Dupilumab in the management of moderate-to-severe asthma: The data so far

Therapeutics and Clinical Risk Management

Volumn 13, Issue , 2017, Pages 1139-1149

  Barranco, Pilar ^a   Phillips Angles, Elsa ^a   Dominguez Ortega, Javier ^a   Quirce, Santiago ^a  

^a HOSPITAL UNIVERSITARIO LA PAZ IDIPAZ   (Spain)

Author keywords

Asthma; Dupilumab; Interleukin 13; Interleukin 4; Monoclonal antibodies; Treatment

Indexed keywords

ANRUKINZUMAB; BIOLOGICAL MARKER; DUPILUMAB; INTERLEUKIN 13; INTERLEUKIN 4; LEBRIKIZUMAB; PITRAKINRA; PLACEBO; STAT6 PROTEIN; TRALOKINUMAB;

ASTHMA; BINDING AFFINITY; DISEASE SEVERITY; DRUG EFFICACY; DRUG INDICATION; DRUG SAFETY; DRUG TOLERABILITY; DRUG WITHDRAWAL; FORCED EXPIRATORY VOLUME; HEADACHE; HUMAN; INJECTION SITE REACTION; NAUSEA; OUTCOME ASSESSMENT; PATHOPHYSIOLOGY; PHASE 1 CLINICAL TRIAL (TOPIC); PHASE 2 CLINICAL TRIAL (TOPIC); PHASE 3 CLINICAL TRIAL (TOPIC); PROTEIN EXPRESSION; PROTEIN FUNCTION; PROTEIN TARGETING; REVIEW; RHINOPHARYNGITIS;

EID: 85029186994     PISSN: 11766336     EISSN: 1178203X     Source Type: Journal    
DOI: 10.2147/TCRM.S125964     Document Type: Review

References (82)

