Biologic Shows Positive Outcomes in CRSwNP Regardless of Baseline Asthma Status

Baseline asthma characteristics did not adversely affect outcomes among patients with who received dupilumab for their comorbid chronic rhinosinusitis with nasal polyps (CRSwNP). The monoclonal antibody improved patient outcomes in both chronic diseases, study authors noted in Journal of Asthma and Allergy.

CRSwNP and asthma are type 2 inflammatory conditions that frequently coexist, the authors noted, with the latter increasing the symptom burden of the former. Their analysis used data from the SINUS-24 and SINUS-52 studies; data were pooled for outcomes at week 24, while SINUS-52 only provided week 52 data. The dosing schedule for dupilumab was 300 mg every 2 weeks per 3 baseline measures:

• Blood eosinophils: ≥ 150 or ≥ 300 cells/mcL (indicates type 2 inflammation)
• 5-item Asthma Control Questionnaire (ACQ-5) score: < 1.5 (controlled asthma) or > 1.5 (uncontrolled asthma)
• Forced expiratory volume in 1 second (FEV₁): < 80% predicted (reduced lung function)

Outcomes in CRSwNP were evaluated with nasal polyp score (range, 0-8), nasal congestion (range, 0-3), 22-item Sino-Nasal Outcome Test (SNOT-22; range, 0-110), loss of smell score (range, 0-3), and University of Pennsylvania Smell Identification Test (range, 0-40); asthma outcomes were measured via the ACQ-5 (range, 0-6) and prebronchodilator FEV₁.

“Dupilumab, which blocks the shared receptor component for interleukin-4 and -13, demonstrated efficacy in adults with severe CRSwNP in the phase 3 SINUS-24 and SINUS-52 studies, including in patients with coexisting asthma/nonsteroidal anti-inflammatory drug-exacerbated respiratory disease (NSAID-ERD),” the investigators wrote. “However, the impact of different asthma characteristics on dupilumab treatment in this population is unknown.”

Fifty-nine percent (n = 428 patients) of the overall cohort (N = 724) had self-reported coexisting asthma. And of that group, 50.9% had uncontrolled asthma (ACQ-5 score > 1.5) and 40.7% had predicted FEV₁ below 80%. In addition, 42.3% had NSAID-ERD.

At week 24, the following results were seen from dupilumab:

• All CRSwNP and asthma outcomes were significantly improved vs placebo regardless of the 3 baseline measures (P < .001); this was seen even among the patients with NSAID-ERD
• Improvements exceeded the minimum clinically important difference (MCID) for the ACQ-5 and SNOT-22 measures:
  • ACQ-5: from 35.2% to 74.2%
  • SNOT-22: from 72.0% to 78.7%

At week 52, data from SINUS-52 show similar improvements compared with the baseline measures.

Drilling down on the SNOT-22 score improvements seen, with the MCID being 8.9 points, this outcome following dupilumab treatment vs placebo was seen in the following patient groups (all P < .0001):

• 76.1% with baseline eosinophils of at least 150/mcL
• 77.3% with baseline eosinophils of at least 300/mcL
• 78.7% who had controlled asthma
• 77.4% who had uncontrolled asthma
• 72.0% with reduced lung function

At week 52, in SINUS-52, the corresponding percentages slightly dropped, but still were better vs placebo (all P < .001): 73.0%, 74.6%, 78.6%, 67.5%, and 67.5%, respectively.

For the ACQ-5 measure, the significant improvements seen at week 52 had been maintained from week 24 (P < .0001), and the MCID of 0.5 points was exceeded in the following patient groups (all P < .0001):

• 53.0% with baseline eosinophils of at least 150/mcL
• 53.4% with baseline eosinophils of at least 300/mcL
• 35.2% who had controlled asthma
• 74.2% who had uncontrolled asthma
• 61.7% with reduced lung function

Again at week 52 in SINUS-52, the respective results dropped but still marked an improvement (all P < .01): 45.9%, 45.8%, 28.6%, 62.5%, and 47.5%.

For FEV₁, almost universal improvements were seen among the patients with comorbid asthma at weeks 24 (P < .001) and 52 (P < .05), the exception being patients with uncontrolled baseline asthma (P = .0511).

In addition, regardless of baseline NSAID-ERD, dupilumab had improved most asthma-related outcomes among the patients with CRSwNP and asthma by week 24, a finding the study authors considered significant (P < .05), “except for change in FEV₁ in patients with an ACQ-5 score <1.5 and without NSAID-ERD at baseline (P = .0743),” the authors wrote.

“Dupilumab significantly improved upper and lower airway outcomes in patients with severe CRSwNP and coexisting asthma, in line with other studies of biologics in the treatment of coexisting disease,” the investigators concluded. “These data add to our understanding of the effects of dupilumab in patients with coexisting upper and lower airway disease.”

Reference

Busse WW, Pavord ID, Siddiqui S, et al. Dupilumab improves outcomes in patients with chronic rhinosinusitis with nasal polyps and coexisting asthma irrespective of baseline asthma characteristics. J Asthma Allergy. 2023;16:411-419. doi:10.2147/JAA.S391896