Efficacy of anti-IL-5 therapy with mepolizumab for severe bronchial asthma and concomitant inflammatory nasal diseases in real clinical practice

Cover Page


Cite item

Full Text

Open Access Open Access
Restricted Access Access granted
Restricted Access Subscription or Fee Access

Abstract

BACKGROUND: T2 inflammation underlies nonallergic eosinophilic severe bronchial asthma and chronic rhinosinusitis with nasal polyposis. Existing targeted anti-IL-5 drugs can improve the clinical and functional parameters in patients with a combination of severe asthma and CRSwNP.

AIM: To evaluate mepolizumab efficacy in patients with nonallergic severe asthma and concomitant inflammatory nasal diseases in real clinical practice.

MATERIALS AND METHODS: The study was conducted without a control group, by comparing related populations (before–after analysis) and based on the Sverdlovsk regional register of adult patients with severe asthma and concomitant inflammatory nasal diseases. The primary endpoints were asthma control achievement (ACT questionnaire) and a decrease in the proportion of patients with uncontrolled severe asthma. The number of asthma exacerbations, emergency calls and hospitalizations, quality of life according to the AQLQ questionnaire, peripheral blood eosinophil level, and respiratory function (the volume of forced exhalation in the first second, the forced vital capacity of the lungs, as well as the ratio of these parameters) were also assessed. The dynamics of nasal symptoms was assessed using the SNOT-22 questionnaire and visual analog scale.

RESULTS: During 12 months of therapy with mepolizumab, the ACT score increased from 9 (Q1–Q3, 7–11) to 22 (Q1–Q3, 21–24) points (p <0.001). The proportion of patients with uncontrolled asthma decreased from 100% to 10% (p <0.001). The number of asthma exacerbations decreased from 3.18±2.8 per patient per year to 0 (p <0.001), and that of hospitalizations decreased from 0.57±0.9 per patient per year to 0 (p=0.007). The quality of life according to the AQLQ increased from 3.48±1.05 (95% CI, 2.73–4.24) to 5.59±0.88 points (95% CI, 4.96–6.22) (p <0.001). The number of blood eosinophils decreased from 442 (Q1–Q3, 336–853) to 90 (Q1–Q3, 73–117) cells/µL (p <0.001). There was increase in FEV1 from 63.9%±24.2% (95% CI, 46.6–81.2) to 80.5%±18.3% (95% CI, 67.4–93.6) (p=0.015). Decreases in the SNOT-22 questionnaire score by 33 points, from 45±30 to 22±15 (p=0.006), and in the visual analog scale score by 5 points, from 8 (Q1–Q3, 5–8) to 3 (Q1–Q3, 3–5) (p=0.017), were also noted.

CONCLUSIONS: Based on the study results, there were asthma control improvement, a decrease in asthma exacerbations, and quality of life improvement according to the AQLQ. A statistically significant decrease in the number of peripheral blood eosinophils and respiratory function improvement were also revealed. In patients with concomitant inflammatory nasal diseases, significant improvement in nasal breathing was noted, which was confirmed by the scores of the SNOT-22 questionnaire and visual analog scale.

Full Text

Restricted Access

About the authors

Veronika V. Naumova

Ural State Medical University

Author for correspondence.
Email: nika.naumova@gmail.com
ORCID iD: 0000-0002-3028-2657
SPIN-code: 8210-6478
ResearcherId: AAI-1588-2020

MD, Cand. Sci. (Med.), assistant of the Department of Faculty Therapy, Endocrinology, Allergology and Immunology

Russian Federation, 3, Repina str., Ekaterinburg, 620028

Evgeny K. Beltyukov

Ural State Medical University

Email: asthma@mail.ru
ORCID iD: 0000-0003-2485-2243
SPIN-code: 6987-1057
ResearcherId: AAI-1608-2020

MD, Dr. Sci. (Med.), Professor, Professor of the Department of Faculty Therapy, Endocrinology, Allergology and Immunology

Russian Federation, 3, Repina str., Ekaterinburg, 620028

Darina V. Kiseleva

Ural State Medical University

Email: darinakiseljova@mail.ru
ORCID iD: 0000-0002-7847-5415
SPIN-code: 9446-7866

MD, Assistant of the Department of Faculty Therapy, Endocrinology, Allergology and Immunology

