When sequential use of mepolizumab and dupilumab in a severe atopic eosinophilic asthmatic questions the role of eosinophils in mediating the clinical expression of the disease: a case report.
[en] [en] BACKGROUND: The advent of biologics has resulted in major progress in the treatment of severe T2 high asthmatics. There are currently several classes of biologics approved for severe asthma including anti-immunoglobulin E, anti-interleukin-5/interleukin 5R, anti-interleukin 4/interleukin 13R, and anti-thymic stromal lymphopoietin.
CASE PRESENTATIONS: Here we report the case of a 55-year-old Caucasian man with severe eosinophilic atopic asthma, who sequentially benefited from a treatment with mepolizumab, an anti-interleukin-5 monoclonal antibody, followed by treatment with dupilumab, an anti-interleukin-4/interleukin-13R antibody, the switch being justified by a flare-up of dermatitis while on mepolizumab. Overall, the patient has been followed for 72 months, including 42 months on mepolizumab and 30 months on dupilumab. Close monitoring of exacerbations, asthma control, lung function, asthma quality of life, and biomarkers shows that both biologics reduced asthma exacerbation and provided an improvement in asthma control and quality of life, with the patient achieving remission after 30 months on dupilumab. However, the effects of the two biologics on the biomarkers were very different, with mepolizumab controlling eosinophilic inflammation and dupilumab reducing serum immunoglobulin E and fractional exhaled nitric oxide levels.
CONCLUSION: The originality of this case resides in the description of clinical status and biomarker evolution after a sequential use of mepolizumab and dupilumab in a severe atopic eosinophilic asthmatic. It shows that mepolizumab reduces exacerbation and improves asthma control by curbing eosinophilic inflammation whereas dupilumab provides asthma remission without controlling airway eosinophilic inflammation.
Louis, Renaud ; Université de Liège - ULiège > Département des sciences cliniques > Pneumologie - Allergologie
Language :
English
Title :
When sequential use of mepolizumab and dupilumab in a severe atopic eosinophilic asthmatic questions the role of eosinophils in mediating the clinical expression of the disease: a case report.
Chung KF. Target the interleukin pathway in the treatment of asthma. Lancet. 2015;386:1086–96. DOI: 10.1016/S0140-6736(15)00157-9
McGregor MC, Krings JG, Nair P, Castro M. Role of biologics in asthma. Am J Respir Crit Care med. 2019;199(4):443–5. DOI: 10.1164/rccm.201810-1944CI
Agache I, Beltran J, Akdis C, Akdis M, Canelo-Aybar C, WalterCanonica G, Casale T, Chivato T, Corren J, Del Giacco S, Eiwegger T, Firinu D, Gern JE, Hamelmann E, Hanania N, Mäkelä M, Hernandez-Martin I, Nair P, O’Mahony L, Papadopoulos NG, Papi A, Park H-S, Perez de Liano L, Posso M, Rocha C, Quirce S, Sastre J, Shamji M, Song Y, Steiner C, Schwarze J, Alonso-Coello P, Palomares O, Jutel M. Efficacy and safety of treatment with biologicals (benralizumab, dupilumab and omalizumab) for severe allergic asthma: a systematic review for the EAACI Guidelines—recommendations on the use of biologicals in severe asthma. Allergy. 2020;75(5):1043–57. DOI: 10.1111/all.14235
Brusselle G, Koppelman G. Biologic therapies for asthma. N England J Med. 2022;386:157–71. DOI: 10.1056/NEJMra2032506
Maurer M, Rosen K, Hsieh H, Saini S, Grattan C, Gimenez-Arnau A, Agarwal S, Doyle R, Canvin J, Kaplan A, Casale T. Omalizumab for the treatment of chronic idiopathic or spontaneous urticaria. N Engl J Med. 2013;368:324–935. DOI: 10.1056/NEJMoa1215372
Morse JC, Miller C, Senior B. Management of chronic rhinosinutis with nasal polyposis in the era of biologics. J Asthma Allergy. 2021;14:873–82. DOI: 10.2147/JAA.S258438
Han JK, Bachert C, Fokkkens W, Lee SE, Smith SG, Martin N, Mayer B, Yancey SW, Sousa AR, Cham R, Hopkins C. Mepolizumab for chronic rhinosinutis with nasal polyps (synapse): a randomised double-blind, placebo-controlled, phase 3 trial. Lancet Respir Med. 2021;9(10):1141–53. DOI: 10.1016/S2213-2600(21)00097-7
Haldar P, Brightling CE, Hargadon B, Gupta S, Monteiro W, Sousa A, Marshall RP, Bradding P, Green RH, Wardlaw AJ, Parvord ID. Mepolizumab and exacerbations of refractory eosinophilic asthma. N Engl J Med. 2009;360(1):973–84. DOI: 10.1056/NEJMoa0808991
Calzetta L, Aiello M, Frizzelli A, Bertorelli G, Ritondo BL, Rogliani P, Chetta A. The impact of monoclonal antibodies on airway smooth muscle contractility in asthma: a systematic review. Biomedicines. 2021;9(9):1281. DOI: 10.3390/biomedicines9091281
