In a phase 3 study, dupilumab reduced nasal polyp scores and nasal congestion compared to placebo in patients with chronic rhinosinusitis with nasal polyps.
A phase 3 study of dupilumab (Dupixent) has shown that the monoclonal antibody significantly improved nasal polyp scores in patients with chronic rhinosinusitis with nasal polyps, compared to placebo.
Dupilumab was additionally safe and well-tolerated—participants in the placebo group even experienced more frequent treatment-emergent adverse effects (TEAEs) and serious TEAEs.
Study author Joseph K. Han, MD, FARS, FAAOA, Division of Allergy, Eastern Virginia Medical School, Norfolk, VA, noted that symptom severity in these patients is often “underappreciated” by health care providers.
“If you look at the quality of life questionnaires in these patients with chronic sinusitis with nasal polyps, it’s very similar to that of patients with COPD and congestive heart failure,” said Han in his presentation at the 2019 Annual Meeting of the American Academy of Allergy, Asthma & Immunology (AAAAI).
The multicenter, double-blind study included 276 patients who were randomized (1:1) to receive either dupilumab 300 mg (n = 143) or placebo (n = 133) subcutaneously every 2 weeks for a 24-week treatment period. All participants received mometasone furoate nasal spray for 4 weeks before the randomized period, which continued throughout the randomized period and 24-week off-treatment follow-up period.
The participants were patients with chronic rhinosinusitis with nasal polyps (CRSwNP) who had been treated with systemic corticosteroids and/or surgery. Patients with asthma were allowed to participate, but those with FEV1 of ≤50% of the predicted normal were excluded.
“These are patients with severe sinusitis,” said Han. “These are also patients who, based on nasal endoscopy, had pretty severe nasal polyps.”
A majority of patients in both groups had at least one prior disease-related surgery (dupilumab, 69.2%; placebo, 74.4%), had systemic corticosteroid use in the prior 2 years (64.3%, 65.4%, respectively), and had comorbid asthma (57.3%, 59.4%, respectively).
Meeting its 2 primary efficacy endpoints, dupilumab significantly improved the nasal polyp score (-2.06) and nasal congestion score (-0.89) from baseline to week 24 (LS-mean differences versus placebo; P < .0001 for both).
While the endpoints were supported by data from week 24, Han said that improvements were observed much earlier. “We saw symptoms improve as early as week 4, I would say maybe even as early as week 2,” he noted.
The investigators also analyzed the effect on lung function (FEV1) and asthma control (ACQ-6) for participants with asthma. “Not only did dupilumab improve the subjective and objective findings of sinusitis, but it also seemed to help patients with comorbid asthma,” said Han.
In participants with asthma, dupilumab improved both FEV1 (0.21; P = .0004) and ACQ-6 (-0.76; P = .0001) (LS-mean differences versus placebo).
In an interview with MD Magazine®, Han explained how achieving improved symptoms—as treated patients did in the secondary endpoints—could also result in improved quality of life.
"If you asked a patient which is more important for them, they would say the change of smell or loss
of smell is more important for them," Han said. "And in this study, we were able to show that the patients now who did not have any sense of smell in the beginning were able to get their sense of smell back, which is remarkable, because that increases our quality of life tremendously."
When addressing the adverse effects observed in the study, Han announced an unusual data point.
“I’ve been in a lot of clinical studies and read a lot of clinical studies, but I rarely ever see where the adverse effect is higher in the placebo group than it is in the treatment group,” he said.
In fact, overall treatment-emergent adverse effects (TEAEs) were more common in the placebo group (n = 93; 70.5%) than the dupilumab group (n = 93; 65.0%). Serious TEAEs were also more common in placebo versus dupilumab (14.4% versus 4.2%).
The some of the most common TEAEs occurring in >5% of patients were nasopharyngitis (placebo, 15.2%; dupilumab, 13.3%), nasal polyps (18.2%; 11.9%), and injection-site erythema (9.1%; 5.6%). The most common TEAE occurring with more frequency in the dupilumab group was epistaxis (7.7% versus 3.0% in placebo).
The abstract, “Efficacy and Safety of Dupilumab in Patients with Chronic Rhinosinusitis with Nasal Polyps: Results from the Randomized Phase 3 Sinus-24 Study,” was presented in a late-breaking session at the Annual Meeting of AAAAI on Saturday, February 23, 2019.