Product menu

A close-up photograph of a woman with dark hair, gazing into the distance with a concerned or pensive expression. Her hand is gently touching her face, and her eyebrows are slightly furrowed. The background is soft and blurred with a muted blue tone. There are thin, rectangular outlines over parts of the image.

Severe eosinophilic asthma and co-morbid chronic rhinosinusitis with nasal polyps

Understanding these related and often co-existing inflammatory airway conditions.

The image above is a fictional patient for illustrative purposes.

Explore these frequently co-existing conditions

What is severe asthma?

Understand the condition and its subtypes, including severe eosinophilic asthma (SEA).

Read more

What is chronic rhinosinusitis (CRS)?

Learn about chronic rhinosinusitis and the impact of nasal polyps.

Read more

The shared pathology of SEA and CRSwNP

Appreciate the important role of interleukin (IL)-5 in both SEA and chronic rhinosinusitis with nasal polyps (CRSwNP).

Read more

The impact of severe asthma, CRSwNP, and co-morbid disease

Understand the challenges of treating both SEA and CRSwNP.

Read more

Understanding the role of biologics

Consider the role of biologic therapies to address the underlying disease pathology in appropriate patients with co-morbid disease.

Read more

What is severe asthma?

Severe asthma is asthma that requires treatment with high-dose inhaled corticosteroids and a second controller (and/or systemic corticosteroids) to prevent it from becoming ‘uncontrolled’, or which remains ‘uncontrolled’ despite this therapy.1

Of the estimated 5.4 million people living with asthma in the UK, severe asthma affects approximately 200,000 people.2

Severe asthma can be categorised as either:3

  • Type-2 inflammation: Including allergic and eosinophilic asthma, which is present in around 54% of people with severe asthma in the UK (n=1,202/2,225 from analysis of patients in the UK Severe Asthma Registry),4 and 55–70% of people with severe asthma worldwide5
  • Non-type 2 inflammation: Non-eosinophilic asthma

Severe eosinophilic asthma (SEA) is a distinct phenotype occurring in 45% of patients with severe asthma (n=992/2,225 from analysis of patients in the UK Severe Asthma Registry).4,6

SEA is a difficult condition to control and can include:7

An infographic explaining that severe eosinophilic asthma is a difficult to control condition.

Airway inflammation

An infographic explaining that severe eosinophilic asthma is a difficult to control condition.

Increased eosinophil levels

An infographic explaining that severe eosinophilic asthma is a difficult to control condition.

Poor asthma control

An infographic explaining that severe eosinophilic asthma is a difficult to control condition.

Increased rates of exacerbations

What is chronic rhinosinusitis (CRS)?

CRS is a complex inflammatory condition involving the paranasal sinuses and linings of the nasal passages that lasts 12 weeks or longer.8,9

CRS is one of the most common medical conditions worldwide with 10-11% of UK adults affected (self-reported CRS by EPOS criteria in adult responders to a randomised postal questionnaire, London (n=183/1,825); Southampton (n=133/1,191))10 and 5-12% of the adult population globally.11

CRS can be categorised into two clinical subgroups:8

  • CRS with nasal polyps (CRSwNP), accounting for ~25–30% of patients12
  • CRS without nasal polyps, accounting for 70–75% of patients12

CRSwNP has a severe impact on quality of life.13

Those living with the condition experience nasal symptoms such as obstruction, congestion, discharge, pain, and pressure, as well as broader problems including impacts on sleep, cognitive function, fatigue, depression, and well-being.13

CRSwNP is a common co-morbidity with severe asthma.14,15 Around 40% of severe asthmatics suffer from CRSwNP (n=321/822 from an international prospective cohort study).16,17

Type 2 inflammation accounts for approximately 85% of CRSwNP cases in Europe.8

Indicators associated with CRSwNP

An infographic showing the common indicators of nasal polyps with type 2 cytokines.

