Patients with severe asthma with or without coexisting chronic rhinosinusitis and nasal polyps (CRSwNP) experienced continued improvements in exacerbations and lung function in an extension study.
Long-term use of dupilumab is effective at reducing the annualized exacerbation rate while maintaining lung function improvements in patients with asthma with or without chronic rhinosinusitis and nasal polyps (CRSwNP), according to a study published in Annals of Allergy, Asthma & Immunology.
Type 2 inflammatory cytokines play a role in the process by which asthma and CRSwNP develop. In addition, the existence of CRSwNP alongside asthma substantially increases the burden of asthma.
“In addition, the presence of coexisting (CRSwNP) may affect treatment choices and disease management, and as these patients often relapse, they may particularly benefit from monoclonal antibody therapies that target underlying type 2 inflammatory processes,” the authors explained.
Dupixent (dupilumab) is a monoclonal antibody that targets the key drivers of type 2 inflammation, which has been shown to significantly reduce asthma exacerbations compared with placebo. TRAVERSE OLE, an open-label extension study, reported on the long-term efficacy of Dupixent in patients with uncontrolled, moderate-to-severe asthma or oral corticosteroid (OCS)-dependent severe asthma with or without self-reported coexisting CRSwNP. The trial included patients enrolled in 2 previous phase 3 studies: LIBERTY ASTHMA QUEST and LIBERTY ASTHMA VENTURE.
The study included 317 patients with and 1,213 patients without coexisting CRSwNP from the QUEST trial and 61 patients with and 126 patients without coexisting CRSwNP from the VENTURE trial.
Quest: The study analyzed add-on Dupixent 200 mg and 300 mg every 2 weeks compared with placebo in patients with uncontrolled, moderate-to-severe asthma. The full study was 52 weeks.
There were larger decreases in the unadjusted annualized exacerbation rate in patients on Dupixent vs patients on placebo regardless of the CRSwNP status. In patients with CRSwNP, the rate decreased from 2.36 to 1.48 for patients on placebo and from 2.39 to 0.49 for patients on Dupixent. Exacerbation rates for patients without CRSwNP had decreased from 2.21 to 0.91 on placebo and from 2.00 to 0.51 on Dupixent.
The decreases from QUEST were continued into TRAVERSE, which was 96 weeks. In patients with CRSwNP who were on placebo in QUEST and changed to Dupixent in TRAVERSE, the annualized exacerbation rate decreased further to 0.41. For patients with CRSwNP on Dupixent who stayed on the treatment, the rate decreased to 0.32. The rate for patients without CRSwNP initially dropped to 0.34 for those initially on placebo and to 0.33 for patients on Dupixent the whole time.
VENTURE: The study evaluated add-on Dupixent 300 mg every 2 weeks compared with placebo in patients with OCS-dependent severe asthma. The full study was 24 weeks.
The decrease in the annualized exacerbation rate was similar to what was seen in QUEST. By the end of TRAVERSE, the rate for patients with CRSwNP who were initially on placebo was down to 0.45 and the rate for patients initially on Dupixent was down to 0.35. Patients without CRSwNP had rates down to 0.21 for those initially on placebo and 0.41 for those initially on Dupixent.
Patients also reduced their mean OCS dose further during TRAVERSE. At Week 96, the mean reduction from parent study baseline was:
Improvements in the Asthma Control Questionnaire 5 score continued through week 48 of TRAVERSE for patients enrolled from QUEST and VENTURE, and changes seen in both study in the Asthma Quality of Life Questionnaire were also observed through week 48.
The substantial improvements in lung function, measured by forced expiratory volume in 1 second (FEV1), that were observed during QUEST were maintained in TRAVERSE. Patients in VENTURE who were on placebo had no changes in FEV1 from parent study baseline to week 0 of TRAVERSE, but there were observed improvements in this group by week 96.
Rates of treatment-emergent adverse events (TEAEs) were similar to those seen in QUEST and VENTURE in patients with and without CRSwNP. A higher proportion of patients with CRSwNP reported serious TEAEs regardless of which study they were enrolled through.
“By the end of the TRAVERSE study, patients previously in the placebo arms of the parent studies improved as much as patients who had also received dupilumab in the previous parent studies,” the authors noted.