Dupilumab efficacy and safety in adults with uncontrolled persistent asthma despite use of medium-to-high-dose inhaled corticosteroids plus a long-acting β2 agonist: a randomised double-blind placebo-controlled pivotal phase 2b dose-ranging trial

The Lancet

Volumn 388, Issue 10039, 2016, Pages 31-44

  Wenzel, Sally ^a   Castro, Mario ^b   Corren, Jonathan ^c   Maspero, Jorge ^d   Wang, Lin ^e   Zhang, Bingzhi ^e   Pirozzi, Gianluca ^e   Sutherland, E Rand ^e   Evans, Robert R ^f   Joish, Vijay N ^f   Eckert, Laurent ^e   Graham, Neil M H ^f   Stahl, Neil ^f   Yancopoulos, George D ^f   Louis Tisserand, Mariana ^e   Teper, Ariel ^e  

^a UNIVERSITY OF PITTSBURGH SCHOOL OF MEDICINE   (United States)

^b WASHINGTON UNIVERSITY SCHOOL OF MEDICINE   (United States)

^c UNIVERSITY OF CALIFORNIA   (United States)

^d Fundacion CIDEA   (Argentina)

^e SANOFI   (France)

^f REGENERON PHARMACEUTICALS INC   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

BETA 2 ADRENERGIC RECEPTOR STIMULATING AGENT; BUDESONIDE; CORTICOSTEROID; DUPILUMAB; FLUTICASONE PROPIONATE; FLUTICASONE PROPIONATE PLUS SALMETEROL; FORMOTEROL; MOMETASONE FUROATE; PLACEBO; SALBUTAMOL; ANTIASTHMATIC AGENT; BUDESONIDE PLUS FORMOTEROL; FLUTICASONE PROPIONATE PLUS SALMETEROL XINAFOATE; FORMOTEROL FUMARATE PLUS MOMETASONE FUROATE; MONOCLONAL ANTIBODY; NITRIC OXIDE;

ADD ON THERAPY; ADULT; ARTICLE; ASTHMA; BACTERIAL INFECTION; BLOOD; BRONCHITIS; COMPARATIVE STUDY; CONTROLLED STUDY; DRUG EFFICACY; DRUG MEGADOSE; DRUG SAFETY; EMERGENCY CARE; EOSINOPHIL; EOSINOPHIL COUNT; FEMALE; FORCED EXPIRATORY VOLUME; HEADACHE; HERPES SIMPLEX; HOSPITAL ADMISSION; HUMAN; INFLUENZA; INJECTION SITE ERYTHEMA; INJECTION SITE REACTION; INTENTION TO TREAT ANALYSIS; LOADING DRUG DOSE; MAJOR CLINICAL STUDY; MALE; MEDICAL CARE; OUTCOME ASSESSMENT; PHASE 2 CLINICAL TRIAL; PRIORITY JOURNAL; QUALITY OF LIFE; RHINOPHARYNGITIS; SIGNAL TRANSDUCTION; SINUSITIS; SMOKING; TREATMENT DURATION; UNCONTROLLED PERSISTENT ASTHMA; UPPER RESPIRATORY TRACT INFECTION; BREATH ANALYSIS; CLINICAL TRIAL; COMBINATION DRUG THERAPY; DISEASE COURSE; DOUBLE BLIND PROCEDURE; INHALATIONAL DRUG ADMINISTRATION; MIDDLE AGED; MULTICENTER STUDY; PATHOPHYSIOLOGY; RANDOMIZED CONTROLLED TRIAL; SUBCUTANEOUS DRUG ADMINISTRATION; TREATMENT OUTCOME;

ADMINISTRATION, INHALATION; ADULT; ANTI-ASTHMATIC AGENTS; ANTIBODIES, MONOCLONAL; ASTHMA; BREATH TESTS; BUDESONIDE, FORMOTEROL FUMARATE DRUG COMBINATION; DISEASE PROGRESSION; DOUBLE-BLIND METHOD; DRUG THERAPY, COMBINATION; FEMALE; FLUTICASONE PROPIONATE, SALMETEROL XINAFOATE DRUG COMBINATION; FORCED EXPIRATORY VOLUME; HUMANS; INJECTIONS, SUBCUTANEOUS; MALE; MIDDLE AGED; MOMETASONE FUROATE, FORMOTEROL FUMARATE DRUG COMBINATION; NITRIC OXIDE; TREATMENT OUTCOME;

EID: 84964573673     PISSN: 01406736     EISSN: 1474547X     Source Type: Journal    
DOI: 10.1016/S0140-6736(16)30307-5     Document Type: Article

References (30)

