Results of a subgroup analysis within a randomized, controlled trial show that the monoclonal antibody dupilumab (Dupixent) improved clinical and patient-reported outcomes among patients with chronic rhinosinusitis (CRS) with nasal polyps and comorbid asthma.
Results of a subgroup analysis within a randomized, controlled trial show that the monoclonal antibody dupilumab (Dupixent) improved clinical and patient-reported outcomes among patients with chronic rhinosinusitis (CRS) with nasal polyps and comorbid asthma.1
The nasal polyps sometimes seen with CRS cause chronic symptoms that include nasal congestion, loss of smell, and facial pain. The two-thirds of these patients who also have asthma tend to have worse nasal obstruction and experience higher levels of lower-airway inflammation.
Dupilumab inhibits signaling of the antibodies that drive type 2 inflammatory diseases. Findings of previous studies in patients with CRS with nasal polyps and comorbid asthma demonstrated that dupilumab resulted in significant improvements in endoscopic nasal polyp score, sense of smell, and disease severity versus placebo.2
Patients in the main double-blind, placebo-controlled study were required to have bilateral nasal polyps and chronic symptoms of rhinosinusitis despite 2 months of treatment with inhaled corticosteroid treatment. They were randomized 1:1 to receive either placebo or dupilumab 300 mg weekly as an add-on to mometasone furoate nasal spray (MFNS) for the 16-week study period.
The subgroup analysis concentrated on patients with CRS with nasal polyps and comorbid asthma. Dupilumab’s effect on their self-rated health-related quality of life (HRQoL) was measured via 2 scales: the 5-dimension EuroQoL questionnaire (EQ-5D), which measures self-rated health, and the 36-item Short-Form Health Survey (SF-36), which measures 8 domains, including functioning, limitations, mental health, and vitality. Investigators also assessed 5-item Asthma Control Questionnaire (ACQ-5) scores to measure asthma control and tracked levels of inflammatory biomarkers.
The proportion of patients considered responders based on the minimal clinically important difference in ACQ-5 score was significantly greater in patients receiving dupilumab versus placebo (62.5% vs 15.8%; P = .038). The dupilumab group also saw greater improvements from baseline in each of the individual ACQ-5 scores.
The ACQ-5 item with the greatest least-squares mean difference for dupilumab versus placebo was the score for waking in the morning with asthma symptoms (mean change from baseline, —1.46 in dupilumab group and 0.01 in placebo group). The differences in mean changes between the groups were also significant, favoring dupilumab, for the other 4 items: woken at night by asthma, limited in activities, shortness of breath, and wheezing time.
Patients receiving dupilumab experienced significant improvements from baseline in 5 of the SF-36 domains, whereas the placebo group saw significant improvement in just 2 domains. The dupilumab group also reported significant improvements in health status on the EQ-5D scale. Additionally, patients receiving dupilumab had a significantly larger reduction from baseline in both serum and nasal secretion levels of total immunoglobulin E antibodies.
The study authors wrote that this subgroup analysis “extends the previously reported observations that adding dupilumab to MFNS treatment improves nasal polyp burden, asthma control, lung function, and HRQoL.” These results indicate that dupilumab has effects on clinical and patient-reported outcomes in patients with CRS with nasal polyps and comorbid asthma that are similar to the effects seen in the overall population. Benefits were observed for both disease and symptom severity, as well as asthma control, “reflecting a reduced impact of asthma on daily activities and an improved HRQoL,” they wrote.
“Significant improvement from baseline in general health perception, physical functioning, and vitality was only observed with dupilumab treatment and not in the placebo arm,” the investigators concluded, noting that the improvements included both asthma-specific and nasal polyp—specific outcomes.
1. Bachert C, Hellings PW, Mullol J, et al. Dupilumab improves patient-reported outcomes in patients with chronic rhinosinusitis with nasal polyps and comorbid asthma [published online March 27, 2019]. J Allergy Clin Immunol Pract. doi: 10.1016/j.jaip.2019.03.023.
2. Bachert C, Mannent L, Naclerio RM, et al. Effect of subcutaneous dupilumab on nasal polyp burden in patients with chronic sinusitis and nasal polyposis: a randomized clinical trial. JAMA. 2016;315(5):469-479. doi: 10.1001/jama.2015.19330.