Switching biologics in chronic rhinosinusitis with nasal polyps: A multicenter Canadian experience

Abstract

Background: Type 2 biologics have been used increasingly for the treatment of chronic rhinosinusitis with nasal polyps (CRSwNP). However, patterns of biologic switching are understudied, and established guidelines for sequential or simultaneous use do not yet exist.

Methods: This is a Canadian multicenter retrospective study of real-world patient data. Patients were included if they had recurrent CRSwNP despite maximal medical and surgical management, and received at least one dose of a type 2 biologic. Patients who remained on their initial biologic comprised the continuous group. Patients with sequential or simultaneous use of more than one biologic comprised the switched group. We compared the characteristics of patients who continued and switched biologics.

Results: Note that 225 consecutive patients were included. Thirty-six (16%) switched biologics at least once, and six (3%) switched twice. The most common switch was from mepolizumab to dupilumab, with poor control of CRSwNP symptoms being the leading cause for this switch. Lack of efficacy was the main reason for switching off mepolizumab and omalizumab, while adverse events were the leading cause for switching off dupilumab. Additionally, mepolizumab patients were more likely to switch biologics late in their treatment, while dupilumab patients rarely switched after 12 months of therapy (p-value < 0.001).

Conclusions: Switching biologics for CRSwNP is frequent in Canadian rhinology practices, with 16% of patients switching at least once. The most common switch is from mepolizumab to dupilumab with inadequate CRSwNP control driving this switch. This study may help guide sequential or simultaneous use of biologics in CRSwNP patients.

Keywords: asthma; biologics; chronic rhinosinusitis; chronic rhinosinusitis with nasal polyposis; lower airway disease; type 2 inflammation; upper airway disease.

FIGURE 1

Sankey diagram depicting the transitions between different biologic therapies in patients with chronic rhinosinusitis with nasal polyps (CRSwNP). From left to right, the columns represent first‐, second‐, and third‐line biologics, respectively, with each color representing a distinct biologic. The flow of patients from one biologic treatment to another is illustrated, with the width of connecting lines directly proportional to the number of patients switching between therapies.

FIGURE 2

Reason for switching (A) all patients, and by (B) mepolizumab and C) dupilumab as initial biologic. Purple represents patients who switched due to lack of efficacy, orange for adverse events, yellow for insurance issues, and gray for a medical reason unrelated to drug efficacy.

FIGURE 3

Kaplan–Meier survival curve comparing time‐to‐switch between patients initially on mepolizumab versus dupilumab. Within the first 18 months, switching rates were similar for both biologics. After 18 months, switching became significantly more frequent among mepolizumab patients (p‐value < 0.001). Switching before 2 months was mostly due to adverse events and coverage, while those switching after 4 months did so mostly due to lack of efficacy.