1. Global Initiative for Asthma. GINA. [homepage on the Internet]. Available from: www.ginasthma.org. Accessed June 7, 2017.
2. Global Burden of Disease Study 2013 Collaborators. Global, regional, and national incidence, prevalence, and years lived with disability for 301 acute and chronic diseases and injuries in 188 countries, 1990-2013: a systematic analysis for the Global Burden of Disease Study 2013. Lancet. 2015;386(9995):743-800.
3. Chung KF, Wenzel SE, Brozek JL, et al. International ERS/ATS guidelines on definition, evaluation and treatment of severe asthma. Eur Respir J. 2014;43(2):343-373.
4. Sullivan PW, Campbell JD, Ghushchyan VH, Globe G. Outcomes before and after treatment after escalation to Global Initiative for Asthma steps 4 and 5 in severe asthma. Ann Allergy Asthma Immunol. 2015;114(6):462-469.
5. Accordini S, Corsico AG, Braggion M, et al. The cost of persistent asthma in Europe: an international population-based study in adults. Int Arch Allergy Immunol. 2013;160(1):93-101.
6. Porsbjerg C, Menzies-Gow A. Co-morbidities in severe asthma: clinical impact and management. Respirology. 2017;22(4):651-661.
7. Bagnasco D, Ferrando M, Varricchi G, Passalacqua G, Canonica GW. A critical evaluation of anti-IL-13 and anti-IL-4 strategies in severe asthma. Int Arch Allergy Immunol. 2016;170(2):122-131.
8. Quirce S, Phillips-Angles E, Dominguez-Ortega J, Barranco P. Biologics in the treatment of severe asthma. Allergo Immunopathol. In press 2017.
9. Woodruff PG, Modrek B, Choy DF, et al. T-helper type 2-driven inflammation defines major sub-phenotypes of asthma. Am J Respir Crit Care Med. 2009;180(5):388-395.
10. Liu YJ. Thymic stromal lymphopoietin: master switch for allergic inflammation. J Exp Med. 2006;203(2):269-273.
11. Larché M, Robinson DS, Kay AB. The role of T lymphocytes in the pathogenesis of asthma. J Allergy Clin Immunol. 2003;111(3):450-463.
12. 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.
13. Corren J. Role of interleukin-13 in asthma. Curr Allergy Asthma Rep. 2013;13(5):415-420.
14. Barnes PJ. The cytokine network in asthma and chronic obstructive pulmonary disease. J Clin Invest. 2008;118(11):3546-3556.
15. Paul WE, Zhu J. How are T(H)2-type immune responses initiated and amplified? Nat Rev Immunol. 2010;10(4):225-235.
16. Auger L, Mailhot-Larouche S, Tremblay F, Poirier M, Farah C, Bossé Y. The contractile lability of smooth muscle in asthmatic airway hyperresponsiveness. Expert Rev Respir Med. 2016;10(1):19-27.
17. Oh CK, Geba GP, Molfino N. Investigational therapeutics targeting the IL-4/IL-13/STAT-6 pathway for the treatment of asthma. Eur Respir Rev. 2010;19(115):46-54.
18. Andrews R, Rosa L, Daines M, Khurana HG. Reconstitution of a functional human type II IL-4/IL-13 in mouse B cells: demonstration of species specificity. J Immunol. 2001;166(3):1716-1722.
19. Chiba Y, Goto K, Misawa M. Interleukin-13-induced activation of signal transducer and activator of transcription 6 is mediated by an activation of Janus kinase 1 in cultured human bronchial smooth muscle cells. Pharmacol Rep. 2012;64(2):454-458.
20. LaPorte SL, Juo ZS, Vaclavikova J, et al. Molecular and structural basis of cytokine receptor pleiotropy in the interleukin-4/13 system. Cell. 2008;132(2):259-272.
21. Zheng T, Liu W, Oh SY, et al. IL-13 receptor α2 selectively inhibits IL-13-induced responses in the murine lung. J Immunol. 2008;180(1):522-529.
22. Vatrella A, Fabozzi I, Calabrese C, Maselli R, Pelaia G. Dupilumab: a novel treatment for asthma. J Asthma Allergy. 2014;7:123-130.
23. Maes T, Joos GF, Brusselle GG. Targeting IL-4 in asthma: lost in translation? Am J Respir Cell Mol Biol. 2012;47(3):261-270.
24. Daher S, Santos LM, Sole D, De Lima MG, Naspitz CK, Musatti CC. Interleukin-4 and soluble CD23 serum levels in asthmatic atopic children. J Investig Allergol Clin Immunol. 1995;5(5):251-254.
25. Walker C, Bauer W, Braun RK, et al. Activated T cells and cytokines in bronchoalveolar lavages from patients with various lung diseases associated with eosinophilia. Am J Respir Crit Care Med. 1994;150(4):1038-1048.
26. Corren J. Anti-interleukin-13 antibody therapy for asthma: one step closer. Eur Respir J. 2013;41(2):255-256.
