SYNAPSE
Trial question
What is the role of mepolizumab in patients with recurrent, refractory severe chronic rhinosinusitis with nasal polyps?
Study design
Multi-center
Double blinded
RCT
Population
Characteristics of study participants
35.0% female
65.0% male
N = 407
407 patients (143 female, 264 male).
Inclusion criteria: adult patients with recurrent, refractory, severe, bilateral nasal polyp symptoms.
Key exclusion criteria: cystic fibrosis; eosinophilic granulomatosis with polyangiitis; antrochoanal polyps; nasal septal deviation occluding one nostril; ongoing rhinitis medicamentosa; HIV infection; use of systemic corticosteroids or corticosteroid nasal solution in the last 4 weeks.
Interventions
N=206 mepolizumab (at a SC dose of 100 mg once every 4 weeks plus standard of care for 52 weeks).
N=201 placebo (matching placebo plus standard of care for 52 weeks).
Primary outcome
Median reduction in total endoscopic nasal polyp score at week 52
1 point
0 point
1.0 point
0.8 point
0.5 point
0.3 point
0.0 point
Mepolizumab
Placebo
Significant
increase ▲
Significantly greater reduction in median total endoscopic nasal polyp score at week 52 (1 point vs. 0 point; MD 0.73, 95% CI 0.34 to 1.11).
Secondary outcomes
Significantly greater reduction in median nasal obstruction VAS score during weeks 49-52 (4.41 points vs. 0.82 points; MD 3.14, 95% CI 2.18 to 4.09).
Significant decrease in the proportion of patients having nasal surgery up to week 52 (9% vs. 23%; HR 0.43, 95% CI 0.25 to 0.76).
Significantly greater reduction in median SNOT-22 total score at week 52 (30 points vs. 14 points; MD 16.49, 95% CI 9.42 to 23.57).
Safety outcomes
No significant difference in adverse or serious adverse events.
Conclusion
In adult patients with recurrent, refractory, severe, bilateral nasal polyp symptoms, mepolizumab was superior to placebo with respect to median reduction in total endoscopic nasal polyp score at week 52.
Reference
Joseph K Han, Claus Bachert, Wytske Fokkens et al. Mepolizumab for chronic rhinosinusitis with nasal polyps (SYNAPSE): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Respir Med. 2021 Oct;9(10):1141-1153.
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