Clinical trial NCT06017427: Evaluation of Patient Satisfaction During Treatment With Dupilumab in Severe and Recurrent Nasosinusal Polyposis Despite Appropriate Medical and Surgical Treatment.
Official title: Evaluation of Patient Satisfaction During Treatment With Dupilumab in Severe and Recurrent Nasosinusal Polyposis Despite Appropriate Medical and Surgical Treatment.
Study type: OBSERVATIONAL
Overall status: TERMINATED
Conditions: Chronic Rhinosinusitis With Nasal Polyps
Keywords: CRSwNP
decreased quality of life
Nasal polyps
Rhinosinusitis
recurrent CRSwNP
severe CRSwNP
Lead sponsor: IHU Strasbourg
Sponsor class: OTHER
First posted: 2023-08-30
Enrollment: 32
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Adult patients, men or women, of any age, having received treatment with Dupilumab for the indication of recurrent severe nasal polyposis despite surgery and appropriate medical treatment

Brief summary: Chronic rhinosinusitis with nasal polyps (CRSwNP) or nasal polyposis is a frequent disease leading to a decreased quality of life. The validated course of treatment is firstly a medical one with saline irrigations and topical corticosteroids, followed by surgery (ethmoidectomy) if the medical treatment fails.

In many cases, CRSwNP becomes a recurrent disease despite maximal treatment as previously indicated and it becomes refractory, with a chronically reduced quality of life.

New treatments known as Biologics or Biotherapies in France such as Dupilumab are now available in situations of severe recurrent CRSwNP despite the appropriate treatment.

The goal of this study is to assess the clinical effectiveness of Dupilumab and patient satisfaction, in a cohort of french patients, focusing on the change in quality of life that is expected from said treatment, over a period of one year.

Patients will undergo 6 months of treatment with Dupilumab, the treatment will then be stopped for the next 6 months.

The primary judgment criteria will be the SNOT 22 score, measured before treatment, after 6 months of treatment, and 6 months after stopping treatment, over a telephonic conversation.

Detailed description: CRSwNP has existed for over 5000 years, it is a frequent disease, affecting 1 to 4 % of the general population, especially older men and is defined by inflammatory modification of the sinuses and nasal cavities with benign growths of the mucosa known as polyps. It leads to numerous symptoms (nasal blockage, anosmia, nasal dripping, fatigue, pain), which have important consequences in terms of quality of life, social interactions, and by the heavy costs that are brought by medical and surgical treatment.

It is a multifactorial disease for which physiopathology is not well established.

No definitive treatment exists. The appropriate course of treatment aims to control the disease, but not cure it, via topical corticosteroids application which can be facilitated by endoscopic surgery (polypectomy, ethmoidectomy).

Recurrence is frequent after surgery (40 %, 18 months after surgery), which leads to more surgeries that get more complicated and riskier each time.

CRSwNP is also an expensive disease (several thousands of euros per year for one patient), especially in cases of recurrence after surgical treatment. The indirect costs are also high with work absenteeism and decreased productivity making CRSwNP one of the 10 most costly diseases for US employers.

Dupilumab, a biologic treatment targeting the receptors of IL4 and IL13 which are major actors of the inflammatory reaction at hand in CRSwNP, has recently appeared on the market for treatment of severe recurrent CRSwNP despite the appropriate medical and surgical treatment, and has proved its efficacy in randomized clinical trials.

It is a very expensive treatment (1400 euros a month for one patient in France), which is why its clinical effectiveness in a real-life setting must be assessed.

Hypothesis : Dupilumab improves symptoms and quality of life in severe recurrent CRSwNP despite the appropriate medical and surgical treatment.

Objectives : To assess the effect of Dupilumab and patient satisfaction during treatment and after its discontinuation, on symptoms and quality of life in patients suffering from severe and recurrent CRSwNP despite having benefited from the appropriate medical and surgical treatment, in a French real-life cohort.

Eligibility criteria: Inclusion Criteria:

1. Women and men over 18 years old
2. Suffering from severe and recurrent Chronic Rhinosinusitis with Nasal Polyps despite having benefited from the appropriate medical and surgical treatment.
3. CRSwNP diagnosis established on the basis of clinical presentation and patient interrogation by their referent ENT surgeon.
4. Patient treated with Dupilumab in the indication depicted in bullet point 2.
5. Patient having voiced their non-opposition to this research, having received clear and appropriate information.
6. Patient affiliated to the French Social Security.

