Dupilumab Improves Upper, Lower Airway Outcomes in SINUS Trials
MAY 20, 2019
Cecilia Pessoa Gingerich
Jorge F. Maspero, MD
Jorge F. Maspero, MD, Fundación CIDEA, Buenos Aires, Argentina, presented the research in a late-breaking clinical trial session at the 2019 American Thoracic Society (ATS) International Conference in Dallas, TX.
In his presentation, Maspero noted that asthma and chronic rhinosinusitis with nasal polyps (CRSwNP) are frequently comorbid conditions with up to 67% of patients with CRSwNP having asthma as well.
Both phase 3 SINUS trials were double-blind and placebo-controlled in patients with CRSwNP. Patients remained on their asthma treatment regimens for the duration of the trial and all were treated with mometasone furoate nasal spray (MFNS).
In SINUS-24, participants were randomized 1:1 to subcutaneous dupilumab 300 mg or placebo every 2 weeks (q2w). SINUS-52 participants were randomized 1:1:1 to 52 weeks of subcutaneous dupilumab 300 mg q2w, 52 weeks of placebo q2w, or to 24 weeks of subcutaneous dupilumab 300 mg q2w followed by 28 weeks of dupilumab 300 mg q4w. This analysis at 24 weeks pooled patients in both trials who received dupilumab 300 mg q2w (n = 170) and placebo (n = 258).
At 24 weeks, patients receiving dupilumab had significant improvements compared to placebo in upper airway measures including nasal peak inspiratory flow (Least Squares [LS] mean difference, 46.15 L/minute, 95% Confidence Interval [CI], 37.82 to 54.47) and 22-item Sino-Nasal Outcome Test score (LS mean difference -21.42; 95% CI, -24.97 to -17.87) (P <.0001 for both).
Patients receiving dupilumab also had significant improvements compared to placebo at 24 weeks in lower airway outcomes including FEV1 (LS mean difference, 0.21; 95% CI, 0.13 to 0.29) and the 6-item Asthma Control Questionnaire score (LS mean difference -0.82; 95% CI, -0.98 to -0.67) (P <.0001 for both).
“Dupilumab was effective in improving lower airway outcome measures regardless of blood eosinophil levels,” Masperos shared in his presentation.
Adverse events occurring in >5% of patients were nasopharyngitis, nasal polyps, headache, injection site erythema, asthma, and epistaxis, all of which occurred more frequently in patients treated with placebo.
In March 2019, the US Food and Drug Administration (FDA) accepted a supplemental Biologics License Application (sBLA) for dupilumab (Dupixent) as an add-on therapy for adults with inadequately controlled CRSwNP. The application was granted Priority Review and a decision is expected by June 26, 2019.
The abstract, “Dupilumab Improves Upper and Lower Airway Outcome Measures in Patients with Severe Chronic Rhinosinusitis with Nasal Polyps and Comorbid Asthma: Pooled Results from the SINUS-24 and SINUS-52 Phase 3 Studies,” was presented on May 20 at the ATS 2019 International Conference.