27. Prieto J, Lensmar C, Roquet AI, et al. Increased interleukin-13 mRNA expression in bronchoalveolar lavage cells of atopic patients with mild asthma after repeated low-dose allergen provocations. Respir Med. 2000;94(8):806-814.
28. Zhu Z, Homer RJ, Wang Z, et al. Pulmonary expression of interleukin-13 causes inflammation, mucus hypersecretion, subepithelial fibrosis, physiologic abnormalities, and eotaxin production. J Clin Invest. 1999;103(6):779-788.
29. Zheng T, Oh MH, Oh SY, Schroeder JT, Glick AB, Zhu Z. Transgenic expression of interleukin-13 in the skin induces a pruritic dermatitis and skin remodeling. J Invest Dermatol. 2009;129(3):742-751.
30. Rankin JA, Picarella DE, Geba GP, et al. Phenotypic and physiologic characterization of transgenic mice expressing interleukin 4 in the lung: lymphocytic and eosinophilic inflammation without airway hyperreactivity. Proc Natl Acad Sci U S A. 1996;93(15):7821-7825.
31. Chan LS, Robinson N, Xu L. Expression of interleukin-4 in the epidermis of transgenic mice results in a pruritic inflammatory skin disease: an experimental animal model to study atopic dermatitis. J Invest Dermatol. 2001;117(4):977-983.
32. Bartminski G, Crossley M, Turcanu V. Novel biomarkers for asthma stratification and personalized therapy. Expert Rev Mol Diagn. 2015;15(3):415-430.
33. Muñoz X, Bustamante V, Lopez-Campos JL, Cruz MJ, Barreiro E. Usefulness of noninvasive methods for the study of bronchial inflammation in the control of patients with asthma. Int Arch Allergy Immunol. 2015;166(1):1-12.
34. Wenzel S, Ford L, Pearlman D, et al. Dupilumab in persistent asthma with elevated eosinophil levels. N Engl J Med. 2013;368(26):2455-2466.
35. Jia G, Erickson RW, Choy DF, et al; Bronchoscopic Exploratory Research Study of Biomarkers in Corticosteroid-refractory Asthma (BOBCAT) Study Group. Periostin is a systemic biomarker of eosinophilic airway inflammation in asthmatic patients. J Allergy Clin Immunol. 2012;130(3):647-654.
36. Takayama G, Arima K, Kanaji T, et al. Periostin: a novel component of subepithelial fibrosis of bronchial asthma downstream of IL-4 and IL-13 signals. J Allergy Clin Immunol. 2006;118(1):98-104.
37. Corren J, Lemanske RF, Hanania NA, et al. Lebrikizumab treatment in adults with asthma. N Engl J Med. 2011;365(12):1088-1098.
38. Peters MC, Mekonnen ZK, Yuan S, Bhakta NR, Woodruff PG, FahyJV. Measures of gene expression in sputum cells can identify T2-high and T2-low subtypes of asthma. J Allergy Clin Immunol. 2014;133(2):388-394.
39. Smith AD, Cowan JO, Brassett KP, et al. Exhaled nitric oxide: a predictor of steroid response. Am J Respir Crit Care Med. 2005;172(4):453-459.
40. Chibana K, Trudeau JB, Mustovich AT, et al. IL-13 induced increases in nitrite levels are primarily driven by increases in inducible nitric oxide synthase compared with effects on arginases in human primary bronchial epithelial cells. Clin Exp Allergy. 2008;38(6):936-946.
41. Piper E, Brightling C, Niven R, et al. A phase II placebo-controlled study of tralokinumab in moderate-to-severe asthma. Eur Respir J. 2013;41(2):330-338.
42. Brightling CE, Chanez P, Leigh R, et al. Efficacy and safety of tralokinumab in patients with severe uncontrolled asthma: a randomized, double-blind, placebo-controlled, phase 2b trial. Lancet Respir Med. 2015;3(9):692-701.
43. AstraZeneca. A phase 3 study to evaluate the efficacy and safety of tralokinumab in adults and adolescents with uncontrolled asthma (STRATOS2). Available from: https://clinicaltrials.gov/ct2/show/NCT02194699. NLM identifier: NCT02194699. Accessed April 24, 2017.
44. Hua F, Ribbing J, Reinisch W, Cataldi F, Martin S. A pharmacokinetic comparison of anrukinzumab, an anti-IL-13 monoclonal antibody, among healthy volunteers, asthma and ulcerative colitis patients. Br J Clin Pharmacol. 2015;80(1):101-109.
45. Gauvreau GM, Boulet LP, Cockcroft DW, et al. Effects of interleukin-13 blockade on allergen-induced airway responses in mild atopic asthma. Am J Respir Crit Care Med. 2011;183(8):1007-1014.
