Effect of Subcutaneous Dupilumab on Nasal Polyp Burden in Patients With Chronic Sinusitis and Nasal Polyposis

Bachert, Claus; Mannent, Leda; Naclerio, Robert M.; Mullol, Joaquim; Ferguson, Berrylin J.; Gevaert, Philippe; Hellings, Peter W.; Jiao, Lixia; Wang, Ling; Evans, Rachel C.; Pirozzi, Gianluca; Graham, Neil M.H.; Swanson, Brian N.; Hamilton, Jennifer D.; Radin, Allen; Gandhi, Namita A.; Stahl, Neil; Yancopouloš, George D.; Sutherland, E. Rand

doi:10.1001/jama.2015.19330

Cited by 704 publications

(673 citation statements)

References 21 publications

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“…Finally, in the study of Bachert et al (22) dupilumab showed a significant improvement in TPS in the treatment group as compared to mometasone sprays alone (p<0,001). The difference was seen at week 4 and continued until the end of the treatment period (week 16).…”

Section: Literature Searchmentioning

confidence: 85%

“…Six studies fulfilled the inclusion criteria (18)(19)(20)(21)(22)(23) . Αll studies were RCTs and were published between 2006 and 2017.…”

Section: Study Characteristicsmentioning

confidence: 99%

“…Three of the studies were single-site (19)(20)(21) while the other three were multisite (18,22,23) . Subjects were randomized to receive: anti-IL5 therapy with reslizumab (18) or mepolizumab (20,23) in three studies, anti-IgE therapy with omalizumab in two studies (19,21) and anti-IL-4Rα therapy with dupilumab in the last RCT (22) . The characteristics of the six included studies as well as baseline demographic and clinical characteristics of the patients are presented in Table 2 and 3.…”

Section: Study Characteristicsmentioning

confidence: 99%

“…Specifically, in three studies the outcome was the improvement in the percentage of sinus opacification in CT images (19,20) , in one study it was the Lund-Mackay CT score (21) and in the last one both opacification in CT and the Lund-Mackay CT score were computed for the same purpose (22) .…”

Section: Ct Scorementioning

confidence: 99%

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Monoclonal antibodies for the treatment of chronic rhinosinusitis with nasal polyposis: a systematic review

Tsetsos

Goudakos

Daskalakis

et al. 2018

Rhin

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Background: Μonoclonal antibodies have been proposed as a novel therapy in patients suffering from chronic rhinosinusitis with nasal polyposis (CRSwNP). The purpose of this systematic review was to evaluate their efficacy and safety.Methodology: A literature search was performed in MEDLINE, Web of Science, the Cochrane Library and multiple trial registries followed by extensive hand-searching for the identification of relevant studies. Only randomized controlled trials (RCTs) comparing the use of monoclonal antibodies with placebo or another therapy in adult patients with CRSwNP were included.Results: Anti-immunoglobin E (IgE) therapy with omalizumab was assessed in two studies, anti-interleukin (IL)-5 therapy in three studies (1 reslizumab, 2 mepolizumab) and finally anti-IL-4 and anti-IL-13 therapy in only one. With the exception of one study, biologic therapy was proved to be effective in reducing total nasal endoscopic polyp score (TPS) in treatment as compared to placebo groups. Monoclonal antibodies brought about improvement in several other outcomes, such as opacification in computed tomography (CT), quality of life measures, nasal airflow, olfaction and type 2 helper T-cell (Th2) associated biomarkers. Overall, the use of these agents was deemed safe and well-tolerated.Conclusions: This is the first systematic review showing encouraging results for the use of all three main categories of monoclonal antibodies in CRSwNP patients and highlights the need for further well-designed and with larger sample sizes RCTs.

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Section: Literature Searchmentioning

confidence: 85%

“…Six studies fulfilled the inclusion criteria (18)(19)(20)(21)(22)(23) . Αll studies were RCTs and were published between 2006 and 2017.…”

Section: Study Characteristicsmentioning

confidence: 99%

Section: Study Characteristicsmentioning

confidence: 99%

Section: Ct Scorementioning

confidence: 99%

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Monoclonal antibodies for the treatment of chronic rhinosinusitis with nasal polyposis: a systematic review

Tsetsos

Goudakos

Daskalakis

et al. 2018

Rhin

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“…Another investigated biological strategy to treat CRSwNP is blocking the IL-13/IL-4 pathways: they are important drivers of Th2 differentiation activating type 2 inflammatory responses via IgE synthesis and related cell types. Dupilumab is a fully human monoclonal antibody directed against IL-4 receptor alpha (IL-4Rα), the common receptor for both IL-13 and IL-4; a phase II multinational, multicenter, randomized, double-blind, placebocontrolled study, evaluated dupilumab in patients with CRSwNP refractory to intranasal corticosteroids: treated patients obtained significant reduction in polyp burden in a four-week treatment period, significant improvements in SNOT-22 symptom score, Lund-McKay (CT) scores, olfaction (by means of the University of Pennsylvania Smell Identification Test) and nasal peak inspiratory flow [16].…”

