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Meta-Analysis
. 2021 Mar 12;3(3):CD013513.
doi: 10.1002/14651858.CD013513.pub3.

Biologics for chronic rhinosinusitis

Lee-Yee Chong  1 , Patorn Piromchai  2 , Steve Sharp  3 , Kornkiat Snidvongs  4 , Katie E Webster  5 , Carl Philpott  6 , Claire Hopkins  7 , Martin J Burton  8
Affiliations
Meta-Analysis

Biologics for chronic rhinosinusitis

Lee-Yee Chong et al. Cochrane Database Syst Rev. .

Abstract

Background: This living systematic review is one of several Cochrane Reviews evaluating the medical management of patients with chronic rhinosinusitis. Chronic rhinosinusitis is common. It is characterised by inflammation of the nasal and sinus linings, nasal blockage, rhinorrhoea, facial pressure/pain and loss of sense of smell. It occurs with or without nasal polyps. 'Biologics' are medicinal products produced by a biological process. Monoclonal antibodies are one type, already evaluated in other inflammatory conditions (e.g. asthma and atopic dermatitis).

Objectives: To assess the effects of biologics for the treatment of chronic rhinosinusitis.

Search methods: The Cochrane ENT Information Specialist searched the Cochrane ENT Register; CENTRAL (2020, Issue 9); Ovid MEDLINE; Ovid Embase; Web of Science; ClinicalTrials.gov; ICTRP and additional sources for published and unpublished studies. The date of the search was 28 September 2020.

Selection criteria: Randomised controlled trials (RCTs) with at least three months follow-up comparing biologics (monoclonal antibodies) against placebo/no treatment in patients with chronic rhinosinusitis.

Data collection and analysis: We used standard Cochrane methodological procedures. Our primary outcomes were disease-specific health-related quality of life (HRQL), disease severity and serious adverse events (SAEs). The secondary outcomes were avoidance of surgery, extent of disease (measured by endoscopic or computerised tomography (CT) score), generic HRQL and adverse effects (nasopharyngitis, including sore throat). We used GRADE to assess the certainty of the evidence for each outcome.

Main results: We included 10 studies. Of 1262 adult participants, 1260 had severe chronic rhinosinusitis with nasal polyps; 43% to 100% of participants also had asthma. Three biologics, with different targets, were evaluated: dupilumab, mepolizumab and omalizumab. All of the studies were sponsored or supported by industry. For this update (2021) we have included two new studies, including 265 participants, which reported data relating to omalizumab. Anti-IL-4Rα mAb (dupilumab) versus placebo/no treatment (all receiving intranasal steroids) Three studies (784 participants) evaluated dupilumab. Disease-specific HRQL was measured with the SNOT-22 (a 22-item questionnaire, with a score range of 0 to 110; minimal clinically important difference (MCID) 8.9 points). At 24 weeks, dupilumab results in a large reduction (improvement) in the SNOT-22 score (mean difference (MD) -19.61, 95% confidence interval (CI) -22.54 to -16.69; 3 studies; 784 participants; high certainty). At between 16 and 52 weeks of follow-up, dupilumab probably results in a large reduction in disease severity, as measured by a 0- to 10-point visual analogue scale (VAS) (MD -3.00, 95% CI -3.47 to -2.53; 3 studies; 784 participants; moderate certainty). This is a global symptom score, including all aspects of chronic rhinosinusitis symptoms. At between 16 and 52 weeks of follow-up, dupilumab may result in a reduction in serious adverse events compared to placebo (5.9% versus 12.5%, risk ratio (RR) 0.47, 95% CI 0.29 to 0.76; 3 studies, 782 participants; low certainty). Anti-IL-5 mAb (mepolizumab) versus placebo/no treatment (all receiving intranasal steroids) Two studies (137 participants) evaluated mepolizumab. Disease-specific HRQL was measured with the SNOT-22. At 25 weeks, the SNOT-22 score may be reduced (improved) in participants receiving mepolizumab (MD -13.26 points, 95% CI -22.08 to -4.44; 1 study; 105 participants; low certainty; MCID 8.9). It is very uncertain whether there is a difference in disease severity at 25 weeks: on a 0- to 10-point VAS, disease severity was -2.03 lower in those receiving mepolizumab (95% CI -3.65 to -0.41; 1 study; 72 participants; very low certainty). It is very uncertain if there is a difference in the number of serious adverse events at between 25 and 40 weeks (1.4% versus 0%; RR 1.57, 95% CI 0.07 to 35.46; 2 studies; 135 participants, very low certainty). Anti-IgE mAb (omalizumab) versus placebo/no treatment (all receiving intranasal steroids) Five studies (329 participants) evaluated omalizumab. Disease-specific HRQL was measured with the SNOT-22. At 24 weeks omalizumab probably results in a large reduction in SNOT-22 score (MD -15.62, 95% CI -19.79 to -11.45; 2 studies; 265 participants; moderate certainty; MCID 8.9). We did not identify any evidence for overall disease severity. It is very uncertain whether omalizumab affects the number of serious adverse events, with follow-up between 20 and 26 weeks (0.8% versus 2.5%, RR 0.32, 95% CI 0.05 to 2.00; 5 studies; 329 participants; very low certainty).

Authors' conclusions: Almost all of the participants in the included studies had nasal polyps (99.8%) and all were using topical nasal steroids for their chronic rhinosinusitis symptoms. In these patients, dupilumab improves disease-specific HRQL compared to placebo. It probably also results in a reduction in disease severity, and may result in a reduction in the number of serious adverse events. Mepolizumab may improve disease-specific HRQL. It is very uncertain if there is a difference in disease severity or the number of serious adverse events. Omalizumab probably improves disease-specific HRQL compared to placebo. It is very uncertain if there is a difference in the number of serious adverse events. There was no evidence regarding the effect of omalizumab on disease severity (using global scores that address all symptoms of chronic rhinosinusitis).

Trial registration: ClinicalTrials.gov NCT01920893 NCT01362244 NCT01393340 NCT02912468 NCT02898454 NCT03280550 NCT03280537 NCT03170271 NCT04185012 NCT04157335 NCT03085797.

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Conflict of interest statement

Lee‐Yee Chong: none known.

Patorn Piromchai: none known.

Steve Sharp: Steve Sharp's employer, the National Institute for Health and Care Excellence (NICE), has produced guidance on related topics such as sinusitis, which he has not contributed to.

Kornkiat Snidvongs: none known.

Katie Webster: none known.

Carl Philpott: Carl Philpott has previously received consultancy fees for GSK, Sanofi, Acclarent, Navigant, Aerin Medical and Entellus, and is a trustee of the patient charity Fifth Sense. He is an investigator on a clinical trial that may be included in this review, but will have no role in the data extraction, risk of bias assessment or data analysis for this study.

Claire Hopkins: Claire Hopkins has participated in advisory boards for Olympus, Chordate, Smith & Nephew and Sanofi to provide expertise with regards to study design and outcome assessment, and interpretation of trial data. She is an investigator on a clinical trial that is included in this review, but had no role in the data extraction, risk of bias assessment or data analysis for this study (LIBERTY SINUS 24; LIBERTY SINUS 52).

Martin J Burton: Professor Martin Burton is joint Co‐ordinating Editor of Cochrane ENT, but had no role in the editorial process for this review.