Patients with CRSwNP or severe asthma should be assessed for co-existing disease

The shared pathology of SEA and CRSwNP

Type 2 inflammation accounts for 55–70% of severe asthma5 and approximately 85% of CRSwNP.8

Type 2 inflammation is characterised by the presence of eosinophilic airway inflammation associated with type 2‐related cytokines, such as interleukin (IL)-4, IL-5, and/or IL-13, and circulating and/or local immunoglobulin E (IgE).8,19

IL-5 can be triggered by varied environmental stimuli and is produced by multiple sources in the cell, including T helper-2 lymphocytes, group 2 innate lymphoid cells, natural killer T cells, mast cells, and eosinophils themselves.20,21

As IL-5 is responsible for the growth, activity, and survival of eosinophils, elevated eosinophil levels are indicative of an increased IL-5 systemic drive in severe asthma and CRSwNP.20,22

Patients with CRSwNP and co-morbid asthma have higher blood eosinophil levels versus patients with CRSwNP alone.22

Patients with CRSwNP and co-morbid asthma have higher blood eosinophil levels versus CRSwNP alone and control, indicative of an increased IL-5 systemic drive22

Scatter plot showing blood eosinophil percentages for three groups: Control, CRSwNP-alone, and CRSwNP + asthma, with statistical details and a study population summary.

Reproduced from: Wang M, et al. Clin Transl Allergy. 2020;10:26. Figure 1a.

The impact of severe asthma, CRSwNP, and co-morbid disease

Compared to those without co-morbid disease, people with co-morbid CRSwNP and severe asthma experience:

  • Greater disease severity15
  • Higher exacerbation rates23
  • A heavier reliance on oral corticosteroids23
  • Higher likelihood of undergoing repeat sinus surgery which can result in loss of smell25

Patients with co-morbid CRSwNP also have a high risk of experiencing polyp recurrence and repeated surgeries.26–28 In a UK retrospective cohort study, 23.5% (n=7,793/33,107) of patients with CRSwNP required ≥1 surgeries with a follow-up median of 5.3 years. Of patients with severe asthma and CRSwNP, 32.8% (n=326/993) required more than one surgery.24

Medical management of CRSwNP attempts to control the underlying inflammation that drives the growth of polyp tissue and symptoms such as nasal blockage and loss of smell.29 Treatment for CRSwNP typically involves saline nasal irrigation, intranasal corticosteroids, and OCS.12

Increased short-term OCS usage is associated with:30

Infographic showing relative risk increases for different complications associated with oral corticosteroid use in users vs. non-users

Fracture

RR: 1.87; 95% CI: 1.69–2.07; p<0.001

n=1,657 of 327,452 in users vs n=4,735 of 1,221,493 in non-users

Infographic showing relative risk increases for different complications associated with oral corticosteroid use in users vs. non-users

Venous thromboembolism

RR: 3.33; 95% CI: 2.78–3.99; p<0.001

n=472 of 327,452 in users vs n=1,054 of 1,221,493 in non-users

Infographic showing relative risk increases for different complications associated with oral corticosteroid use in users vs. non-users

Sepsis

RR: 5.30; 95% CI: 3.80–7.41; p<0.001

n=170 of 327,452 in users vs n=293 of 1,221,493 in non-users

Patients treated with short-term OCS (<30 days) had higher rates of all three adverse events assessed vs non-users of OCS.*,30

*In a retrospective cohort study of privately insured adults (aged 18–64 years) in the US (N=1,548,945), evaluating the frequency of prescriptions for short-term OCS and associated adverse events, 21% of patients (n=327,452) received ≥1 outpatient prescription for short-term OCS during the 3-year study period. Short-term OCS was defined as a course of OCS of less than 30 days’ duration. Overall, the median prednisone equivalent daily dose was 20 mg/day (interquartile range [IQR], 17.5–36.8 mg/day) with 23.4% (n=76,701/327,452) receiving ≥40 mg/day.30

In cases of failing medical treatment, sinus surgery is the treatment option for those with CRSwNP.31

Surgery can achieve durable symptomatic benefits, but is associated with polyp recurrence.26,32

Up to 40% of patients with CRSwNP experience polyp recurrence within 18 months of surgery and are retreated with nasal OCS and repeated surgery.26,32

Have you considered the use of biologic therapy for your patients with SEA and co-morbid CRSwNP?

