In the phase 3 SINUS-24 and SINUS-52 trials, dupilumab improved clinical outcomes and and health-related quality of life among patients with chronic rhinosinusitis with nasal polyps (CRSwNP) and clinical features of obstructive lung disease.
In the phase 3 SINUS-24 and SINUS-52 trials, dupilumab improved clinical and health-related quality of life (HRQOL) outcomes among patients with chronic rhinosinusitis with nasal polyps (CRSwNP) and clinical features of obstructive lung disease. The post-hoc analysis findings, published in Journal of Asthma and Allergy, also suggest dupilumab can improve lung function among patients who have a history of asthma.
CRSwNP is an inflammatory disease that causes such chronic symptoms as nasal congestion, runny nose, loss of smell, headaches, pain, sinus inflammation, and nasal polyps. Inflammation in these cases is often type 2, involving interleukin (IL)-4 and IL-13. Dupilumab inhibits the receptor for IL-4 and IL-13, mitigating the inflammation caused by these cytokines.
Dupilumab demonstrated efficacy in reducing the endoscopic, radiologic, clinical, and HRQOL effects of severe CRSwNP vs a placebo in the randomized phase 3 SINUS-24 and SINUS-52 studies. These results suggest that type 2 inflammation may drive CRSwNP, according to the authors.
The current study, a post-hoc analysis of the SINUS-24 and SINUS-52 populations, aimed to provide insight into the potential responses of patients with chronic obstructive pulmonary disease (COPD) in a surrogate population of patients showing features for obstructive lung disease.
A total of 724 patients with severe CRSwNP were included across both studies, and of those patients, 131 (18%) met the broad definition criteria for features of obstructive lung disease. To meet the broad definition, patients had clinical features of obstructive lung disease with any of the following criteria: prebronchodilator forced expiratory volume in 1 second (FEV1)/forced vital capacity (FVC) lower than 0.70 and a history of smoking, patient-reported medical history of COPD, or asthma with a smoking history of more than 10 pack-years.
Additionally, 115 patients (16%) met the narrow definition criteria, which included criteria 1 or 2 from the broad definition.
Among the patients meeting the broad definition, 90 (69%) also had asthma. In the narrow definition group, 74 (64%) also had asthma.
In both the broad and narrow patient subgroups, CRSwNP outcomes and patients’ HRQOL improved when treated with dupilumab vs a placebo. The least squares mean difference in nasal polyp score (NPS) from baseline to week 24 was –1.72 (95% CI, −2.27 to −1.16). The difference in University of Pennsylvania Smell Identification Test (UPSIT) score also improved, with a least squares mean difference of 9.25 (95% CI, 6.52-11.99) from baseline to week 24.
The mean Sino Nasal Outcome Test (SNOT-22), a measure of HRQOL in CRSwNP, also improved in the broad definition group. From baseline to week 8, the least squares mean difference between dupilumab and the placebo was −13.14 (95% CI, −19.77 to −6.52), and by week 24, −15.45 (95% CI, −21.88 to −9.02).
In the narrow definition and overall asthma groups, dupilumab showed similar effects on NPS, UPSIT, and SNOT-22 scores.
In both the broad and narrow subgroups of patients, dupilumab improved prebronchodilator FEV1 and FEV1-to-FVC ratio at week 16, and the improvements were persistent through week 24 of the study.
“In this analysis, based on pooled data from the randomized phase 3 SINUS-24 and SINUS-52 studies, dupilumab treatment was associated with improvements in CRSwNP outcomes in patients with CRSwNP and clinical features of obstructive lung disease, and with improvements in lung function among those patients with CRSwNP, clinical features of obstructive lung disease, and self-reported asthma,” the authors concluded.
Limitations of the post-hoc analysis included the heterogeneity in the subgroups with clinical features of obstructive lung disease, as well as its reliance on retrospective data and use of a surrogate population of patients.
While the results are exploratory and may not be applicable to patients who are clinically determined to have COPD, the results are consistent with the mechanism of dupilumab and support further research in populations with COPD and type 2 inflammation.
Maspero JF, Bachert C, Martinez FJ, et al. Clinical efficacy among patients with chronic Rrhinosinusitis with nasal polyps and clinical features of obstructive lung disease: post hoc analysis of the phase III SINUS-24 and SINUS-52 studies. J Asthma Allergy. 2023;16:333-342. doi:10.2147/JAA.S357393