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Published in: Journal of Medical Case Reports 1/2024

Open Access 01-12-2024 | Mepolizumab | Case report

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

Authors: M. Sabbe, F. Schleich, P. Janssens, R. Louis

Published in: Journal of Medical Case Reports | Issue 1/2024

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Abstract

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.
Literature
2.
3.
go back to reference McGregor MC, Krings JG, Nair P, Castro M. Role of biologics in asthma. Am J Respir Crit Care med. 2019;199(4):443–5.CrossRef McGregor MC, Krings JG, Nair P, Castro M. Role of biologics in asthma. Am J Respir Crit Care med. 2019;199(4):443–5.CrossRef
4.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
5.
go back to reference Brusselle G, Koppelman G. Biologic therapies for asthma. N England J Med. 2022;386:157–71.CrossRef Brusselle G, Koppelman G. Biologic therapies for asthma. N England J Med. 2022;386:157–71.CrossRef
6.
go back to reference 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.CrossRef 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.CrossRef
8.
go back to reference 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.CrossRef 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.CrossRef
9.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
10.
go back to reference 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.CrossRefPubMedPubMedCentral 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.CrossRefPubMedPubMedCentral
11.
go back to reference 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.CrossRefPubMedPubMedCentral 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.CrossRefPubMedPubMedCentral
12.
go back to reference 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.CrossRefPubMedPubMedCentral 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.CrossRefPubMedPubMedCentral
13.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
14.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
15.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
16.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
17.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
18.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
19.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
20.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
21.
go back to reference 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.CrossRef 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.CrossRef
22.
go back to reference 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.CrossRefPubMedPubMedCentral 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.CrossRefPubMedPubMedCentral
23.
go back to reference ClinicalTrials.gov Identifier: NCT02573233. ClinicalTrials.gov Identifier: NCT02573233.
24.
go back to reference 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.CrossRefPubMedPubMedCentral 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.CrossRefPubMedPubMedCentral
25.
go back to reference 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.CrossRefPubMedPubMedCentral 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.CrossRefPubMedPubMedCentral
26.
go back to reference 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.CrossRefPubMedPubMedCentral 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.CrossRefPubMedPubMedCentral
27.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
28.
go back to reference 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.CrossRefPubMedPubMedCentral 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.CrossRefPubMedPubMedCentral
Metadata
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
Authors
M. Sabbe
F. Schleich
P. Janssens
R. Louis
Publication date
01-12-2024
Publisher
BioMed Central
Published in
Journal of Medical Case Reports / Issue 1/2024
Electronic ISSN: 1752-1947
DOI
https://doi.org/10.1186/s13256-023-04255-8

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