1. 1 Peters, SP, Ferguson, G, Deniz, Y, Reisner, C, Uncontrolled asthma: a review of the prevalence, disease burden and options for treatment. Respir Med 100 (2006), 1139–1151.
2. 2 Forno, E, Celedón, JC, Predicting asthma exacerbations in children. Curr Opin Pulm Med 18 (2012), 63–69.
3. 3 Bateman, ED, Buhl, R, O'Byrne, PM, et al. Development and validation of a novel risk score for asthma exacerbations: the risk score for exacerbations. J Allergy Clin Immunol 135 (2015), 1457–1464.
4. 4 Chung, KF, Wenzel, SE, Brozek, JL, et al. International ERS/ATS guidelines on definition, evaluation and treatment of severe asthma. Eur Respir J 43 (2014), 343–373.
5. 5 Global Initiative for Asthma (GINA). Global Strategy for Asthma Management and Prevention. http://www.ginasthma.org, 2015 (accessed Dec 30, 2015).
6. 6 Wenzel, S, Wilbraham, D, Fuller, R, et al. Effect of an interleukin-4 variant on late phase asthmatic response to allergen challenge in asthmatic patients: results of two phase 2a studies. Lancet 370 (2007), 1422–1431.
7. 7 Wenzel, S, Ford, L, Pearlman, D, et al. Dupilumab in persistent asthma with elevated eosinophil levels. N Engl J Med 368 (2013), 2455–2466.
8. 8 Voehringer, D, Reese, TA, Huang, X, et al. Type 2 immunity is controlled by IL-4/IL-13 expression in hematopoietic non-eosinophil cells of the innate immune system. J Exp Med 203 (2006), 1435–1446.
9. 9 Locksley, RM, Asthma and allergic inflammation. Cell 140 (2010), 777–783.
10. 10 Woodruff, PG, Modrek, B, Choy, DF, et al. T-helper type 2-driven inflammation defines major subphenotypes of asthma. Am J Respir Crit Care Med 180 (2009), 388–395.
11. 11 Corren, J, Lemanske, RF, Hanania, NA, et al. Lebrikizumab treatment in adults with asthma. N Engl J Med 365 (2011), 1088–1098.
12. 12 Chung, KF, Targeting the interleukin pathway in the treatment of asthma. Lancet 386 (2015), 1086–1096.
13. 13 Fahy, JV, Type 2 inflammation in asthma — present in most, absent in many. Nat Rev Immunol 15 (2015), 57–65.
14. 14 Gandhi, NA, Bennett, BL, Graham, NM, Pirozzi, G, Stahl, N, Yancopoulos, GD, Targeting key proximal drivers of type 2 inflammation in disease. Nat Rev Drug Discov 15 (2016), 35–50.
15. 15 Katz, LE, Gleich, GJ, Hartley, BF, Yancey, SW, Ortega, H, Blood eosinophil count is a useful biomarker to identify patients with severe eosinophilic asthma. Ann Am Thorac Soc 11 (2014), 531–536.
16. 16 Beck, LA, Thaçi, D, Hamilton, JD, et al. Dupilumab treatment in adults with moderate-to-severe atopic dermatitis. N Engl J Med 371 (2014), 130–139.
17. 17 Thaçi, 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 randomised, placebo-controlled, dose-ranging phase 2b trial. Lancet 387 (2016), 40–52.
18. 18 Bingefors, K, Svensson, Å, Isacson, D, Lindberg, M, Self-reported lifetime prevalence of atopic dermatitis and co-morbidity with asthma and eczema in adulthood: a population-based cross-sectional survey. Acta Derm Venereol 93 (2013), 438–441.
19. 19 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 315 (2016), 469–479.
20. 20 Global Initiative for Asthma (GINA). Global Strategy for Asthma Management and Prevention. http://www.ginasthma.org, 2009 (accessed Dec 30, 2015).
21. 21 Juniper, EF, Svensson, K, Mörk, AC, Ståhl, E, Measurement properties and interpretation of three shortened versions of the asthma control questionnaire. Respir Med 99 (2005), 553–558.
22. 22 Juniper, EF, Guyatt, GH, Epstein, RS, Ferrie, PJ, Jaeschke, R, Hiller, TK, Evaluation of impairment of health related quality of life in asthma: development of a questionnaire for use in clinical trials. Thorax 47 (1992), 76–83.
23. 23 Juniper, EH, Guyatt, GH, Willan, A, Griffith, LE, Determining a minimal important change in a disease-specific Quality Of Life Questionnaire. J Clin Epidemiol 47 (1994), 81–87.
24. 24 Kerstjens, HA, Disse, B, Schröder-Babo, W, et al. Tiotropium improves lung function in patients with severe uncontrolled asthma: a randomized controlled trial. J Allergy Clin Immunol 128 (2011), 308–314.
25. 25 Humbert, M, Busse, W, Hanania, NA, et al. Omalizumab in asthma: an update on recent developments. J Allergy Clin Immunol Pract 2 (2014), 525–536.
26. 26 Hanania, NA, Alpan, O, Hamilos, DL, et al. Omalizumab in severe allergic asthma inadequately controlled with standard therapy: a randomized trial. Ann Intern Med 154 (2011), 573–582.
27. 27 Normansell, R, Walker, S, Milan, SJ, Walters, EH, Nair, P, Omalizumab for asthma in adults and children. Cochrane Database Syst Rev, 1, 2014 CD003559.
28. 28 Castro, M, Zangrilli, J, Wechsler, M, et al. Reslizumab for inadequately controlled asthma with elevated blood eosinophil counts: results from two multicentre, parallel, double-blind, randomised, placebo-controlled, phase 3 trials. Lancet Respir Med 3 (2015), 355–366.
29. 29 Ortega, HG, Liu, MC, Pavord, ID, et al. Mepolizumap treatment in patients with severe eosinophilic asthma. N Engl J Med 371 (2014), 1198–1207.
30. 30 Gittler, JK, Shemer, A, Suárez-Fariñas, M, et al. Progressive activation of T(H)2/T(H)22 cytokines and selective epidermal proteins characterizes acute and chronic atopic dermatitis. J Allergy Clin Immunol 130 (2012), 1344–1354.