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Look beyond the symptoms to identify and manage Patients with Type 2 Inflammation

Identify > Target > Treat

Identify

80% of Patients with CRSwNP Have Type 2 Inflammation1,a

Look for other signs of type 2 inflammation in patients with CRSwNP2,3

History of asthma and/or other Type 2 comorbidities (allergic rhinitis, NSAID-ERD, etc.) 

and/or 

Elevated EOS and/or elevated total IgE levels 

and/or 

Need for systemic corticosteroids

Consider Type 2 inflammation as the key underlying cause of CRSwNP4,5

~3x    more revision surgeries in CRSwNP patients with coexisting asthma6

50%    of CRSwNP patients have coexisting asthma7

 In Western countries.

Abbreviations

EOS, eosinophils; NSAID-ERD, nonsteroidal anti-inflammatory drug-exacerbated–respiratory disease.

Target

Target key and central drivers of Type 2 Inflammation

IL-4 and IL-13 are key and central drivers of Type 2 inflammation in CRSwNP4,5

Tissue remodeling, polyp formation, and symptoms, including nasal obstruction, nasal discharge, and loss of smell

Abbreviation

ILC2, type 2 innate lymphoid cells.

Target Key and Central Drivers of Type 2 Inflammation

IL-4, IL-13, and IL-5 have distinct and overlapping roles with a broad impact on CRSwNP symptoms4,5

  IL-14 IL-3 IL-5
Th2 cell differentiation    
B-cell class switching and IgE production  
Epithelial barrier dysfunction, goblet cell hyperplasia, and mucus hypersecretion  
Tissue remodeling and polyp formation  
Eosinophilic recruitment and trafficking to nasal mucosa and polyp tissue
Eosinophil differentiation in bone marrow    

Current Standard-of-Care does not specifically target chronic underlying Type 2 Inflammation

Systemic corticosteroids

  • Treat inflammation broadly3
  • Frequent use leads to risk of short-term and long-term adverse effects8

Targeting Type 2 inflammation can help you achieve treatment goals.

Sino-nasal surgery

  • Removes nasal obtrsuction, but does not aedssd r underlying chronic type 2 inflammation, which may lead to polyp recurrence and refractory symptoms2,3
  • Many patients don't ecrover their sense of s m ell after surgery9
  • Revision sugrery is saosciated with an ienacsred risk of surgical complications10,11

Many patients with Type 2 inflammation experienced Polyp recurrence within 5 years of Sino-nasal surgery12

Type 2 inflammation is the underlying cause of CRSwNP in 80% of patients1

Treat

Consider a Biologic that targets Type 2 Inflammation in patients with uncontrolled CRSwNP

  • Type 2 inflammation is the underlying cause of CRSwNP in 80% of patients1

  • IL-4 and IL-13 are key and central type 2 cytokines in the pathophysiology of CRSwNP
    • IL-4, IL-13, and IL-5 are key type 2 cytokines4,5
  • CRSwNP and asthma frequently coexist, adding substantially to the overall disease burden and limiting the effectiveness of surgery and systemic steroids1-3,13-16
  • Guidelines recommend use of biologics in CRSwNP patients to address type 2 inflammation2,3

Guidelines

Guidelines Recommend Use of Biologics in CRSwNP Patients to Address Type 2 Inflammation

EPOS and EUFOREA recommend biological treatments for patients with bilateral polyps who have had prior ESS if they meet at least 3 of the 5 following criteria2,3:

  • Evidence of Type 2 Inflammationa
  • Need for systemic corticosteroids or contraindication to systemic steroids
  • Significantly impaired quality of life
  • Significant loss of smell
  • Diagnosis of comorbid asthma

In patients who have had no prior sinus surgery, 4 out of 5 criteria should be fulfilled2

a Tissue EOS ≥10/hpf, OR blood EOS ≥250, OR total IgE ≥100.0

Abbreviations

EPOS, European Position Paper on Rhinosinusitis and Nasal Polyps 2020; ESS, endoscopic sinus surgery; EUFOREA, European Forum for Research and Education in Allergy and Airway Diseases.

