Dupilumab (Dupixent®) tends to be an effective therapy for uncontrolled severe chronic rhinosinusitis with nasal polyps: real data of a single-centered, retrospective single-arm longitudinal study from a university hospital in Germany

Abstract

Introduction Chronic rhinosinusitis with nasal polyps (CRSwNP) is an inflammatory disease, which is usually type 2-mediated in the western hemisphere, associated with severe therapeutic and socioeconomic challenges. The first targeted systemic treatment option for severe uncontrolled CRSwNP is a human monoclonal antibody against the interleukin-4 receptor α (IL-4Rα) subunit called dupilumab, which was approved for subcutaneous administration in Germany in October 2019. The purpose of this study is to investigate the efficacy of dupilumab in real life in patients treated with dupilumab in label according to license in our department in 2019–2021. Materials and methods Since October 2019, we have investigated 40 patients (18 men, 22 women) treated with dupilumab in a single-center, retrospective single-arm longitudinal study. The following parameters were collected before treatment (baseline), at 1 month, 4 months, 7 months, 10 months, and 13 months: the Sino-Nasal Outcome Test-22 (SNOT-22), the forced expiratory pressure in 1 s (FEV-1), the olfactometry using Sniffin' Sticks-12 identification test (SSIT), a visual analog scale of the total complaints, the Nasal Polyp Score (NPS), histologic findings as well as total serum IgE, eosinophilic cationic protein in serum and blood eosinophils. Results The average age was 52.7 years (± 15.3). The follow-up period was 13 months. The SNOT-22 average was 60 points (± 22.2) at the first visit, 28.2 points (± 17.1) after 4 months and 20.8 points (± 17.7) after 13 months. The NPS was 4.3 points (± 1.5), after 4 months 2.1 points (± 1.3) and after 13 months 1.4 points (± 1.1). Olfactometry showed 3.2 points (± 3.7) at the baseline, 7.0 points (± 4.0) after 4 months and 7.8 points (± 3.5) after 13 months. The other parameters also improved. Most parameters showed linear dependence in the slopes under therapy (p < 0.001). Adverse side effects were mostly only mild, and no rescue therapy was needed. Conclusion There is a clear improvement in the medical condition and symptoms in all categories mentioned under therapy with dupilumab, as well as a reduction in the need for systemic glucocorticoids and revision surgery as rescue treatment. Our results show that dupilumab tends to be an effective therapy alternative for severe CRSwNP.

Two‐year results of tapered dupilumab for CRSwNP demonstrates enduring efficacy established in the first 6 months

“…31,32,38 In several studies so far, real-world data on therapeutic efficacy and safety of dupilumab in CRSwNP is reported, with limited follow-up. [39][40][41][42][43] Therapeutic efficacy is principally established within 24 weeks and endures while tapering dupilumab conditional to treatment response and CRS control.…”

“…Its efficacy and safety as add‐on therapy in CRSwNP has been demonstrated in the phase‐II and ‐III trials LIBERTY NP SINUS‐24 and ‐52 (LNPS‐24 and ‐52) 31,32,38 . In several studies so far, real‐world data on therapeutic efficacy and safety of dupilumab in CRSwNP is reported, with limited follow‐up 39–43 …”

Influence of Prior Endoscopic Sinus Surgery Extent on Dupilumab Effectiveness in CRSwNP Patients

“…However, when Dupilumab was initiated, those with higher ACCESS scores (subjected to more “partial” surgeries) showed better VAS loss of smell scores, as measured at 1 month up to 12 months. Sudden and remarkable improvement of smell has widely been described in all the Dupilumab cohorts analyzed so far in the literature 18,27 . However, no prognostic factors capable of influencing olfaction restoration were recognized, to the authors’ knowledge.…”

Prevalence of type 2 inflammatory signatures and efficacy of dupilumab in patients with chronic rhinosinusitis with nasal polyps from two phase 3 clinical trials: SINUS‐24 and SINUS‐52

“…Given these limitations, these results may not be generalizable to the wider population of patients with CRSwNP. However, recent publications conducted with dupilumab in real-world practice do indicate high rates of response in patients with severe CRSwNP, [16][17][18] while an ongoing registry in patients with CRSwNP may provide an opportunity for further investigations in realworld populations. 19 In conclusion, the majority of patients with severe CRSwNP in the SINUS population exhibit characteristics of T2 pathology, across a range of algorithm-based definitions of T2 inflammation.…”

“…Given these limitations, these results may not be generalizable to the wider population of patients with CRSwNP. However, recent publications conducted with dupilumab in real‐world practice do indicate high rates of response in patients with severe CRSwNP, 16–18 while an ongoing registry in patients with CRSwNP may provide an opportunity for further investigations in real‐world populations 19 …”