Mepolizumab treatment is associated with physical activity and cardiorespiratory fitness irrespective of endoscopic sinus surgery in patients with chronic rhinosinusitis with nasal polyps: a randomised controlled trial

Background: Cardiorespiratory fitness is a strong predictor of life expectancy and all-cause mortality. Patients with chronic rhinosinusitis with nasal polyps (CRSwNP) often experience reduced physical activity levels due to nasal obstruction and high disease burden Objective: To evaluate whether mepolizumab, with or without sinus surgery, is associated with changes in habitual physical activity and cardiorespiratory fitness. Methods: In this randomized trial (NCT05598814), 58 adults with severe CRSwNP were randomized (1:1) to receive either sinus surgery with mepolizumab (FESS) or mepolizumab alone (nonFESS). Inclusion criteria included CRS symptoms, nasal polyp score (NPS) ≥4, SNOT-22 score > 35, signs of type 2 inflammation, and prior functional endoscopic sinus surgery (FESS). Patients received 100 mg of mepolizumab every four weeks for six months. No exercise was prescribed, though participants were aware activity was being tracked. Physical activity (step count), fitness score (VO₂max/kg), and disease burden were assessed at baseline and follow-up. Results: The FESS (n = 29) and nonFESS (n = 29) groups had a mean age of 52 (14) years, with 74% male participants. Both groups demonstrated significant increases in VO₂max (FESS: +1.95 ml/min/kg, +6%, p < 0.001; nonFESS: +1.50 ml/min/kg, +5%, p < 0.001) and daily step count (FESS: +1117 steps, p < 0.001; nonFESS: +1087 steps, p = 0.001). SNOT-22 scores decreased significantly in both groups, with greater improvement in the FESS group (−42 vs. −32 points, p = 0.040). Conclusion: Mepolizumab was associated with improvement in physical activity, fitness, and quality of life. FESS provided additional quality-of-life benefits but did not further enhance fitness outcomes.