Biologics for chronic rhinosinusitis with nasal polyps

Abstract

With the increasing recognition of the role of type 2 immune responses in chronic rhinosinusitis, its severity, recurrence, and comorbidities, several biologics targeting IL-4, IL-5, and IL-13 as well as IgE have been administered in small proof-of-concept studies. Recently, the first phase 3 trials have been reported with dupilumab, an IL-4 receptor antagonist, demonstrating a significant and clinically relevant reduction of the disease burden from polyp size and sinus involvement to symptoms and smell; these changes consecutively led to an important increase in quality of life. Finally, the biologic versus placebo treatment reduced the need for systemic glucocorticosteroids and sinus surgery significantly and clinically meaningfully. Dupilumab today is registered for the treatment of chronic rhinosinusitis with nasal polyps in Europe and the United States. Within a year, 2 further phase 3 trials with omalizumab and mepolizumab will be reported. With this development, without any doubt, a new era for the treatment of severe uncontrolled chronic rhinosinusitis with nasal polyps has begun. Questions on the indication of the biologics, the selection of patients, and finally criteria for monitoring the efficacy in individual patients need to be urgently answered, and care pathways need to be established integrating the current standard of care including surgery.

Care about patients with chronic rhinosinusitis and type-2 inflammation

“…In the scenario of Precision Medicine, identifying the specific pathophysiologic process of a patient's endotype may permit more effective treatments, better patient's outcomes and lower expenditures [35]. Also, defining the endotype is required to access the use of new targeted biotherapeutic molecules, such as anti-IgE and anti-cytokine monoclonal antibodies [36].…”

“…However, some patients suffer from a recalcitrant form of disease despite best practice. In recent years, the advancement in pharmaceutical therapies has reached application also in CRSwNP, with molecules (monoclonal antibodies) that specifically target the major players in the inflammation cascade of CRSwNP [36]. For what concerns the use of biologics, the European Forum for Research and Education in Allergy and Airway Diseases (EUFOREA) suggested five criteria that should be satisfied to prescribe them in CRSwNP [44].…”

“…The critical players that have been targeted so far are IgE, IL-5, IL-4 and IL-13, as well as some of their receptors [36]. The continuous local activation of mast cells, basophils and dendritic cells by IgE can be reduced by selective binding to free circulating IgE, thanks to an anti-IgE antibody (omalizumab) [45].…”

“…Similarly, blood eosinophils decreased. Results of phase 3 trials for mepolizumab in CRSwNP are expected to be published within a year [36]. Also, RCTs on benralizumab, a monoclonal antibody directed towards the alpha subunit of IL-5 receptor (IL-5Rα), are ongoing.…”

“…Dupilumab significantly improved nasal polyp score (NPS), nasal congestion or obstruction, and sinus Lund-Mackay CT scores in two phase-3 big trials (SINUS-24 and SINUS-52) [50]. At the moment, it is the only monoclonal antibody approved for the treatment of CRSwNP [1,36].…”