Dupilumab improves outcomes in chronic rhinosinusitis with nasal polyps and asthma

Expert Name
Dr Jorge Maspero
Expert Affiliation
Fundación CIDEA, Argentina
American Thoracic Society 2019 International Conference, Dallas, TX

In a pooled analysis of the SINUS-24 and SINUS-52 trials, dupilumab significantly improved both upper and lower airway outcomes compared with placebo in patients with severe chronic rhinosinusitis with nasal polyps and comorbid asthma [1].

Dr Jorge Maspero (Fundación CIDEA, Argentina) presented the research in a late-breaking clinical trial session, pointing out 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. CRSwNP is a chronic type 2 inflammatory disease with a high symptom burden and poor quality of life. CRSwNP is characterised by an inflammatory signature involving interleukin(IL)-4, IL-5, and IL -13, with prominent tissue infiltration by eosinophils, lymphocytes, basophils, and mast cells.

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). Dupilumab acts as a receptor agonist by binding to the alpha subunit of the IL-4 receptor (IL-4Rα). Through blockade of IL-4Rα, dupilumab modulates signalling of both the IL-4 and IL-13 pathways.

In SINUS-24, participants were randomised 1:1 to subcutaneous dupilumab 300 mg or placebo every 2 weeks (q2w). SINUS-52 participants were randomised 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 with placebo in upper airway measures including nasal peak inspiratory flow (Least Squares [LS] mean difference 46.15 L/minute; 95% 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<0.0001 for both).

Patients receiving dupilumab also had significant improvements compared with 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, see Table). 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. “Dupilumab was effective in improving lower airway outcome measures regardless of blood eosinophil levels,” Dr Maspero shared in his presentation.

Table: Change from baseline at week 24 in upper and lower airway outcome measures [1]

  1. Laidlaw T, et al. A7536ATS 2019, 17-22 May, Dallas, Texas, USA.

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