Real-life Evaluation of the Efficacy of Biologicals in Chronic Rhinosinusitis With Nasal Polyposis (CRSwNP)

Official title

Real-life Evaluation of the Efficacy of Biologicals in CRSwNP

Overview

The goal of this observational study is to learn more about the real-world efficacy of biologics in patients with chronic rhinosinusitis with nasal polyposis (CRSwNP). All patients who are 18 years or older, who have CRSwNP and are eligible for reimbursement of a biological for the indication of CRSwNP can be included. The main question is the efficacy of biologics in real life after 24 weeks. The main focus are patient reported outcomes measured via several questionnaires and the nasal polyp score, scored with nasal endoscopy.

Detailed description

Chronic rhinosinusitis with nasal polyps (CRSwNP) has a prevalence of 5-10% in adults. It is often associated with other comorbidities, such as asthma (30-70% of CRSwNP patients) and aspirin exacerbated respiratory disease (AERD) (16% of CRSwNP patients) leading to a significant reduced quality of life (QoL). CRSwNP is diagnosed in patients with nasal polyps who have 2 or more of the following symptoms for more than 12 weeks:

* Nasal blockage or nasal congestion * Runny nose or postnasal drip * Impaired sense of smell * Facial pain/pressure. Nasal rinses, intranasal or systemic corticosteroids, long-term antibiotics, and sinus surgery are the current standard of care. However, many patients fail to achieve complete therapeutic benefit and relapse after time, even after surgery. Moreover, oral corticosteroids are associated with significant side effects, and repeated sino-nasal surgery becomes progressively more complex with higher risk of complications. Patients with CRSwNP and most patients with asthma share a common type 2 inflammatory response, characterised by elevated levels of interleukin (IL)-4, IL-5, IL-13, eosinophils, T helper 2 (Th2)cells, and type 2 innate lymphoid cells. In addition, locally produced immunoglobulin E (IgE) is able to activate mast cells and induce local inflammation in CRSwNP.

Biologicals are a specific kind of treatment with recombinant DNA-derived humanized monoclonal antibody that selectively binds specific targets in the inflammatory cascade which contributes to the pathophysiology of CRSwNP. Different biologicals have already been reimbursement for the treatment of Asthma for years, slowly these biologicals start to get their approval and reimbursement for CRSwNP. In Belgium (omalizumab (Xolair®), mepolizumab (Nucala®) and dupilumab (Dupixent ®) are reimbursed for patients with CRSwNP. Their efficacy has been demonstrated through large double-blind placebo-controlled clinical studies. However, until now only very limited reports on real-world data regarding this therapy have been published. This real-world data is important because it enables us to go beyond data gathered throughout a traditional randomised controlled trial (RCT). Traditional RCTs gather data from a controlled sample population with limited comorbidities and concomitant medications, who are likely to be compliant with the study requirements, whereas in real life patients might have poorer performance status and compliance and consist of a higher proportion of elderly patients.

Therefore, this real-world data study aims to investigate how clinical outcomes of biologic therapy in real-world application (real-world efficacy) corresponds to outcomes in clinical trials (efficacy) and to look into factors that might explain an efficacy gap.

Interventions

• Biological Omalizumab
  biological prescribed as add-on treatment as part of the standard of care
• Biological Dupilumab
  biological prescribed as add-on treatment as part of the standard of care
• Biological Mepolizumab 100 mg
  biological prescribed as add-on treatment as part of the standard of care

Primary outcome measures

• To evaluate the effect of biologicals (omalizumab, mepolizumab and dupilumab) on the nasal congestion score (NCS). [Time frame: From enrollment until 3 years of treatment]

Secondary outcome measures (7)

• To evaluate the effect of biologicals (omalizumab, mepolizumab and dupilumab) on the nasal polyp score (NPS). [Time frame: From enrollment until 3 years of treatment]
• To evaluate the effect of biologicals (omalizumab, mepolizumab and dupilumab) on the Visual analogue scale (VAS). [Time frame: From enrollment until 3 years of treatment]
• To evaluate the effect of biologicals (omalizumab, mepolizumab and dupilumab) on the Sino-Nasal Outcome Test-22 items (SNOT-22). [Time frame: From enrollment until 3 years of treatment]
• To compare the effect of biologicals (omalizumab, mepolizumab and dupilumab) on the asthma control questionnaires 5-item version(ACQ-5). [Time frame: From enrollment until 3 years of treatment]
• To compare the effect of biologicals (omalizumab, mepolizumab and dupilumab) on the asthma quality of life questionnaire (AQLQ). [Time frame: From enrollment until 3 years of treatment]
• To compare the effect of omalizumab, mepolizumab and dupilumab on the sense of smell with the short questionnaire of olfactory disorders: negative statements (sQOD-NS). [Time frame: From enrollment until 3 years of treatment]
• To evaluate patient's adherence to their biological add-on treatment. [Time frame: form enrollment until 3 years of treatment]

Eligibility criteria

Inclusion criteria

• Participant must be at least 18 years of age at the time of signing the informed consent.
• Capable of giving signed informed consent.
• Participants should have CRSwNP.
• Participants should fulfil the reimbursement criteria for their prescribed biological (omalizumab, mepolizumab and/or dupilumab).

