Prof. Brightling

Risankizumab Found Ineffective in Severe Asthma

MedicalResearch.com Interview with:

Prof. Brightling

Prof. Brightling

Professor Chris Brightling, NIHR Senior Investigator
Department of Respiratory Sciences
University of Leicester
Leicester, UK

MedicalResearch.com: What is the background for this study? What are the main findings? 

Response: Risankizumab is an anti-IL23 monoclonal antibody. It is a very effective licensed therapy for plaque psoriasis. IL23 has been implicated in asthma and therefore we chose to study the effect of risankizumab in people with severe asthma.

The time to first asthma worsening was earlier and the frequency of asthma worsenings was higher in those treated with risankizumab versus placebo.

We found that the gene expression of key molecules involved in the response to infection were decreased in airway samples in those treated with risankizumab. It is possible that the increased asthma worsening following risankizumab was related to this suppression of anti-microbial immunity. 
MedicalResearch.com: What should readers take away from your report?

Response: Not only was targeting the IL23 pathway in asthma not beneficial those treated with risankizumab had worse outcomes than those treated with placebo. This might be due to risankizumab impairing the response to infection in severe asthma.

MedicalResearch.com: Did risankizumab affect type-2/eosinophilic inflammation which is the target for current asthma biologics?

Response: Risakizumab neither affected the number of eosinophils nor the gene expression of T2 molecules. This suggests this type of inflammation would have continued in the asthma patients during the trial irrespective of receiving risankizumab or placebo.

MedicalResearch.com: What recommendations do you have for future research as a result of this work?

Response: We do not recommend further trials of anti-IL23 in asthma. Further studies of the reasons why in some people asthma treatments can work, be ineffective or might cause harm is critical in helping to develop precision medicines.

Who funded the trial? The clinical trial was sponsored and funded by BI/Abbvie. Additional gene expression analyses were supported by the Leicester NIHR BRC and the EU IMI programme 3TR. 

Citation:

Risankizumab in Severe Asthma — A Phase 2a, Placebo-Controlled Trial

Christopher E. Brightling, F.Med.Sci., Parameswaran Nair, M.D., Ph.D., David J. Cousins, Ph.D., Renaud Louis, M.D., Ph.D., and Dave Singh, M.D.
October 28, 2021
N Engl J Med 2021; 385:1669-1679
DOI: 10.1056/NEJMoa2030880

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Last Updated on October 27, 2021 by Marie Benz MD FAAD