Targeting IL-5 in COPD

Dharani K Narendra, Nicola A Hanania, Dharani K Narendra, Nicola A Hanania

Abstract

Many patients with chronic obstructive pulmonary disease (COPD) continue to experience exacerbations despite receiving standard-of-care treatments. Novel approaches to COPD treatment focus on understanding and targeting molecular mechanisms of airway inflammation, airway obstruction, remodeling and lung destruction. Several identified phenotypes and endotypes of COPD will pave the future path for a more personalized approach to therapy. Although well known to be associated with neutrophilic inflammation, COPD may also be driven by eosinophilic inflammation both at stable states and during exacerbation. Targeting eosinophilic inflammation has been successful in managing severe eosinophilic asthma and may hold promise in certain phenotypes of COPD. The most promising biologic treatments at an advanced stage of development are agents blocking interleukin (IL)-5 or its receptor. This review examines our current understanding of the eosinophilic inflammation in COPD and the rationale for IL-5 targeting agents.

Keywords: COPD; IL-5; airway inflammation; benralizumab; eosinophils; mepolizumab.

Conflict of interest statement

DKN has no conflicts of interest to disclose in this work. NAH received honoraria for serving as consultant or on advisory boards for GSK, Astra Zeneca, Sanofi/Regeneron, Novartis, Boehringer Ingelheim, Sunovion, Mylan and Gossamer Bio. His institutions have received research grant support on his behalf from Astra Zeneca, GSK, Boehringer Ingelheim.

Figures

Figure 1
Figure 1
T2 inflammatory pathway and the target site for anti-IL-5 agents. Abbreviations: CRTh2, chemoattractant receptor homolog from Th2 cells; ILC2, innate lymphoid cells; TSLP, thymic stromal lymphopoietin; IL, Interleukin.