Figures

1
1
PRISMA flow diagram
2
2
'Risk of bias graph': review authors' judgements about each risk of bias item presented as percentages across all included studies.
3
3
'Risk of bias' summary: review authors' judgements about each risk of bias item for each included study.
1.1
1.1. Analysis
Comparison 1: Anti‐IL‐4Rα mAb (dupilumab) versus placebo (on top of topical steroids), Outcome 1: HRQL ‐ disease‐specific  (SNOT‐22, 0 to 110, lower = better)
1.2
1.2. Analysis
Comparison 1: Anti‐IL‐4Rα mAb (dupilumab) versus placebo (on top of topical steroids), Outcome 2: Disease severity ‐ VAS (0 to 10, lower = better)
1.3
1.3. Analysis
Comparison 1: Anti‐IL‐4Rα mAb (dupilumab) versus placebo (on top of topical steroids), Outcome 3: Serious adverse events
1.4
1.4. Analysis
Comparison 1: Anti‐IL‐4Rα mAb (dupilumab) versus placebo (on top of topical steroids), Outcome 4: Avoidance of surgery ‐ number of patients who had surgery as rescue treatment
1.5
1.5. Analysis
Comparison 1: Anti‐IL‐4Rα mAb (dupilumab) versus placebo (on top of topical steroids), Outcome 5: Extent of disease ‐ endoscopy ('nasal polyps score', 0 to 8, higher = worse)
1.6
1.6. Analysis
Comparison 1: Anti‐IL‐4Rα mAb (dupilumab) versus placebo (on top of topical steroids), Outcome 6: Extent of disease ‐ CT scan (Lund Mackay, 0 to 24, higher = worse)
1.7
1.7. Analysis
Comparison 1: Anti‐IL‐4Rα mAb (dupilumab) versus placebo (on top of topical steroids), Outcome 7: HRQL ‐ generic (EQ‐5D VAS, 0 to 100, higher = better)
1.8
1.8. Analysis
Comparison 1: Anti‐IL‐4Rα mAb (dupilumab) versus placebo (on top of topical steroids), Outcome 8: Adverse events ‐ nasopharyngitis, including sore throat (longest available data)
2.1
2.1. Analysis
Comparison 2: Anti‐IL‐5 mAb (mepolizumab) versus placebo (on top of topical steroids), Outcome 1: HRQL ‐ SNOT‐22 (1 to 100, lower = better) up to 25 weeks
2.2
2.2. Analysis
Comparison 2: Anti‐IL‐5 mAb (mepolizumab) versus placebo (on top of topical steroids), Outcome 2: Disease severity ‐ VAS (0 to 10, lower = better)
2.3
2.3. Analysis
Comparison 2: Anti‐IL‐5 mAb (mepolizumab) versus placebo (on top of topical steroids), Outcome 3: Serious adverse events
2.4
2.4. Analysis
Comparison 2: Anti‐IL‐5 mAb (mepolizumab) versus placebo (on top of topical steroids), Outcome 4: Avoidance of surgery ‐ patients still meeting criteria for surgery at end of follow‐up
2.5
2.5. Analysis
Comparison 2: Anti‐IL‐5 mAb (mepolizumab) versus placebo (on top of topical steroids), Outcome 5: Extent of disease ‐ endoscopic score
2.6
2.6. Analysis
Comparison 2: Anti‐IL‐5 mAb (mepolizumab) versus placebo (on top of topical steroids), Outcome 6: HRQL ‐ generic measured using EQ‐5D VAS (range 0 to 100;  0 = worst, 100 = best imaginable health state) at week 25
2.7
2.7. Analysis
Comparison 2: Anti‐IL‐5 mAb (mepolizumab) versus placebo (on top of topical steroids), Outcome 7: Adverse events ‐ nasopharyngitis, including sore throat
3.1
3.1. Analysis
Comparison 3: Anti‐IgE mAb (omalizumab) versus placebo (on top of topical steroids), Outcome 1: HRQL disease‐specific ‐ SNOT‐22 (0 to 110, lower = better)
3.2
3.2. Analysis
Comparison 3: Anti‐IgE mAb (omalizumab) versus placebo (on top of topical steroids), Outcome 2: Serious adverse events
3.3
3.3. Analysis
Comparison 3: Anti‐IgE mAb (omalizumab) versus placebo (on top of topical steroids), Outcome 3: Avoidance of surgery
3.4
3.4. Analysis
Comparison 3: Anti‐IgE mAb (omalizumab) versus placebo (on top of topical steroids), Outcome 4: Extent of disease ‐ endoscopic score (nasal polyps score, range 0 to 8, lower = better)
3.5
3.5. Analysis
Comparison 3: Anti‐IgE mAb (omalizumab) versus placebo (on top of topical steroids), Outcome 5: Extent of disease ‐ CT scan (lower score = better)
3.6
3.6. Analysis
Comparison 3: Anti‐IgE mAb (omalizumab) versus placebo (on top of topical steroids), Outcome 6: Adverse events ‐ nasopharyngitis, including sore throat
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References

References to studies included in this review

Bachert 2016 {published and unpublished data}
    1. Bachert C, Hellings P, Mullol J, Hamilos D, Naclerio R, Joish VN, et al. Dupilumab improves patient-reported outcomes in chronic sinusitis with nasal polyps patients with comorbid asthma: results from a phase 2a trial. European Respiratory Journal 2016;48(Suppl 60):OA251. [5632585]
    1. Bachert C, Hellings PW, Mullol J, Hamilos DL, Gevaert P, Naclerio RM, et al. Dupilumab improves health-related quality of life in patients with chronic rhinosinusitis with nasal polyposis. Allergy 2019;71:12. [PMID: ] - PubMed
    1. Bachert C, Hellings PW, Mullol J, Naclerio RM, Hamilos DL, Gevaert P, et al. Atopic comorbidities and biomarkers of type 2 inflammation in patients with chronic rhinosinusitis with nasal polyposis (CRSwNP) who failed intranasal corticosteroids. Journal of Allergy and Clinical Immunology 2018;141(2 Suppl 1):AB90. [7912807]
    1. Bachert C, Mannent L, Naclerio RM, Mullol J, Ferguson BJ, Gevaert P, et al. Effect of subcutaneous dupilumab on nasal polyp burden in patients with chronic sinusitis and nasal polyposis: a randomized clinical trial. JAMA 2016;315(5):469-79. [1861626] [PMID: ] - PubMed
    1. Bachert C, Mannent L, Naclerio RM, Mullol J, Ferguson BJ, Jiao L, et al. Dupilumab in chronic sinusitis with nasal polyposis, with and without asthma. Allergy 2015;70:107. [1866543]
Bachert 2017 {published and unpublished data}
    1. Bachert C, Sousa AR, Lund VJ, Scadding GK, Gevaert P, Nasser S, et al. Reduced need for surgery in severe nasal polyposis with mepolizumab: randomized trial. Journal of Allergy and Clinical Immunology 2017;140(4):1024-31.e14. [7111780] [PMID: ] - PubMed
    1. EUCTR2008-003772-21-NL. A two-part, randomised, double-blind, placebo controlled, multi-center study to investigate the use of mepolizumab (SB-240563) in reducing the need for surgery in subjects with severe bilateral nasal polyposis. https://www.clinicaltrialsregister.eu/ctr-search/trial/2008-003772-21/NL (first received 27 February 2009). [1743659]
    1. NCT01362244. A randomised, double-blind, placebo controlled, multi-center study to investigate the use of mepolizumab (Sb-240563) in reducing the need for surgery in subjects with severe bilateral nasal polyposis. https://clinicaltrials.gov/show/nct01362244 (first received 26 May 2011). [1629203]
Gevaert 2011 {published data only}
    1. Gevaert P, Van Bruaene N, Cattaert T, Van Steen K, Van Zele T, Acke F, et al. Mepolizumab, a humanized anti-IL-5 mAb, as a treatment option for severe nasal polyposis. Journal of Allergy and Clinical Immunology 2011;128(5):989-95.e1-8. [DOI: 10.1016/j.jaci.2011.07.056] [1601924] [PMID: ] - DOI - PubMed
Gevaert 2013 {published and unpublished data}
    1. EUCTR2006-003524-11-BE. Clinical and biological effects of anti-IgE (omalizumab) in patients with bilateral nasal polyposis and asthma [A randomized, double-blind, phase 2, placebo controlled, 2 arm study to evaluate dupilumab in patients with bilateral nasal polyposis and chronic symptoms of sinusitis]. http://apps.who.int/trialsearch/Trial2.aspx?TrialID=EUCTR2006-003524-11-BE (first received 11 August 2006). [1770331]
    1. Gevaert P, Calus L, Van Zele T, Blomme K, De Ruyck N, Bauters W, et al. Omalizumab is effective in allergic and non-allergic patients with nasal polyps and asthma. Journal of Allergy and Clinical Immunology 2012;129(2 Suppl 1):AB69. [1765640] - PubMed
    1. Gevaert P, Calus L, Van Zele T, Blomme K, De Ruyck N, Bauters W, et al. Omalizumab is effective in allergic and nonallergic patients with nasal polyps and asthma. Journal of Allergy and Clinical Immunology 2013;131(1):110-6.e1. [1617401] [PMID: ] - PubMed
    1. NCT01393340. Clinical and biological effects of anti-IgE (omalizumab) in patients with bilateral nasal polyposis and asthma. https://clinicaltrials.gov/show/NCT01393340 (first received 13 July 2011). [1629212]