Exclusion criteria

1\. Patients treated with other biological therapies in the 3 months prior to the current biological (this is not applicable to patients who are in the trial and switch biological).

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Observational model

Cohort

Study locations

Belgium · 8 centers

• Onze Lieve Vrouw hospital Aalst — Aalst
• General hospital Sint-Jan Bruges — Bruges
• University hospital Saint-Luc — Brussels
• University hospital of Antwerp — Edegem
• Hospital Zuid-Oost Limburg — Genk
• University Hospital Brussels — Jette
• University hospitals Leuven — Leuven
• CHU de Liège — Liège

Publications

• Kilty SJ, Lasso A. Canadian real-world study of access and clinical results using dupilumab for chronic rhinosinusitis with polyps. J Otolaryngol Head Neck Surg. 2022 Apr 25;51(1):17. doi: 10.1186/s40463-022-00570-0. PMID 35468866
• Bachert C, Corren J, Lee SE, Zhang H, Harel S, Cunoosamy D, Khan AH, Jacob-Nara JA, Siddiqui S, Nash S, Rowe PJ, Deniz Y. Dupilumab efficacy and biomarkers in chronic rhinosinusitis with nasal polyps: Association between dupilumab treatment effect on nasal polyp score and biomarkers of type 2 inflammation in patients with chronic rhinosinusitis with nasal polyps in the phase 3 SINUS-24 and SINUS-5 PMID 34970860
• Han JK, Bachert C, Fokkens W, Desrosiers M, Wagenmann M, Lee SE, Smith SG, Martin N, Mayer B, Yancey SW, Sousa AR, Chan R, Hopkins C; SYNAPSE study investigators. Mepolizumab for chronic rhinosinusitis with nasal polyps (SYNAPSE): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Respir Med. 2021 Oct;9(10):1141-1153. doi: 10.1016/S2213-2600(21)00097-7. Epub 2021 Apr 16. PMID 33872587
• Gevaert P, Omachi TA, Corren J, Mullol J, Han J, Lee SE, Kaufman D, Ligueros-Saylan M, Howard M, Zhu R, Owen R, Wong K, Islam L, Bachert C. Efficacy and safety of omalizumab in nasal polyposis: 2 randomized phase 3 trials. J Allergy Clin Immunol. 2020 Sep;146(3):595-605. doi: 10.1016/j.jaci.2020.05.032. Epub 2020 Jun 7. PMID 32524991
• Zhang N, Holtappels G, Gevaert P, Patou J, Dhaliwal B, Gould H, Bachert C. Mucosal tissue polyclonal IgE is functional in response to allergen and SEB. Allergy. 2011 Jan;66(1):141-8. doi: 10.1111/j.1398-9995.2010.02448.x. PMID 20659077
• Tomassen P, Vandeplas G, Van Zele T, Cardell LO, Arebro J, Olze H, Forster-Ruhrmann U, Kowalski ML, Olszewska-Ziaber A, Holtappels G, De Ruyck N, Wang X, Van Drunen C, Mullol J, Hellings P, Hox V, Toskala E, Scadding G, Lund V, Zhang L, Fokkens W, Bachert C. Inflammatory endotypes of chronic rhinosinusitis based on cluster analysis of biomarkers. J Allergy Clin Immunol. 2016 May;137(5):1449-1456.e PMID 26949058
• Fokkens WJ, Lund VJ, Mullol J, Bachert C, Alobid I, Baroody F, Cohen N, Cervin A, Douglas R, Gevaert P, Georgalas C, Goossens H, Harvey R, Hellings P, Hopkins C, Jones N, Joos G, Kalogjera L, Kern B, Kowalski M, Price D, Riechelmann H, Schlosser R, Senior B, Thomas M, Toskala E, Voegels R, Wang de Y, Wormald PJ. EPOS 2012: European position paper on rhinosinusitis and nasal polyps 2012. A summary PMID 22469599
• Stevens WW, Peters AT, Hirsch AG, Nordberg CM, Schwartz BS, Mercer DG, Mahdavinia M, Grammer LC, Hulse KE, Kern RC, Avila P, Schleimer RP. Clinical Characteristics of Patients with Chronic Rhinosinusitis with Nasal Polyps, Asthma, and Aspirin-Exacerbated Respiratory Disease. J Allergy Clin Immunol Pract. 2017 Jul-Aug;5(4):1061-1070.e3. doi: 10.1016/j.jaip.2016.12.027. Epub 2017 Mar 9. PMID 28286156

Identifiers

NCT: NCT06683261 · S66646

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