Patients with severe chronic rhinosinusitis with nasal polyps treated with Dupixent showed improvements in nasal polyp size, nasal congestion severity, chronic sinus disease, sense of smell and comorbid asthma outcomes, according to data presented at the American Academy of Allergy, Asthma and Immunology Annual Scientific Meeting.
“[The] clinical, economic and humanistic burden of chronic rhinosinusitis with nasal polyps is mostly unrecognized,” Joseph Han, MD, chief of the division of rhinology and the division of allergy at Eastern Virginia Medical School and lead author of SINUS-24 study, told Healio Primary Care Today. “Patients with chronic rhinosinusitis with nasal polyps have very high symptom burden and poor quality of life due to the chronic, relapsing nature of the disease.”
“Clinically speaking, [Dupixent (dupilumab, Sanofi, Regeneron)] is a completely new type of medication for the treatment of chronic rhinosinusitis with nasal polyposis,” he said. “Current treatment options for patients with the disease have limitations; [the] treatment paradigm is characterized by the need for recurrent courses of systemic steroids and surgeries. We have not had any new innovation in the management of chronic sinusitis for over 30 years that targets the underlying root cause of the disease.”
Han and colleagues conducted two randomized, double-blind, placebo-controlled phase 3 trials, known as the SINUS-24 and SINUS-52 studies, to evaluate the safety and efficacy of dupilumab for the treatment of chronic rhinosinusitis with nasal polyps at 24 and 52 weeks, respectively. Both studies included patients with ongoing moderate to severe symptoms of nasal congestion, blockage, loss of smell or nasal discharge despite previous treatment with systemic corticosteroids and/or nasal polyp surgery.
In SINUS-24, 276 patients were randomly assigned to receive either 300 mg of dupilumab every 2 weeks for 24 weeks or placebo every 2 weeks for 24 weeks. In SINUS-52, 448 patients were randomly assigned to receive either 300 mg of dupilumab every 2 weeks for 52 weeks, 300 mg of dupilumab every 2 weeks for 24 weeks, followed by every 4 weeks for 28 weeks, or placebo every 2 weeks for 52 weeks.
The researchers assessed changes from baseline in nasal polyp score, as well as patient-reported nasal congestion, CT Lund–Mackay, University of Pennsylvania Smell Identification Test, Sino-Nasal Outcome Test-22, forced expiratory volume over 1 second and Asthma Control Questionnaire-6 scores.
In both trials, patients who received dupilumab every 2 weeks demonstrated greater improvement in sinus opacification at 24 weeks compared with those receiving placebo (SINUS-24: 42% vs. 4%; SINUS-52: 27% vs. 0%). In SINUS-52, patients who received dupilumab every 2 weeks demonstrated greater improvement in sinus opacification at 52 weeks compared with those receiving placebo (37% vs. 2%).
In SINUS-24 and SINUS-52, there was a 146% and 108% improvement in ability to identify different smells at 24 weeks among patients who received dupilumab every 2 weeks vs. 19% and 7% among those who received placebo, respectively, according to a press release. Patients treated with dupilumab experienced heightened sense of smell as early as 1 month in both trials, according to the release.
Health-related quality of life improved more in dupilumab-treated patients at 24 weeks than those treated with placebo in both trials (SINUS-24: 60% vs. 18%; SINUS-52: 51% vs. 18%). This improvement in health-related quality of life remained at 52 weeks (58% vs. 14%).
At 24 weeks, lung function also improved in patients receiving dupilumab in SINUS-24, with an absolute change from baseline of 0.15L compared with –0.06L for placebo, and in SINUS-52, with an absolute change from baseline of 0.17L compared with –0.015L for placebo.
There was a 73% decline in the need for rescue treatment with systemic corticosteroids or nasal polyp surgery at 24 weeks among patients treated with dupilumab compared with placebo in both trials.
There were similar rates of adverse events between the dupilumab and placebo group overall. Patients in the dupilumab group had lower rates of treatment-emergent adverse events compared with those in the placebo group (SINUS-24: 65% vs. 71%; SINUS-52: 83% vs. 91%). Nosebleeds occurred more often in the dupilumab group than in the placebo group in SINUS-24 (8% vs. 3%), whereas bronchitis (6% vs. 5%), cough (6% vs. 5%) and injection site reactions (3% vs. 2%) occurred more often in the dupilumab group in SINUS-52.
Additionally, the rate of serious adverse events was lower with dupilumab treatment than with placebo in SINUS-24 (4% vs. 14%) and SINUS-52 (5% vs. 10%).
“The study results are very impressive and demonstrate that Dupixent is very effective in the management of nasal polyps and improving patient’s symptoms of nasal polyposis, very similar to symptom relief after sinus surgery,” Han said. “Physicians now have a new and effective option to treat these difficult-to-manage nasal polyps in chronic rhinosinusitis patients who suffer severely from this disease.” – by Alaina Tedesco
Bachert C, et al. Abstract L36. Presented at: American Academy of Allergy, Asthma and Immunology Annual Scientific Meeting; Feb. 22-25, 2019; San Francisco.
Han J, et al. Abstract L4. Presented at: American Academy of Allergy, Asthma and Immunology Annual Scientific Meeting; Feb. 22-25, 2019; San Francisco.
Disclosure: Han reports being a member of Regeneron Pharmaceuticals Inc. and Sanofi advisory boards.