Dupilumab improves disease control, QoL outcomes in asthma patients with rhinosinusitis
The use of the anti-interleukin-4 receptor α monoclonal antibody dupilumab led to improved patient-reported and sino-nasal outcomes in asthma patients with chronic rhinosinusitis with or without nasal polyposis (CRS/NP), a common comorbidity of asthma, according to two prespecified analyses results of the LIBERTY ASTHMA QUEST* trial presented at ERS 2018.
Researchers evaluated 1,902 patients (20 percent with comorbid CRS/NP) with persistent asthma for ≥12 months who were on a stable treatment regimen of medium-to-high dose inhaled glucocorticoids plus up to two additional controllers. Participants were randomized 2:2:1:1 to receive either dupilumab 200 or 300 mg or placebo 1.1 or 2.0 mL every 2 weeks for 52 weeks. [ERS 2018, abstract PA1124]
Overall, dupilumab 200 and 300 mg significantly reduced annual severe exacerbation rates by 48 percent and 46 percent, respectively, vs placebo (p<0.001 for both). Both doses of dupilumab also improved FEV1** at week 12 (least squares [LS] mean, 0.32 and 0.34 L, respectively), with LS mean differences of 0.14 and 0.13 L vs placebo (p<0.001 for both).
“[The] improvement in FEV1 was rapid, with differences … seen at the first evaluation [at week 12 which] was sustained throughout the 52-week treatment period,” said the researchers.
At week 52, ACQ-5*** scores of patients with CRS/NP were also significantly improved with both dupilumab regimens vs placebo (p<0.001), which appeared to be greater than those without CRS/NP, noted the researchers.
AQLQ(S)# LS mean scores of those with CRS/NP also improved with both dupilumab regimens vs placebo (p<0.05), with the greatest difference observed at weeks 36 and 52 (p<0.01 for both).
Another prespecified analysis demonstrated a significant improvement in SNOT-22## scores, a CRS disease-specific health-related quality of life (HRQoL) outcome, with both dupilumab regimens vs placebo at week 12 (p<0.05), which continued through weeks 24 and 52 (p<0.01 for both). [ERS 2018, abstract PA1125]
Overall, dupilumab was generally well tolerated and had similar incidences of treatment-emergent adverse events with placebo (81 percent vs 83 percent), with the most frequent being viral upper respiratory tract infection, injection-site erythema, upper respiratory tract infection, and bronchitis.
It is important to establish a targeted regimen for CRS/NP, noted the researchers, considering the associated nasal obstruction/congestion and discharge compounded with facial pain and/or loss of smell. [Rhinol Suppl 2007;20:1-136; Allergy 2013;68:1314-1321] These factors can increase the risk for poor asthma control, exacerbations, and poor HRQoL, they added. The findings provide insight on the potential of dupilumab to address these issues given the improved asthma control and asthma-related HRQoL outcomes, they said.