Defining the Efficacy of Omalizumab in Nasal Polyposis: A POLYP 1 and POLYP 2 Subgroup Analysis

Abstract

Background

Chronic rhinosinusitis with nasal polyps (CRSwNP) is a heterogeneous disease with variable underlying pathophysiologies. Numerous patient factors have been linked to differences in disease severity, control, and response to treatment, including asthma status, aspirin sensitivity, previous sinonasal surgery, and blood eosinophil levels.

Objective

The present study examines the efficacy of the anti-immunoglobulin E therapy, omalizumab, versus placebo in patients with CRSwNP from the replicate POLYP 1 (NCT03280550) and POLYP 2 (NCT03280537) trials, grouped by inherent patient characteristics to determine the response to therapy.

Methods

Patients in prespecified subgroups from POLYP 1 and POLYP 2 (studies pooled for analysis) were examined. Subgroups included blood eosinophil count at baseline (>300 or ≤300 cells/μL), previous sinonasal surgery (yes or no), asthma status (yes or no), and aspirin sensitivity status (yes or no). Subgroups were examined for subgroup-specific adjusted mean difference (95% confidence interval [CI]) (omalizumab–placebo) in change from baseline at week 24 in Nasal Congestion Score (NCS), Nasal Polyp Score (NPS), Sino-Nasal Outcome Test-22 (SNOT-22), Total Nasal Symptom Score (TNSS), and University of Pennsylvania Smell Identification Test (UPSIT).

Results

Adjusted mean difference (95% CI) (omalizumab–placebo) in NCS, NPS, SNOT-22, TNSS, and UPSIT change from baseline at week 24 consistently favored omalizumab treatment over placebo in patients with blood eosinophil count >300 and ≤300 cells/μL, with or without previous sinonasal surgery, asthma, and aspirin sensitivity.

Conclusion

Together, these data suggest broad efficacy of omalizumab across clinical and patient-reported outcomes in patients with CRSwNP, independent of the underlying patient factors examined, including those with high eosinophil levels and those who have undergone previous surgery, which are associated with high recurrence.

Clinical Trial Registration

ClinicalTrials.gov identifiers: POLYP 1: ClinicalTrials.gov identifier NCT03280550 (https://clinicaltrials.gov/ct2/show/NCT03280550); POLYP 2: ClinicalTrials.gov identifier NCT03280537 (https://clinicaltrials.gov/ct2/show/NCT03280537).

Keywords

aspirin sensitivity asthma CRSwNP eosinophil immunoglobulin E Nasal Congestion Score Nasal Polyp Score nasal polyposis omalizumab sinonasal surgery SNOT-22 TNSS UPSIT

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References

. Will we ever cure nasal polyps? Ann R Coll Surg Engl. 2019;101(1):35–39.

Koennecke

Klimek

Mullol

, et al. Subtyping of polyposis nasi: phenotypes, endotypes and comorbidities. Allergo J Int. 2018;27(2):56–65.

Bachert

Zhang

Gevaert

. Current and future treatment options for adult chronic rhinosinusitis: focus on nasal polyposis. J Allergy Clin Immunol. 2015;136(6):1431–1440.

Hulse

Stevens

Tan

, et al. Pathogenesis of nasal polyposis. Clin Exp Allergy. 2015;45(2):328–346.

Kato

. Immunopathology of chronic rhinosinusitis. Allergol Int. 2015;64(2):121–130.

Bachert

Humbert

Hanania

, et al. Staphylococcus aureus and its IgE-inducing enterotoxins in asthma: current knowledge. Eur Respir J. 2020;55(4):1901592.

Meng

Yan

Wang

, et al. Diagnosis and management of nonallergic rhinitis with eosinophilia syndrome using cystatin SN together with symptoms. World Allergy Organ J. 2020;13(7):100134.

Gevaert

Omachi

Corren

, et al. Efficacy and safety of omalizumab in nasal polyposis: 2 randomized phase 3 trials. J Allergy Clin Immunol. 2020;146(3):595–605.

DeConde

Mace

Levy

, et al. Prevalence of polyp recurrence after endoscopic sinus surgery for chronic rhinosinusitis with nasal polyposis. Laryngoscope. 2017;127(3):550–555.

10.

Graefe

Roebke

Schäfer

, et al. Aspirin sensitivity and chronic rhinosinusitis with polyps: a fatal combination. J Allergy (Cairo). 2012;2012:817910.

11.

Cao

P-P

Liang

G-T

, et al. Diagnostic significance of blood eosinophil count in eosinophilic chronic rhinosinusitis with nasal polyps in Chinese adults. Laryngoscope. 2012;122(3):498–503.

12.

Kowalski

Agache

Bavbek

, et al. Diagnosis and management of NSAID-exacerbated respiratory disease (N-ERD)—a EAACI position paper. Allergy. 2019;74(1):28–39.

13.

Langdon

Mullol

. Nasal polyps in patients with asthma: prevalence, impact, and management challenges. J Asthma Allergy. 2016;9:45–53.

14.

