The safety and efficacy complementary findings to the multicenter, double-blind trials further support use of the interleukin 4 and 13 (IL-4; IL-13)-targeting monoclonal antibody in the symptom-burdened patient population—following the therapy’s approval for such an indication by the US Food and Drug Administration (FDA) this June.
It also shows dupilumab’s overall benefit in an adult severe CRSwNP patient population who may or may not have had previous corticosteroid treatment or invasive care, or both.
A team of investigators, led by Claus Bachert, MD, PhD, of the Upper Airways Research Laboratory at Ghent University, conducted a pair of multi-national, randomized, double-blind, placebo-controlled, placebo-groups trials in which both added dupilumab to standard care for severe CRSwNP.
Eligible patients were ≥18 years old, with bilateral CRSwNP and symptoms despite intranasal corticosteroid use. Patients had also been receiving systemic corticosteroids in the past 2 years, or had previous sinonasal surgery.
Patients in SINUS-24 were assigned randomly (1:1) to either subcutaneous dupilumab 300 mg or placebo every 2 weeks for 24 weeks. SINUS-52 patients were randomly assigned (1:1:1) to either dupilumab 300 mg every 2 weeks for 52 weeks; dupilumab every 2 weeks for 24 weeks then every 4 weeks for 28 weeks; or placebo every 2 weeks for 52 weeks.
Investigators stratified randomization based on asthma or non-steroidal anti-inflammatory drug-exacerbated respiratory disease status at screening, previous surgery, and country. They assessed for coprimary endpoints of changes from baseline to week 24 in nasal polyp score (NPS) and nasal congestion or obstruction. Japan-based patients were assessed for an additional endpoint of sinus Lund-Mackay CT scores.
A total of 276 patients were enrolled for SINUS-24 randomization, and 448 patients in SINUS-52. Bauchert and colleagues reported significant improvement in dupilumab-treated patients for both coprimary endpoints in both trials.
At 24 weeks, NPS least squares mean difference between dupilumab and placebo was -2.06 (95% CI, -2.43 to -1.69; P< .0001) in SINUS-24, and -1.80 (95% CI, -2.10 to -1.51; P< .0001) in SINUS-52.
Nasal congestion or obstruction score was -0.89 (95% CI, -1.07 to -0.71; P< .0001) in SINUS-24, and -0.87 (95% CI, -1.03 to -0.71; P< .0001) in SINUS-52. Treated patients also reported significant improvement in the Lund-Mackay CT score outcome versus placebo.
Common adverse events in patients—including nasopharyngitis, worsening of nasal polyps and asthma, headache, epistaxis, and injection-site erythema—were more common in placebo-treated patients.
Bauchert and colleagues concluded the finidngs indicate add-on dupilumab’s benefit for all disease measures of CRSwNP observed in both trials—including some comorbid outcomes, as well.
“In patients with CRSwNP who have a history of asthma, Dupixent was also effective in improving asthma symptoms, lung function and asthma control, as well as upper airway outcomes,” Bauchert said in a statement. “This is important news for these patients as they often suffer from high disease burden and are not controlled by standard treatment."
The praise surrounding dupilumab for the treatment of CRSwNP—as well as other type 2 inflammation-based conditions it is currently marketed toward, including asthma and atopic dermatitis—has been emphasized prior to the results of SINUS-24 and -52.
At the American Thoracic Society (ATS) 2019 Annual Meeting in Dallas, TX this May, study author Stella Lee, MD, director of Sino-Nasal Disorders & Allergy at the University of Pittsburgh, detailed the clinical background of patients featured in both trials, in an interview with MD Magazine®.
“When you meet a patient who has not been able to smell or breathe for a decade, you wonder, ‘Is surgery even going to help them? I don't think even oral steroids are going to help them’,” Lee said.
Lee and the research team observed patients recover their sense of taste and smell—sometimes in as soon as a week into biologic-added therapy.