LIBERTY SINUS 24 {published and unpublished data}
    1. Bachert C, Han JK, Desrosiers M, Hellings PW, Amin N, Lee SE, et al. Efficacy and safety of dupilumab in patients with severe chronic rhinosinusitis with nasal polyps (LIBERTY NP SINUS-24 and LIBERTY NP SINUS-52): results from two multicentre, randomised, double-blind, placebo-controlled, parallel-group phase 3 trials. Lancet 2019;394(10209):1638-50. [12131774] [PMID: ] - PubMed
    1. EUCTR2015-003101-42-BG. Controlled clinical study of dupilumab in patients with nasal polyps [A randomized, 24-week treatment, double-blind, placebo-controlled efficacy and safety study of dupilumab 300 mg every other week, in patients with bilateral nasal polyposis on a background therapy with intranasal corticosteroids - SYNUS-24]. https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_nu... (first received 4 January 2017). [10716209]
    1. Han JK, Bachert C, Desrosiers M, Laidlaw TM, Hopkins C, Fokkens WJ, et al. Efficacy and safety of dupilumab in patients with chronic rhinosinusitis with nasal polyps: results from the randomized phase 3 sinus-24 study. Journal of Allergy and Clinical Immunology 2019;143(2):AB422. [10639235]
    1. NCT02912468. A controlled clinical study of dupilumab in patients with bilateral nasal polyps [A randomized, 24-week treatment, double-blind, placebo-controlled efficacy and safety study of dupilumab 300 mg every other week, in patients with bilateral nasal polyposis on a background therapy with intranasal corticosteroids]. https://clinicaltrials.gov/show/NCT02912468 (first received 23 September 2016). [6978608]
LIBERTY SINUS 52 {published and unpublished data}
    1. Bachert C, Desrosiers M, Mullol J, Hellings PW, Cervin A, Sher L, et al. A randomized phase 3 study, sinus-52, evaluating the efficacy and safety of dupilumab in patients with severe chronic rhinosinusitis with nasal polyps. Journal of Allergy and Clinical Immunology 2019;143(2):AB433. [9965830]
    1. Bachert C, Han JK, Desrosiers M, Hellings PW, Amin N, Lee SE, et al. Efficacy and safety of dupilumab in patients with severe chronic rhinosinusitis with nasal polyps (LIBERTY NP SINUS-24 and LIBERTY NP SINUS-52): results from two multicentre, randomised, double-blind, placebo-controlled, parallel-group phase 3 trials. Lancet 2019;394(10209):1638-50. [12131774] [PMID: ] - PubMed
    1. Bachert C, Hellings PW, Mullol J, Naclerio RM, Chao J, Amin N, et al. Dupilumab improves patient-reported outcomes in patients with chronic rhinosinusitis with nasal polyps and comorbid asthma. Journal of Allergy and Clinical Immunology: In Practice 2019;7(7):2447-9.e2. [12043116] [PMID: ] - PubMed
    1. EUCTR2015-001314-10-ES. Controlled clinical study of dupilumab in patients with nasal polyps [A randomized, double-blind, 52-week, placebo controlled efficacy and safety study of dupilumab, in patients with bilateral nasal polyposis on a background therapy with intranasal corticosteroids]. https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_nu... (first received 10 October 2016). [10715675]
    1. NCT02898454. Controlled clinical study of dupilumab in patients with nasal polyps [A randomized, double-blind, 52-week, placebo controlled efficacy and safety study of dupilumab, in patients with bilateral nasal polyposis on a background therapy with intranasal corticosteroids]. https://clinicaltrials.gov/show/NCT02898454 (first received 13 September 2016). [6978611]
NCT01066104 {unpublished data only}
    1. NCT01066104. Subcutaneous omalizumab for treatment of chronic rhinosinusitis with nasal polyposis. https://clinicaltrials.gov/show/nct01066104 2009.
Pinto 2010 {published data only}
    1. Mehta NJ, Pinto J, Tineo M, Baroody FM, Naclerio RM. A randomized, double-blind, placebo-controlled clinical trial of omalizumab for chronic rhinosinusitis. Journal of Allergy and Clinical Immunology 2009;123(2 Suppl 1):S201.
    1. NCT00117611. Xolair in patients with chronic sinusitis [Effects of anti-IgE antibody omalizumab (Xolair) on patients with chronic sinusitis and a positive allergen test]. https://clinicaltrials.gov/show/NCT00117611 2005.
    1. Pinto JM, Mehta N, DiTineo M, Wang J, Baroody FM, Naclerio RM. A randomized, double-blind, placebo-controlled trial of anti-IgE for chronic rhinosinusitis. Rhinology 2010;48(3):318-24. [PMID: ] - PubMed
POLYP 1 {unpublished data only}
    1. EUCTR2017-001724-22-PL. A phase 3 clinical trial of omalizumab for chronic rhinosinusitis with nasal polyps [A phase III, randomized, multicenter, double-blind, placebo-controlled clinical trial of omalizumab in patients with chronic rhinosinusitis with nasal polyps]. https://www.clinicaltrialsregister.eu/ctr-search/trial/2017-001724-22/GB (first received 6 November 2017). [CENTRAL: CN-01889769]
    1. Gevaert P, Bachert C, Corren J, Mullol J, Han J, Ow R, et al. Omalizumab efficacy and safety in nasal polyposis: results from two parallel, double-blind, placebo-controlled trials. Annals of Allergy, Asthma and Immunology 2019;123(5 Suppl):S17. [CENTRAL: CN-01996751] [EMBASE: 2003401171]
    1. Gevaert P, Omachi TA, Corren J, Mullol J, Han J, Lee SE, et al. Efficacy and safety of omalizumab in nasal polyposis: two randomized phase III trials. Journal of Allergy and Clinical Immunology 2020;146(3):595-605. [DOI: 10.1016/j.jaci.2020.05.032] [EMBASE: 632051241] [PMID: ] - DOI - PubMed
    1. Lee SE, Yoo B, Saenz R, Braid J, Millette LA, Rajput Y. PRS2 Proportion of patients with nasal polyposis achieving clinically important improvements in quality of life with omalizumab treatment. Value in Health 2020;23(Suppl 1):S349. [CENTRAL: CN-02122072] [EMBASE: 2005868755]
    1. NCT03280550. A clinical trial of omalizumab in participants with chronic rhinosinusitis with nasal polyps [A phase III, randomized, multicenter, double-blind, placebo-controlled clinical trial of omalizumab in patients with chronic rhinosinusitis with nasal polyps]. https://clinicaltrials.gov/show/NCT03280550 (first received 12 September 2017). [CENTRAL: CN-01415214]
POLYP 2 {unpublished data only}
    1. EUCTR2017-001718-28-BE. A phase 3 clinical trial of omalizumab for chronic rhinosinusitis with nasal polyps [A phase III, randomized, multicenter, double-blind, placebo-controlled clinical trial of omalizumab in patients with chronic rhinosinusitis with nasal polyps]. https://www.clinicaltrialsregister.eu/ctr-search/trial/2017-001718-28/BE (first received 10 November 2017). [CENTRAL: CN-01908643]
    1. Gevaert P, Bachert C, Corren J, Mullol J, Han J, Ow R, et al. Omalizumab efficacy and safety in nasal polyposis: results from two parallel, double-blind, placebo-controlled trials. Annals of Allergy, Asthma and Immunology 2019;123(5 Suppl):S17. [CENTRAL: CN-01996751] [EMBASE: 2003401171]
    1. Gevaert P, Omachi TA, Corren J, Mullol J, Han J, Lee SE, et al. Efficacy and safety of omalizumab in nasal polyposis: two randomized phase III trials. Journal of Allergy and Clinical Immunology 2020;146(3):595-605. [DOI: 10.1016/j.jaci.2020.05.032] [EMBASE: 632051241] [PMID: ] - DOI - PubMed
    1. Lee SE, Yoo B, Saenz R, Braid J, Millette LA, Rajput Y. PRS2 Proportion of patients with nasal polyposis achieving clinically important improvements in quality of life with omalizumab treatment. Value in Health 2020;23(Suppl 1):S349. [CENTRAL: CN-02122072] [EMBASE: 2005868755]
    1. NCT03280537. A clinical trial of omalizumab in participants with chronic rhinosinusitis with nasal polyps [A phase III, randomized, multicenter, double-blind, placebo-controlled clinical trial of omalizumab in patients with chronic rhinosinusitis with nasal polyps]. https://clinicaltrials.gov/show/NCT03280537 (first received 12 September 2017). [CENTRAL: CN-01415096]

