Eosinophilic inflammation can drive recurrent nasal polyps1,2

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Recurrent nasal polyps and eosinophilic inflammation

Up to 90% of nasal polyps have predominantly eosinophilic inflammation

*Based on studies that examined the presence of eosinophil leukocyte infiltration in nasal polyp biopsy tissue of patients in the US and Europe.1-4

Chart showing after surgery, nasal polyp recurrence was 3X more likely in patients with elevated eosinophils

†Based on a retrospective, single-center study to investigate the relationship between eosinophil density in nasal polyp tissue and recurrence in adults who underwent endoscopic sinus surgery for massive nasal polyposis (filled at least half of each nostril). Patients were categorized as higher density (>4 eosinophils/1000 μm2) or lower density (≤3 eosinophils/1000 μm2) by examining digital images taken at x400 magnification.2

NP=nasal polyp.

Red blood eosinophils to represent NUCALA as targeted therapy for 4 eosinophil-driven diseases

Elevated eosinophils in nasal polyps are associated with1-4:

  • Presence of INFLAMMATION
  • Greater likelihood of NASAL POLYP RECURRENCE after surgical removal

How NUCALA targets eosinophils

The MOA of NUCALA in CRSwNP has not been definitively established.

  • IL-5 binds to complex on EOS

    Interleukin-5 (IL-5) is the major cytokine responsible for eosinophil growth and survival. IL-5 binds to the IL-5 receptor complex expressed on the eosinophil surface. 

  • How IL-5 impacts EOS

    Downstream signaling by IL-5 promotes the growth and differentiation, recruitment, activation, and survival of eosinophils. 

  • NUCALA targets IL-5

    NUCALA, a humanized monoclonal antibody, targets IL-5 and binds to it. NUCALA blocks IL-5 binding to the alpha chain of the IL-5 receptor complex. 

  • How NUCALA reduces EOS

    NUCALA inhibits IL-5 signaling, reducing the production and survival of eosinophils.

Red blood eosinophils in white

Reduced blood eosinophil levels and maintained within normal‡ levels5,6

 

Reduced blood eosinophil levels chart Reduced blood eosinophil levels chart
Blood eosinophil level reduction with NUCALA graphic 80% reduction in blood eosinophil levels with NUCALA at Week 4, maintained at 84% at Week 52

in blood eosinophil levels with NUCALA at Week 4, maintained at 84% at Week 525,6

NUCALA ratio to baseline: Week 4, 0.20; Week 52, 0.16.

All results are descriptive. The clinical significance of these pharmacodynamics data is unknown.

Mean blood eosinophil levels (NUCALA, placebo)
• Baseline: 390 cells/µL, 400 cells/µL
• At Week 52: 60 cells/µL, 360 cells/µL

All results are descriptive. The clinical significance of these pharmacodynamics data is unknown.

‡Mean normal blood eosinophil levels in a general population of subjects without confounding factors have been reported as 100 cells/µL (range: 34-257) and 107 cells/µL (5th, 95th percentile: 30, 395); levels vary based on age, sex, environmental exposures, and comorbid conditions.7,8

SYNAPSE study design

What role do blood eosinophils play?

Eosinophils play a role in maintaining health, including regulation of the immune system, regenerating and repairing tissue, and protecting the host (eg, defending the body against parasitic infection).9 In CRSwNP, however, elevated eosinophils are a key driver of CRSwNP pathophysiology, including inflammation.2,3

Eosinophils cells diagram
Patient profiles with nasal polyps Patient profiles with nasal polyps

YOU MAY KNOW PATIENTS LIKE MICHAEL IN YOUR PRACTICE

GO TO PATIENT PROFILES
Nasal polyps with comorbid AERD patient profile Nasal polyps with comorbid AERD patient profile

EXPLORE NUCALA DATA IN CRSwNP PATIENTS

VIEW NUCALA EFFICACY

References

  1. Lou H, Meng Y, Piao Y, et al. Cellular phenotyping of chronic rhinosinusitis with nasal polyps. Rhinology. 2016;54(2):150-159.
  2. Tosun F, Arslan HH, Karslioglu Y, Deveci MS, Durmaz A. Relationship between postoperative recurrence rate and eosinophil density of nasal polyps. Ann Otol Rhinol Laryngol. 2010;119(7):455-459.
  3. Fujieda S, Imoto Y, Kato Y, et al. Eosinophilic chronic rhinosinusitis. Allergol Int. 2019;68(4):403-412.
  4. Stoop AE, van der Heijden HA, Biewenga J, van der Baan S. Eosinophils in nasal polyps and nasal mucosa: an immunohistochemical study. J Allergy Clin Immunol. 1993;91(2):616-622.
  5. Han JK, Bachert C, Fokkens W, et al. Mepolizumab for chronic rhinosinusitis with nasal polyps (SYNAPSE): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Respir Med. 2021;9(10):1141-1153.
  6. Data on file, GSK.
  7. Felarca AB, Lowell FC. The total eosinophil count in a nonatopic population. J Allergy. 1967;40(1):16-20.
  8. Hartl S, Breyer MK, Burghuber OC, et al. Blood eosinophil count in the general population: typical values and potential confounders. Eur Respir J. 2020;55(5):1901874.
  9. Weller PF, Spencer LA. Functions of tissue-resident eosinophils. Nat Rev Immunol. 2017;17(12):746-760.