IL-5 antagonist showed efficacy in chronic rhinosinusitis with nasal polyps

Results from the phase 3 SYNAPSE trial showed that mepolizumab significantly improved nasal polyp score and nasal obstruction. Patients treated with the IL-5 antagonist also had less need for surgery compared with placebo [1].

Chronic rhinosinusitis with nasal polyps (CRSwNP) involves chronic inflammation of the rhinosinal cavities, mostly of type 2 signature, combined with growth of polyps in the nasal airway [2,3]. CRSwNP, entailing symptoms like congestion, facial pain, and hyposmia, also negatively impacts quality of life [2,4,5]. The current standard of care relies on intranasal corticosteroids (CS) with short courses of systemic CS if needed and nasal surgery in case of CS failure [3]. “Unfortunately, the benefit of this is often short-lived, recurrences are common, and many patients suffer from ongoing inadequate control of their disease and symptoms,” said Dr Claire Hopkins (Guy’s and St Thomas Hospital and King’s College London, UK).

Previous investigations with 750 mg mepolizumab IV detected an improvement of CRSwNP with this IL-5 antibody [6,7]. The current phase 3, randomised, placebo-controlled SYNAPSE trial evaluated subcutaneous mepolizumab at a dose of 100 mg every 4 weeks over 52 weeks as add-on to standard of care (i.e. mometasone furoate plus saline nasal douching) for adult patients with CRSwNP. The 407 participants had at least 1 previous surgery and were deemed to need further surgery. The mean age was 49 years, mean duration of nasal polyposis was 11.45 years, and 38% in the placebo versus 33% in the mepolizumab group were female. Rescue treatment with oral prednisolone antibiotics or surgery was permitted. The co-primary endpoints were defined as change from baseline in endoscopic nasal polyp score at week 52 in addition to change from baseline in nasal obstruction in visual analogue scale (VAS) score during weeks 49-52. The key secondary endpoint consisted of time-to-first actual nasal surgery up to week 52.

“More than 50% of patients achieved significant reduction in nasal polyp score with some patient achieving a greater than 5-point score reduction,” Dr Hopkins revealed. The median difference in total endoscopic nasal polyp score was -0.73 (95% CI -1.11 to -0.34; P<0.001) (see Figure). In the nasal obstruction VAS score, 44% of participants achieved a reduction of >5 points in the mepolizumab group compared with 23% in the placebo group (see Figure). With reference to surgery, only 9% of the patients with add-on mepolizumab underwent surgery versus 23% receiving placebo.

Figure: Co-primary endpoints of the SYNAPSE trial [1]



NP, nasal polyps; VAS, visual analogue scale.

 

In terms of safety, on-treatment adverse events were reported by 82% of the mepolizumab participants and 84% by the participants in the placebo group. Serious adverse events were noted in <1% on placebo and 6% on mepolizumab, but these were rated as unelated to study treatment.

“In conclusion, we demonstrated in the SYNAPSE study that add-on mepolizumab is an effective and safe treatment for adults with chronic rhinosinusitis with nasal polyps,” Dr Hopkins concluded her talk.

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1. 
   
   1. Hopkins C. Add-on mepolizumab for chronic rhinosinusitis with nasal polyps: SYNAPSE study. LBA 4616, ERS International Virtual Congress 2020, 7-9 Sept.
   2. Stevens WW, et al. J Allergy Clin Immunol Pract. 2016;4:565-572.
   3. Fokkens WJ, et al. Allergy. 2019;74:2312-2319.
   4. Schleimer RP, et al. Annu Rev Pathol. 2017;12:331-357.
   5. Kim J, et al. Ther Clin Risk Manag. 2020;16:31-37.
   6. Bachert C, et al. J Allergy Clin Immunol. 2017;140:1024-1031.
   7. Gevaert P, et al. J Allergy Clin Immunol. 2011;128:989-995.

 



Posted on 29 October 20203 November 2020