Asthma

Targeting Type 2 inflammation: treating the common denominator


Type 2 inflammation is emerging as a unifying feature of multiple inflammatory diseases, including asthma. As part of the ADVENT Advances in Type 2 Inflammatory Diseases medical education series run by Sanofi Genzyme, allergy specialist and immunologist Professor Connie Katelaris talks about how Type 2 inflammatory pathway-focused treatments have major implications in the management of severe asthma. This is the third feature of three, based on the ADVENT interactive clinical tutorials. The first and second features can be viewed here and here.

Type 2 inflammation – the common denominator

Type 2 inflammation is an immune response involving the innate and adaptive arms of the immune system. Its main function is to promote barrier immunity at mucosal surfaces and eliminate parasites.1 However, the type 2 inflammatory cascade is now known to affect a range of organs.1–3 Components of the type 2 inflammatory cascade that are common to these conditions are the cytokines IL-4, IL-5 and IL-13. However, inhibition of one of these components alone may not be enough to relieve symptoms, as they have overlapping functions.1,4–7

We know now that type 2 inflammation is  the common denominator in multiple inflammatory diseases. The availability of pathway-focused treatments especially treatments that inhibit more than one driver of type 2 inflammation (IgE, IL-4, IL5, IL13)- has major implications for the management of atopic disorders.”

Professor Connie Katelaris, MBBS, PhD, FRACP

Understanding the role of IL-4, IL-5, and IL-13 in type 2 inflammatory asthma is of particular importance as a number of therapies have become available in recent years.8-11

Targeting type 2 inflammation: a new treatment paradigm

Box 1. Biologics registered in Australia to treat severe asthma

Year registered in Australia Name of medicine Target Indication
2005 omalizumab IgE Allergic asthma
2015 mepolizumab Anti-IL5 Eosinophilic asthma
2018 benralizumab Anti-IL5R Eosinophilic asthma
2019 dupilumab IL-4 receptor alpha (targets both IL-4 and IL-13) Asthma with type 2 inflammation (elevated eosinophils or elevated FeNO). Also indicated for maintenance therapy for oral corticosteroid dependent asthma

 

 

How many people have type 2 Inflammatory severe asthma?

We now know that type 2 inflammatory asthma is common. The latest GINA guidelines recognise the significance of type 2 inflammatory asthma.  Approximately 50–70% of severe asthma patients have type 2 inflammation.5,12,13

Precision medicine:  a proposed new treatment approach to manage severe asthma

Now that the heterogenous nature of severe asthma Is understood, a ‘one size fits all’ approach is no longer considered appropriate to manage this condition. Instead, precision medicine has been proposed for the management of these patients.14

“Precision medicine allows a particular medicine to be used for a particular phenotype to provide a better clinical benefit and to avoid side effects.”

Professor Phil Bardin. FRACP, PhD

In conclusion: which biologic for which patient?

While no head to head studies comparing biologics exist, clinicians will need to decide which biologic to use based on the patient’s characteristics and available clinical data.

A few factors influence the choice of biologic therapy, such as:

  • The presence of co-morbidities (i.e atopic dermatitis or nasal polyps), where choosing a biologic that targets more than one element of the pathway is likely to result in a beneficial effect on co-morbid conditions.
  • For patients who are dependent on oral steroids, using a biologic that enables a reduction in OCS medication is important.
  • The opportunity to use precision medicine targeted to the patient’s specific characteristics.
  • Where patients have uncontrolled severe asthma, a biologic which targets more than one element of the pathway may lead to an improvement in symptoms.

“Clinicians may consider what matters most to patients, for example, a significant improvement in lung function makes a big difference to patients and their perception of their symptoms”

Professor Phil Bardin. FRACP, PhD

For more details on each biologic, please view the ADVENT program tutorial here

 Box 2: Eligibility criteria and predictors of good response for various biologic therapies.

Some of the following questions may be considered when choosing a biologic:

  • Does the patient have co-morbid asthma?
  • Does the patient have childhood asthma or adult onset asthma?
  • Is the patient currently depend on oral corticosteroids?
  • Does the patient have high FENO or high eosinophils?
Eligibility criteria Predictors of good response
Anti-IgE for severe allergic asthma (omalizumab)
  • Sensitisation on skin prick testing or specific IgE
  • Total serum IgE and weight within dosage range
  • Exacerbations in last year
  • Blood eosinophils ≥260/μl ++
  • FeNO≥20 ppb +
  • Allergen-driven symptoms +
  • Childhood-onset asthma +
Anti-IL-5/5R for severe eosinophilic asthma (mepolizumab, benralizumab)
  • Exacerbations in last year
  • Blood eosinophils ≥300/µL
  • Higher blood eosinophils +++
  • More exacerbations in previous year +++
  • Adult-onset asthma ++
  • Nasal polyposis ++
Anti-IL-4R (dual inhibition of IL-4 and IL-13 signalling) for severe eosinophilic/type 2 asthma or OCS-dependent severe asthma

 (dupilumab)

  • Exacerbations in last year
  • Blood eosinophils ≥150/µL or FeNO ≥25 ppb
  • OR need for maintenance oral corticosteroids
  • Higher blood eosinophils +++
  • Higher FeNO+++

 

Anti-IL4/R may also be used to treat

  • Moderate/severe atopic dermatitis
  • Nasal polyposis*

*Not registered In Australia for nasal polyposis

For further information about ADVENT program click here.

Please click here for a copy of the currently approved Dupixent product information in Australia.

References:

  1. Gandhi NA, et al. Nat Rev Drug Discov. 2016;15:35-50.
  2. Carr S, et al. Allergy Asthma Clin Immunol. 2011;7(suppl1):S8.
  3. Steinke JW, Wilson JM. J Asthma Allergy. 2016;9:37-43.
  4. Fahy JV. Nat Rev Immunol. 2015;15:57-65.
  5. Global Initiative for Asthma (GINA). Difficult-to-treat & severe asthma in adolescent and adult patients: diagnosis and management. A GINA pocket guide for health professionals, V2.0 April 2019. https://ginasthma.org/severeasthma . Accessed November, 2020.
  6. Shinkai A, et al. J Immunol. 1999;163:1602-1610.
  7. Borchers MT, et al. J Leukoc Biol. 2002;71:1033-1041.
  8. Australian Product Information Xolair (omalizumab), January 2020.
  9. Australian Product Information Nucala (mepolizumab) December 2019.
  10. Australian Product Information Fasenra (benralizumab) January 2020.
  11. Australian Product Information Dupixent (dupilumab) October 2020.
  12. Seys SF, et al. Respir Res. 2017;18:39.
  13. Peters MC, et al. J Allergy Clin Immunol. 2014;133:388-394.
  14. Papaioannou AI, et al. Respir Med. 2018;142:15-22.

Sanofi-aventis Australia Pty ltd trading as Sanofi Genzyme, ABN 31 008 558 807. Talavera Corporate Centre, Building D, 12-24 Talavera Rd, Macquarie Park, NSW 2113. www.sanofi.com.au MAT-AU-2002409 First Issued November 2020.

Already a member?

Login to keep reading.

OR
Email me a login link
logo

© 2022 the limbic