46. Hanania NA, Noonan M, Corren J, et al. Lebrikizumab in moderate-to-severe asthma: pooled data from two randomized placebo-controlled studies. Thorax. 2015;70(8):748-756.
47. Hanania NA, Korenblat P, Chapman KR, et al. Efficacy and safety of lebrikizumab in patients with uncontrolled asthma (LAVOLTA I and LAVOLTA II): replicate, phase 3, randomised, double-blind, placebo-controlled trials. Lancet Respir Med. 2016;4(10):781-796.
48. De Boever EH, Ashman C, Cahn AP, et al. Efficacy and safety of an anti-IL-13 mAb in patients with severe asthma: a randomized trial. J Allergy Clin Immunol. 2014;133(4):989-996.
49. Wenzel S, Wilbraham D, Fuller R, Getz EB, Longphre M. Effect of an interleukin-4 variant on late phase asthmatic response to allergen challenge in asthmatic patients: results of two phase 2a studies. Lancet. 2007;370(9596):1422-1431.
50. Slager RE, Otulana BA, Hawkins GA, et al. IL-4 receptor polymorphisms predict reduction in asthma exacerbations during response to an anti-IL-4 receptor alpha antagonist. J Allergy Clin Immunol. 2012;130(2):516-522.
51. Corren J, Busse W, Meltzer EO, et al. A randomized, controlled, phase 2 study of AMG 317, an IL-4Ralpha antagonist, in patients with asthma. Am J Respir Crit Care Med. 2010;181(8):788-796.
52. Hart TK, Blackburn MN, Brigham-Burke M, et al. Preclinical efficacy and safety of pascolizumab (SB 2406683): a humanized anti-interleukin-4 antibody with therapeutic potential in asthma. Clin Exp Immunol. 2002;130(1):93-100.
53. Reichert JM. Antibodies to watch in 2015. MAbs. 2015;7(1):1-8.
54. Wenzel S, Castro M, Corren J, et al. Dupilumab efficacy and safety in adults with uncontrolled persistent asthma despite use medium-to-high-dose inhaled corticosteroids plus a long-acting β2 agonist: a randomised double-blind placebo-controlled pivotal phase 2b dose-ranging trial. Lancet. 2016;388(10039):31-44.
55. Beeck LA, Thaci D, Hamilton JD, et al. Dupilumab treatment in adults with moderate-to severe atopic dermatitis. N Engl J Med. 2014;371(2):130-139.
56. Thaci D, Simpson EL, Beck LA, et al. Efficacy and safety of dupilumab in adults with moderate-to-severe atopic dermatitis inadequately controlled by topical treatments: a randomized, placebo-controlled, dose-ranging phase 2b trial. Lancet. 2016;387(10013):40-52.
57. Regeneron Pharmaceuticals. Ascending dose study of the safety and tolerability of REGN668 (SAR231893) in normal healthy volunteers. Available from: https://clinicaltrials.gov/ct2/show/NCT01015027. NLM identifier: NCT01015027. Accessed May 18, 2017.
58. Regeneron Pharmaceuticals. Study of the safety, tolerability, pharmacokinetics, and immunogenicity of REGN668 administered subcutaneously to healthy volunteers. Available from: https://clinicaltrials.gov/ct2/show/NCT01484600. NLM identifier: NCT01484600. Accessed May 18, 2017.
59. Sanofi. Safety, tolerability and pharmacokinetics of SAR231893 (REGN668) in healthy Japanese adult male subjects. Available from: https://clinicaltrials.gov/ct2/show/NCT01537653. NLM identifier: NCT01537653. Accessed May 18, 2017.
60. Sanofi. Comparison of the pharmacokinetics and safety of two SAR231893 (REGN668) drug products in healthy subjects. Available from: https://clinicaltrials.gov/ct2/show/NCT01537640. NLM identifier: NCT01537640. Accessed May 18, 2017.
61. Andrew DP, Chang MS, McNinch J, et al. STCP-1 (MDC) CC chemokine acts specifically on chronically activated Th2 lymphocytes and is produced by monocytes on stimulation with Th2 cytokines IL-4 and IL-13. J Immunol. 1998;161(9):5027-5038.
62. Sanofi. An evaluation of dupilumab in patients with moderate to severe uncontrolled asthma. Available from: https://clinicaltrials.gov/ct2/show/NCT01854047?term=NCT01854047&rank=1. NLM identifier: NCT01854047. Accessed June 7, 2017.
63. Sanofi. An evaluation of dupilumab in patients with nasal polyposis and chronic symptoms of sinusitis. Available from: https://clinicaltrials.gov/ct2/show/NCT01920893?term=NCT01920893&rank=1. NLM identifier: NCT01920893. Accessed June 7, 2017.
64. Bachert C, Mannent L, Naclerio RM, et al. Effect of subcutaneous dupilumab on nasal polyp burden in patients with chronic sinusitis and nasal polyposis: a randomized clinical trial. JAMA. 2016;315(5):469-479.
