Canadian Rhinology Working Group consensus statement: Biologic therapies for chronic rhinosinusitis

Abstract

Background Recent evidence suggests that biologic therapy with targeted activity within the Type 2 inflammatory pathway can improve the clinical signs and symptoms of chronic rhinosinusitis with nasal polyposis (CRSwNP). There remains a population in CRSwNP that despite medical therapy and endoscopic sinus surgery have persistent signs and symptoms of disease. Therefore, biologics, monoclonal antibody agents, could be beneficial therapeutic treatments for these patients. There have been eight randomized, double-blind, placebo-controlled trails performed for CRSwNP targeted components of the Type 2 inflammatory pathway, notably interleukin (IL)-4, IL-5 and IL-13, IL-5R, IL-33, and immunoglobulin (Ig)E. However, there are no formal recommendations for the optimal use of biologics in managing Chronic Rhinosinusitis (CRS) within the Canadian health care environment. Methods A Delphi Method process was utilized involving three rounds of questionnaires in which the first two were completed individually online and the third was discussed on a virtual platform with all the panelists. 17 fellowship trained rhinologists across Canada evaluated the 28 original statements on a scale of 1–10 and provided comments. A rating within 1–3 indicated disagreement, 8–10 demonstrated agreement and 4–7 represented being neutral towards a statement. All ratings were quantitively reviewed by mean, median, mode, range and standard deviation. Consensus was defined by removing the highest and lowest of the scores and using the “3 point relaxed system”. Results After three rounds, a total of 11 statements achieved consensus. This white paper only contains the final agreed upon statements and clear rationale and support for the statements regarding the use of biologics in patients with CRS. Conclusion This white paper provides guidance to Canadian physicians on the use of biologic therapy for the management of patients with CRS, but the medical and surgical regimen should ultimately be individualized to the patient. As more biologics become available and additional trials are published we will provide updated versions of this white paper every few years. Graphical abstract

Canadian real-world study of access and clinical results using dupilumab for chronic rhinosinusitis with polyps

“…The Canadian Rhinology Working Group recommends that biologic therapies for chronic rhinosinusitis be considered only for patients who have failed medical therapy and have undergone sufficient sinus surgery or for patients who cannot undergo sinus surgery and have failed medical therapy [ 6 ]. However, at this time, access to dupilumab for Canadian patients and specifically in the province of Ontario, remains limited to only a fraction of those with private insurance.…”

“…Given the inexperience of clinicians managing patients with CRSwNP, the Canadian Rhinology Working Group produced a white paper providing guidance to treating physicians, both in Canada and internationally, when considering monoclonal antibody therapy for patients with CRSwNP [ 6 ]. Despite this guidance, questions about real-world efficacy of the processes for accessing treatment and treatment related outcomes in comparison to clinical trial results, are a concern for any new therapy [ 7 ].…”

Developments and Emerging Trends in the Global Treatment of Chronic Rhinosinusitis From 2001 to 2020: A Systematic Bibliometric Analysis

“…It has been have reported that all three biologics, dupilumab, omalizumab, and mepolizumab, can reduce the size of nasal polyps and improved nasal symptoms, with dupilumab having the best efficacy and omalizumab and mepolizumab being equivalent, and all three having similar effects on improving quality of life ( 41 , 42 ). These effects decrease use of oral glucocorticoids and need for reoperation, thereby providing new treatment for refractory CRSwNP ( 39 , 40 ). However, application of biologic agents in the clinical setting for CRS treatment has three main limitations.…”

A Practical Clinical Protocol for Monitoring Patients with Severe Uncontrolled Chronic Rhinosinusitis with Nasal Polyposis Treated with Biologics

“…Any co-management of asthma further complicates medical management by increasing the dosage and administration of steroids, in this case preferably oral, increasing the risk of adverse side effects and the potential for antibiotic prophylaxis and bacterial resistance [ 24 ].…”