Russian Federation, 3, Repina str., Ekaterinburg, 620028

References

  1. Global Initiative for Asthma. Diagnosis and Management of Difficult-to-treat and Severe Asthma in adolescent and adult patients. v. 2.0, April 2019. Available from: https://ginasthma.org/wp-content/uploads/2019/04/GINA-Severe-asthma-Pocket-Guide-v2.0-wms-1.pdf. Accessed: 15.01.2022.
  2. Taillé C, Chanez P, Devouassoux G, et al. Mepolizumab in a population with severe eosinophilic asthma and corticosteroid dependence: Results from a French early access programme. Eur Res J. 2020;55(6):1902345. doi: 10.1183/13993003.02345-2019
  3. Heffler E, Blasi F, Latorre M, et al. The Severe Asthma Network in Italy: findings and perspectives. J Allergy Clin Immunol Pract. 2019;7(5):1462–1468. doi: 10.1016/j.jaip.2018.10.016
  4. Harrison T, Canonica GW, Chupp G, et al. Real-world mepolizumab in the prospective severe asthma REALITI-A study: initial analysis. Eur Res J. 2020;56(4):2000151. doi: 10.1183/13993003.00151-2020
  5. Trojan TD, Bird AJ. Mepolizumab for severe eosinophilic asthma (DREAM): A multicentre, double-blind, placebo-controlled trial. Pediatrics. 2013;132(Suppl 1):S48–S48. doi: 10.1542/peds.2013-2294bbbb
  6. Chupp GL, Bradford ES, Albers FC, et al. Efficacy of mepolizumab add-on therapy on health-related quality of life and markers of asthma control in severe eosinophilic asthma (MUSCA): a randomised, double-blind, placebo-controlled, parallel-group, multicentre, phase 3b trial. Lancet Res Med. 2017;5(5):390–400. doi: 10.1016/s2213-2600(17)30125-x
  7. Ortega HG, Liu MC, Pavord ID, et al. Mepolizumab treatment in patients with severe eosinophilic asthma. New England J Med. 2014;371(13):1198–1207. doi: 10.1056/NEJMoa1403290
  8. Harvey ES, Langton D, Katelaris C, et al. Mepolizumab effectiveness and identification of super-responders in severe asthma. Eur Res J. 2020;55(5):1902420. doi: 10.1183/13993003.02420-2019
  9. Lemiere C, Taillé C, Lee JK, et al. Impact of baseline clinical asthma characteristics on the response to mepolizumab: a post hoc meta-analysis of two Phase III trials. Respiratoty Research. 2021;22(1):184. doi: 10.1186/s12931-021-01767-z
  10. Detoraki A, Tremante E, D’Amato M, et al. Mepolizumab improves sino-nasal symptoms and asthma control in severe eosinophilic asthma patients with chronic rhinosinusitis and nasal polyps: a 12-month real-life study. Therapeutic Adv Res Dis. 2021;15:175346662110093. doi: 10.1177/17534666211009398
  11. Numata T, Nakayama K, Utsumi H, et al. Efficacy of mepolizumab for patients with severe asthma and eosinophilic chronic rhinosinusitis. BMC Pulmonary Med. 2019;19(1):176. doi: 10.1186/s12890-019-0952-1
  12. Crimi C, Campisi R, Cacopardo G, et al. Real-life effectiveness of mepolizumab in patients with severe refractory eosinophilic asthma and multiple comorbidities. World Allergy Org J. 2020;13(9):100462. doi: 10.1016/j.waojou.2020.100462
  13. Kurosawa M, Ogawa K, Sutoh E. Favorable clinical efficacy of mepolizumab on the upper and lower airways in severe eosinophilic asthma: A 48-week pilot study. Eur Annals Allergy Clin Immunol. 2019;51(5):213–221. doi: 10.23822/eurannaci.1764-1489.94
  14. Yilmaz İ, Türk M, Bahçecıoğlu S, et al. Efficacy of mepolizumab treatment in oral corticosteroid-dependent severe eosinophilic asthma patients with chronic rhinosinusitis with nasal polyps: Single center, real life study. Turkish J Med Sci. 2020;44(2):433–441. doi: 10.3906/sag-1912-62
  15. Chung KF, Wenzel SE, Brozek JL, et al. International ERS/ATS guidelines on definition, evaluation and treatment of severe asthma. Eur Res J. 2013;43(2):343–373. doi: 10.1183/09031936.00202013
  16. Global Initiative for Asthma. Global strategy for asthma management and prevention, updated 2018. Available from: https://ginasthma.org/wp-content/uploads/2018/04/wms-GINA-2018-report-V1.3-002.pdf. Accessed: 15.01.2022.
  17. Beltyukov EK, Shelyakin VA, Naumova VV, et al. Organization of immunobiological therapy of severe bronchial asthma in the Sverdlovsk region. Russ Allergol J. 2021;18(1):6–17. (In Russ). doi: 10.36691/RJA1414an
  18. Buhl R., Humbert M., Bjermer L., et al. Expert group of the European Consensus Meeting for Severe Eosinophilic Asthma. Severe eosinophilic asthma: a roadmap to consensus. Eur Res J. 2017;49(5):1700634. doi: 10.1183/13993003.00634-2017
  19. Ilina NI, Kurbacheva OM, Pavlova KS, Polner SA. Federal clinical recommendations. Allergic rhinitis. Russ J Allergy. 2018;15(4):43–53. (In Russ). doi: 10.36691/rja135
  20. The Russian Association of Allergology and Clinical Immunology, National Medical Association of Otorhinolaryngologists, the Union of Pediatricians of Russia. Clinical recommendations. Allergic rhinitis. 2020. (In Russ). Available from: https://cr.minzdrav.gov.ru/clin_recomend. Accessed: 15.01.2022.
  21. Korn S, Both J, Jung M, et al. Prospective evaluation of current asthma control using ACQ and ACT compared with GINA criteria. Ann Allergy Asthma Immunol. 2011;107(6):474–479.e2. doi: 10.1016/j.anai.2011.09.001
  22. Schleich F, Graff S, Nekoee H, et al. Real-word experience with mepolizumab: does it deliver what it has promised? Clin Exp Allergy. 2020;50(6):687–695. doi: 10.1111/cea.13601
  23. Haldar P, Brightling CE, Hargadon B, et al. Mepolizumab and exacerbations of refractory eosinophilic asthma. New England J Med. 2009;360(10):973–984. doi: 10.1056/NEJMoa0808991
  24. Chan R, Rui Wen Kuo C, Lipworth B. Disconnect between effects of mepolizumab on severe eosinophilic asthma and chronic rhinosinusitis with nasal polyps. J Allergy Clin Immunol Pract. 2020;8(5):1714–1716. doi: 10.1016/j.jaip.2020.01.009
  25. Hopkins C, Gillett S, Slack R, et al. Psychometric validity of the 22-item Sinonasal Outcome Test. Clin Otolaryngol. 2009;34(5): 447–454. doi: 10.1111/j.1749-4486.2009.01995.x

