In this phase 3 study, dupilumab improved outcomes for patients with recurring severe chronic rhinosinusitis with nasal polyps.
Claus Bachert, MD
Dupilumab (Dupixent) as an add-on to standard of care improved a variety of outcomes in patients with recurring severe chronic rhinosinusitis with nasal polyps (CRSwNP).
The research, which was presented at the 2019 Annual Meeting of the American Academy of Allergy, Asthma & Immunology (AAAAI) in San Francisco, CA, came from the phase 3 SINUS-52 study. In a similar, 24-week study—SINUS-24—dupilumab also improved outcomes for patients with CRSwNP.
"Dupixent is the first biologic therapy to demonstrate the potential to produce disease-modifying effects in severe CRSwNP, significantly improving all disease measures in the study, including sense of smell, one of the most troublesome and challenging-to-treat symptoms for patients," said Claus Bachert, MD, Professor and Head of Clinics of the Department of Otorhinolaryngology at Ghent University and principal investigator of the trials.
In SINUS-52, patients received subcutaneous dupilumab 300 mg every 2 weeks up to week 24, after which a group of patients received dupilumab every 4 weeks in addition to a group that continued on the 2-week schedule. All patients also received standard of care daily mometasone furoate nasal spray (MFNS). The study included 448 patients randomized (1:1:1) to the 3 study groups.
As Bachert mentioned, dupilumab improved participants’ sense of smell significantly. At 24 weeks, patients receiving dupilumab saw 108% improvement, versus 7% in placebo (P <.001). The absolute change from baseline was 9.71 and -0.81, respectively. In a separate assessment, patients in the dupilumab treatment group reported improved sense of smell as early as 4 weeks.
Patients receiving dupilumab every 2 weeks experienced a 27% improvement in sinus opacification compared to 0% for those on placebo (P <.0001). The absolute change from baseline was -5.21 and -0.09 for dupilumab and placebo, respectively.
The study also found that dupilumab improved asthma in the participants with the condition. In the 59.6% of participants with asthma, dupilumab improved lung function (FEV1) by 0.21 L compared to placebo, at week 24 (P = .0004). Dupilumab also improved asthma control as measured by ACQ-6 (P < .0001).
"Patients with co-morbid CRSwNP and asthma are often more difficult to treat so it is encouraging that Dupixent, which targets key drivers of Type 2 inflammation, may address both conditions in these patients," said Bachert.
Rates of adverse events were similar between treatment and placebo groups, overall. Treatment emergent adverse events (TEAEs) actually occurred less frequently in patients receiving dupilumab than placebo, 83% vs 91%, respectively. TEAEs that occurred more frequently with dupilumab versus placebo were bronchitis (6% versus 5%), cough (6% versus 5%) and injection site reactions (3% versus 2%).
The rate of serious adverse events was 5% with dupilumab compared to 10% with placebo, and adverse events leading to discontinuation occurred in 4% of those receiving dupilumab versus 11% of those receiving placebo.
The poster, “A Randomized Phase 3 Study, Sinus-52, Evaluating the Efficacy and Safety of Dupilumab in Patients with Severe Chronic Rhinosinusitis with Nasal Polyps,” was presented at a late-breaking session at the Annual Meeting of AAAAI on Monday, February 25, 2019.