References to studies excluded from this review

ANDHI {published data only}
    1. Harrison TW, Chanez P, Menzella F, Canonica GW, Louis R, Cosio BG, et al. Exacerbation reduction and early and sustained improvements in SGRQ, lung function, and symptoms of nasal polyposis with benralizumab for severe, eosinophilic asthma: phase IIIb ANDHI trial. American Journal of Respiratory and Critical Care Medicine 2020;201(1):A4274. [CENTRAL: CN-02137562] [EMBASE: 632377736]
    1. NCT03170271. A study of the safety and effectiveness of benralizumab to treat patients with severe uncontrolled asthma [A multicenter, randomized, double-blind, parallel group, placebo controlled, phase 3b study to evaluate the safety and efficacy of benralizumab 30 mg SC in patients with severe asthma uncontrolled on standard of care treatment]. https://clinicaltrials.gov/show/NCT03170271 (first received 26 May 2017). [CENTRAL: CN-01494562]
Bachert 2020 {published data only}
    1. Bachert C, Gevaert P, Corren J, Mullol J, Han J, Ow R, et al. Omalizumab improves outcomes in patients with chronic rhinosinusitis with nasal polyps irrespective of asthma status. Journal of Allergy and Clinical Immunology 2020;145(2 Suppl):AB149. [EMBASE: 2004875715]
Bagnasco 2020 {published data only}
    1. Bagnasco D, Passalacqua G. Efficacy of benralizumab in severe asthma in real life and focus on nasal polyposis. Chest 2020;157(6 Suppl):A9. [EMBASE: 2006705574] - PubMed
Boguniewicz 2019 {published data only}
    1. Boguniewicz M, Thaci D, Lio PA, Hultsch T, Rossi AB, Eckert L, et al. Dupilumab improves outcomes of concurrent asthma and chronic sino-nasal conditions in patients with atopic dermatitis-a pooled analysis of four phase 3 studies (LIBERTY AD SOLO 1 & 2, CHRONOS, and CAFE). Journal of Allergy and Clinical Immunology 2019;143(2 Suppl):AB123.
Castro 2011 {published data only}
    1. Castro M, Mathur S, Hargreave F, Boulet LP, Xie F, Young J, et al. Reslizumab for poorly controlled, eosinophilic asthma: a randomized, placebo-controlled study. American Journal of Respiratory and Critical Care Medicine 2011;184(10):1125-32. [PMID: ] - PubMed
    1. Mathur S, Castro M, Hargreave F, Xie F, Wilkins HJ, Henkel T, et al. Efficacy of reslizumab in patients with poorly controlled eosinophilic asthma: subgroup analysis of patients with nasal polyps [Abstract]. Journal of Allergy and Clinical Immunology 2011;127(2 Suppl 1):AB84. [CENTRAL: CN-00793509]
Chan 2020 {published data only}
    1. Chan R, RuiWen Kuo C, Lipworth B. Disconnect between effects of mepolizumab on severe eosinophilic asthma and chronic rhinosinusitis with nasal polyps. Journal of Allergy and Clinical Immunology: in Practice 2020;8(5):1714-6. [CENTRAL: CN-02120814] [EMBASE: 2004759183] [PMID: ] - PubMed
ChiCTR1900026575 {published data only}
    1. ChiCTR1900026575. Efficacy of omalizumab in patients with chronic sinusitis and nasal polyps combined with asthma [Study for omalizumab in the treatment of chronic sinusitis and nasal polyps with asthma and allergic rhinitis]. http://www.chictr.org.cn/showproj.aspx?proj=40553 (first received 14 October 2019).
Corren 2020 {published data only}
    1. Corren J, Bachert C, Gevaert P, Mullol J, Han J, Ow R, et al. Omalizumab improves quality of life in patients with chronic rhinosinusitis with nasal polyps and comorbid asthma. Journal of Allergy and Clinical Immunology 2020;145(2 Suppl):AB250. [EMBASE: 2004875317]
De Schryver 2015 {published data only}
    1. De Schryver E, Van Zele T, Bachert C, Gevaert P. Comparison of different medical treatment options for CRSwNP: doxycycline, methylprednisolone, mepolizumab and omalizumab. Allergy 2015;70:442. [CENTRAL: CN-01135998] [EMBASE: 72029693]
Desrosiers 2019 {published data only}
    1. Desrosiers M, Bachert C, Hellings PW, Hopkins C, Olze H, Han JK, et al. Dupilumab reduces need for systemic corticosteroid use, sinonasal surgery in patients with severe chronic rhinosinusitis with nasal polyps: pooled results from the SINUS-24, SINUS-52 phase 3 studies. Allergy: European Journal of Allergy and Clinical Immunology 2019;74(Suppl 106):330-1. [CENTRAL: CN-02053721] [EMBASE: 629479604]
Dinakar 2018 {published data only}
    1. Dinakar C, Khan DA, Fineman SM, Lang DM, Tilles SA. Biologics. Annals of Allergy, Asthma & Immunology 2018;120(4):354-6. [PMID: ] - PubMed
EUCTR2017‐003450‐16 {published data only}
    1. EUCTR2017-003450-16-GB. A study of omalizumab in patients with chronic rhinosinusitis with nasal polyps [Open-label extension study of omalizumab in patients with chronic rhinosinusitis with nasal polyps]. https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_nu... (first received 10 January 2018).
Gevaert 2006 {published data only}
    1. Gevaert P, can Zele T, Stammberger H, Sacks H, van Cauwenberge, Bachert C. Anti-interleukin-5 treatment in nasal polyposis. Journal of Allergy and Clinical Immunology 2005;115(2):S138. [DOI: 10.1016/j.jaci.2004.12.566] - DOI
    1. Gevaert P, Lang-Loidolt D, Lackner A, Stammberger H, Staudinger H, Van Zele T, et al. Nasal IL-5 levels determine the response to anti-IL-5 treatment in patients with nasal polyps. Journal of Allergy and Clinical Immunology 2006;118(5):1133-41. [CENTRAL: CN-00573474] [EMBASE: 2006535588] [PMID: ] - PubMed
    1. Gevaert P, Van Zele T, Stammberger H, Staudinger H, Tavernier J, Cauwenberge P, et al. Nasal interleukin-5 levels determine the response to anti-interleukin-5 treatment in nasal polyp patients. In: 3rd EAACI Davos Meeting in Basic Immunology in Allergy and Clinical Immunology; 2005 February 3-6; Davos, Switzerland. 2005. [CENTRAL: CN-00519575]
Gevaert 2008 {published data only}
    1. Gevaert P, Van Bruaene N, Blomme K, Sousa AR, Marshal RP, Bachert C. Mepolizumab, a humanised anti-IL-5 monoclonal antibody, as treatment of severe nasal polyposis. Journal of Allergy and Clinical Immunology 2008;121(2 (Suppl 1)):Abstract No. L26. - PubMed
Gonzalez‐Diaz 2014 {published data only}
    1. Gonzalez-Diaz SN, Rangel-Garza L. Omalizumab efficiency in patients with allergic rhinitis and chronic sinusitis. World Allergy Organization Journal 2014;7(Suppl 1):9.
Hayashi 2020 {published data only}
    1. Hayashi H, Fukutomi Y, Mitsui C, Kajiwara K, Watai K, Kamide Y, et al. Omalizumab for aspirin-hypersensitivity and leukotriene overproduction in aspirin-exacerbated respiratory disease: a randomized trial. American Journal of Respiratory and Critical Care Medicine 2020;201(12):1488-98. [CENTRAL: CN-02098334] [DOI: 10.1164/rccm.201906-1215OC] [EMBASE: 631191245] [PMID: ] - DOI - PMC - PubMed
Hellings 2017 {published data only}
    1. Hellings P, Bachert C, Mullol J, Hamilos D, Naclerio R, Joish V, et al. Dupilumab improves all ACQ-5 individual items in patients with chronic rhinosinusitis with nasal polyposis (CRSwNP) and asthma: results from a phase 2a trial. European Respiratory Journal 2017;50(Suppl 61):PA3549.
    1. Hellings P, Bachert C, Mullol J, Hamilos D, Naclerio R, Mannent L, et al. Dupilumab improves ACQ-5 items in CRSwNP patients with comorbid asthma. Respiratology 2018;23(Suppl 1):153. [DOI: 10.1111/resp.13268] - DOI
Hoy 2020 {published data only}
    1. Hoy SM. Dupilumab: a review in chronic rhinosinusitis with nasal polyps. Drugs 2020;80(7):711-7. [PMID: ] - PubMed
Jain 2020 {published data only}
    1. Jain N, Siri D, Yancey S, Price R, Wenzel S. Mepolizumab reduces exacerbations and improves health-related quality of life in patients with severe asthma and nasal polyps, sinusitis, or allergic rhinitis. Journal of Allergy and Clinical Immunology 2020;145(2 Suppl):AB26. [EMBASE: 2004874768]
Katial 2019 {published data only}
    1. Katial R, Siddiqui S, Barker P, Kwiatek J. Clinical efficacy characterization of benralizumab for patients with nasal polyposis and severe, uncontrolled eosinophilic asthma. Annals of Allergy, Asthma and Immunology 2019;123(5 Suppl):S26. [CENTRAL: CN-02081766] [EMBASE: 2003401224]
Laidlaw 2019 {published data only}
    1. Laidlaw TM, Mullol J, Fan C, Zhang D, Amin N, Khan A, et al. Dupilumab improves nasal polyp burden and asthma control in patients with CRSwNP and AERD. Journal of Allergy and Clinical Immunology: In Practice 2019;7(7):2462-5.e1. - PubMed
Laidlaw 2019b {published data only}
    1. Laidlaw T, Cho S, Maspero JF, Canonica GW, Sher L, Bachert C, et al. Dupilumab improves upper and lower airway outcome measures in patients with severe chronic rhinosinusitis with nasal polyps and comorbid asthma: pooled results from the SINUS-24 and SINUS-52 phase 3 studies. American Journal of Respiratory and Critical Care Medicine 2019;199:A7356. [CENTRAL: CN-02073638] [EMBASE: 630355441]
Laidlaw 2019c {published data only}
    1. Laidlaw TM, Mullol J, Canonica GW, Bachert C, Han JK, Zhang M, et al. Dupilumab (DPL) improves upper and lower airway outcomes in chronic rhinosinusitis with nasal polyps (CRSwNP) with nonsteroidal anti-inflammatory drug-exacerbated respiratory disease (NSAID-ERD): pooled results from SINUS-24, SINUS-52 phase 3 trials. European Respiratory Journal 2019;54(Suppl 63):PA539. [CENTRAL: CN-02087661] [EMBASE: 630917140]
Laidlaw 2020a {published data only}
    1. Laidlaw TM, Mullol J, Canonica GW, Bachert C, Han JK, Lu X, et al. Dupilumab improves upper and lower airway outcomes in chronic rhinosinusitis with nasal polyps (CRSwNP) with nonsteroidal anti-inflammatory drug-exacerbated respiratory disease (NSAID-ERD): pooled results from SINUS-24, SINUS-52 phase 3 trials. Canadian Journal of Respiratory, Critical Care, and Sleep Medicine 2020;4(Suppl 2):31-2. [EMBASE: 632510990]
Liberty Asthma Quest {published data only}
