Mepolizumab add-on shrinks nasal polyp, relieves symptoms in CRSwNP

Add-on treatment with the anti-IL-5 biologic mepolizumab significantly reduces nasal polyp size and nasal obstruction, along with less need for surgery and systemic corticosteroid use compared with standard care alone in patients with recurrent, refractory, and severe chronic rhinosinusitis with nasal polyps (CRSwNP), the SYNAPSE study shows.

“The standard of care for patients with CRSwNP includes intranasal corticosteroids, short courses of oral corticosteroids, and nasal surgery,” wrote Drs Guy Brusselle and Philippe Gevaert from Ghent University Hospital and Ghent University in Ghent, Belgium, respectively, in a linked commentary. [Lancet Respir Med 2021;9:1081-1082]

“However, nasal surgery might induce mucosal damage and scarring, and is associated with high recurrence rates,” they continued, while noting that long-term systemic steroid use is associated with adverse effects. “Therefore, there is a high medical need for novel therapies that improve symptoms and quality of life of patients with CRSwNP and reduce the need for oral corticosteroids and surgery.”

The large, multinational, double-blind, phase III study enrolled 414 patients (mean age 49 years) with recurrent, refractory, severe CRSwNP, despite continuous medical treatment and at least one nasal surgery within the previous 10 years, who were eligible to undergo a repeat nasal surgery. They were randomized 1:1 to receive subcutaneous mepolizumab 100 mg or placebo Q4W for 52 weeks, in addition to standard care. [Lancet Respir Med 2021;9:1141-1153]

“The patient population in SYNAPSE reflects a population who are candidates for biological treatment,” the researchers explained. All patients had prior nasal surgery in the past decade, which implies that their condition was refractory to both medical and surgical treatment.

At week 52, mepolizumab significantly shrank nasal polyp size from baseline, as reflected in improvement in total endoscopic nasal polyp score, compared with placebo (adjusted difference in medians, –0.73; p<0.0001).  

The coprimary endpoint of nasal obstruction as assessed by visual analogue score (VAS) score was also significantly improved in the mepolizumab vs the placebo arm (adjusted difference in medians, –3.14; p<0.0001).

In addition, patients treated with mepolizumab were less likely to require nasal surgery (9 percent vs 23 percent; hazard ratio, 0.43; p=0.0032) and systemic corticosteroids (25 percent vs 37 percent; odds ratio, 0.58; p=0.020) by week 52.

Similarly, other secondary endpoints such as loss of smell (adjusted difference in medians of VAS symptom score, –0.37; p=0.020) and disease-specific HRQoL* indicated by the SNOT-22** total score were significantly improved (adjusted difference in medians, –16.49; p=0.0032) in the mepolizumab group compared with the placebo group at week 52.

“Treatment effects were seen at 4 weeks after the first dose and were sustained until week 52,” the researchers pointed out.

There were no new safety signals observed with mepolizumab add-on. Adverse events (AEs) that were considered to be treatment-related occurred 15 percent of patients in the mepolizumab group compared with 9 percent in the placebo group. On-treatment serious adverse events were reported in 6 percent of patients in each treatment group, and none were considered to be treatment-related among those receiving mepolizumab.

“These findings suggest that mepolizumab provides an effective add-on treatment option to standard of care in this population,” the researchers stated.

Role of biomarkers?

Although the difference in outcomes was statistically significant between treatment groups, Brusselle and Gevaert questioned whether this equates to clinical relevance. Given that ≥1-point improvement in nasal polyp score was achieved in only half of the patients treated with mepolizumab, they raised that there is a “need for predictors of response to mepolizumab” in these patients.

“Subgroup analyses of the SYNAPSE study suggest that the efficacy of mepolizumab is higher with higher baseline blood eosinophil count,” noted Brusselle and Gevaert.

“A thorough investigation of previously resected nasal polyp tissue to check for eosinophilic inflammation and IL-5 amounts might help to target mepolizumab treatment to those patients who will benefit the most,” they suggested.

*HRQoL: health-related quality of life

**SNOT-22: The 22-item Sino-Nasal Outcome Test