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

“A new drug is showing remarkable efficacy in treating allergic conditions, primarily eczema. The side effects are trivial considering the morbidity of atopic eczema. This publication shows that it’s also effective in nasal polyps for people who are affected with allergies and have sinus polyps develop.   Dupilumab is in clinical trials now. The government site for clinical trials, clinical trials.gov, predicts t will be release in November 2016.

I anticipate that there will the other uses of this remarkable technique of inhibiting the blood cells involved in the inflammatory response of allergies.” Bill Chesnut, MD.

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

Claus Bachert, MD, PhD1,2; Leda Mannent, MD3; Robert M. Naclerio, MD4; Joaquim Mullol, MD, PhD5; Berrylin J. Ferguson, MD6; Philippe Gevaert, MD, PhD1; Peter Hellings, MD, PhD7; Lixia Jiao, PhD8; Lin Wang, PhD8; Robert R. Evans, PharmD9; Gianluca Pirozzi, MD, PhD8; Neil M. Graham, MD, MPH9; Brian Swanson, PhD8; Jennifer D. Hamilton, PhD9; Allen Radin, MD9; Namita A. Gandhi, PhD9; Neil Stahl, PhD9; George D. Yancopoulos, MD, PhD9; E. Rand Sutherland, MD, MPH10


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.

Chronic sinusitis, an inflammatory condition of the sinuses, is common with estimates of prevalence as high as 12% in Western populations.1,2 It is characterized by specific symptoms often lasting for many years including nasal congestion, discharge and postnasal drip, decreased or lost sense of smell, facial pain and pressure, headache, and the consequences thereof.3 Based on endoscopic findings, the condition can be divided into chronic sinusitis with or without nasal polyposis. Typically observed in the context of eosinophilic inflammation of the upper airways, nasal polyps originate in the sinuses and obstruct the sinus and nasal passages.

Medical management of chronic sinusitis with nasal polyposis focuses on controlling tissue inflammation and, depending on severity, includes use of intranasal corticosteroids, nasal saline irrigation, antibiotics, or short-course oral steroids.3 In patients in whom polyps and symptoms persist despite medical treatment, surgical excision is considered. However, disease recurrence after surgery approaches 50% in patients with tissue eosinophilia,4 and resolution of symptoms, including sense of smell loss, is often incomplete.

Epidemiological data from a large European cohort indicate that chronic sinusitis is associated with a 3.5-fold increase in comorbid asthma prevalence.5 Although type 2 helper T-cell inflammation is implicated in this association, the mechanisms of this association have not been fully elucidated.6– 8

Dupilumab is a fully human monoclonal antibody to the interleukin 4 (IL-4) receptor α subunit, which inhibits signaling of IL-4 and IL-13, 2 cytokines central to type 2 helper T-cell–mediated inflammation. Dupilumab has demonstrated clinical efficacy in the type 2 helper T-cell–mediated diseases of asthma and atopic dermatitis,9– 11 and also improved sinonasal symptoms in patients with asthma.9

We hypothesized that the addition of dupilumab to intranasal corticosteroids would improve endoscopic, radiographic, and patient-reported measures of disease activity in those with chronic sinusitis and nasal polyposis, while also improving lung function and disease control in patients with comorbid asthma.