    1. Bousquet J, Maspero JF, Chipps BE, Corren J, FitzGerald JM, Chen Z, et al. Dupilumab consistently improves rhinoconjunctivitis-specific health-related quality of life in patients with uncontrolled, moderate-to-severe asthma and comorbid allergic rhinitis: results from the phase 3 LIBERTY ASTHMA QUEST study. Journal of Allergy and Clinical Immunology 2019;143(2 Suppl):AB101. [CENTRAL: CN-01932317] [EMBASE: 2001510554]
    1. Busse W, Maspero JF, Katelaris CH, Saralaya D, Guillonneau S, Zhang B, et al. Dupilumab improves SNOT-22 scores in asthma patients with chronic rhinosinusitis or nasal polyposis (CRS/NP) in LIBERTY ASTHMA QUEST. European Respiratory Journal 2018;52(Suppl 62):PA1125. [DOI: 10.1183/13993003.congress-2018.PA1125] - DOI
    1. Busse WW, Maspero JF, Hanania NA, FitzGerald JM, Ford LB, Rice M, et al. Dupilumab improves lung function and reduces severe exacerbation rate in patients with uncontrolled, moderate-to-severe asthma with or without comorbid allergic rhinitis: results from the phase 3 LIBERTY ASTHMA QUEST study. Journal of Allergy and Clinical Immunology 2019;143(2 Suppl):AB97. [CENTRAL: CN-01945651] [EMBASE: 2001510335]
    1. Busse WW, Maspero JF, Rabe KF, Papi A, Wenzel SE, Ford LB, et al. Liberty asthma QUEST: phase 3 randomized, double-blind, placebo-controlled, parallel-group study to evaluate dupilumab efficacy/safety in patients with uncontrolled, moderate-to-severe asthma. Advances in Therapy 2018;35(5):1-12. [CENTRAL: CN-01612071] [EMBASE: 622013044] [PMID: ] - PMC - PubMed
    1. Castro M, Busse WW, Zhang B, Maroni J, Rowe P, Amin N, et al. Dupilumab treatment produces rapid and sustained improvements in FEV1 in patients with uncontrolled, moderate-to-severe asthma from the LIBERTY ASTHMA QUEST study. American Journal of Respiratory and Critical Care Medicine 2018;197:A6163. [CENTRAL: CN-01619354] [EMBASE: 622964392]
Mullol 2020 {published data only}
    1. Mullol J, Han J, Bosso J, Mannent L, Amin N, Cho S, et al. Dupilumab treatment improves sense of smell in patients with chronic rhinosinusitis with nasal polyps - pooled results from the SINUS-24 and SINUS-52 phase 3 trials. Journal of Allergy and Clinical Immunology 2020;145(2 Suppl):AB169. [CENTRAL: CN-02084828] [EMBASE: 2004875825]
MUSCA {published data only}
    1. NCT02281318. Efficacy and safety study of mepolizumab adjunctive therapy in participants with severe eosinophilic asthma on markers of asthma control [A randomised, double-blind, placebo-controlled, parallel-group, multi-centre 24-week study to evaluate the efficacy and safety of mepolizumab adjunctive therapy in subjects with severe eosinophilic asthma on markers of asthma control]. https://clinicaltrials.gov/show/nct02281318 (first received 3 November 2014).
    1. Nelsen L, Bradford ES, Bratton DJ, Albers FC, Brusselle G. Improvement in rhinosinusitis health related quality of life in patients with severe eosinophilic asthma. European Respiratory Journal 2017;50(Suppl 61):PA3583. [DOI: 10.1183/1393003.congress-2017.PA3583] - DOI
Mustafa 2020 {published data only}
    1. Mustafa S, Vadamalai K, Scott B, Ramsey A. Dupilumab as add-on therapy for aspirin-exacerbated respiratory disease (AERD). Journal of Allergy and Clinical Immunology February 2020;145(2 Suppl):AB173. [EMBASE: 2004875309]
    1. Mustafa SS, Vadamalai K, Scott B, Ramsey A. Dupilumab as add-on therapy for chronic rhinosinusitis with nasal polyposis in aspirin exacerbated respiratory disease. American Journal of Rhinology & Allergy 2020 Sep 23 [Epub ahead of print]. [DOI: 10.1177/1945892420961969] [PMID: ] - DOI - PubMed
Naclerio 2017 {published data only}
    1. Naclerio RM, Hamilos DL, Ferguson BJ, Bachert C, Hellings PW, Mullol J, et al. Dupilumab improves sense of smell and reduces anosmia among patients with nasal polyposis and chronic sinusitis: results from a phase 2a trial. Journal of Allergy and Clinical Immunology 2017;139(2 Suppl):AB90.
NCT00603785 {published data only}
    1. NCT00603785. Effects of anti-IgE antibody omalizumab on patients with chronic sinusitis [Effects of anti-IgE antibody omalizumab (Xolair) on patients with chronic sinusitis and a positive allergen test]. https://clinicaltrials.gov/show/nct00603785 (first received 29 January 2008).
NCT01285323 {published data only}
    1. Castro M, Zangrilli J, Wechsler ME, Bateman ED, Brusselle GG, Bardin P, et al. Reslizumab for inadequately controlled asthma with elevated blood eosinophil counts: results from two multicentre, parallel, double-blind, randomised, placebo-controlled, phase 3 trials. Lancet Respiratory Medicine 2015;3(5):355-66. [PMID: ] - PubMed
    1. NCT01285323. A study to evaluate the efficacy and safety of reslizumab in patients with eosinophilic asthma [A 12-month, double-blind, placebo-controlled, parallel-group study to evaluate the efficacy and safety of reslizumab (3.0 mg/kg) in the reduction of clinical asthma exacerbations in patients (12-75 years of age) with eosinophilic asthma]. https://clinicaltrials.gov/show/NCT01285323 (first received 28 January 2011).
    1. Weinstein SF, Germinaro M, Bardin P, Korn S, Bateman ED. Efficacy of reslizumab with asthma, chronic sinusitis with nasal polyps and elevated blood eosinophils. Journal of Allergy and Clinical Immunology 2016;137(2 Suppl 1):AB86. - PubMed
    1. Weinstein SF, Katial RK, Bardin P, Korn S, McDonald M, Garin M, et al. Effects of reslizumab on asthma outcomes in a subgroup of eosinophilic asthma patients with self-reported chronic rhinosinusitis with nasal polyps. Journal of Allergy & Clinical Immunology in Practice 2019;7(2):589-96.e3. [CENTRAL: CN-01922720] [EMBASE: 2001152799] [PMID: ] - PubMed
NCT02170337 {published data only}
    1. NCT02170337. A study to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of AMG 282 in healthy subjects and subjects with chronic rhinosinusitis with nasal polyps [A randomized, double-blind, placebo-controlled, ascending multiple-dose study to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of AMG 282 in healthy subjects and subjects with chronic rhinosinusitis with nasal polyps]. https://clinicaltrials.gov/show/nct02170337 (first received 19 June 2014).
NCT02734849 {published data only}
    1. NCT02734849. Study to evaluate multiple doses in patients with nasal polyposis [A phase 2, randomized, double-blind, placebo-controlled, study to evaluate multiple doses of AK001 in patients with moderate to severe nasal polyposis]. https://clinicaltrials.gov/show/NCT02734849 (first received 12 April 2016). [CENTRAL: CN-01415083]
NCT02743871 {published data only}
    1. NCT02743871. Study of PF-06817024 in healthy subjects, in patients with chronic rhinosinusitis with nasal polyps and in patients with atopic dermatitis [A phase 1, randomized, double-blind, third-party open, placebo-controlled, dose escalating study to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of single and/or multiple intravenous and/or subcutaneous doses of pf-06817024 in healthy subjects who may BE mildly atopic, subjects with chronic rhinosinusitis with nasal polyps, and subjects with moderate-severe atopic dermatitis]. https://clinicaltrials.gov/show/NCT02743871 2016.
NCT03028350 {published data only}
    1. NCT03028350. Oral ifetroban to treat aspirin exacerbated respiratory disease (AERD) [A phase 2 multicenter, double-blind, randomized, placebo-controlled trial to evaluate oral ifetroban in subjects with symptomatic aspirin exacerbated respiratory disease (AERD)]. https://clinicaltrials.gov/show/nct03028350 (first received 19 January 2017). [CENTRAL: CN-01561442]
NCT03681093 {published data only}
    1. NCT03681093. Study of efficacy of fevipiprant in patients with nasal polyposis and asthma [A multicenter, randomized, double-blind, parallel-group, placebo-controlled study of fevipiprant once daily plus standard-of-care (SoC) for assessment of the efficacy in reduction of nasal polyp size in patients with nasal polyposis and concomitant asthma]. https://clinicaltrials.gov/show/nct03681093 (first received 21 September 2018). [CENTRAL: CN-01648506]
NCT03688555 {published data only}
    1. NCT03688555. A study to evaluate the effect of ACT-774312 in subjects with bilateral nasal polyposis [A randomized, double-blind, placebo-controlled, single-center, 12-week study to evaluate the effect of ACT-774312 in subjects with bilateral nasal polyposis]. https://clinicaltrials.gov/show/nct03688555 (first received 28 September 2018). [CENTRAL: CN-01648719]
NCT03956862 {published data only}
    1. NCT03956862. GB001 in adult subjects with chronic rhinosinusitis [A phase 2a, randomized, double-blind, placebo-controlled, multi-center study to evaluate the effect of GB001 in patients with chronic rhinosinusitis with or without nasal polyps]. https://clinicaltrials.gov/show/nct03956862 (first received 21 May 2019). [CENTRAL: CN-01932790]
Perez De Llano 2018 {published data only}
    1. Perez De Llano L, Meizlik P, McDonald M, Mustafa SS. Reslizumab decreases nasal adverse events and upper respiratory-associated concomitant medication use in patients with eosinophilic asthma and nasal polyps. Allergy 2018;73(Suppl 105):91-2.
Tajiri 2013 {published data only}
    1. Tajiri T, Matsumoto H, Hiraumi H, Ikeda H, Morita K, Izuhara K, et al. Efficacy of omalizumab in eosinophilic chronic rhinosinusitis patients with asthma. Annals of Allergy, Asthma, & Immunology 2013;110(5):387-8. - PubMed
Wahba 2019 {published data only}
    1. Wahba AA, Abdelfattah AM. Anti-immunoglobulin E therapy: is it a valid option for the management of chronic rhinosinusitis with nasal polyposis? Egyptian Journal of Otolaryngology 2019;35(3):269-77.
Zangrilli 2019 {published data only}
    1. Zangrilli JG, Maspero J, Harrison T, Werkstrom V, Wu Y. Clinical efficacy of benralizumab in patients with severe, uncontrolled eosinophilic asthma and nasal polyposis: pooled Analysis of the SIROCCO and CALIMA Trials. Pneumologie (Stuttgart, Germany) 2019;73(Suppl 1):AB12. [DOI: 10.1016/j.jaci.2017.12.038] - DOI

