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Effect of subcutaneous dupilumab on nasal polyp burden in patients with chronic sinusitis and nasal polyposis

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Abstract
IMPORTANCE: Dupilumab has demonstrated efficacy in patients with asthma and atopic dermatitis, which are both type 2 helper T-cell-mediated diseases. OBJECTIVE: To assess inhibition of interleukins 4 and 13 with dupilumab in patients with chronic sinusitis and nasal polyposis. DESIGN, SETTING, AND PARTICIPANTS: A randomized, double-blind, placebo-controlled parallel-group study conducted at 13 sites in the United States and Europe between August 2013 and August 2014 in 60 adults with chronic sinusitis and nasal polyposis refractory to intranasal corticosteroids with 16 weeks of follow-up. INTERVENTIONS: Subcutaneous dupilumab (a 600 mg loading dose followed by 300 mg weekly; n = 30) or placebo (n = 30) plus mometasone furoate nasal spray for 16 weeks. MAIN OUTCOMES AND MEASURES: Change in endoscopic nasal polyp score (range, 0-8; higher scores indicate worse status) at 16 weeks (primary end point). Secondary end points included Lund-Mackay computed tomography (CT) score (range, 0-24; higher scores indicate worse status), 22-item SinoNasal Outcome Test score (range, 0-110; higher scores indicating worse quality of life; minimal clinically important difference >= 8.90), sense of smell assessed using the University of Pennsylvania Smell Identification Test (UPSIT) score (range, 0-40; higher scores indicate better status), symptoms, and safety. RESULTS: Among the 60 patients who were randomized (mean [SD] age, 48.4 years [9.4 years]; 34 men [56.7%]; 35 with comorbid asthma), 51 completed the study. The least squares (LS) mean change in nasal polyp score was -0.3 (95% CI, -1.0 to 0.4) with placebo and -1.9 (95% CI, -2.5 to -1.2) with dupilumab (LS mean difference, -1.6 [95% CI, -2.4 to -0.7]; P < .001). The LS mean difference between the 2 groups for the Lund-Mackay CT total score was -8.8 (95% CI, -11.1 to -6.6; P < .001). Significant improvements with dupilumab were also observed for the 22-item SinoNasal Outcome Test (LS mean difference between groups, -18.1 [95% CI, -25.6 to -10.6]; P < .001) and sense of smell assessed by UPSIT (LS mean difference, 14.8 [95% CI, 10.9 to 18.7]; P < .001). The most common adverse events were nasopharyngitis (33% in the placebo group vs 47% in the dupilumab group), injection site reactions (7% vs 40%, respectively), and headache (17% vs 20%). CONCLUSIONS AND RELEVANCE: Among adults with symptomatic chronic sinusitis and nasal polyposis refractory to intranasal corticosteroids, the addition of subcutaneous dupilumab to mometasone furoate nasal spray compared with mometasone alone reduced endoscopic nasal polyp burden after 16 weeks. Further studies are needed to assess longer treatment duration, larger samples, and direct comparison with other medications.
Keywords
CHRONIC RHINOSINUSITIS, ASTHMA CONTROL, QUESTIONNAIRE, ENTEROTOXINS, RELIABILITY, EUROPE, ADULTS, IGE

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Citation

Please use this url to cite or link to this publication:

