Risankizumab, a treatment indicated for psoriasis and Crohn's disease, has not been shown to be effective in severe asthma. A study published this week in The New England Journal of Medicine shows, on the contrary, that this biotherapy worsens symptoms and decreases breath performance in severe asthma.
The international study led by British, Canadian and Belgian researchers involved 214 patients, 105 of whom were randomised to receive an injection of risankizumab every 4 weeks for 24 weeks, and 109 of whom received a placebo.
The researchers measured time to first worsening as determined by increase in symptoms, worsening of breathing tests, increased use of inhalers and need for steroid tablets for exacerbation. The mean time to first worsening was 40 days for patients treated with risankizumab, compared with 86 days for patients treated with placebo.
Risankizumab is a monoclonal antibody known to inhibit Interleukin-23 (IL-23), a cytokine suspected of playing a role in airway inflammation. Based on previous data, IL-23 was known to have the potential to promote both eosinophilia and tissue neutrophilia, and thus to be a key cytokine in severe asthma, which is known to combine both types of granulocytic inflammation in the airways. The researchers hypothesised that IL-23 is a key cytokine in severe asthma, which is known to combine the two types of granulocytic inflammation in the airways, given the proximity of IL-23's mechanisms of action in triggering psoriasis and Crohn's disease, diseases in which risankizumab has good therapeutic results. However, in the case of severe asthma, the results show the exact opposite effect.
Dr Renaud Louis, professor at the ULiège Faculty of Medicine and head of the Pneumology and Allergology Department at the University Hospital of Liège (CHU Liège), is the Belgian leader of the study. About ten of his patients were involved in the study. His team is one of the few in the world to practice induced sputum, a method that allows access to cells specific to deep bronchial inflammation and to carry out cytological analysis.
"The ineffectiveness of risankizumab is not in itself bad news. These results shed light on the pathophysiology of asthma. It allows us to rule out the hypothesis of IL-23-induced asthma aggravation. In severe forms of asthma, we now know that the action of IL-23 should not be blocked," explains Renaud Louis.
"One of the reasons we put forward in the publication to explain the deterioration of patients on rizankizumab is that by blocking IL-23, we decrease local immunity in the airways as we have demonstrated by transcriptomic analysis on sputum cells."
"This also shows us that asthma and Crohn's disease, although both chronic inflammatory mucosal diseases, are diseases with different fine immunological mechanisms. Fortunately, we already have very effective monoclonal antibodies to treat eosinophilic asthma (anti-IL-5 and anti-IL5 receptor) and severe allergic asthma (Anti-IgE). Even if the outcome of this study is disappointing for the patient, progress in the field of asthma has been remarkable in recent years."
Source
Risankizumab in Severe Asthma: A Phase IIa, Placebo-Controlled Study, dans New England Journal of Medicine, 28 octobre 2021
