Mepolizumab Useful in Refractory Eosinophilic Asthma, a Rare Subtype of Asthma

Eosinophilic inflammation, which may be a consequence of interleukin-5 action, is a characteristic feature of some forms of asthma.

A study examined the prednisone-sparing effect of mepolizumab (proposed trade name Bosatria), a monoclonal antibody against interleukin-5, in a rare subgroup of patients who have sputum eosinophilia and airway symptoms despite continued treatment with prednisone.


Eosinophil. Image source: Wikipedia.


Eosinophil. Image source: Wikipedia.

Eeosinophilic form of asthma represents less than 5% of cases of adult-onset asthma and is difficult to treat.


Crystal structure of human IL-5. Image source: Wikipedia, public domain.

Mepolizumab reduced the number of blood and sputum eosinophils and allowed prednisone sparing in patients who had asthma with sputum eosinophilia despite prednisone treatment.

Mepolizumab therapy reduced exacerbations by 43% and improved Asthma Quality of Life Questionnaire (AQLQ) scores in patients with refractory eosinophilic asthma.

Eosinophils may have a role as important effector cells in the pathogenesis of severe exacerbations of asthma in patients with eosinophilic asthma.


Cytokine targets for immunomodulators for allergic disorders.


Mediators from Eosinophils


Cytokine-based treatments of asthma and allergic diseases

What is the most potent chemokine (chemoattractant) for eosinophils?

(A) IL-5

(B) IL-8

(C) LTB4

(D) eotaxin

(E) IL-4

(F) IL-13

Answer: D.

Eosinophil chemotactic protein 2 (Eotaxin-2) is the most potent chemoattractant for eosinophils but IL-5 is the most specific stimulant of their production.

The receptors for IL-3, IL-5, and GM-CSF share a common β chain. All 3 cytokines stimulate the development of eosinophils.

References:
Mepolizumab and Exacerbations of Refractory Eosinophilic Asthma. NEJM, Volume 360:973-984 March 5, 2009 Number 10.
Mepolizumab for Prednisone-Dependent Asthma with Sputum Eosinophilia. NEJM, Volume 360:985-993 March 5, 2009 Number 10.
Immunomodulators for allergic respiratory disorders. Casale TB, Stokes JR. J Allergy Clin Immunol. 2008 Feb;121(2):288-96; quiz 297-8.
Eosinophils in Asthma — Closing the Loop or Opening the Door? NEJM, Volume 360:1026-1028 March 5, 2009 Number 10.
Mind Maps: Immunomodulators for allergic disorders
Severe asthma unresponsive to inhaled corticosteroids -- what treatment option is next?
Eosinophils

Monoclonal antibody reslizumab improves lung function in asthma subtype with eosinophilic airway inflammation - ACAAI, 2010 http://goo.gl/UJJHG

Anti-IL5 Antibody Reslizumb (mAb) Looks Promising for Severe Eosinophilic Asthma http://goo.gl/mlGkL