medicine McMaster University Hamilton ON 
      Canada.
FAU - Gauvreau, Gail M
AU  - Gauvreau GM
AD  - Division of Respirology Department of Medicine McMaster University Hamilton ON 
      Canada.
FAU - Upham, John W
AU  - Upham JW
AD  - Diamantina Institute University of Queensland Brisbane QLD Australia.
FAU - Ferreira, Manuel Ar
AU  - Ferreira MA
AUID- ORCID: 0000-0001-9059-1825
AD  - QIMR Berghofer Medical Research Institute Brisbane QLD Australia.
LA  - eng
PT  - Journal Article
DEP - 20190614
PL  - Australia
TA  - Clin Transl Immunology
JT  - Clinical & translational immunology
JID - 101638268
PMC - PMC6566140
OTO - NOTNLM
OT  - GWAS
OT  - IL6
OT  - IL6R
OT  - actemra
OT  - allergy
OT  - rs2228145
OT  - trans-signalling
EDAT- 2019/06/22 06:00
MHDA- 2019/06/22 06:01
PMCR- 2019/06/14
CRDT- 2019/06/22 06:00
PHST- 2019/01/18 00:00 [received]
PHST- 2019/03/03 00:00 [revised]
PHST- 2019/03/04 00:00 [accepted]
PHST- 2019/06/22 06:00 [entrez]
PHST- 2019/06/22 06:00 [pubmed]
PHST- 2019/06/22 06:01 [medline]
PHST- 2019/06/14 00:00 [pmc-release]
AID - CTI21044 [pii]
AID - 10.1002/cti2.1044 [doi]
PST - epublish
SO  - Clin Transl Immunology. 2019 Jun 14;8(6):e1044. doi: 10.1002/cti2.1044. 
      eCollection 2019.