Exclusion Criteria:

1. Patient having undergone endoscopic nasal surgery during their Dupilumab treatment.
2. Patient presenting exclusion criteria for Dupilumab treatment.
3. Patient suffering from immune deficit.
4. Patient suffering from vascularitis with nasal expression.
5. Patient whose autonomy has been reduced by a legal authority.
6. Patient unable to express their agreement to participate in this study.

Primary outcomes:
measure: Assessment of the global effect of Dupilumab 1 day before Dupilumab by the mean of the SNOT 22 score
timeFrame: 1 day before Dupilumab
measure: Assessment of the global effect of Dupilumab 6 months of Dupilumab treatment by the mean of the SNOT 22 score
timeFrame: 6 months of Dupilumab treatment
measure: Assessment of the global effect of Dupilumab 6 months after stopping the treatment by the mean of the SNOT 22 score
timeFrame: 6 months after stopping Dupilumab treatment
Secondary outcomes:
measure: Assessment of the effect of Dupilumab on nasal obstruction by the mean of the Visual Analogic Scale for nasal obstruction
timeFrame: 1 day before Dupilumab, at 6 months of Dupilumab treatment, and 6 months after stopping Dupilumab treatment
measure: Assessment of the effect of Dupilumab on the olfaction by the mean of the Visual Analogic Scale for Olfaction
timeFrame: 1 day before Dupilumab, at 6 months of Dupilumab treatment, and 6 months after stopping Dupilumab treatment
measure: Assessment of the effect of Dupilumab on the severity of the nasal polyposis by the mean of the Nasal Polyp Score
timeFrame: 1 day before Dupilumab, at 6 months of Dupilumab treatment, and 6 months after stopping Dupilumab treatment
measure: Assessment of the effect of Dupilumab on the severity of the nasal polyposis on an iconographic level by the mean of the Lund McKay score
timeFrame: 1 day before the treatment initiation
measure: Assessment of the effect of Dupilumab on the quality of life by the mean of the EQ 5D 5L score
timeFrame: 1 day before Dupilumab, at 6 months of Dupilumab treatment, and 6 months after stopping Dupilumab treatment
measure: Assessment of the effect of Dupilumab on the severity of the asthma by the mean of the ACT score
timeFrame: 1 day before Dupilumab, at 6 months of Dupilumab treatment, and 6 months after stopping Dupilumab treatment
measure: Assessment of the time to first improvement in sense of smell and nasal obstruction with Dupilumab
timeFrame: 1 day
measure: Time between stopping Dupilumab and possible deterioration of the sense of smell and nasal obstruction
timeFrame: 1 day
measure: Evolution of a potential middle ear chronic inflammation during treatment
timeFrame: 1 day
measure: Necessity to use oral corticosteroids during or after Dupilumab treatment
timeFrame: 1 day
measure: Evolution to nasosinus superinfections during and after Dupilumab treatment
timeFrame: 1 day
measure: Collect of adverse effects during Dupilumab treatment
timeFrame: 1 day
Other outcomes:
Locations:
city: Strasbourg
country: France
facility: Hautepierre Hospital
Study officials:
affiliation: HUS
name: Léa FATH, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Settipane RA, Peters AT, Chiu AG. Chapter 6: Nasal polyps. Am J Rhinol Allergy. 2013 May-Jun;27 Suppl 1:S20-5. doi: 10.2500/ajra.2013.27.3926.
citation: Stjarne P, Odeback P, Stallberg B, Lundberg J, Olsson P. High costs and burden of illness in acute rhinosinusitis: real-life treatment patterns and outcomes in Swedish primary care. Prim Care Respir J. 2012 Jun;21(2):174-9; quiz 10p following 179. doi: 10.4104/pcrj.2012.00011.