References to studies awaiting assessment

Gevaert 2004 {published data only}
    1. Gevaert P, Cauwenberge P, Bachert C. Future therapeutic possibilities: from anti-IL5 therapy onwards. In: 3rd International Consensus Conference on Nasal Polyposis; 2004 Apr 23-25; Brussels, Belgium. 2004. [CENTRAL: CN-00519574]
Nsouli 2019 {published data only}
    1. Nsouli S. Dupilumab a human anti-interleukin-4 receptor alpha monoclonal antibody for uncontrolled chronic rhinosinusitis with nasal polyps. Annals of Allergy, Asthma and Immunology 2019;123(5 Suppl):S59. [CENTRAL: CN-01998190] [EMBASE: 2003401315]

References to ongoing studies

EUCTR2020‐000421‐76 {published data only}
    1. EUCTR2020-000421-76-FI. Aggravated airway inflammation: research on biological treatment (mepolizumab) AirGOs-biologics. https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_nu... (first received 26 March 2020).
NAPPREB {unpublished data only}
    1. Heffler E, Puggioni F, Mauri P, Riccio AM, Racca F, Malvezzi L, et al. NAPPREB study protocol: a pivotal clinical trial to investigate clinical efficacy and potential response biomarkers to benralizumab treatment in chronic rhinosinusitis with nasal polyps. Allergy: European Journal of Allergy and Clinical Immunology 2019;74(Suppl 106):889. [CENTRAL: CN-01996992] [EMBASE: 629483549]
    1. NCT04185012. Nasal polyps: inflammatory & molecular phenotyping of responders to benralizumab. https://clinicaltrials.gov/show/NCT04185012 (first received 4 December 2019). [CENTRAL: CN-02078990]
NCT02772419 {published data only}
    1. NCT02772419. Study of benralizumab (KHK4563) in patients with eosinophilic chronic rhinosinusitis [A phase 2, double-blind, placebo-controlled study of benralizumab (KHK4563) in patients with eosinophilic chronic rhinosinusitis]. https://clinicaltrials.gov/show/NCT02772419 (first received 13 May 2016). [CENTRAL: CN-01415166]
NCT02799446 {published data only}
    1. NCT02799446. Effect of reslizumab in chronic rhinosinusitis [Efficacy of reslizumab for the treatment of chronic rhinosinusitis a double blind, randomized, placebo-controlled, phase III trial]. https://clinicaltrials.gov/show/NCT02799446 (first received 14 June 2016).
NCT03450083 {published data only}
    1. NCT03450083. Benralizumab effect on severe chronic rhinosinusitis with eosinophilic polyposis [Benralizumab effect on severe chronic rhinosinusitis with eosinophilic polyposis: a phase II randomized placebo controlled trial]. https://clinicaltrials.gov/show/nct03450083 (first received 17 August 2017).
NCT03614923 {published data only}
    1. NCT03614923. Etokimab in adult patients with chronic rhinosinusitis with nasal polyps (CRSwNP) [A phase 2 double-blind, placebo-controlled multi-dose study to investigate etokimab (ANB020) activity in adult patients with chronic rhinosinusitis with nasal polyps]. https://clinicaltrials.gov/show/NCT03614923 (first received 3 August 2018).
NCT04362501 {published data only}
    1. NCT04362501. Efficacy of dupilumab for patients with chronic rhinosinusitis without nasal polyps (CRSsNP) [Efficacy of dupilumab for patients with chronic rhinosinusitis without nasal polyps (CRSsNP): a randomized double blind placebo controlled phase II study]. https://clinicaltrials.gov/show/NCT04362501 (first received 27 April 2020). [CENTRAL: CN-02103467]
NCT04430179 {published data only}
    1. NCT04430179. Dupilumab severe eosinophilic chronic sinusitis without nasal polyposis [An evaluation of dupilumab in patients with severe eosinophilic chronic sinusitis without nasal polyposis]. https://clinicaltrials.gov/show/NCT04430179 (first received 12 June 2020). [CENTRAL: CN-02125522]
ORCHID {unpublished data only}
    1. NCT04157335. Efficacy and safety study of benralizumab in patient with eosinophilic chronic rhinosinusitis with nasal polyps (ORCHID) [A multicentre, randomised, double-blind, parallel-group, placebo-controlled phase 3 efficacy and safety study of benralizumab in patients with eosinophilic chronic rhinosinusitis with nasal polyps (ORCHID)]. https://clinicaltrials.gov/show/NCT04157335 (first received 8 November 2019). [CENTRAL: CN-01995031]
    1. TCTR20190820003. A multicentre, randomised, double-blind, parallel-group, placebo- controlled phase 3 efficacy and safety study of benralizumab in patients with eosinophilic chronic rhinosinusitis with nasal polyps (ORCHID). http://www.thaiclinicaltrials.org/export/pdf/pdf.php?RID=3855 (first received 20 August 2019). [CENTRAL: CN-02071818]
OSTRO {published data only}
    1. EUCTR2017-003675-61-BE. Efficacy and safety study of benralizumab for patients with severe nasal polyposis [A multicenter, randomized, double-blind, parallel-group, placebo-controlled phase 3 efficacy and safety study of benralizumab in patients with severe nasal polyposis - OSTRO]. https://www.clinicaltrialsregister.eu/ctr-search/trial/2017-003675-61/BE (first received 7 December 2017). [CENTRAL: CN-01908741]
    1. NCT03401229. Efficacy and safety study of benralizumab for patients with severe nasal polyposis [A multicenter, randomized, double-blind, parallel-group, placebo-controlled phase 3 efficacy and safety study of benralizumab in patients with severe nasal polyposis]. https://clinicaltrials.gov/show/NCT03401229 (first received 17 January 2018).
SYNAPSE {published data only}
    1. EUCTR2016-004255-70-SE. Effect of mepolizumab in severe bilateral nasal polyps [A randomised, double-blind, parallel group PhIII study to assess the clinical efficacy and safety of 100 mg SC mepolizumab as an add on to maintenance treatment in adults with severe bilateral nasal polyps - SYNAPSE (StudY in NAsal Polyps patients to assess the Safety and Efficacy of mepolizumab)]. https://www.clinicaltrialsregister.eu/ctr-search/trial/2016-004255-70/SE (first received 4 October 2017).
    1. NCT03085797. Effect of mepolizumab in severe bilateral nasal polyps [A randomised, double-blind, parallel group PhIII study to assess the clinical efficacy and safety of 100 mg SC mepolizumab AS an add on to maintenance treatment in adults with severe bilateral nasal polyps - SYNAPSE (study in nasal polyps patients to assess the safety and efficacy of mepolizumab)]. https://clinicaltrials.gov/show/NCT03085797 (first received 21 March 2017).