Anai M, Yoshida C, Izumi H, Muramoto K, Saruwatari K, Tomita Y, Ichiyasu H, Sakagami T. Successful treatment with dupilumab for mucus plugs in severe asthma. Respirol Case Rep. 2022;11(1):e01074. DOI: 10.1002/rcr2.1074
Kerstjens HAM, Maspero J, Chapman KR, van Zyl-Smit RN, Hosoe M, Tanase A-M, Lavecchia C, Pethe A, Shu X, D’Andrea P. Once-daily, single-inhaler mometasone-indacaterol-glycopyrronium versus mometasone-indacaterol or twice daily fluticasone-salmeterol in patients with inadequately controlled asthma (IRIDIUM): a randomised, double-blind, controlled phase 3 study. Lancet Respir Med. 2020;8(10):1000–12. DOI: 10.1016/S2213-2600(20)30190-9
Menzies-Gow A, Bafadhel M, Busse WW, Casale TB, Kocks JWH, Parvord ID, Szefler SJ, Woodruff PG, de Giorgio-Miller A, Trudo F, Fageras M, Ambrose CS. An expert consensus framework for asthma remission as a treatment goal. J Allergy Clin Immunol. 2020;145(3):757–65. DOI: 10.1016/j.jaci.2019.12.006
Le Floc’h A, Allinne J, Nagashima K, Scott G, Birchard D, Asrat S, Bai Y, Lim WK, Martin J, Huang T, Potocky TB, Kim JH, Rafique A, Papadopoulos NJ, Stahl N, Yancopoulos GD, Murphy AJ, Sleeman MA, Orengo JM. Dual blockade of Il-4 and Il-13 with dupilumab, an il-4Ralpha antibody, is required to broadly inhibit type 2 inflamation. Allergy. 2020;75:1188–204. DOI: 10.1111/all.14151
Wenzel S, Ford L, Pearlman D, Spector S, Sher L, Skobieranda F, Wang L, Kirkesseli S, Rocklin R, Bock B, Hamilton J, Ming JE, Radin A, Stahl N, Yancopoulos GD, Graham N, Pirozzi G. Dupilumab in persistent asthma with elevated eosinophil levels. N Engl J Med. 2013;368(26):2455–66. DOI: 10.1056/NEJMoa1304048
Ortega HG, Yancey SW, Mayer B, Gunsoy NB, Keene ON, Bleecker ER, Brigthling CE, Parvord ID. Severe eosinophilic asthma treated with mepolizumab stratified by baseline eosinophilic thresholds: a secondary analysis of the DREAM and MENSA studies. Lancet Respir Med. 2016;4(7):549–56. DOI: 10.1016/S2213-2600(16)30031-5
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):687–95. DOI: 10.1111/cea.13601
Moermans C, Brion C, Bock G, Graf S, Gerday S, Nekoee H, Poulet C, Bricmont N, Henket M, Paulus V, Guissard F, Louis R, Schleich F. Sputum Type 2 markers could predict remission in severe asthma treated with anti-IL-5. Chest. 2023;163(6):1368–79. DOI: 10.1016/j.chest.2023.01.037
Castro M, Corren J, Pavord ID, Maspero J, Wenzel S, Rabe KF, Busse WW, Ford L, Sherb L, FitzGerald JM, Katelaris C, Tohda Y, Zhang B, Staudiger H, Pirozzi G, Amin N, Ruddy M, Akinlande B, Khan A, Chao J, Martincova R, Graham NMH, Hamilton JD, Swanson BN, Stahl N, Yancopoulos GD, Teper A. Dupilumab efficacy and safety in moderate-to-severe uncontrolled asthma. N Engl J Med. 2018;378:2486–96. DOI: 10.1056/NEJMoa1804092
Wu AY, Sur S, Grant JA, Tripple JW. Interleukin-4/interleukin-13 versus interleukin-5: a comparison of molecular targets in biologic therapy for the treatment of severe asthma. Curr Opin Allergy Immunol. 2019;19(1):30–7. DOI: 10.1097/ACI.0000000000000490
Steinke JW, Borish L. Th2 cytokines and asthma. Interleukin-4: its role in the pathogenesis of asthma and targeting it for asthma treatment with interleukin-4 receptor antagonists. Respir Res. 2001;2(2):66–70. DOI: 10.1186/rr40
ClinicalTrials.gov Identifier: NCT02573233.
Mesnil C, Raulier S, Paulissen G, Xiao X, Birrell MA, Pirottin D, Jamess T, Starkl P, Ramery E, Henket M, Schleich FN, Radermacker M, Thielemans K, Gillet L, Thiry M, Belvisi MG, Louis R, Desmet C, Marechal T, Bureau F. Lung-resident eosinophils represent a district regulatory eosinophil subset. J Clin Invest. 2016;126(9):3279–95. DOI: 10.1172/JCI85664
Pavord ID, Siddiqui S, Papi A, Corren J, Sher DL, Baffin P, Langton D, Park H, Rice MS, Deniz Y, Rowe P, Staudinger HW, Patel N, Ruddy M, Graham NMH, Teper A. Dupilumab efficacy in patients stratified by baseline treatment intensity and lung function. J Asthma Allergy. 2020;13:701–11. DOI: 10.2147/JAA.S275068
Hamilton JD, Harel S, Swanson BN, Brian W, Chen Z, Rice MS, Amun N, Ardeleanu M, Radin A, Shumel B, Ruddy M, Patel N, Pitozzi G, Mannent L, Graham NMH. Dupilumab suppresses type 2 inflammatory biomarkers across multiple atopic, allergic diseases. Clin Exp Allergy. 2021;51(7):915–31. DOI: 10.1111/cea.13954
Schleich FN, Seidel L, Sele J, Manise M, Quaedvlieg V, Michils A, Louis R. Exhaled nitric oxide threshold associated with a sputum eosinophil count >3% in a cohort of unselected patients with asthma. Thorax. 2010;65(12):1039–44. DOI: 10.1136/thx.2009.124925
Gerday S, Schleich F, Henket M, Guissard F, Paulus V, Louis R. Revisiting differences between atopic and non-atopic asthmatics: when age is shaping airway inflammatory profile. World Allergy Organ J. 2022;15(6):100655. DOI: 10.1016/j.waojou.2022.100655