Section: Monoclonal Antibodies In Crswnpmentioning

confidence: 99%

A Focus on Chronic Rhinosinusitis with Nasal Polyposis: Leaving Aside Endoscopic Surgery, a Step towards Biologic Therapies

Malvezzi

Ferr

Puggioni

et al. 2017

JOENTR

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Traditional surgical treatment of chronic rhinosinusitis with nasal polyps is not always definitive since a high rate of polyps recurrence is reported all over the world. Precision medicine, with the utilization of biological therapies, could be a new opportunity for accurately selected patients with nasal polyp's regrowth that underwent previous surgery. In this review we provide a brief historiography of the surgical treatments of chronic rhinosinusitis with/without nasal polyps and describe the first applications of biological therapies.

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Efficacy and Safety of Dupilumab in Adolescents With Uncontrolled Moderate to Severe Atopic Dermatitis

et al. 2020

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IMPORTANCE Adolescents with atopic dermatitis (AD) have high disease burden negatively affecting quality of life, with limited treatment options. The efficacy and safety of dupilumab, a monoclonal antibody, approved for treatment in adolescent patients with inadequately controlled AD, remain unknown in this patient population. OBJECTIVE To assess the efficacy and safety of dupilumab monotherapy in adolescents with moderate to severe inadequately controlled AD. DESIGN, SETTING, AND PARTICIPANTS A randomized, double-blind, parallel-group, phase 3 clinical trial was conducted at 45 US and Canadian centers between March 21, 2017, and June 5, 2018. A total of 251 adolescents with moderate to severe AD inadequately controlled by topical medications or for whom topical therapy was inadvisable were included. INTERVENTIONS Patients were randomized (1:1:1; interactive-response system; stratified by severity and body weight) to 16-week treatment with dupilumab, 200 mg (n = 43; baseline weight <60 kg), or dupilumab, 300 mg (n = 39; baseline weight Ն60 kg), every 2 weeks; dupilumab, 300 mg, every 4 weeks (n = 84); or placebo (n = 85). MAIN OUTCOMES AND MEASURES Proportion of patients with 75% or more improvement from baseline in Eczema Area and Severity Index (EASI-75) (scores range from 0 to 72, with higher scores indicating greater severity) and Investigator's Global Assessment (IGA) 0 or 1 on a 5-point scale (scores range from 0 to 4, with higher scores indicating greater severity) at week 16. RESULTS A total of 251 patients were randomized (mean [SD] age, 14.5 [1.7] years; 148 [59.0%] male). Of 250 patients with data available on concurrent allergic conditions, most had comorbid type 2 diseases (asthma, 134 [53.6%]; food allergies, 60.8%; allergic rhinitis, 65.6%). A total of 240 patients (95.6%) completed the study. Dupilumab achieved both coprimary end points at week 16. The proportion of patients with EASI-75 improvement from baseline increased (every 2 weeks, 41.5%; every 4 weeks, 38.1%; placebo, 8.2%) with differences vs placebo of 33.2% (95% CI, 21.1%-45.4%) for every 2 weeks and 29.9% (95% CI, 17.9%-41.8%) for every 4 weeks (P < .001). Efficacy of the every-2-week regimen was generally superior to the every-4-week regimen. Patients in the dupilumab arms had higher percentage values of conjunctivitis (every 2 weeks, 9.8%; every 4 weeks, 10.8%; placebo, 4.7%) and injection-site reactions (every 2 weeks, 8.5%; every 4 weeks, 6.0%; placebo, 3.5%), and lower nonherpetic skin infections (every 2 weeks, 9.8%; every 4 weeks, 9.6%; placebo, 18.8%). CONCLUSIONS AND RELEVANCE In this study, dupilumab significantly improved AD signs, symptoms, and quality of life in adolescents with moderate to severe AD, with an acceptable safety profile. Placebo-corrected efficacy and safety of dupilumab were similar in adolescents and adults. TRIAL REGISTRATION ClinicalTrials.gov identifier: NCT03054428

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Effect of Subcutaneous Dupilumab on Nasal Polyp Burden in Patients With Chronic Sinusitis and Nasal Polyposis

Cited by 704 publications

References 21 publications

Monoclonal antibodies for the treatment of chronic rhinosinusitis with nasal polyposis: a systematic review

Monoclonal antibodies for the treatment of chronic rhinosinusitis with nasal polyposis: a systematic review

A Focus on Chronic Rhinosinusitis with Nasal Polyposis: Leaving Aside Endoscopic Surgery, a Step towards Biologic Therapies

Efficacy and Safety of Dupilumab in Adolescents With Uncontrolled Moderate to Severe Atopic Dermatitis

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