References

    1. Vogelmeier CF, Criner GJ, Martinez FJ, et al. Global strategy for the diagnosis, management, and prevention of chronic obstructive lung disease 2017 report: GOLD executive summary. Arch Bronconeumol. 2017;53(3):128–149. doi:10.1016/j.arbres.2017.02.001
    1. ); 2017. Accessed February25, 2019.
    1. Croft JB, Wheaton AG, Liu Y, et al. Urban-rural county and state differences in chronic obstructive pulmonary disease – United States, 2015. Morb Mortal Wkly Rep. 2018;67(7):205–211. doi:10.15585/mmwr.mm6707a1
    1. Donaldson GC, Seemungal TA, Bhowmik A, Wedzicha JA. Relationship between exacerbation frequency and lung function decline in chronic obstructive pulmonary disease. Thorax. 2002;57(10):847–852.
    1. Hurst JR, Vestbo J, Anzueto A, et al. Susceptibility to exacerbation in chronic obstructive pulmonary disease. N Engl J Med. 2010;363(12):1128–1138. doi:10.1056/NEJMoa0909883
    1. Han MK, Agusti A, Calverley PM, et al. Chronic obstructive pulmonary disease phenotypes: the future of COPD. Am J Respir Crit Care Med. 2010;182(5):598–604. doi:10.1164/rccm.200912-1843CC
    1. Lange P, Halpin DM, O‘Donnell DE, MacNee W. Diagnosis, assessment, and phenotyping of COPD: beyond FEV(1). Int J Chron Obstruct Pulmon Dis. 2016;11(Spec Iss):3–12. doi:10.2147/COPD.S85976
    1. Balkissoon R. New treatment options for COPD: how do we decide phenotypes, endotypes or treatable traits? Chronic Obstr Pulm Dis (Miami). 2018;5(1):72–80. doi:10.15326/jcopdf.5.1.2018.0128
    1. Dasgupta A, Neighbour H, Nair P. Targeted therapy of bronchitis in obstructive airway diseases. Pharmacol Ther. 2013;140(3):213–222. doi:10.1016/j.pharmthera.2013.07.001
    1. Tashkin DP, Wechsler ME. Role of eosinophils in airway inflammation of chronic obstructive pulmonary disease. Int J Chron Obstruct Pulmon Dis. 2018;13:335–349. doi:10.2147/COPD.S152291
    1. Singh D, Kolsum U, Brightling CE, Locantore N, Agusti A, Tal-Singer R. Eosinophilic inflammation in COPD: prevalence and clinical characteristics. Eur Respir J. 2014;44(6):1697–1700. doi:10.1183/09031936.00162414
    1. Saha S, Brightling CE. Eosinophilic airway inflammation in COPD. Int J Chron Obstruct Pulmon Dis. 2006;1(1):39–47.
    1. Siva R, Green RH, Brightling CE, et al. Eosinophilic airway inflammation and exacerbations of COPD: a randomised controlled trial. Eur Respir J. 2007;29(5):906–913. doi:10.1183/09031936.00146306
    1. Couillard S, Larivee P, Courteau J, Vanasse A. Eosinophils in COPD exacerbations are associated with increased readmissions. Chest. 2017;151(2):366–373. doi:10.1016/j.chest.2016.10.003
    1. Saetta M, Di Stefano A, Maestrelli P, et al. Airway eosinophilia in chronic bronchitis during exacerbations. Am J Respir Crit Care Med. 1994;150(6 Pt 1):1646–1652. doi:10.1164/ajrccm.150.6.7952628
    1. Chung KF, Adcock IM. Multifaceted mechanisms in COPD: inflammation, immunity, and tissue repair and destruction. Eur Respir J. 2008;31(6):1334–1356. doi:10.1183/09031936.00018908
    1. Yun JH, Lamb A, Chase R, et al. Blood eosinophil count thresholds and exacerbations in patients with chronic obstructive pulmonary disease. J Allergy Clin Immunol. 2018;141(6):2037–2047.e2010. doi:10.1016/j.jaci.2018.04.010
    1. Roche N, Chapman KR, Vogelmeier CF, et al. Blood eosinophils and response to maintenance chronic obstructive pulmonary disease treatment. Data from the FLAME trial. Am J Respir Crit Care Med. 2017;195(9):1189–1197. doi:10.1164/rccm.201701-0193OC
    1. Keene JD, Jacobson S, Kechris K, et al. Biomarkers predictive of exacerbations in the SPIROMICS and COPDGene cohorts. Am J Respir Crit Care Med. 2017;195(4):473–481. doi:10.1164/rccm.201607-1330OC
    1. Lipson DA, Barnhart F, Brealey N, et al. Once-daily single-inhaler triple versus dual therapy in patients with COPD. N Engl J Med. 2018;378(18):1671–1680. doi:10.1056/NEJMoa1713901
    1. Bel EH, Ten Brinke A. New anti-eosinophil drugs for asthma and COPD: targeting the trait! Chest. 2017;152(6):1276–1282. doi:10.1016/j.chest.2017.05.019
    1. Markham A. Benralizumab: first global approval. Drugs. 2018;78(4):505–511. doi:10.1007/s40265-018-0876-8
    1. Varricchi G, Bagnasco D, Borriello F, Heffler E, Canonica GW. Interleukin-5 pathway inhibition in the treatment of eosinophilic respiratory disorders: evidence and unmet needs. Curr Opin Allergy Clin Immunol. 2016;16(2):186–200. doi:10.1097/ACI.0000000000000251
    1. Caramori G, Adcock IM, Di Stefano A, Chung KF. Cytokine inhibition in the treatment of COPD. Int J Chron Obstruct Pulmon Dis. 2014;9:397–412. doi:10.2147/COPD.S42544
    1. Mepolizumab: 240563, anti-IL-5 monoclonal antibody – GlaxoSmithKline, anti-interleukin-5 monoclonal antibody – GlaxoSmithKline, SB 240563. Drugs R D. 2008;9(2):125–130. doi:10.2165/00126839-200809020-00006
    1. GSK. Nucala prescribing information. Available from: . Accessed November 2018.
    1. Ortega HG, Liu MC, Pavord ID, et al. Mepolizumab treatment in patients with severe eosinophilic asthma. N Engl J Med. 2014;371(13):1198–1207. doi:10.1056/NEJMoa1403290
    1. Pavord ID, Chanez P, Criner GJ, et al. Mepolizumab for eosinophilic chronic obstructive pulmonary disease. N Engl J Med. 2017;377(17):1613–1629. doi:10.1056/NEJMoa1708208
    1. Dasgupta A, Kjarsgaard M, Capaldi D, et al. A pilot randomised clinical trial of mepolizumab in COPD with eosinophilic bronchitis. Eur Respir J. 2017;49:3. doi:10.1183/13993003.02486-2016
    1. Kolbeck R, Kozhich A, Koike M, et al. MEDI-563, a humanized anti-IL-5 receptor alpha mAb with enhanced antibody-dependent cell-mediated cytotoxicity function. J Allergy Clin Immunol. 2010;125(6):1344–1353.e1342. doi:10.1016/j.jaci.2010.04.004
    1. FitzGerald JM, Bleecker ER, Nair P, et al. Benralizumab, an anti-interleukin-5 receptor alpha monoclonal antibody, as add-on treatment for patients with severe, uncontrolled, eosinophilic asthma (CALIMA): a randomised, double-blind, placebo-controlled phase 3 trial. Lancet (London, England). 2016;388(10056):2128–2141. doi:10.1016/S0140-6736(16)31322-8
    1. Bleecker ER, FitzGerald JM, Chanez P, et al. Efficacy and safety of benralizumab for patients with severe asthma uncontrolled with high-dosage inhaled corticosteroids and long-acting beta2-agonists (SIROCCO): a randomised, multicentre, placebo-controlled phase 3 trial. Lancet (London, England). 2016;388(10056):2115–2127. doi:10.1016/S0140-6736(16)31324-1
    1. Brightling CE, Bleecker ER, Panettieri RA Jr., et al. Benralizumab for chronic obstructive pulmonary disease and sputum eosinophilia: a randomised, double-blind, placebo-controlled, phase 2a study. Lancet Respir Med. 2014;2(11):891–901. doi:10.1016/S2213-2600(14)70187-0
    1. Benralizumab Efficacy in Moderate to Very Severe Chronic Obstructive Pulmonary Disease (COPD) With Exacerbation History (GALATHEA) NCT02138916; 2018.
    1. Efficacy and Safety of Benralizumab in Moderate to Very Severe Chronic Obstructive Pulmonary Disease (COPD) With Exacerbation History (TERRANOVA) NCT02155660; 2018.

Source: PubMed

Sponzoři a spolupracovníci

Zdravotní podmínky

Drogové intervence

3
Předplatit