Subgroup findings boost dupilumab benefit for CRSwNP, comorbid asthma
In post hoc analyses of the phase III SINUS-24 and SINUS-52 trials, the monoclonal antibody dupilumab continued to render improvements for patients with severe chronic rhinosinusitis with nasal polyps (CRSwNP), as well as among those with comorbid asthma regardless of asthma characteristics.
CRSwNP, comorbid asthma
CRSwNP is associated with significant clinical and economic burden and impaired quality of life. About two-thirds of patients with CRSwNP have comorbid asthma. [Rhinology 2019;57:343-351; J Asthma Allergy 2021;14:127-134; Laryngoscope 2019;129:1969-1975]
“Patients with comorbid asthma are more severely affected and tend to have poorer outcomes for both CRSwNP and asthma than patients without the comorbid condition,” noted Dr William Busse from the University of Wisconsin, Madison, Wisconsin, US, in his poster presentation at ACAAI 2021.
In SINUS-24 and SINUS-52, marked improvements were seen with dupilumab in terms of objective and patient-reported CRSwNP outcomes, lung function, and asthma control. [Lancet 2019;394:1638-1650]
The researchers pooled patient data from SINUS-24 (n=276) and SINUS-52 (n=448) to evaluate the effect of dupilumab on CRSwNP and asthma outcomes in patients with severe CRSwNP and comorbid asthma according to baseline asthma characteristics (ie, eosinophil count of ≥150/μL and ≥300/μL, ACQ-5* <1.5 and ≥1.5, FEV1** <80 percent). Of these, 59 percent had comorbid asthma. Participants were randomized 1:1 to receive SC dupilumab 300 mg*** or placebo. [ACAAI 2021, abstract P183]
CRSwNP outcomes# significantly improved with dupilumab vs placebo at weeks 24 and 52, regardless of baseline asthma characteristics (p<0.0001 for all).
Among patients with severe CRSwNP and comorbid asthma, ACQ-5 improved significantly with dupilumab vs placebo at the same timepoints, also irrespective of baseline asthma characteristics (p<0.0001 for all).
“[These findings show that] dupilumab significantly improved upper and lower airway outcomes in patients with severe CRSwNP and comorbid asthma. The improvements were seen irrespective of differences in clinically relevant baseline asthma characteristics,” said Busse.
Sleep, function scores
In another post hoc analysis using the pooled SINUS-24 and SINUS-52 datasets, SNOT-22## sleep domain scores were significantly better with dupilumab vs placebo, both at week 24 (–1.38 vs –0.41) and week 52 (–1.27 vs –0.34; p<0.0001 for both). The improvements were evident from week 8 onwards, as reflected by the least squares (LS) mean differences from baseline scores in SINUS-24 (–39.94; p<0.0001) and SINUS-52 (–21.98; p=0.01). [ACAAI 2021, abstract P184]
SNOT-22 function domain scores were also significantly improved with dupilumab vs placebo at both timepoints (–1.31 vs –0.44 [weeks 24] and –1.08 vs –0.32 [weeks 52]; p<0.0001 for both). As in the sleep domain scores, LS mean differences in function domain scores from baseline were also seen as early as week 8 in both SINUS-24 and SINUS-52 (–44.23; p<0.0001 and –31.37; p=0.0003, respectively).
The benefit of dupilumab over placebo in terms of sleep and function domain score improvements remained consistent across all predefined patient subgroups### at weeks 24 and 52 (p<0.0001 for all).
“Symptoms of CRSwNP are burdensome and often impair sleep quality, resulting in daytime sleepiness and compromising patient’s ability to function and work … [Our findings show that] CRSwNP patients treated with dupilumab reported rapid improvements in sleep and function scores from week 8 that were sustained throughout the treatment period,” said Busse.