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Residual nasal polyp tissue following dupilumab therapy is associated with periostin-associated fibrosis

  • Rhinology
  • Published:
European Archives of Oto-Rhino-Laryngology Aims and scope Submit manuscript

Abstract

Purpose

Dupilumab, an anti-interleukin-4 receptor alpha monoclonal antibody, is a new treatment for severe uncontrolled chronic rhinosinusitis with nasal polyps. However, data on the effect of dupilumab on histological changes in nasal polyp tissue are lacking. We aimed to investigate the effect of dupilumab on real-life clinical conditions and nasal polyp tissues from patients with eosinophilic chronic rhinosinusitis (ECRS), which is a refractory subtype.

Methods

We conducted an open-label, prospective, observational, single-centre study on 63 patients with refractory ECRS on the basis of the criteria of the Japanese Epidemiological Survey of Refractory Eosinophilic Chronic Rhinosinusitis Study. These patients had a history of surgery and received dupilumab for 24 weeks. Patient-reported sinonasal symptoms, T&T olfactometry and nasal polyp scores were prospectively evaluated. In 23 patients with residual nasal polyps following dupilumab treatment, changes in systemic and local periostin expression, and total collagen deposition in nasal polyp tissues were investigated before and after dupilumab administration.

Results

Dupilumab rapidly improved sinonasal symptoms and reduced the nasal polyp score 24 weeks after initiation. 40 (63.5%) patients had resolution of nasal polyps, but the reduction was limited in the remaining 23 (36.5%) patients. Periostin expression in serum and nasal lavage fluid was decreased, whereas periostin and the total collagen deposition area in subepithelial tissues in residual nasal polyps were enhanced after dupilumab administration.

Conclusion

Dupilumab improves sinonasal symptoms and reduces the nasal polyp score in refractory ECRS. Periostin-associated tissue fibrosis may be involved in the differential effect of dupilumab on nasal polyp reduction.

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Data availability

The datasets used and/or analysed during the current study available from the corresponding author on reasonable request.

Abbreviations

CRS:

Chronic rhinosinusitis

CRSwNP:

Chronic rhinosinusitis with nasal polyps

CRSsNP:

Chronic rhinosinusitis without nasal polyps

CT:

Computed tomography

ECRS:

Eosinophilic chronic rhinosinusitis

ECM:

Extracellular matrix

FeNO:

Fractional exhaled nitric oxide

IL:

Interleukin

JESREC:

Japanese Epidemiological Survey of Refractory Eosinophilic Chronic Rhinosinusitis

NERD:

Nonsteroidal anti-inflammatory drug exacerbated respiratory disease

NLF:

Nasal lavage fluid

NPS:

Nasal polyp score

SNOT-22:

Sino-Nasal Outcome Test-22

SD:

Standard deviation

T1:

Type 1

T2:

Type 2

T3:

Type 3

TARC:

Thymus and activation-regulated chemokine

OCS:

Oral corticosteroid

VAS:

Visual analogue scale

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Acknowledgements

We thank Leah Cannon, PhD and J. Ludovic Croxford, PhD from Edanz for editing a draft of this manuscript.

Funding

This work was supported by a Grant-in-Aid for Early-Career Scientists (JSPS KAKENHI grant number: JP20K18295).

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Authors and Affiliations

  1. Department of Otorhinolaryngology Head and Neck Surgery, School of Medicine, Showa University, 1-5-8 Hatanodai Shinagawa-Ku, Tokyo, 142-8666, Japan

    Isao Suzaki, Yuki Maruyama, Sawa Kamimura, Kojiro Hirano & Hitome Kobayashi

  2. Division of Medical Biochemistry, Department of Biomolecular Sciences, Saga Medical School, Saga, Japan

    Satoshi Nunomura & Kenji Izuhara

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  1. Isao Suzaki
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  2. Yuki Maruyama
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Contributions

IS collected data and prepared the article. YM, SK and KH collected and summarised the data. SN and KI contributed to interpretation of the results regarding periostin. KI and HK critically revised the manuscript for important intellectual content. All authors approved the final version.

Corresponding author

Correspondence to Isao Suzaki.

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Conflict of interest

I.S.: Sanofi—speaker fee and research grant. K.H.: Sanofi—speaker fee.

Ethics approval and consent to participate

This prospective, open-label observational study was approved by the ethical committee of Showa University (approval number 3351, approval date 4 January 2021).

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Written informed consent for the publication of patients’ clinical details and clinical images was obtained from the patients.

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Suzaki, I., Maruyama, Y., Kamimura, S. et al. Residual nasal polyp tissue following dupilumab therapy is associated with periostin-associated fibrosis. Eur Arch Otorhinolaryngol 281, 1807–1817 (2024). https://doi.org/10.1007/s00405-023-08336-8

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