citation: Teul I, Zbislawski W, Baran S, Czerwinski F, Lorkowski J. Quality of life of patients with diseases of sinuses. J Physiol Pharmacol. 2007 Nov;58 Suppl 5(Pt 2):691-7.
citation: Hopkins C, Browne JP, Slack R, Lund V, Topham J, Reeves B, Copley L, Brown P, van der Meulen J. The national comparative audit of surgery for nasal polyposis and chronic rhinosinusitis. Clin Otolaryngol. 2006 Oct;31(5):390-8. doi: 10.1111/j.1749-4486.2006.01275.x.
citation: Leopold DA, Elkayam D, Messina JC, Kosik-Gonzalez C, Djupesland PG, Mahmoud RA. NAVIGATE II: Randomized, double-blind trial of the exhalation delivery system with fluticasone for nasal polyposis. J Allergy Clin Immunol. 2019 Jan;143(1):126-134.e5. doi: 10.1016/j.jaci.2018.06.010. Epub 2018 Jun 19.
citation: Kobayashi Y, Yasuba H, Asako M, Yamamoto T, Takano H, Tomoda K, Kanda A, Iwai H. HFA-BDP Metered-Dose Inhaler Exhaled Through the Nose Improves Eosinophilic Chronic Rhinosinusitis With Bronchial Asthma: A Blinded, Placebo-Controlled Study. Front Immunol. 2018 Sep 25;9:2192. doi: 10.3389/fimmu.2018.02192. eCollection 2018.
citation: Rice DH. Endoscopic sinus surgery. Otolaryngol Head Neck Surg. 1994 Jul;111(1):100-10. doi: 10.1177/019459989411100118. No abstract available.
citation: Benninger MS, Sindwani R, Holy CE, Hopkins C. Impact of medically recalcitrant chronic rhinosinusitis on incidence of asthma. Int Forum Allergy Rhinol. 2016 Feb;6(2):124-9. doi: 10.1002/alr.21652. Epub 2015 Dec 1.
citation: DeConde AS, Mace JC, Levy JM, Rudmik L, Alt JA, Smith TL. Prevalence of polyp recurrence after endoscopic sinus surgery for chronic rhinosinusitis with nasal polyposis. Laryngoscope. 2017 Mar;127(3):550-555. doi: 10.1002/lary.26391. Epub 2016 Nov 12.
citation: Bhattacharyya N. Contemporary assessment of the disease burden of sinusitis. Am J Rhinol Allergy. 2009 Jul-Aug;23(4):392-5. doi: 10.2500/ajra.2009.23.3355.
citation: Wahid NW, Smith R, Clark A, Salam M, Philpott CM. The socioeconomic cost of chronic rhinosinusitis study. Rhinology. 2020 Apr 1;58(2):112-125. doi: 10.4193/Rhin19.424.
citation: Lourijsen ES, Fokkens WJ, Reitsma S. Direct and indirect costs of adult patients with chronic rhinosinusitis with nasal polyps. Rhinology. 2020 Jun 1;58(3):213-217. doi: 10.4193/Rhin19.468.
citation: Bhattacharyya N. Assessing the additional disease burden of polyps in chronic rhinosinusitis. Ann Otol Rhinol Laryngol. 2009 Mar;118(3):185-9. doi: 10.1177/000348940911800305.
citation: Goetzel RZ, Hawkins K, Ozminkowski RJ, Wang S. The health and productivity cost burden of the "top 10" physical and mental health conditions affecting six large U.S. employers in 1999. J Occup Environ Med. 2003 Jan;45(1):5-14. doi: 10.1097/00043764-200301000-00007.
citation: Rudmik L. Economics of Chronic Rhinosinusitis. Curr Allergy Asthma Rep. 2017 Apr;17(4):20. doi: 10.1007/s11882-017-0690-5.
citation: Bachert C, Mannent L, Naclerio RM, Mullol J, Ferguson BJ, Gevaert P, Hellings P, Jiao L, Wang L, Evans RR, Pirozzi G, Graham NM, Swanson B, Hamilton JD, Radin A, Gandhi NA, Stahl N, Yancopoulos GD, Sutherland ER. Effect of Subcutaneous Dupilumab on Nasal Polyp Burden in Patients With Chronic Sinusitis and Nasal Polyposis: A Randomized Clinical Trial. JAMA. 2016 Feb 2;315(5):469-79. doi: 10.1001/jama.2015.19330.