Dupilumab improves patient-reported outcomes in patients with chronic rhinosinusitis with nasal polyps and comorbid asthma

Bachert, Claus; Hellings, Peter; Mullol, Joaquim; Naclerio, Robert M.; Chao, Jingdong; Amin, Nikhil; Grabher, Annette; Swanson, Brian N.; Hamilton, Jennifer D.; Guillonneau, Sophie; Taniou, Christine; Zhang, Donghui; Pirozzi, Gianluca; Graham, Neil M.H.; Staudinger, Heribert; Mannent, Leda; Khan, Asif

doi:10.1016/j.jaip.2019.03.023

Cited by 58 publications

(56 citation statements)

References 9 publications

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“…In study subjects with a history of prior ESS, only 1.5% of patients in the dupilumab group progressed to surgery, compared to 11.4% in the mometasone only group. 13,55 In addition, Bachert et al reported a modest, yet significant, 2-point reduction (0-8 scale) in bilateral nasal polyp score in both the SINUS-24 and SINUS-52 Phase 3 studies. 13 This reduction in the need for ESS, as well as improvement in outcome measures, suggest an important role of biologic therapy in the treatment of CRSwNP patients.…”

Section: Discussionmentioning

confidence: 99%

Cost Utility Analysis of Dupilumab Versus Endoscopic Sinus Surgery for Chronic Rhinosinusitis With Nasal Polyps

et al. 2020

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Objective Both endoscopic sinus surgery (ESS) and biologic therapies have shown effectiveness for medically‐refractory chronic rhinosinusitis with nasal polyps (CRSwNP) without severe asthma. The objective was to evaluate cost‐effectiveness of dupilumab versus ESS for patients with CRSwNP. Study Design Cohort‐style Markov decision‐tree economic model with a 36‐year time horizon. Methods A cohort of 197 CRSwNP patients who underwent ESS were compared with a matched cohort of 293 CRSwNP patients from the SINUS‐24 and SINUS‐52 Phase 3 studies who underwent treatment with dupilumab 300 mg every 2 weeks. Utility scores were calculated from the SNOT‐22 instrument in both cohorts. Decision‐tree analysis and a 10‐state Markov model utilized published event probabilities and primary data to calculate long‐term costs and utility. The primary outcome measure was incremental cost per quality‐adjusted life year (QALY), which is expressed as an Incremental Cost Effectiveness Ratio. One‐way and probabilistic sensitivity analyses were performed. Results The ESS strategy cost $50,436.99 and produced 9.80 QALYs. The dupilumab treatment strategy cost $536,420.22 and produced 8.95 QALYs. Because dupilumab treatment was more costly and less effective than the ESS strategy, it is dominated by ESS in the base case. One‐way sensitivity analyses showed ESS to be cost‐effective versus dupilumab regardless of the frequency of revision surgery and at any yearly cost of dupilumab above $855. Conclusions The ESS treatment strategy is more cost effective than dupilumab for upfront treatment of CRSwNP. More studies are needed to isolate potential phenotypes or endotypes that will benefit most from dupilumab in a cost‐effective manner. Level of Evidence 2C Laryngoscope, 131:E26–E33, 2021

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Section: Discussionmentioning

confidence: 99%

Cost Utility Analysis of Dupilumab Versus Endoscopic Sinus Surgery for Chronic Rhinosinusitis With Nasal Polyps

et al. 2020

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“…102 In patients with CRSwNP with comorbid asthma, a significant difference versus placebo was also observed for each of the individual ACQ-5 item scores. 103 The changes in CT scan sinus opacification were seen in all sinuses. 104 In line with the biologic effects, dupilumab significantly reduced total serum IgE and the serum eosinophil chemokine concentrations for thymus and activation-regulated chemokine and eotaxin-3, but had a temporary effect (increase due to reduced tissue migration) only on blood eosinophils.…”

Section: The Anti-il-4r Alpha Approach: Dupilumab In Crswnpmentioning

confidence: 90%

Biologics for chronic rhinosinusitis with nasal polyps

Bachert

Zhang

Cavaliere

et al. 2020

Journal of Allergy and Clinical Immunology

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With the increasing recognition of the role of type 2 immune responses in chronic rhinosinusitis, its severity, recurrence, and comorbidities, several biologics targeting IL-4, IL-5, and IL-13 as well as IgE have been administered in small proof-of-concept studies. Recently, the first phase 3 trials have been reported with dupilumab, an IL-4 receptor antagonist, demonstrating a significant and clinically relevant reduction of the disease burden from polyp size and sinus involvement to symptoms and smell; these changes consecutively led to an important increase in quality of life. Finally, the biologic versus placebo treatment reduced the need for systemic glucocorticosteroids and sinus surgery significantly and clinically meaningfully. Dupilumab today is registered for the treatment of chronic rhinosinusitis with nasal polyps in Europe and the United States. Within a year, 2 further phase 3 trials with omalizumab and mepolizumab will be reported. With this development, without any doubt, a new era for the treatment of severe uncontrolled chronic rhinosinusitis with nasal polyps has begun. Questions on the indication of the biologics, the selection of patients, and finally criteria for monitoring the efficacy in individual patients need to be urgently answered, and care pathways need to be established integrating the current standard of care including surgery.

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“…Dupilumab was able decrease the least squares (LS) mean in compared to placebo group . At the molecular level, type 2 biomarkers (eg eotaxin‐2, total IgE, pulmonary and activation‐regulated chemokine and IL‐13) were significantly reduced in the patients receiving Dupilumab compared to the placebo group . Another pathway relevant to chronic rhinosinusitis and nasal polyps involves ALOX15 , encoding 15‐Lipoxygenase A, whose expression is strictly dependent on IL‐4 and IL‐13 .…”

Section: Dupilumab In Chronic Rhinosinusitis With Nasal Polyposismentioning

confidence: 98%

Mechanisms of Dupilumab

Harb

Chatila

2019

Clin Experimental Allergy

280

241

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The Th2 cytokines interleukin 4 (IL‐4) and IL‐13 and the heterodimeric IL‐4 receptor (IL‐4R) complexes that they interact with play a key role in the pathogenesis of allergic disorders. Dupilumab is a humanized IgG4 monoclonal antibody that targets the IL‐4 receptor alpha chain (IL‐4Rα), common to both IL‐4R complexes: type 1 (IL‐4Rα/γc; IL‐4 specific) and type 2 (IL‐4Rα/IL‐13Rα1; IL‐4 and IL‐13 specific). In this review, we detail the current state of knowledge of the different signalling pathways coupled to the IL‐4R complexes and examine the possible mechanisms of Dupilumab action and survey its clinical efficacy in different allergic disorders. The development of Dupilumab and the widening spectrum of its clinical applications is relevant to the current emphasis on precision medicine approaches to the blockade of pathways involved in allergic diseases.

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Dupilumab improves patient-reported outcomes in patients with chronic rhinosinusitis with nasal polyps and comorbid asthma

Cited by 58 publications

References 9 publications

Cost Utility Analysis of Dupilumab Versus Endoscopic Sinus Surgery for Chronic Rhinosinusitis With Nasal Polyps

Cost Utility Analysis of Dupilumab Versus Endoscopic Sinus Surgery for Chronic Rhinosinusitis With Nasal Polyps

Biologics for chronic rhinosinusitis with nasal polyps

Mechanisms of Dupilumab

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