Simultaneous Dual Type 2 Biologic Therapy Improves Sinonasal Outcomes in Selected Patients With Chronic Rhinosinusitis With Nasal Polyps

BACKGROUND: Due to the shared underlying pathophysiological mechanism, chronic rhinosinusitis with nasal polyps (CRSwNP) is frequently associated with comorbid systemic type 2 diseases. Rare, complex cases treated simultaneously with two biologics due to inadequate disease control have been reported. The aim of this study was to assess current use of dual biologic therapy in patients with CRSwNP. METHODS: This retrospective, multicentric study included adult patients with a diagnosis of severe uncontrolled CRSwNP and simultaneous dual type-2 biologic therapy, one of which had to be approved for the treatment of CRSwNP. Indication for dual therapy was made on an individual basis after interdisciplinary consultation. RESULTS: Thirty-four patients diagnosed with CRSwNP from six study centers in Germany, the Netherlands, and Italy were included (mean age 49.1, 55.9% female). Most patients showed complex medical histories with type 2 comorbidities and several futile treatment attempts. The combination therapy consisted of dupilumab/mepolizumab (n = 14), mepolizumab/tezepelumab (n = 2), or benralizumab/dupilumab (n = 14), dupilumab/omalizumab (n = 3), or dupilumab/tezepelumab (n = 1), with a median follow-up time of 25 months (IQR = 6-34). Most frequent comorbidities were asthma (n = 32), eosinophilic granulomatous polyangiitis (n = 13), and hypereosinophilic syndrome (n = 5). CRSwNP disease outcomes significantly improved under dual therapy at 6 months compared to baseline under single biologic therapy (SNOT22: -32.8, p < 0.0001; NPS: -3.2, p < 0.0001; Smell: +3.4, p = 0.003; VAS overall disease severity: -4.3, p = 0.054). Cessation of dual therapy was attempted in four patients, but reintroduced again due to loss of disease control. Five adverse reactions were reported in 4 (11.8%) patients: urticaria, erythema, gastrointestinal symptoms, weight gain, and arthralgia (each n = 1). CONCLUSIONS: In rare cases, dual biologic therapy can be indicated to control CRSwNP and comorbid type 2 diseases. The long-term efficacy and safety of this approach remain unknown and should be reserved for carefully selected cases only, considering the off-label use in some European countries and high associated costs.