Effectiveness and safety of dupilumab in patients with chronic rhinosinusitis with nasal polyps and associated comorbidities: a multicentric prospective study in real life
Authors: Nettis Eustachio , Brussino Luisa , Patella Vincenzo , Bonzano Laura , Detoraki Aikaterini , Di Leo Elisabetta , Sirufo Maria Maddalena , Caruso Cristiano , Lodi Rizzini Fabio , Conte Mariaelisabetta , Yacoub Mona-Rita , Triggiani Massimo , Ridolo Erminia , Macchia Luigi , Rolla Giovanni , Brancaccio Raffaele , De Paulis Amato , Spadaro Giuseppe , Di Bona Danilo , D’Uggento Angela Maria , Ginaldi Lia , Gaeta Francesco , Nucera Eleonora , Jaubashi Kliljeda , Villalta Danilo , Dagna Lorenzo , Ciotta Domenico , Pucciarini Francesco , Bagnasco Diego , Celi Giorgio , Chieco Bianchi Fulvia , Cosmi Lorenzo , Costantino Maria Teresa , Crivellaro Maria Angiola , D’Alò Simona , del Biondo Pietro , Del Giacco Stefano , Di Gioacchino Mario , Di Pietro Linda , Favero Elisabetta , Gangemi Sebastiano , Guarnieri Gabriella , Heffler Enrico , Leto Barone Maria Stefania , Lombardo Carla , Losa Francesca , Matucci Andrea , Minciullo Paola Lucia , Parronchi Paola , Passalacqua Giovanni , Pucci Stefano , Rossi Oliviero , Salvati Lorenzo , Schiappoli Michele , Senna Gianenrico , Vianello Andrea , Vultaggio Alessandra , Baoran Yang , Incorvaia Cristoforo , Canonica Giorgio Walter 
Published: May 2022

Abstract
Background
Biologics are currently one of the main treatment options for a number of diseases. The IgG4 monoclonal antibody dupilumab targets the Interleukin-4 receptor alpha chain, thus preventing the biological effects of the cytokines IL-4 and IL-13, that are essential for the Th2 response. Several controlled trials showed that dupilumab is effective and safe in patients with atopic dermatitis (AD), severe asthma and chronic rhinosinusitis with nasal polyps (CRSwNP), thus resulting in approval by regulatory agencies. Aim of the study was to evaluate the efficacy and safety of dupilumab in adult patients with CRSwNP stratified by common overlapping comorbid conditions.

Methods
We performed a multicenter, observational, prospective study enrolling adult patients with severe CRSwNP who had started dupilumab treatment in the context of standard care from January 2021 to October 2021. Data were collected from twentynine Italian secondary care centers for allergy and clinical immunology, all of which were part of the Italian Society of Allergy, Asthma and Clinical Immunology (SIAAIC). A number of efficacy parameters were used. Patient data were compared using the Wilcoxon test for paired data. All statistical analyses were performed with SPSS version 20 (IBM, Armonk, NY, USA).

Results
In total, 82 patients with nasal polyposis were identified. A significant improvement was detected for all the applied efficacy parameters, i.e. 22-item Sino-Nasal Outcome Test (SNOT-22) and bilateral endoscopic nasal polyp score (NPS) scores for CRSwNP, Rhinitis Control Scoring System (RCSS) and Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) scores for allergic perennial rhinitis, Forced Expiratory Volume in the 1st second (FEV1) and Asthma Quality of Life Questionnaire (AQLQ) scores for asthma, Eczema Area and Severity Index (EASI) and Dermatology Life Quality Index (DLQI) scores for AD. A non-significant improvement was also obtained in the Urticaria Activity Score over 7 days (UAS7) for chronic spontaneous urticaria. Treatment with dupilumab was well tolerated.

Conclusions
These data suggest that dupilumab treatment in patients suffering from CRSwNP and associated comorbidities may be suitable. Such outcome, although confirmation by trials is warranted, suggests the possibility to treat different disorders with a single therapy, with favorable effects especially under the cost-effectiveness aspect.