Current Understanding of the Role of Eosinophils in CRSwNP and Implications for Treatment with Mepolizumab and Benralizumab

BACKGROUND: International consensus statements now subdivide chronic rhinosinusitis (CRS) into several phenotypes and endotypes, including the presence of polyps (CRSwNP) and eosinophilia (eCRSwNP). Biological treatments aimed at blocking eosinophilic inflammation in CRSwNP via interleukin 5 (IL5) or the interleukin 5 receptor (IL5R) have demonstrated limited efficacy thus far. OBJECTIVE: To review the pathophysiology of eCRSwNP, the evidence for mepolizumab (anti-IL5) and benralizumab (anti-IL5R) in CRSwNP, and to highlight areas for future research and therapeutic intervention. METHODS: Primary and secondary literature search. RESULTS: Clinical trials on mepolizumab and benralizumab in CRSwNP are limited and restricted by trial design which prevents direct comparison with other interventions, including surgery. Both agents would appear to provide some benefit in reducing nasal polyp size but limited clinical patient benefit. Molecular biological research highlights that eCRSwNP can occur in the absence of IL5 and that other cells/cytokines play an important part in the disease's pathophysiology. CONCLUSION: Blockade of IL5/IL5R alone would appear to provide limited "real life" clinical benefit in patients with CRSwNP due to the complexities of the pathophysiology of the condition. Therapy aimed at several simultaneous cytokine targets has logic but well-designed trials are unlikely to be forthcoming in the short term due to the financial cost and commercial conflicts of interest.