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Newer Biological Agents in the Treatment of Severe Asthma: Real-World Results from a Tertiary Referral Center

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Abstract

Purpose

To determine the efficacy of IL-5 inhibitory therapy in severe, refractory asthma in a real-world clinical setting from a tertiary referral center.

Methods

A retrospective chart review of patients with severe asthma treated with IL-5 biologic therapy for ≥ 6 months at Mayo Clinic in Rochester, Minnesota between January 1, 2013 and August 31, 2019.

Results

Over the study period, we identified 63 patients with a mean age of 54 who received an IL-5 inhibitor for ≥ 6 months. A total of 55 patients received mepolizumab, 2 received benralizumab, and 9 patients received both. Patients were followed up for a mean of 25 months. The mean number of months of oral prednisone use prior to biologic initiation was 64. There was a significant reduction in the median dose of prednisone in the 24 months after drug initiation (15 mg vs. 0 mg; p = < 0.0001). Similarly; there was a significant decline in the median number of asthma exacerbations in the 24 months before and after drug initiation (7 vs. 2; p = < 0.0001). The mean number of emergency room (ER) visits and hospitalizations decreased from 5.1 and 2.0 to 1.6 and 0.4 in the 24 months before and after therapy initiation (p < 0.0001 and p = 0.007, respectively)

Conclusions

IL-5 inhibitory therapy is associated with significant and long-term sustained reductions in asthma exacerbation frequency, ER visits, hospitalizations, as well as oral steroid usage in a patient population with refractory steroid-dependent asthma referred to a tertiary referral center.

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Abbreviations

FeNO:

Fractional excretion of exhaled nitric oxide

ED:

Emergency department

FEV1:

Forced expiratory volume in 1 s

FVC:

Forced vital capacity

IgE:

Immunoglobulin E

IL-5:

Interleukin 5

IL-4:

Interleukin 4

IL-13:

Interleukin 13

RCT:

Randomized control trial

SD:

Standard deviation

References

  1. Kaur R, Chupp G (2019) Phenotypes and endotypes of adult asthma: moving toward precision medicine. J Allergy Clin Immunol 144(1):1–12

    Article  Google Scholar 

  2. Moore WC, Bleecker ER, Curran-Everett D et al (2007) National heart, lung, blood institute’s severe asthma research program. Characterization of the severe asthma phenotype by the national heart, lung, and blood institute’s severe asthma research program. J Allergy Clin Immunol 119:405–413

    Article  Google Scholar 

  3. Mcgregor MC, Krings JG, Nair P, Castro M (2019) Role of biologics in asthma. Am J Respir Crit Care Med 199(4):433–445

    Article  CAS  Google Scholar 

  4. Chung KF, Wenzel SE, Brozek JL et al (2014) International ERS/ATS guidelines on definition, evaluation and treatment of severe asthma. Eur Respir J 43:343–373

    Article  CAS  Google Scholar 

  5. Antonicelli L, Bucca C, Neri M et al (2004) Asthma severity and medical resource utilisation. Eur Respir J 23:723–729

    Article  CAS  Google Scholar 

  6. Hyland ME, Whalley B, Jones RC, Masoli M (2015) A qualitative study of the impact of severe asthma and its treatment showing that treatment burden is neglected in existing asthma assessment scales. Qual Life Res 24:631–639

    Article  Google Scholar 

  7. Wenzel SE, Schwartz LB, Langmack EL et al (1999) Evidence that severe asthma can be divided pathologically into two inflammatory subtypes with distinct physiologic and clinical characteristics. Am J Respir Crit Care Med 160:1001–1008

    Article  CAS  Google Scholar 

  8. Anderson GP (2008) Endotyping asthma: new insights into key pathogenic mechanisms in a complex, heterogeneous disease. Lancet 372:1107–1119

    Article  Google Scholar 

  9. Wenzel SE (2012) Asthma phenotypes: the evolution from clinical to molecular approaches. Nat Med 18:716–725

    Article  CAS  Google Scholar 

  10. Pavord ID, Brightling CE, Woltmann G, Wardlaw AJ (1999) Non-eosinophilic corticosteroid unresponsive asthma. Lancet 353:2213–2214

    Article  CAS  Google Scholar 

  11. Lötvall J, Akdis CA, Bacharier LB et al (2011) Asthma endotypes: a new approach to classification of disease entities within the asthma syndrome. J Allergy Clin Immunol 127(2):355–360

    Article  Google Scholar 

  12. Fuhlbrigge A, Peden D, Apter AJ et al (2012) Asthma outcomes: exacerbations. J Allergy Clin Immunol 129(3 Suppl):S34–S48

    Article  Google Scholar 

  13. Farne HA, Wilson A, Powell C, Bax L, Milan SJ (2017) Anti-IL5 therapies for asthma. Cochrane Database Syst Rev 9:CD010834

    PubMed  Google Scholar 

  14. Haldar P, Brightling CE, Hargadon B et al (2009) Mepolizumab and exacerbations of refractory eosinophilic asthma. N Engl J Med 360:973–984

    Article  CAS  Google Scholar 

  15. Nair P, Pizzichini MM, Kjarsgaard M et al (2009) Mepolizumab for prednisone-dependent asthma with sputum eosinophilia. N Engl J Med 360:985–993

