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

• Published in: JAMA : the journal of the American Medical Association 2016-02, Vol.315 (5), p.469-479
• Main Authors: Bachert, Claus, Mannent, Leda, Naclerio, Robert M, Mullol, Joaquim, Ferguson, Berrylin J, Gevaert, Philippe, Hellings, Peter, Jiao, Lixia, Wang, Lin, Evans, Robert R, Pirozzi, Gianluca, Graham, Neil M, Swanson, Brian, Hamilton, Jennifer D, Radin, Allen, Gandhi, Namita A, Stahl, Neil, Yancopoulos, George D, Sutherland, E. Rand
• Format: Article
• Language: English
• Subjects: Adult; Adults; Aged; Anti-Inflammatory Agents - administration & dosage; Anti-Inflammatory Agents - adverse effects; Antibodies, Monoclonal - administration & dosage; Antibodies, Monoclonal - adverse effects; Asthma - drug therapy; Chronic Disease; Clinical trials; Cytokines; Double-Blind Method; Drug Administration Schedule; Female; Genetic disorders; Humans; Injections, Subcutaneous; Interleukin-13 - antagonists & inhibitors; Interleukin-4 - antagonists & inhibitors; Least-Squares Analysis; Male; Medicin och hälsovetenskap; Middle Aged; Mometasone Furoate - administration & dosage; Monoclonal antibodies; Nasal Polyps - drug therapy; Nasal Sprays; Nose; Quality of Life; Sinuses; Sinusitis - complications; Sinusitis - drug therapy
• ISSN: 0098-7484; 1538-3598; 1538-3598
• DOI: 10.1001/jama.2015.19330

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