Effects of interleukin‐6 receptor blockade on allergen‐induced airway responses in mild asthmatics

• Published in: Clinical & translational immunology Vol. 8; no. 6; pp. e1044 - n/a
• Main Authors: Revez, Joana A, Bain, Lisa M, Watson, Rick M, Towers, Michelle, Collins, Tina, Killian, Kieran J, O'Byrne, Paul M, Gauvreau, Gail M, Upham, John W, Ferreira, Manuel AR
• Format: Journal Article
• Language: English
• Published: Australia John Wiley & Sons, Inc 2019; John Wiley and Sons Inc; Wiley
• Subjects: actemra; Allergens; Allergies; allergy; Asthma; Bronchoconstriction; Cardiovascular disease; Clinical medicine; Clinical trials; Cytokines; Gene expression; GWAS; Hospitals; IL6; IL6R; Inhalation; Medical research; Monoclonal antibodies; Neutropenia; Original; Patients; Proteins; Research centers; Respiratory tract; rs2228145; Serum levels; Studies; trans‐signalling; Australia; IL6; GWAS; trans‐signalling; actemra; allergy; IL6R; rs2228145
• ISSN: 2050-0068; 2050-0068
• DOI: 10.1002/cti2.1044

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). In this study, we performed a randomised clinical trial to test the hypothesis that tocilizumab (TCZ), a human monoclonal antibody that blocks IL‐6 signalling, can prevent the development of allergen‐induced bronchoconstriction. A total of 11 patients were randomised to a single dose of tocilizumab between September 2014 and August 2017, when the trial was stopped for futility based on results from an interim analysis. Both the primary and secondary efficacy endpoints were not significantly different between the TCZ‐ (n = 6) and placebo‐ (n = 5) treated groups, indicating that a single dose of tocilizumab was not able to prevent allergen‐induced bronchoconstriction.