The future of biologics?
Reviewed by Joanna Stephens

This paper takes a deep dive into how eosinophilia affects the responsiveness of the host to the two monoclonal antibodies mepolizumab and bendralizumab, both of which are active against IL5. We know that eosinophils are attracted and trapped into the nasal mucosa by adhesion molecules, IL4 and platelet-activating factors amongst other mechanisms. The eosinophils degranulate and encourage chemotaxis of other inflammatory cells in the T2 inflammatory response and these damage the nasal mucosa, affecting healing. Multiple other factors in the inflammatory pathway also contribute to the symptoms experienced in CRSwNP and CRSsNP. The authors suggest that the benefits from bendralizumab and mepolizumab, with regards to sinus and smell symptoms, are limited and somewhat disappointing - which may be a slightly controversial view. They propose that “targeting IL5 (or its receptor) can only ever block one part of an incredibly complex system of dysfunctional cytokine-mediated inflammation”. Perhaps a combination of IL5 biologics with anti-IgE, anti-ILR4 and/or ILR3 may be more effective. This paper demonstrates the complexity of the pathway and the science, and provides some food for thought for future therapies.

Current understanding of the role of eosinophils in CRSwNP and Implications for treatment with Mepolizumab and Bendralizumab.
Carney AS, Smith PK.
AM J RHINOL ALLERGY
2023;37(2):175-81.