Supplementary files

Supplementary Files
Action
1. Fig. 1. Primary results of the study: а ― changes of AАT scores (ptotal <0.001; рААТ baseline - ААТ 4 month = 0.020; рААТ baseline - ААТ 12 month = 0.006); b ― asthma control level trend (ptotal <0.001; pcontrol baseline - control 4 month = 0.043; pcontrol baseline - control 12 month = 0.004). Note: AAT ― aspartate aminotransferase, BА ― bronchial asthma.

Download (251KB)
Indexing metadata
2. Fig. 2. Additional research results: а ― trend of SABA demand (рtotal <0.001; pSABA baseline - SABA 4 month = 0.035; pSABA baseline - SABA 12 month = 0.002); b ― trend of use mode of systemic corticosteroids (pSGCS mode baseline - SGCS mode 12 month = 0.032). Note: SABA ― short-acting β2-agonists, SGCS ― systemic corticosteroids.

Download (285KB)
Indexing metadata
3. Fig. 3. Additional research results: а ― asthma exacerbations trend, hospitalizations and emergency medicine services (EMS) calls due to asthma exacerbations; b ― blood eosinophilic level trend (ptotal <0.001; pEosinophils baseline - Eosinophils 4 month = 0.007; pEosinophils baseline - Eosinophils 12 month = 0.008); с ― FEV1 trend, % (p=0.015). Note: BA ― bronchial asthma; EMC ― emergency medical care; FEV1 ― volume of forced exhalation in the first second.

Download (357KB)
Indexing metadata
4. Fig. 4. Additional study results: а ― trend of quality of life according to AQLQ (ptotal <0.001; pAQLQ 12 month - AQLQ 4 month = 0.005; pAQLQ 12 month - AQLQ baseline <0.001; pAQLQ 4 month - AQLQ baseline = 0.005); b ― trend of SNOT-22 scores (ptotal = 0.006; рSNOT 12 month - SNOT baseline = 0.037; рSNOT 4 month - SNOT baseline = 0.037); с ― VAS scores trend (р=0.017).

Download (270KB)
Indexing metadata
5. Fig. 5. Trend of basic therapy volume in patients with severe asthma receiving mepolizumab. Note: IGCS ― inhaled glucocorticosteroids, SGCS ― systemic corticosteroids, LRA ― leukotriene receptor antagonist, LAMA ― long-acting muscarinic antagonist.

Download (392KB)
Indexing metadata

Copyright © Pharmarus Print Media, 2022



This website uses cookies

You consent to our cookies if you continue to use our website.

About Cookies