65. Chung KF. Dupilumab: a potential new treatment for severe asthma. Lancet. 2016;388(10039):3-4.
66. Darveaux J, Busse WW. Biologics in asthma - the next step toward personalized treatment. J Allergy Clin Immunol Pract. 2015;3(2):152-160.
67. Sanofi. Evaluation of dupilumab’s effects on airway inflammation in patients with asthma (EXPEDITION). Available from: https://clinicaltrials.gov/ct2/show/NCT02573233. NLM identifier: NCT02573233. Accessed May 18, 2017.
68. Sanofi. Evaluation of dupilumab in children with uncontrolled asthma (VOYAGE). Available from: https://clinicaltrials.gov/ct2/show/NCT02948959. NLM identifier: NCT02948959. Accessed May 18, 2017.
69. Sanofi. Evaluation of dupilumab in patients with persistent asthma (Liberty asthma quest). Available from: https://clinicaltrials.gov/ct2/show/NCT02414854. NLM identifier: NCT02414854. Accessed May 18, 2017.
70. Sanofi. Evaluation of dupilumab in patients with severe steroid dependent asthma (VENTURE). Available from: https://clinicaltrials.gov/ct2/show/NCT02528214. NLM identifier: NCT02528214. Accessed May 18, 2017.
71. Sanofi. Long-Term Safety Evaluation of dupilumab in patients with asthma (Liberty asthma traverse). Available from: https://clinicaltrials.gov/ct2/show/NCT02134028. NLM identifier: NCT02134028. Accessed May 18, 2017.
72. Wenzel SE. Dupilumab compassionate use study. Available from: https://clinicaltrials.gov/ct2/show/NCT03020810. NLM identifier: NCT03020810. Accessed May 18, 2017.
73. Sanofi. Controlled clinical study of dupilumab in patients with nasal polyps (SINUS-52). Available from: https://clinicaltrials.gov/ct2/show/NCT02898454. NLM identifier: NCT02898454. Accessed May 18, 2017.
74. Regeneron Pharmaceuticals. Open-label study of dupilumab (REGN668/SAR231893) in patients with atopic dermatitis. Available from: https://clinicaltrials.gov/ct2/show/NCT01949311. NLM identifier: NCT01949311. Accessed May 18, 2017.
75. Regeneron Pharmaceuticals. Study of dupilumab (REGN668/SAR231893) monotherapy administered to adult patients with moderate-to-severe atopic dermatitis (SOLO 2). Available from: https://clinicaltrials.gov/ct2/show/NCT02277769. NLM identifier: NCT02277769. Accessed May 18, 2017.
76. Regeneron Pharmaceuticals. Study of dupilumab (REGN668/SAR231893) monotherapy administered to adult patients with moderate-to-severe atopic dermatitis (SOLO 1). Available from: https://clinicaltrials.gov/ct2/show/NCT02277743. NLM identifier: NCT02277743. Accessed May 18, 2017.
77. Regeneron Pharmaceuticals. Study to assess the efficacy andlong-term safety of dupilumab (REGN668/SAR231893) in adult patients with moderate-to-severe atopic dermatitis. Available from: https://clinicaltrials.gov/ct2/show/NCT02260986. NLM identifier: NCT02260986. Accessed May 18, 2017.
78. Regeneron Pharmaceuticals. A study to assess the efficacy and safety of dupilumab in patients with severe atopic dermatitis (AD) that are not controlled with oral cyclosporine A (CSA) or for those who cannot take oral CSA because it is not medically advisable. Available from: https://clinicaltrials.gov/ct2/show/NCT02755649. NLM identifier: NCT02755649. Accessed May 18, 2017.
79. Regeneron Pharmaceuticals. A study to confirm the efficacy and safety of different dupilumab dose regimens in adults with atopic dermatitis (AD) (SOLO-continue). Available from: https://clinicaltrials.gov/ct2/show/NCT02395133. NLM identifier: NCT02395133. Accessed May 18, 2017.
80. Regeneron Pharmaceuticals. A study to assess the long-term safety of dupilumab (REGN668/SAR231893) administered in patients 6 to, 18year of age with atopic dermatitis (AD). Available from: https://clinicaltrials.gov/ct2/show/NCT02612454. NLM identifier: NCT02612454. Accessed May 18, 2017.
81. Regeneron Pharmaceuticals. Study of dupilumab in adult patients with active eosinophilic esophagitis (EoE). Available from: https://clinicaltrials.gov/ct2/show/NCT02379052. NLM identifier: NCT02379052. Accessed May 18, 2017.
82. Shaw DE, Sousa AR, Fowler SJ, et al; U-BIOPRED Study Group. Clinical and inflammatory characteristic of the European U-BIOPRED adult severe asthma cohort. Eur Respir J. 2015;46(5):1308-1321.