title: Effect of Subcutaneous Dupilumab on Nasal Polyp Burden in Patients With Chronic Sinusitis and Nasal Polyposis: A Randomized Clinical Trial.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  METHODS
  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.
  
  
  METHODS
  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
  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.
  
  
  BACKGROUND
  clinicaltrials.gov Identifier: NCT01920893.
authors.affiliation: Upper Airway Research Laboratory, Department of Otorhinolaryngology, Ghent University Hospital, Ghent, Belgium2Clintec, Karolinska Institute, Stockholm, Sweden.
authors.forename: Claus
authors.initials: C
authors.lastname: Bachert
authors.affiliation: Research and Development, Sanofi, Chilly Mazarin, France.
authors.forename: Leda
authors.initials: L
authors.lastname: Mannent
authors.affiliation: University of Chicago, Chicago, Illinois.
authors.forename: Robert M
authors.initials: RM
authors.lastname: Naclerio
authors.affiliation: Hospital Clinic, Institut d'Investigacions Biomèdiques August Pi i Sunyer, Barcelona, Spain.
authors.forename: Joaquim
authors.initials: J
authors.lastname: Mullol
authors.affiliation: University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania.
authors.forename: Berrylin J
authors.initials: BJ
authors.lastname: Ferguson
authors.affiliation: Upper Airway Research Laboratory, Department of Otorhinolaryngology, Ghent University Hospital, Ghent, Belgium.
authors.forename: Philippe
authors.initials: P
authors.lastname: Gevaert
authors.affiliation: Laboratory of Experimental Immunology, Department of Otorhinolaryngology-Head and Neck Surgery, University Hospitals Leuven, Leuven, Belgium.
authors.forename: Peter
authors.initials: P
authors.lastname: Hellings
authors.affiliation: Research and Development, Sanofi, Bridgewater, New Jersey.
authors.forename: Lixia
authors.initials: L
authors.lastname: Jiao
authors.affiliation: Research and Development, Sanofi, Bridgewater, New Jersey.
authors.forename: Lin
authors.initials: L
authors.lastname: Wang
authors.affiliation: Regeneron Pharmaceuticals Inc, Tarrytown, New York.
authors.forename: Robert R
authors.initials: RR
authors.lastname: Evans
authors.affiliation: Research and Development, Sanofi, Bridgewater, New Jersey.
authors.forename: Gianluca
authors.initials: G
authors.lastname: Pirozzi
authors.affiliation: Regeneron Pharmaceuticals Inc, Tarrytown, New York.
authors.forename: Neil M
authors.initials: NM
authors.lastname: Graham
authors.affiliation: Research and Development, Sanofi, Bridgewater, New Jersey.
authors.forename: Brian
authors.initials: B
authors.lastname: Swanson
authors.affiliation: Regeneron Pharmaceuticals Inc, Tarrytown, New York.
authors.forename: Jennifer D
authors.initials: JD
authors.lastname: Hamilton
authors.affiliation: Regeneron Pharmaceuticals Inc, Tarrytown, New York.
authors.forename: Allen
authors.initials: A
authors.lastname: Radin
authors.affiliation: Regeneron Pharmaceuticals Inc, Tarrytown, New York.
authors.forename: Namita A
authors.initials: NA
authors.lastname: Gandhi
authors.affiliation: Regeneron Pharmaceuticals Inc, Tarrytown, New York.
authors.forename: Neil
authors.initials: N
authors.lastname: Stahl
authors.affiliation: Regeneron Pharmaceuticals Inc, Tarrytown, New York.
authors.forename: George D
authors.initials: GD
authors.lastname: Yancopoulos
authors.affiliation: Immunology and Inflammation Development Franchise, Sanofi Research and Development, Cambridge, Massachusetts.
authors.forename: E Rand
authors.initials: ER
authors.lastname: Sutherland
mesh_terms: D000328:Adult; D000368:Aged; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage* / Q000009:adverse effects; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000009:adverse effects; D061067:Antibodies, Monoclonal, Humanized; D001249:Asthma / Q000188:drug therapy; D002908:Chronic Disease; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007279:Injections, Subcutaneous; D018793:Interleukin-13 / Q000037:antagonists & inhibitors*; D015847:Interleukin-4 / Q000037:antagonists & inhibitors*; D016018:Least-Squares Analysis; D008297:Male; D008875:Middle Aged; D000068656:Mometasone Furoate / Q000008:administration & dosage; D009298:Nasal Polyps / Q000188:drug therapy; D059085:Nasal Sprays; D011788:Quality of Life; D012852:Sinusitis / Q000150:complications / Q000188:drug therapy*
chemical_list: D000893:Anti-Inflammatory Agents; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D018793:Interleukin-13; D059085:Nasal Sprays; D000068656:Mometasone Furoate; D015847:Interleukin-4; C582203:dupilumab