Chicago
Bachert, Claus, Leda Mannent, Robert M Naclerio, Joaquim Mullol, Berrylin J Ferguson, Philippe Gevaert, Peter Hellings, et al. 2016. “Effect of Subcutaneous Dupilumab on Nasal Polyp Burden in Patients with Chronic Sinusitis and Nasal Polyposis.” Jama-journal of the American Medical Association 315 (5): 469–479.
APA
Bachert, Claus, Mannent, L., Naclerio, R. M., Mullol, J., Ferguson, B. J., Gevaert, P., Hellings, P., et al. (2016). Effect of subcutaneous dupilumab on nasal polyp burden in patients with chronic sinusitis and nasal polyposis. JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION, 315(5), 469–479.
Vancouver
1.
Bachert C, Mannent L, Naclerio RM, Mullol J, Ferguson BJ, Gevaert P, et al. Effect of subcutaneous dupilumab on nasal polyp burden in patients with chronic sinusitis and nasal polyposis. JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION. 2016;315(5):469–79.
MLA
Bachert, Claus, Leda Mannent, Robert M Naclerio, et al. “Effect of Subcutaneous Dupilumab on Nasal Polyp Burden in Patients with Chronic Sinusitis and Nasal Polyposis.” JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION 315.5 (2016): 469–479. Print.
@article{8506382,
  abstract     = {IMPORTANCE: Dupilumab has demonstrated efficacy in patients with asthma and atopic dermatitis, which are both type 2 helper T-cell-mediated diseases. 
OBJECTIVE: To assess inhibition of interleukins 4 and 13 with dupilumab in patients with chronic sinusitis and nasal polyposis. 
DESIGN, SETTING, AND PARTICIPANTS: A randomized, double-blind, placebo-controlled parallel-group study conducted at 13 sites in the United States and Europe between August 2013 and August 2014 in 60 adults with chronic sinusitis and nasal polyposis refractory to intranasal corticosteroids with 16 weeks of follow-up. 
INTERVENTIONS: Subcutaneous dupilumab (a 600 mg loading dose followed by 300 mg weekly; n = 30) or placebo (n = 30) plus mometasone furoate nasal spray for 16 weeks. 
MAIN OUTCOMES AND MEASURES: Change in endoscopic nasal polyp score (range, 0-8; higher scores indicate worse status) at 16 weeks (primary end point). Secondary end points included Lund-Mackay computed tomography (CT) score (range, 0-24; higher scores indicate worse status), 22-item SinoNasal Outcome Test score (range, 0-110; higher scores indicating worse quality of life; minimal clinically important difference {\textrangle}= 8.90), sense of smell assessed using the University of Pennsylvania Smell Identification Test (UPSIT) score (range, 0-40; higher scores indicate better status), symptoms, and safety. 
RESULTS: Among the 60 patients who were randomized (mean [SD] age, 48.4 years [9.4 years]; 34 men [56.7\%]; 35 with comorbid asthma), 51 completed the study. The least squares (LS) mean change in nasal polyp score was -0.3 (95\% CI, -1.0 to 0.4) with placebo and -1.9 (95\% CI, -2.5 to -1.2) with dupilumab (LS mean difference, -1.6 [95\% CI, -2.4 to -0.7]; P {\textlangle} .001). The LS mean difference between the 2 groups for the Lund-Mackay CT total score was -8.8 (95\% CI, -11.1 to -6.6; P {\textlangle} .001). Significant improvements with dupilumab were also observed for the 22-item SinoNasal Outcome Test (LS mean difference between groups, -18.1 [95\% CI, -25.6 to -10.6]; P {\textlangle} .001) and sense of smell assessed by UPSIT (LS mean difference, 14.8 [95\% CI, 10.9 to 18.7]; P {\textlangle} .001). The most common adverse events were nasopharyngitis (33\% in the placebo group vs 47\% in the dupilumab group), injection site reactions (7\% vs 40\%, respectively), and headache (17\% vs 20\%). 
CONCLUSIONS AND RELEVANCE: Among adults with symptomatic chronic sinusitis and nasal polyposis refractory to intranasal corticosteroids, the addition of subcutaneous dupilumab to mometasone furoate nasal spray compared with mometasone alone reduced endoscopic nasal polyp burden after 16 weeks. Further studies are needed to assess longer treatment duration, larger samples, and direct comparison with other medications.},
  author       = {Bachert, Claus and Mannent, Leda and Naclerio, Robert M and Mullol, Joaquim and Ferguson, Berrylin J and Gevaert, Philippe and Hellings, Peter and Jiao, Lixia and Wang, Lin and Evans, Robert R and Pirozzi, Gianluca and Graham, Neil M and Swanson, Brian and Hamilton, Jennifer D and Radin, Allen and Gandhi, Namita A and Stahl, Neil and Yancopoulos, George D and Sutherland, E Rand},
  issn         = {0098-7484},
  journal      = {JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION},
  keyword      = {CHRONIC RHINOSINUSITIS,ASTHMA CONTROL,QUESTIONNAIRE,ENTEROTOXINS,RELIABILITY,EUROPE,ADULTS,IGE},
  language     = {eng},
  number       = {5},
  pages        = {469--479},
  title        = {Effect of subcutaneous dupilumab on nasal polyp burden in patients with chronic sinusitis and nasal polyposis},
  url          = {http://dx.doi.org/10.1001/jama.2015.19330},
  volume       = {315},
  year         = {2016},
}

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