Understanding the role of biologics

The use of biologics in severe asthma and CRSwNP offers a means of targeting underlying disease pathology.
Nucala (mepolizumab), is a biologic therapy that blocks IL-5 a dominant cytokine linked to T2 inflammation.33,34

Nucala improves CRSwNP symptoms and delivers asthma control* in SEA patients with co-morbid CRSwNP.35,36
*measured by change from baseline in ACQ-5 score.

Post-hoc analysis of modified intention-to-treat (mITT) population (aged 12 +) in MUSCA.35 MUSCA primary endpoint, change in SGRQ total score from baseline at week 24, was met.37 LS mean change (SE) from baseline in SNOT-22 score of NP patients at week 24 (n=78) Nucala: -13.7 (2.6) n=44, (greater than MCID of -8.9 points); (n=34) placebo: -1.9 (3.0). Treatment difference of −11.8 (95% CI, −19.8 to −3.9).35,33

REALITI-A post hoc analysis at 2-years.2 REALITI-A primary endpoint, rate of clinically significant exacerbations 12-months post-exposure, was met.38 ACQ-5 LS mean score at 24 months with CRSwNP at enrollment, Nucala: 0.98 (n=84) vs. Baseline: 2.72 (n=307). Statistical significance not calculated.36

Nucala is the only anti-IL-5 licensed for both severe eosinophilic asthma and severe CRSwNP.39-41

Nucala is not reimbursed for CRSwNP in the UK. Severe eosinophilic asthma: Nucala is indicated as an add-on treatment for severe refractory eosinophilic asthma in adults, adolescents and children aged 6 years and older. Adults and adolescents aged 12 years and over: Recommended dose is 100 mg administered subcutaneously once every 4 weeks. Children aged 6 to 11 years old: Recommended dose is 40 mg administered subcutaneously once every 4 weeks.39 CRSwNP: Nucala is indicated as an add-on therapy with intranasal corticosteroids for the treatment of adult patients with severe CRSwNP for whom therapy with systemic corticosteroids and/or surgery do not provide adequate disease control. The recommended dose for adults is 100mg administered subcutaneously every four weeks. Nucala is intended for long-term treatment. Consideration can be given to alternative treatments in patients who have shown no response after 24 weeks of treatment for CRSwNP.39

The presence of co-morbid SEA with CRSwNP offers a route to biologic therapy as an add-on therapy with intranasal corticosteroids.

Find out more about Nucala

Explore Nucala Efficacy Data

Explore Nucala Safety Data

NUCALA is indicated as an add-on treatment:
For severe refractory eosinophilic asthma in adults, adolescents and children aged 6 years and older.39
With intranasal corticosteroids for the treatment of adult patients with severe CRSwNP for whom therapy with systemic corticosteroids and/or surgery do not provide adequate disease control.39

NUCALA is not reimbursed for CRSwNP in the UK.

Abbreviations:

AERD, aspirin-exacerbated respiratory disease; CI, confidence interval; CRS, chronic rhinosinusitis; CRSwNP, CRS with nasal polyps; hpf, high-power field; IgE, immunoglobulin E; IL, interleukin; IQR, interquartile range; OCS, oral corticosteroids; QoL, quality of life; RR, rate ratio; SEA, severe eosinophilic asthma; SNOT-22, Sino-Nasal Outcome Test of 22 questions.

