Rhinitis, sinusitis, and upper airway disease
Mepolizumab, a humanized anti–IL-5 mAb, as a treatment option for severe nasal polyposis

https://doi.org/10.1016/j.jaci.2011.07.056Get rights and content

Background

Approximately 85% of nasal polyps (NPs) in white subjects are characterized by prominent eosinophilia. IL-5 is the key driver of eosinophilic differentiation and survival.

Objective

We sought to investigate the therapeutic potential of inhibiting IL-5 with a humanized mAb as treatment for severe nasal polyposis.

Methods

Thirty patients with severe nasal polyposis (grade 3 or 4 or recurrent after surgery) refractory to corticosteroid therapy were randomized in a double-blind fashion to receive either 2 single intravenous injections (28 days apart) of 750 mg of mepolizumab (n = 20) or placebo (n = 10). Change from baseline in NP score was assessed monthly until 1 month after the last dose (week 8). Computed tomographic scans were also performed at week 8.

Results

Twelve of 20 patients receiving mepolizumab had a significantly improved NP score and computed tomographic scan score compared with 1 of 10 patients receiving placebo at week 8 versus baseline.

Conclusion

Mepolizumab achieved a statistically significant reduction in NP size for at least 1 month after dosing in 12 of 20 patients. IL-5 inhibition is a potential novel therapeutic approach in patients with severe eosinophilic nasal polyposis.

Section snippets

Patients

Thirty subjects with chronic rhinosinusitis with primary NPs (grade 3 or 4, see outcome measures) or NPs that are recurrent after surgery (grade 1-4) were included. The inclusion criteria specified that subjects must have had failure of standard care for CRSwNP, and the diagnosis of this condition was based on the European position paper on rhinosinusitis and NPs.1 Use of systemic corticosteroids and surgical intervention was not allowed from 1 month before treatment until the end of the study,

Patients

The baseline characteristics of the study patients are summarized in Table I. The history and symptoms of the mepolizumab and placebo groups were compared. Age and sex were similar. Almost half of the patients were atopic (based on skin prick test responses), and 43% had asthma. The number of patients who had undergone sinus surgery in the past was high. At baseline, our patient population consisted of 3 patients with grade 1, 6 patients with grade 2, 16 patients with grade 3, and 5 patients

Discussion

In this double-blind, randomized, placebo-controlled study we evaluated the effect of 2 intravenous injections of 750 mg of mepolizumab in patients with severe CRSwNP. This treatment produced a significant reduction in TPSs in 12 of 20 patients. These effects were confirmed by changes in CT scan evaluations. Together, the observations support a role for anti–IL-5 in a subgroup of patients with CRSwNP and confirm previous results achieved with a single injection of a different anti–IL-5

References (30)

  • S.A. Joe et al.

    A systematic review of the use of intranasal steroids in the treatment of chronic rhinosinusitis

    Otolaryngol Head Neck Surg

    (2008)
  • Y.J. Kim et al.

    Rebound eosinophilia after treatment of hypereosinophilic syndrome and eosinophilic gastroenteritis with monoclonal anti-IL-5 antibody SCH55700

    J Allergy Clin Immunol

    (2004)
  • W. Fokkens et al.

    European position paper on rhinosinusitis and nasal polyps 2007

    Rhinol Suppl

    (2007)
  • D. Polzehl et al.

    Distinct features of chronic rhinosinusitis with and without nasal polyps

    Allergy

    (2006)
  • T. Van Zele et al.

    Differentiation of chronic sinus diseases by measurement of inflammatory mediators

    Allergy

    (2006)
  • Cited by (515)

    • Critical review of diagnosis in rhinology and its therapeutic implications

      2023, Annales Francaises d'Oto-Rhino-Laryngologie et de Pathologie Cervico-Faciale
    • Critical review of diagnosis in rhinology and its therapeutical implications

      2023, European Annals of Otorhinolaryngology, Head and Neck Diseases
    • Eosinophils and tissue remodeling: Relevance to airway disease

      2023, Journal of Allergy and Clinical Immunology
    View all citing articles on Scopus

    This study (protocol number CRT110178) was supported by GlaxoSmithKline, who also provided mepolizumab. P.G. and T.V.Z. are postdoctoral researchers granted by Research Foundation Flanders (FWO-Vlaanderen). T.C. is a postdoctoral researcher of the Fonds de la Recherche Scientifique (FNRS). T.C. and K.V.S. acknowledge research opportunities offered by the Belgian Network BioMAGNet (Bioinformatics and Modelling: from Genomes to Networks) funded by the Interuniversity Attraction Poles Programme (Phase VI/4) and initiated by the Belgian State, Science Policy Office. Their work was also supported in part by the IST Programme of the European Community under the PASCAL2 Network of Excellence (Pattern Analysis, Statistical Modelling and Computational Learning), IST-2007-216886.

    Disclosure of potential conflict of interest: P. Gevaert and C. Bachert have received research support from GlaxoSmithKline. A. R. Sousa and R. P. Marshall are employees of GlaxoSmithKline. The rest of the authors declare that they have no relevant conflicts of interest.

    These authors contributed equally to this work.

    View full text