Study suggests non-allergy type mechanisms may not be relevant in severe asthma

An international, multi-centre clinical trial has shown that a monoclonal antibody targeting interleukin-23 (IL-23) – known as risankizumab – was not associated with lower airway inflammation or greater disease control in patients with severe asthma. The study also suggested that patients who received risankizumab may fare poorly compared to those who received placebo. Despite the negative study outcome, it has offered fresh insights and raised further questions, and may point to a yet-unrecognized infection contributing to severe asthma.

“This important negative study provides evidence that non-allergic cytokines and neutrophils observed in severe asthma most likely indicate an unrecognized airway infection and therefore blocking these pathways do not lead to clinical improvement in asthma,” said Dr. Parameswaran Nair, Professor of Medicine at McMaster University and staff respirologist at St. Joseph’s Healthcare Hamilton, who led the study in Hamilton.

The study team, consisting of researchers from McMaster University, the University of Leicester, the University of Manchester, and the University of Liege, published their findings in the New England Journal of Medicine on October 28, 2021.

The phase 2a study included 214 participants, with 105 taking risankizumab while the others received a placebo. Researchers noted that while risankizumab did not affect sputum cell counts, which are indicators of severe asthma, it did attenuate the sputum IL-23 dependent gene expression, supporting the view that this monoclonal antibody did have a biologic effect on airway immunity.

Monoclonal antibodies can block specific interleukins – molecules that allow immune system cells to communicate with one another. Interleukins are responsible for coordinating the body’s response to infection, but they can also cause disease.