References:

  1. Chung KF, et al. Eur Respir J. 2014;43:343–373.
  2. Asthma UK. Slipping through the net: The reality facing patients with difficult and severe asthma. Available at: https://www.asthmaandlung.org.uk/sites/default/files/2023-03/auk-severe-asthma-gh-final.pdf. Accessed: March 2025. This site is not owned or controlled by GSK.
  3. American Lung Association. Severe Asthma. Available at: https://www.lung.org/lung-health-diseases/lung-disease-lookup/asthma/learn-about-asthma/types/severe-asthma. Accessed March 2025. This site is not owned or controlled by GSK.
  4. Jackson DJ, et al. Thorax. 2021;76(3):220–227.
  5. Maspero J, et al. ERJ Open Res. 2022;8(3):00576–2021.
  6. Oppenheimer J, et al. Ann Allergy Asthma Immunol. 2022;129(2):169–180.
  7. Buhl R, et al. Eur Respir J. 2017;49(5):1700634.
  8. Bachert C, et al. J Allergy Clin Immunol. 2018;141:1543–1551.
  9. Fokkens WJ, et al. Rhinology. 2012;50(1):1–12.
  10. Hastan D, et al. Allergy. 2011;66:1216–1223.
  11. Fokkens WJ, et al. Rhinology. 2020;58 (Suppl S29):1–464.
  12. Stevens WW, et al. J Allergy Clin Immunol Pract. 2016;4(4):565–572.
  13. Mullol J, et al. J Allergy Clin Immunol: In Practice. 2022;10:1434–1453.
  14. Bakakos A, et al. J Pers Med. 2022;12(6):976.
  15. Bakakos P, et al. J Allergy Clin Immunol Glob. 2024;4(1):100343.
  16. Pilette C, et al. J Allergy Clin Immunol Pract. 2022:10(10):2646–2656.
  17. Liu MC, et al. J Allergy Clin Immunol Pract. 2023;11(12):3650–3661.
  18. Bachert C, et al. J Allergy Clin Immunol. 2020;145:725–739.
  19. Fokkens WJ, et al. Allergy. 2019;74:2312–2319.
  20. Pelaia C, et al. Front Physiol. 2019;10:154.
  21. Gevaert P, et al. Int Forum Allergy Rhinol. 2022;12(11):1413–1423.
  22. Wang M, et al. Clin Transl Allergy. 2020;10:26.
  23. Canonica GW, et al. Respir Med. 2020;166:10594.
  24. Benson VS, et al. Clin Otolaryngol. 2023;48:680–688.
  25. Fokkens WJ, et al. Allergy. 2023;78(3):812–821.
  26. Ren L, et al. World Allergy Organ J. 2019;12:100050.
  27. Langdon C and Mullol J. J Asthma Allergy. 2016;9:45–53.
  28. Schleimer RP. Annu Rev Pathol. 2017;12:331–357.
  29. Marglani O, et al. J Asthma Allergy. 2023;16:1055–1063.
  30. Waljee AK, et al. BMJ. 2017;357;1–8.
  31. Bachert C, et al. J Allergy Clin Immunol. 2015;136:1431–1440.
  32. DeConde A, et al. Laryngoscope. 2017;127:550–555.
  33. GSK Data on File REF-215426
  34. Bel EH; N Engl J Med. 2014;371;1189-1197
  35. Howarth P, et al. J Allergy Clin Immunol. 2020;145:1713-15
  36. Lee et al. 2023. Real-World Benefits of Mepolizumab in Patients with Severe Asthma and Comorbid Chronic Rhinosinusitis with Nasal Polyps (CRSwNP): Post Hoc Analysis of REALITI-A. Poster presented at AAAAI 2023; postern number 48
  37. Chupp GL; Lancet Respir Med; 2017; 5;390-400
  38. Harrison T, et al. Eur Respir J. 2020;56: 2000151
  39. Nucala (mepolizumab) Summary of Product Characteristics
  40. Fasenra (benralizumab) Summary of Product Characteristics
  41. Cinqaero (reslizumab) Summary of Product Characteristics.

Adverse events should be reported. Reporting forms and information can be found at yellowcard.mhra.gov.uk/. Adverse events should also be reported to GlaxoSmithKline on 0800 221 441 or via email UKSafety@gsk.com.

April 2025 | PM-GB-MPL-WCNT-240016 (V1.0)