    Article  CAS  Google Scholar 

  16. Pavord ID, Korn S, Howarth P et al (2012) Mepolizumab for severe eosinophilic asthma (DREAM): a multicentre, double-blind, placebo-controlled trial. Lancet 380:651–659

    Article  CAS  Google Scholar 

  17. Bel EH, Wenzel SE, Thompson PJ, SIRIUS Investigators et al (2014) Oral glucocorticoid-sparing effect of mepolizumab in eosinophilic asthma. N Engl J Med 371:1189–1197

    Article  Google Scholar 

  18. Chupp GL, Bradford ES, Albers FC et al (2017) 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 Respir Med 5:390–400

    Article  Google Scholar 

  19. Castro M, Mathur S, Hargreave F et al (2011) Reslizumab for poorly controlled, eosinophilic asthma: a randomized, placebo-controlled study. Am J Respir Crit Care Med 184:1125–1132

    Article  CAS  Google Scholar 

  20. Bjermer L, Lemiere C, Maspero J et al (2016) Reslizumab for inadequately controlled asthma with elevated blood eosinophil levels: a randomized phase 3 study. Chest 150:789–798

    Article  Google Scholar 

  21. Corren J, Weinstein S, Janka L et al (2016) Phase 3 study of reslizumab in patients with poorly controlled asthma: effects across a broad range of eosinophil counts. Chest 150:799–810

    Article  Google Scholar 

  22. Castro M, Wenzel SE, Bleecker ER et al (2014) Benralizumab, an anti-interleukin 5 receptor a monoclonal antibody, versus placebo for uncontrolled eosinophilic asthma: a phase 2b randomised dose-ranging study. Lancet Respir Med 2:879–890

    Article  CAS  Google Scholar 

  23. Bleecker ER, FitzGerald JM, Chanez P et al (2016) Efficacy and safety of benralizumab for patients with severe asthma uncontrolled with high-dosage inhaled corticosteroids and long-acting b2-agonists (SIROCCO): a randomised, multicentre, placebo-controlled phase 3 trial. Lancet 388:2115–2127

    Article  CAS  Google Scholar 

  24. FitzGerald JM, Bleecker ER, Nair P et al (2016) Benralizumab, an antiinterleukin-5 receptor a monoclonal antibody, as add-on treatment for patients with severe, uncontrolled, eosinophilic asthma (CALIMA): a randomised, double-blind, placebo-controlled phase 3 trial. Lancet 388:2128–2141

    Article  CAS  Google Scholar 

  25. Nair P, Wenzel S, Rabe KF et al (2017) Oral glucocorticoid-sparing effect of benralizumab in severe asthma. N Engl J Med 376:2448–2458

    Article  CAS  Google Scholar 

  26. Toor JJV, Mark SCVD, Kappen JH et al (2020) Mepolizumab add-on therapy in a real world cohort of patients with severe eosinophilic asthma: response rate, effectiveness, and safety. J Asthma. https://doi.org/10.1080/02770903.2020.1723623

    Article  PubMed  Google Scholar 

  27. Llanos J-P, Ortega H, Bogart M et al (2020) Real-world effectiveness of mepolizumab in patients with severe asthma: an examination of exacerbations and costs. J Asthma Allergy 13:77–87. https://doi.org/10.2147/jaa.s236609

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Schäcke H, Döcke WD, Asadullah K (2002) Mechanisms involved in the side effects of glucocorticoids. Pharmacol Ther 96:23

    Article  Google Scholar 

  29. Saag KG, Koehnke R, Caldwell JR et al (1994) Low dose long-term corticosteroid therapy in rheumatoid arthritis: an analysis of serious adverse events. Am J Med 96:115

    Article  CAS  Google Scholar 

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Authors and Affiliations

  1. Mayo Clinic School of Graduate Medical Education, Mayo Clinic-Rochester, 200 First Street SW, Rochester, MN, 55905, USA

    Dayne Voelker

  2. Department of Pediatrics, Mayo Clinic-Rochester, Rochester, MN, USA

    Yahya Almodallal

  3. Division of Pulmonary and Critical Care Medicine, Mayo Clinic-Rochester, Rochester, MN, USA

    Megan Dulohery Scrodin, Kaiser Lim, Karina Keogh, Ashokkumar Patel & Vivek Iyer

Authors
  1. Dayne Voelker
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  2. Yahya Almodallal
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  3. Megan Dulohery Scrodin
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  4. Kaiser Lim
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  5. Karina Keogh
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  6. Ashokkumar Patel
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  7. Vivek Iyer
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Corresponding author

Correspondence to Dayne Voelker.

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Conflict of interest

Karina Keogh-pharmaceutical drug trial site invest, relationship with GSK. Monograph relationship with BMJ. No other conflicts of interest to report.

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Voelker, D., Almodallal, Y., Scrodin, M.D. et al. Newer Biological Agents in the Treatment of Severe Asthma: Real-World Results from a Tertiary Referral Center. Lung 198, 653–659 (2020). https://doi.org/10.1007/s00408-020-00369-8

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  • DOI: https://doi.org/10.1007/s00408-020-00369-8

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