Additional references

Cho 2012
    1. Cho SH, Hong SJ, Han B, Lee SH, Suh L, Norton J, et al. Age-related differences in the pathogenesis of chronic rhinosinusitis. Journal of Allergy and Clinical Immunology 2012;129(3):858-60.e2. - PMC - PubMed
Chong 2016a
    1. Chong LY, Head K, Hopkins C, Philpott C, Schilder AGM, Burton MJ. Intranasal steroids versus placebo or no intervention for chronic rhinosinusitis. Cochrane Database of Systematic Reviews 2016, Issue 4. Art. No: CD011996. [DOI: 10.1002/14651858.CD011996.pub2] - DOI - PMC - PubMed
Chong 2016b
    1. Chong LY, Head K, Hopkins C, Philpott C, Glew S, Scadding G, et al. Saline irrigation for chronic rhinosinusitis. Cochrane Database of Systematic Reviews 2016, Issue 4. Art. No: CD011995. [DOI: 10.1002/14651858.CD011995.pub2] - DOI - PMC - PubMed
Chong 2016c
    1. Chong LY, Head K, Hopkins C, Philpott C, Burton MJ, Schilder AGM. Different types of intranasal steroids for chronic rhinosinusitis. Cochrane Database of Systematic Reviews 2016, Issue 4. Art. No: CD011993. [DOI: 10.1002/14651858.CD011993.pub2] - DOI - PMC - PubMed
Codispoti 2019
    1. Codispoti CD, Mahdavinia M. A call for cost-effectiveness analysis for biologic therapies in chronic rhinosinusitis with nasal polyps. Annals of Allergy, Asthma and Immunology 2019;123(3):232-9. 12028312 [EMBASE: 2002434399] - PubMed
DeMarcantonio 2011
    1. DeMarcantonio MA, Han JK. Nasal polyps: pathogenesis and treatment implications. Otolaryngologic Clinics of North America 2011;44(3):685-95, ix. - PubMed
Ebbens 2010
    1. Ebbens FA, Toppila-Salmi SK, Renkonen JA, Renkonen RL, Mullol J, Drunen CM, et al. Endothelial L-selectin ligand expression in nasal polyps. Allergy 2010;65(1):95-102. - PubMed
Ebbens 2011
    1. Ebbens FA, Toppila-Salmi S, Groot EJ, Renkonen J, Renkonen R, Drunen CM, et al. Predictors of post-operative response to treatment: a double blind placebo controlled study in chronic rhinosinusitis patients. Rhinology 2011;49(4):413-9. - PubMed
Egger 1997
    1. Egger M, Davey Smith G, Schneider M, Minder C. Bias in meta-analysis detected by a simple, graphical test. BMJ (Clinical research ed.) 1997;315(7109):629-34. - PMC - PubMed
EPOS 2007
    1. Fokkens W, Lund V, Mullol J, European Position Paper on Rhinosinusitis and Nasal Polyps Group. European position paper on rhinosinusitis and nasal polyps 2007. Rhinology. Supplement 2007;45 Suppl 20:1-136. - PubMed
EPOS 2012
    1. Fokkens WJ, Lund VJ, Mullol J, Bachert C, Alobid I, Baroody F, et al. European Position Paper on Rhinosinusitis and Nasal Polyps 2012. Rhinology. Supplement 2012;50 Suppl 23:1‐298. - PubMed
EudraCT 2020‐000195‐38
    1. A multicentre, randomised, double-blind, parallel-group, placebo-controlled phase 3 efficacy and safety study of benralizumab for the prevention of recurrence of nasal polyps following surgical removal in patients with chronic rhinosinusitis with nasal polyps (OXALIS). https://www.clinicaltrialsregister.eu/ctr-search/trial/2020-000195-38/HU (first received 16 June 2020).
Farne 2017
    1. Farne HA, Wilson A, Powell C, Bax L, Milan SJ. Anti‐IL5 therapies for asthma. Cochrane Database of Systematic Reviews 2017, Issue 9. Art. No: CD010834. [DOI: 10.1002/14651858.CD010834.pub3] - DOI - PMC - PubMed
FDA 2018
    1. US Food & Drug Administration. CFR - Code of Federal Regulations Title 21. https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/cfrsearch.cfm?f... (accessed 18 February 2019).
Gliklich 1995
    1. Gliklich RE, Metson R. The health impact of chronic sinusitis in patients seeking otolaryngologic care. Otolaryngology - Head and Neck Surgery 1995;113(1):104-9. - PubMed
Handbook 2011
    1. Higgins JPT, Green S (editors). Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 [updated March 2011]. The Cochrane Collaboration, 2011. Available from www.cochrane-handbook.org.
Handbook 2019
    1. Higgins JPT, Thomas J, Chandler J, Cumpston M, Li T, Page MJ, Welch VA (editors). Cochrane Handbook for Systematic Reviews of Interventions version 6.0 (updated July 2019). Cochrane, 2019. Available from www.training.cochrane.org/handbook.
Hastan 2011
    1. Hastan D, Fokkens WJ, Bachert C, Newson RB, Bislimovska J, Bockelbrink A, et al. Chronic rhinosinusitis in Europe - an underestimated disease. A GA2LEN study. Allergy 2011;66(9):1216-23. - PubMed
Head 2016a
    1. Head K, Chong LY, Hopkins C, Philpott C, Burton MJ, Schilder AGM. Short-course oral steroids alone for chronic rhinosinusitis. Cochrane Database of Systematic Reviews 2016, Issue 4. Art. No: CD011991. [DOI: 10.1002/14651858.CD011991.pub2] - DOI - PMC - PubMed
Head 2016b
    1. Head K, Chong LY, Hopkins C, Philpott C, Schilder AGM, Burton MJ. Short-course oral steroids as an adjunct therapy for chronic rhinosinusitis. Cochrane Database of Systematic Reviews 2016, Issue 4. Art. No: CD011992. [DOI: 10.1002/14651858.CD011992.pub2] - DOI - PMC - PubMed
Head 2016c
    1. Head K, Chong LY, Piromchai P, Hopkins C, Philpott C, Schilder AGM, et al. Systemic and topical antibiotics for chronic rhinosinusitis. Cochrane Database of Systematic Reviews 2016, Issue 4. Art. No: CD011994. [DOI: 10.1002/14651858.CD011994.pub2] - DOI - PMC - PubMed
Head 2018
    1. Head K, Sacks PL, Chong LY, Hopkins C, Philpott C. Topical and systemic antifungal therapy for chronic rhinosinusitis. Cochrane Database of Systematic Reviews 2018, Issue 9. Art. No: CD012453. [DOI: 10.1002/14651858.CD012453.pub2] - DOI - PMC - PubMed
Hoehle 2019
    1. Hoehle LP, Phillips KM, Speth MM, Caradonna DS, Gray ST, Sedaghat AR. Responsiveness and minimal clinically important difference for the EQ-5D in chronic rhinosinusitis. Rhinology 2019;57(2):110-6. - PubMed
Hong 2015
    1. Hong CJ, Tsang AC, Quinn JG, Bonaparte JP, Stevens A, Kilty SJ. Anti-IgE monoclonal antibody therapy for the treatment of chronic rhinosinusitis: a systematic review. Systematic Reviews 2015;4:166. [DOI: 10.1186/s13643-015-0157-5] - DOI - PMC - PubMed
Hopkins 2009
    1. Hopkins C, Gillett S, Slack R, Lund VJ, Browne JP. Psychometric validity of the 22-item Sinonasal Outcome Test. Clinical Otolaryngology 2009;34(5):447-54. [DOI: 10.1111/j.1749-4486.2009.01995.x] - DOI - PubMed
Hopkins 2018
    1. Hopkins C, Hettige R, Soni-Jaiswal A, Lakhani R, Carrie S, et al. CHronic Rhinosinusitis Outcome MEasures (CHROME), developing a core outcome set for trials of interventions in chronic rhinosinusitis. Rhinology 2018;56(1):22-32. [PMID: ] - PubMed
Iqbal 2020
    1. Iqbal IZ, Kao SS, Ooi EH. The role of biologics in chronic rhinosinusitis: a systematic review. International Forum of Allergy & Rhinology 2020;10(2):165-74. - PubMed
Jefferson 2018
    1. Jefferson T, Doshi P, Boutron I, Golder S, Heneghan C, Hodkinson A, et al. When to include clinical study reports and regulatory documents in systematic reviews. BMJ Evidence-Based Medicine 2018;23(6):210-7. [DOI: 10.1136/bmjebm-2018-110963] - DOI - PubMed
Kariyawasam 2019
    1. Kariyawasam HH. Chronic rhinosinusitis with nasal polyps: insights into mechanisms of disease from emerging biological therapies. Expert Review of Clinical Immunology 2019;15(1):59-71. [DOI: 10.1080/1744666X.2019.1541738] - DOI - PubMed
Kern 2008
    1. Kern RC, Conley DB, Walsh W, Chandra R, Kato A, Tripathi-Peters A, et al. Perspectives on the etiology of chronic rhinosinusitis: an immune barrier hypothesis. American Journal of Rhinology 2008;22(6):549-59. - PMC - PubMed
Keswani 2012
    1. Keswani A, Chustz RT, Suh L, Carter R, Peters AT, Tan BK, et al. Differential expression of interleukin-32 in chronic rhinosinusitis with and without nasal polyps. Allergy 2012;67(1):25-32. - PMC - PubMed
Laidlaw 2020b
    1. Laidlaw TM, Buchheit KM. Biologics in chronic rhinosinusitis with nasal polyposis. Annals of Allergy, Asthma & Immunology 2020 Apr;124(4):326-32. 13832842 [PMID: ] - PMC - PubMed
Larsen 2004
    1. Larsen P, Tos M. Origin of nasal polyps: an endoscopic autopsy study. Laryngoscope 2004;114(4):710-9. - PubMed
Liberty ‐ CRSsNP
    1. NCT04678856. Dupilumab in CRSsNP [A randomized, double-blind, placebo-controlled, 2-part study to evaluate the efficacy and safety of dupilumab in patients with uncontrolled, chronic rhinosinusitis without nasal polyposis (CRSsNP)]. https://clinicaltrials.gov/show/NCT04678856 (first received 22 December 2020).
Marshal 2018
    1. Marshall J, Noel-Storr AH, Kuiper J, Thomas J, Wallace BC. Machine learning for identifying randomized controlled trials: an evaluation and practitioner's guide. Research Synthesis Methods 2018;9(4):602-14. - PMC - PubMed
McDonald 2017
    1. McDonald S, Noel-Storr AH, Thomas J. Harnessing the efficiencies of machine learning and Cochrane Crowd to identify randomised trials for individual Cochrane reviews. In: Global Evidence Summit; 2017 Sep 13-17; Cape Town, South Africa. 2017.