International Council for Harmonisation. Guideline for Good Clinical Practice E6, https://ichgcp.net/. Accessed February 9, 2021.

15.

World Medical Association. World Medical Association Declaration of Helsinki – ethical principles for medical research involving human subjects, https://www.wma.net/policies-post/wma-declaration-of-helsinki-ethical-principles-for-medical-research-involving-human-subjects/. Accessed February 9, 2021.

16.

Massoth

Anderson

McKinney

. Asthma and chronic rhinosinusitis: diagnosis and medical management. Med Sci (Basel). 2019;7(4):53.

17.

Hopkins

Han

Lee

, et al. Dupilumab efficacy in patients with chronic rhinosinusitis with nasal polyps by history of prior sinonasal surgery: pooled results from the SINUS-24 and SINUS-52 phase 3 studies. Presented at: American Rhinologic Society, Virtual Congress, 2020.

18.

Wang

Deng

Yang

, et al. Concordant systemic and local eosinophilia relates to poorer disease control in patients with nasal polyps. World Allergy Organ J. 2019;12(8):100052.

19.

Laidlaw

Prussin

Panettieri

, et al. Dexpramipexole depletes blood and tissue eosinophils in nasal polyps with no change in polyp size. Laryngoscope. 2019;129(2):E61–E66.

20.

Casale

Luskin

Busse

, et al. Omalizumab effectiveness by biomarker status in patients with asthma: evidence from PROSPERO, a prospective real-world study. J Allergy Clin Immunol Pract. 2019;7(1):156–164. e1.

21.

Humbert

Taillé

Mala

, et al. Omalizumab effectiveness in patients with severe allergic asthma according to blood eosinophil count: the STELLAIR study. Eur Respir J. 2018;51(5):1702523.

22.

Scadding

Hellings

Alobid

, et al. Diagnostic tools in rhinology EAACI position paper. Clin Transl Allergy. 2011;1(1):2.

23.

Fokkens

Lund

Mullol

, et al. European position paper on rhinosinusitis and nasal polyps 2012. Rhinol Suppl. 2012;23(3):1–298.

24.

Ellis

Soliman

Steacy

, et al. Clinical validation of controlled exposure to birch pollen in the environmental exposure unit (EEU). Allergy Asthma Clin Immunol. 2016;12:53.

25.

Feng

Wesely

Hoehle

, et al. A validated model for the 22-item sino-nasal outcome test subdomain structure in chronic rhinosinusitis. Int Forum Allergy Rhinol. 2017;7(12):1140–1148.

26.

Doty

Shaman

Kimmelman

, et al. University of Pennsylvania smell identification test: a rapid quantitative olfactory function test for the clinic. Laryngoscope. 1984;94(2 Pt 1):176–178.

27.

Tomassen

Vandeplas

Van Zele

, et al. Inflammatory endotypes of chronic rhinosinusitis based on cluster analysis of biomarkers. J Allergy Clin Immunol. 2016;137(5):1449–1456. e4.

28.

Gon

Hashimoto

. Role of airway epithelial barrier dysfunction in pathogenesis of asthma. Allergol Int. 2018;67(1):12–17.

29.

Yuksel

Turkeli

. Airway epithelial barrier dysfunction in the pathogenesis and prognosis of respiratory tract diseases in childhood and adulthood. Tissue Barriers. 2017;5(4):e1367458.

30.

De Schryver

Devuyst

Derycke

, et al. Local immunoglobulin E in the nasal mucosa: clinical implications. Allergy Asthma Immunol Res. 2015;7(4):321–331.

31.

Humbert

Bousquet

Bachert

, et al. IgE-mediated multimorbidities in allergic asthma and the potential for omalizumab therapy. J Allergy Clin Immunol Pract. 2019;7(5):1418–1429.

32.

Platzer

Stout

Fiebiger

. Functions of dendritic-cell-bound IgE in allergy. Mol Immunol. 2015;68(2 Pt A):116–119.

33.

Redhu

Gounni

. The high affinity IgE receptor (FcεRI) expression and function in airway smooth muscle. Pulm Pharmacol Ther. 2013;26(1):86–94.

34.

Shin

Greer

. The role of FcεRI expressed in dendritic cells and monocytes. Cell Mol Life Sci. 2015;72(12):2349–2360.

35.

Messingham

Holahan

Frydman

, et al. Human eosinophils express the high affinity IgE receptor, FcεRI, in bullous pemphigoid. PLoS One. 2014;9(9):e107725.

36.

Pant

Schembri

Wormald

, et al. IgE-mediated fungal allergy in allergic fungal sinusitis. Laryngoscope. 2009;119(6):1046–1052.

37.

Takabayashi

Schleimer

. Formation of nasal polyps: the roles of innate type 2 inflammation and deposition of fibrin. J Allergy Clin Immunol. 2020;145(3):740–750.

38.

Bachert

Han

Wagenmann

, et al. EUFOREA expert board meeting on uncontrolled severe chronic rhinosinusitis with nasal polyps (CRSwNP) and biologics: definitions and management. J Allergy Clin Immunol. 2021;147(1):29–36.