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JAMA. 2016 Feb 2;315(5):469-79. doi: 10.1001/jama.2015.19330.

Effect of Subcutaneous Dupilumab on Nasal Polyp Burden in Patients With Chronic Sinusitis and Nasal Polyposis: A Randomized Clinical Trial.

Author information

  • 1Upper Airway Research Laboratory, Department of Otorhinolaryngology, Ghent University Hospital, Ghent, Belgium2Clintec, Karolinska Institute, Stockholm, Sweden.
  • 2Research and Development, Sanofi, Chilly Mazarin, France.
  • 3University of Chicago, Chicago, Illinois.
  • 4Hospital Clinic, Institut d'Investigacions Biomèdiques August Pi i Sunyer, Barcelona, Spain.
  • 5University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania.
  • 6Upper Airway Research Laboratory, Department of Otorhinolaryngology, Ghent University Hospital, Ghent, Belgium.
  • 7Laboratory of Experimental Immunology, Department of Otorhinolaryngology-Head and Neck Surgery, University Hospitals Leuven, Leuven, Belgium.
  • 8Research and Development, Sanofi, Bridgewater, New Jersey.
  • 9Regeneron Pharmaceuticals Inc, Tarrytown, New York.
  • 10Immunology and Inflammation Development Franchise, Sanofi Research and Development, Cambridge, Massachusetts.

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.

TRIAL REGISTRATION:

clinicaltrials.gov Identifier: NCT01920893.

PMID:
26836729
[PubMed - indexed for MEDLINE]
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