NCT04596189
    1. Dupilumab for prevention of recurrence of CRSwNP after ESS. https://clinicaltrials.gov/ct2/show/NCT04596189 (first received 22 October 2020).
NCT04607005
    1. Efficacy and safety of mepolizumab in adults with chronic rhinosinusitis with nasal polyps (CRSwNP)/eosinophilic chronic rhinosinusitis (ERCS) (MERIT). https://clinicaltrials.gov/ct2/show/NCT04607005 (first received 28 October 2020).
NCT04783389
    1. NCT04783389. A study assessing the efficacy and safety of CBP-201 in adult patients with chronic rhinosinusitis with nasal polyps [A multi-center, randomized, double-blind, placebo-controlled study to evaluate CBP-201 in adult patients with chronic rhinosinusitis with nasal polyps]. https://clinicaltrials.gov/show/NCT04783389 (first received 5 March 2021).
NCT04805398
    1. NCT04805398. Subcutaneously CM310/placebo in patients with chronic rhinosinusitis with nasal polyposis (CRSwNP) [A randomized, double blind, placebo-controlled phase 2 study to evaluate the efficacy, safety, PK, PD and immunogenicity of subcutaneously given multiple-dose CM310 in patients with chronic rhinosinusitis with nasal polyps (CRSwNP)]. https://clinicaltrials.gov/show/NCT04805398 (first received 18 March 2021).
NCT04823585
    1. NCT04823585. Aggravated airway inflammation: research on biological treatment (mepolizumab). https://clinicaltrials.gov/show/NCT04823585 (first received 1 April 2021).
NICE 2020
    1. National Institute for Health and Care Excellence (NICE). Omalizumab for treating chronic rhinosinusitis with nasal polyps ID1650. https://www.nice.org.uk/guidance/indevelopment/gid-ta10558 (accessed 24 September 2020).
Noel‐Storr 2018
    1. Noel-Storr AH, The Project Transform Team. Cochrane Crowd: new ways of working together to produce health evidence. In: Evidence Live; 2018 Jun 18-20; Oxford, UK. 2018.
Nsouli 2020
    1. Nsouli S. Reslizumab an interleukin-5 antagonist monoclonal antibody for uncontrolled chronic rhinosinusitis with nasal polyps. Annals of Allergy, Asthma & Immunology 2020;125(5 Suppl):S49-50.
Philpott 2015
    1. Philpott C, Hopkins C, Erskine S, Kumar N, Robertson A, et al. The burden of revision sinonasal surgery in the UK—data from the Chronic Rhinosinusitis Epidemiology Study (CRES): a cross-sectional study. BMJ Open 2015;5:e006680. [DOI: 10.1136/bmjopen-2014-006680] - DOI - PMC - PubMed
Ragab 2004
    1. Ragab SM, Lund VJ, Scadding G. Evaluation of the medical and surgical treatment of chronic rhinosinusitis: a prospective, randomised, controlled trial. Laryngoscope 2004;114(5):923-30. - PubMed
Ragab 2010
    1. Ragab SM, Lund VJ, Scadding G, Saleh HA, Khalifa MA. Impact of chronic rhinosinusitis therapy on quality of life: a prospective randomized controlled trial. Rhinology 2010;48(3):305-11. - PubMed
RevMan Web 2019 [Computer program]
    1. Review Manager Web (RevMan Web). The Cochrane Collaboration, 2019. Available at: revman.cochrane.org.
Rivero 2017
    1. Rivero A, Liang J. Anti-IgE and anti-IL5 biologic therapy in the treatment of nasal polyposis: a systematic review and meta-analysis. Annals of Otology, Rhinology, and Laryngology 2017;126(11):739-47. [DOI: 10.1177/0003489417731782] - DOI - PubMed
Simmonds 2017
    1. Simmonds M, Salanti G, McKenzie J, Elliott J, Living Systematic Review Network. Living systematic reviews: 3. Statistical methods for updating meta-analyses. Journal of Clinical Epidemiology 2017;91:38-46. [DOI: 10.1016/j.jclinepi.2017.08.008] - DOI - PubMed
Smith 2018
    1. Smith KA, Pulsipher A, Gabrielsen DA, Alt JA. Biologics in chronic rhinosinusitis: an update and thoughts for future directions. American Journal of Rhinology & Allergy 2018;32(5):412-23. [DOI: 10.1177/1945892418787132] - DOI - PMC - PubMed
Smith 2019
    1. Smith KA, Orlandi RR, Oakley G, Meeks H, Curtin K, Alt JA. Long-term revision rates for endoscopic sinus surgery. International Forum of Allergy & Rhinology 2019;9(4):402-8. - PMC - PubMed
Sterne 2019
    1. Sterne JAC, Savovic J, Page MJ, Elbers RG, Blencowe NS, Boutron I, et al. RoB 2: a revised tool for assessing risk of bias in randomised trials. BMJ (Clinical research ed.) 2019;366:l4898. [DOI: 10.1136/bmj.l4898] [PMID: ] - DOI - PubMed
Takabayashi 2021
    1. Takabayashi T, Asaka D, Okamoto Y, Himi T, Haruna S, Yoshida N, et al. A phase II, multicenter, randomized, placebo-controlled study of benralizumab, a humanized anti-il-5r alpha monoclonal antibody, in patients with eosinophilic chronic rhinosinusitis. American Journal of Rhinology & Allergy 2021 Apr 11 [Epub ahead of print]. - PubMed
Tan 2011
    1. Tan BK, Li QZ, Suh L, Kato A, Conley DB, Chandra RK, et al. Evidence for intranasal antinuclear autoantibodies in patients with chronic rhinosinusitis with nasal polyps. Journal of Allergy and Clinical Immunology 2011;128(6):1198-206.e1. - PMC - PubMed
Thomas 2017
    1. Thomas J, Noel-Storr AH, Marshall I, Wallace B, McDonald S, Mavergames C, et al, Living Systematic Review Network. Living systematic reviews 2: combining human and machine effort. Journal of Clinical Epidemiology 2017;91:31-7. [DOI: 10.1016/j.jclinepi.2017.08.011] - DOI - PubMed
Tomassen 2011
    1. Tomassen P, Van Zele T, Zhang N, Perez-Novo C, Van Bruaene N, Gevaert P, et al. Pathophysiology of chronic rhinosinusitis. Proceedings of the American Thoracic Society 2011;8(1):115-20. - PubMed
Tsetsos 2018
    1. Tsetsos N, Goudakos JK, Daskalakis D, Konstantinidis I, Markou K. Monoclonal antibodies for the treatment of chronic rhinosinusitis with nasal polyposis: a systematic review. Rhinology 2018;56(1):11-21. [DOI: 10.4193/Rhin17.156] - DOI - PubMed
Tsetsos 2020
    1. Tsetsos N, Markou K, Konstantinidis I. Effect of monoclonal antibodies on olfactory dysfunction caused by chronic rhinosinusitis with nasal polyps: a systematic review and meta-analysis. International Forum of Allergy & Rhinology 2020;10(7):893-900. 14209699 [EMBASE: 631457134] [PMID: ] - PubMed
Tversky 2021
    1. Tversky J, Lane AP, Azar A. Benralizumab effect on severe chronic rhinosinusitis with nasal polyps (CRSwNP): a randomized double-blind placebo-controlled trial. Clinical and Experimental Allergy 2021 Feb 17 [Epub ahead of print]. - PubMed
van Drunen 2009
    1. Drunen CM, Reinartz SM, Wigman J, Fokkens W. Inflammation in chronic rhinosinusitis and nasal polyposis. Immunology and Allergy Clinics of North America 2009;29(4):621-9. - PubMed
Wallace 2017
    1. Wallace BC, Noel-Storr AH, Marshall IJ, Cohen AM, Smalheiser NR, et al. Identifying reports of randomized controlled trials (RCTs) via a hybrid machine learning and crowdsourcing approach. Journal of the American Medical Informatics Association 2017;24(6):1165-8. [DOI: 10.1093/jamia/ocx053] - DOI - PMC - PubMed
Walter 2020
    1. Walter S, Ho J, Alvarado R, Rimmer J, Campbell R, Kalish L, et al. Effect of monoclonal antibody drug therapy on mucosal biomarkers in airway disease: a systematic review. Clinical and Experimental Allergy 2020 Aug 17 [Epub ahead of print]. 14371723 [DOI: 10.1111/cea.13721] [PMID: ] - DOI - PubMed
WAYPOINT
    1. NCT04851964. Efficacy and safety of tezepelumab in participants with severe chronic rhinosinusitis with nasal polyposis [A multicentre, randomised, double-blind, parallel-group, placebo-controlled phase 3 efficacy and safety study of tezepelumab in participants with severe chronic rhinosinusitis with nasal polyposis (WAYPOINT)]. https://clinicaltrials.gov/show/NCT04851964 (first received 21 April 2021).
Zhang 2008
    1. Zhang N, Van Zele T, Perez-Novo C, Van Bruaene N, Holtappels G, DeRuyck N, et al. Different types of T-effector cells orchestrate mucosal inflammation in chronic sinus disease. Journal of Allergy and Clinical Immunology 2008;122(5):961-8. - PubMed
Zhang 2009
    1. Zhang XH, Lu X, Long XB, You XJ, Gao QX, Cui YH, et al. Chronic rhinosinusitis with and without nasal polyps is associated with decreased expression of glucocorticoid-induced leucine zipper. Clinical and Experimental Allergy 2009;39(5):647-54. - PubMed

References to other published versions of this review

Chong 2019
    1. Chong LY, Piromchai P, Sharp S, Snidvongs K, Philpott C, Hopkins C, Burton MJ. Biologics for chronic rhinosinusitis. Cochrane Database of Systematic Reviews 2019, Issue 12. Art. No: CD013513. [DOI: 10.1002/14651858.CD013513] - DOI - PMC - PubMed
Chong 2020
    1. Chong LY, Piromchai P, Sharp S, Snidvongs K, Philpott C, Hopkins C, Burton MJ. Biologics for chronic rhinosinusitis. Cochrane Database of Systematic Reviews 2020, Issue 2. Art. No: CD013513. [ART. NO.: ] [DOI: 10.1002/14651858.CD013513.pub2] - DOI - PMC - PubMed

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