References

  1. Chaaban MR, Walsh EM, Woodworth BA. Epidemiology and differential diagnosis of nasal polyps. Am J Rhinol Allergy. 2013;27(6):473-478. doi:10.2500/ajra.2013.27.3981
  2. Fokkens WJ, Lund V, Bachert C, et al. EUFOREA consensus on biologics for CRSwNP with or without asthma. Allergy. 2019;74:2312-2319. doi:10.1111/all.13875 
  3. Fokkens WJ, Lund VJ, Hopkins C, et al. European position paper on rhinosinusitis and nasal polyps 2020. Rhinology. 2020;58(suppl S29):1-464. doi:10.4193/Rhin20.600
  4. Gandhi NA, Bennett BL, Graham NMH, Pirozzi G, Stahl N, Yancopoulos GD. Targeting key proximal drivers of type 2 inflammation in disease. Nat Rev Drug Discov. 2016;15(1):35-50. doi:10.1038/nrd4624
  5. Schleimer RP. Immunopathogenesis of chronic rhinosinusitis and nasal polyposis. Annu Rev Pathol. 2017;12:331-357. doi:10.1146/annurev-pathol-052016-100401
  6. Loftus CA, Soler ZM, Koochakzadeh S, et al. Revision surgery rates in chronic rhinosinusitis with nasal polyps: meta-analysis of risk factors. Int Forum Allergy Rhinol. 2020;10(2):199-207. doi:10.1002/alr.22487
  7. Khan A, Vandeplas G, Huynh TMT, et al. The Global Allergy and Asthma European Network (GALEN) rhinosinusitis cohort: a large European cross-sectional study of chronic rhinosinusitis patients with and without nasal polyps. Rhinology. 2019;57(1):32-42. doi:10.4193/Rhin17.255
  8. Head K, Chong LY, Hopkins C, et al. Short-course oral steroids alone for chronic rhinosinusitis (review). Cochrane Database Syst Rev. 2016;4:CDOl 1991. doi:10.1002/14651858.CDOl 1991.pub2
  9. DeConde AS, Mace JC, Alt JA, Schlosser RJ, Smith TL, Soler ZM. Comparative effectiveness of medical and surgical therapy on olfaction in chronic rhinosinusitis: a prospective, multi-institutional study. Int Forum Allergy Rhinol. 2014;4(9):725-733. doi:10.1002/alr.21350
  10. Hosemann W, Draf C. Danger points, complications and medico-legal aspects in endoscopic sinus surgery. GMS Curr Top Otorhinolaryngol Head Neck Surg. Published online December 13, 2016. doi:0.3205/cto000098
  11. Stankiewicz JA, Lal D, Connor M, Welch K. Complications in endoscopic sinus surgery for chronic rhinosinusitis: a 25-year experience. Laryngoscope. 2011;121(12):2684-2701. doi:10.1002/lary.21446
  12. Bassiouni A, Wormald PJ. Role of frontal sinus surgery in nasal polyp recurrence. Laryngoscope. 2013;123(1):36-41. doi:10.1002/lary.23610
  13. DeConde AS, Mace JC, Levy JM, Rudmik L, Alt JA, Smith TL. Prevalence of polyp recurrence after endoscopic sinus surgery for chronic rhinosinusitis with nasal polyposis. Laryngoscope. 2017;127(3):550-555. doi:10.1002/lary.26391
  14. Abdalla S, Alreefy H, Hopkins C. Prevalence of sinonasal outcome test (SNOT-22) symptoms in patients undergoing surgery for chronic rhinosinusitis in the England and Wales National prospective audit. Clin Otolaryngol. 2012;37(4):276-282. doi:10.1111/j.1749-4486.2012.02527.x
  15. Stevens WW, Peters AT, Hirsch AG, et al. Clinical characteristics of patients with chronic rhinosinusitis with nasal polyps, asthma, and aspirin-exacerbated respiratory disease. J Allergy Clin Immunol Pract. 2017;5(4):1061-1070.e3. doi:10.1016/j.jaip.2016.12.027
  16. Langdon C, Mullol J. Nasal polyps in patients with asthma: prevalence, impact, and management challenges. J Asthma Allergy. 2016;9:45-53. doi:10.2147/JAA.S86251
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