Mepolizumab reduces risk for repeat surgery for chronic rhinosinusitis with nasal polyps

Key takeaways:

• A greater proportion of patients with severe chronic rhinosinusitis with nasal polyps who received mepolizumab (Nucala, GSK) vs. placebo did not require surgery throughout the 52-week study period (72% vs. 51%).
• Mepolizumab-treated patients also were more likely to experience greater than one-point improvements in their total endoscopic nasal polyp scores and VAS scores.
• Patients in both groups who had sinus surgery during the study period had higher baseline blood eosinophil counts.

Patients with previous sinus surgery for severe chronic rhinosinusitis with nasal polyps experienced less risk for further surgery while taking mepolizumab compared with placebo, according to a study published by Allergy.

These risks remained low for patients on the medication regardless of their baseline characteristics, Wytske J. Fokkens, MD, professor in the department of otolaryngology at University of Amsterdam, and colleagues wrote in the study.

The phase 3 randomized, double-blind, placebo-controlled, parallel-group SYNAPSE trial included 407 patients with at least one previous sinus surgery for CRSwNP.

Patients received 100 mg subcutaneous mepolizumab (Nucala, GSK; n = 206) or placebo (n = 201) every 4 weeks. Standard-of-care treatment including daily mometasone furoate nasal spray, saline nasal irrigations and systemic corticosteroids with or without antibiotics was provided as well.

According to the researchers, 72% of the mepolizumab patients no longer needed sinus surgery through the 52-week study period, compared with 51% of the placebo group. The researchers attributed the high rates of success among the placebo group to improved adherence to the standard of care.

Also, 16% of the patients assigned mepolizumab and 30% of those assigned placebo were placed on a waiting list for sinus surgery during the 52-week study period. The risks for being placed on a waiting list included 13.9% (95% CI, 9.8-19.5) for the mepolizumab group and 28.5% (95% CI, 22.7-35.4) for the placebo group.

Overall, a smaller proportion of patients assigned mepolizumab vs. placebo had one or more sinus surgeries during the study period (9% vs. 23%), including one (8% vs. 21%) or two (< 1% vs. 1%) surgeries. These surgeries included functional endoscopic sinus surgery (mepolizumab, n = 11; placebo, n = 35) and nasal polypectomies (mepolizumab, n = 9; placebo, n = 14).

These data equated to crude annualized sinus surgery rates of 0.1 events per year for the mepolizumab group and 0.25 events per year for the placebo group.

Treatment with mepolizumab vs. placebo reduced the risk for sinus surgery regardless of whether the time since patients’ last sinus surgery was less than 3 years (HR = 0.28; 95% CI, 0.09-0.84) or 3 or years or longer (HR = 0.5; 95% CI, 0.26-0.98). Still, researchers noted that a numerically higher proportion of patients who had not had surgery within the last 3 years required surgery during the study period, regardless of which treatment they received.

When total endoscopic nasal polyp scores and VAS scores were analyzed, a greater proportion of the mepolizumab-treated patients experienced improvements of greater than one point compared with the placebo group, regardless of when their most recent sinus surgery before the study screening had occurred.

Patients in both groups who had sinus surgery during the study period had higher baseline blood eosinophil counts (430 cells/µL; standard deviation [SD], 0.78) than those who did not have surgery (390 cells/µL; SD, 0.76). In general, patients whose baseline blood eosinophil counts were 300 cells/µL or greater had a shorter time since their most recent sinus surgery than those who had lower blood eosinophil counts.

Overall, the researchers concluded that mepolizumab was more effective at improving nasal polyp symptoms and in reducing the proportion of patients requiring sinus surgery than placebo, even among patients who had not had surgery in several years.

Higher baseline blood eosinophil counts have previously been associated with greater efficacy in mepolizumab treatment, the researchers added, although they cautioned that the role of these counts in predicting nasal polyp recurrence and the need for surgery requires further investigation.