Dupilumab prospective RCT for CRSwNP, a multinational trial of 60 patients with a 16-week CT follow-up
Reviewed by Suki Ahluwalia

This transcontinental work describes a randomised, double blind, placebo controlled parallel group study over a 16-week period, assessing 60 patients with CRSwNP by CT scan scores. All patients had a four-week period of intranasal corticosteroids followed by randomisation to add on therapy or placebo for 16 weeks. The add-on therapy was a loading dose of dupilumab 600mg, followed by 300mg weekly. This group has previously published evidence from this study that 16 weeks of treatment with dupilumab in adults with symptomatic CRSwNP refractory to intranasal corticosteroids led to a significant improvement in nasal polyp score, Lund-Mackay score, rhinosinusitis severity as assessed by VAS, HRQoL as assessed by SNOT‑22, and sense of smell assessed by UPSIT. This study presents the CT score findings. Included patients were aged 18-65 with a nasal polyp score of at least five and symptoms of CRS, despite INCS for at least two months. Their symptomatology included at least two from: nasal obstruction, reduction or loss of sense of smell, nasal discharge, and facial pain or pressure. CT sinus scans were performed initially, and at week 16. Images were independently, blindly assessed using two validated scoring systems: the gold standard Lund-Mackay (score 0-24) and also the zLMK system based on percentage sinus opacification (score 0-48), which provides increased disease representation and sensitivity to change in partially opacified sinuses. Statistical analysis using Pearsons correlation coefficient was used to assess LMK and zLMK score at 0 and 16 weeks. Endoscopic bilateral nasal polyp score, patient-reported disease severity using VAS, SNOT, and UPSIT were all included and previously published. Baseline demographics and patient characteristics were similar in the placebo and dupilumab groups. Initial CT total scores indicated patients had substantial sinus involvement, with mean total LMK scores elevated in both the placebo (18.7 ± 5.5) and dupilumab (18.6 ± 5.0) groups. Mean zLMK total scores at baseline were 35.7 ± 10.7 and 34.8 ± 8.8 for the placebo and dupilumab groups respectively. After the 16 weeks of treatment, statistically significant (p < 0.0001) improvement with dupilumab was observed in total bilateral CT scores using both standard LMK (9.4 ± 5.0) and zLMK scoring systems (17.2 ± 8.8). Significant improvements were observed for individual sinuses using both scoring systems. At the end of 16 weeks of treatment, the majority of patients treated with dupilumab had a sinus LMK score of 0 or 1 for each sinus. Post-treatment obstruction in the OMC was 81% in the placebo group compared with 40% in the dupilumab group. Although almost complete obstruction was observed for all four segments of the OMC included in the zLMK system at baseline, after 16 weeks of dupilumab treatment at least 40% of patients had patent frontal recess and middle meatus, and more than 60% of patients had patent infundibulum and sphenoethmoidal recess. In contrast, there were only small improvements in patency across these segments in the placebo group. Dupilumab added to intranasal steroid background therapy significantly decreased opacification across all sinuses after 16 weeks of treatment, as measured using the LMK and zLMK scoring systems, while also significantly improving NPS, disease severity, HRQoL, and sense of smell.

Dupilumab reduces opacification across all sinuses and related symptoms in patients with CRSwNP.
Bachert C, Zinreich J, Hellings P, et al.
RHINOLOGY
2020:58(1):10-7.