Anti-IL5 Antibody Mepolizumab is Effective in Eosinophilic Asthma

Mepolizumab, a humanized monoclonal antibody that binds to and inactivates interleukin-5 (IL5), has been shown to reduce asthma exacerbations in patients with severe eosinophilic asthma.


Eosinophil. Image source: Wikipedia.

Effect on oral steroid use

In a randomized, double-blind trial involving 135 patients with severe eosinophilic asthma, mepolizumab 100 mg was administered subcutaneously once a month for 5 months. The monoclonal antibody had a significant oral steroid-sparing effect, reduced exacerbations, and improved control of asthma symptoms (http://bit.ly/WGyOZ3).

Effect on high-dose ICS use

In another randomized, double-blind trial, 576 patients with recurrent asthma exacerbations and eosinophilic inflammation despite high doses of inhaled glucocorticoids were assigned to receive mepolizumab either a 75-mg intravenous dose (IV) or a 100-mg subcutaneous dose (SC) once a month for 8 months. The rate of exacerbations was reduced by 47% (IV group) and by 53% (SC group). Exacerbations necessitating an ED visit or hospitalization were reduced by 32% in IV group and by 61% in SC group. FEV1 and ACQ-5 score also improved. The safety profile of mepolizumab was similar to that of placebo (http://bit.ly/WGyREh).

It is reasonable to consider anti–interleukin-5 therapy for patients with severe asthma who are receiving high doses of systemic glucocorticoids and who continue to have an elevated eosinophil count in sputum or blood.

Both studies were funded by GlaxoSmithKline and published in the NEJM.

Practical implications

As of 2014, mepolizumab is not yet FDA-approved for asthma treatment.

Here are a few things to consider:

- Blood test will be needed. In the future, more patients with asthma will need basic screening with CBCD to identify the subgroup with eosinophilic asthma. CBCD is a relatively inexpensive test, priced at $30-60. The phenotype determination based on a blood test (CBCD) is more practical from a real-life perspective as compared to sputum eosinophils.

- What is the cutoff limit for blood eosinophils? The inclusion criteria for the studies was a blood eosinophil count  at baseline oof more than 300 cells per microliter despite concurrent treatment with high doses of glucocorticoids,

- Limited number of patients will qualify for therapy. Based on the criteria above, not many patients with qualify for treatment with mepolizumab. Previous studies have estimated that only 5% of patients with severe asthma have eosinophilic asthma. However, for those patients who qualify, treatment with mepolizumab can be life- and FEV1-changing.

- Mepolizumab improves FEV1. This a significant difference compared to the only monoclonal antibody approved for asthma therapy, omalizumab (Xolair). Omalizumab reduces asthma symptoms and ER visits but does not significantly increase FEV1.

References:

Effect on oral steroid use: Oral Glucocorticoid-Sparing Effect of Mepolizumab in Eosinophilic Asthma — NEJM http://bit.ly/WGyOZ3

Effect on high-dose ICS use: Mepolizumab Treatment in Patients with Severe Eosinophilic Asthma — NEJM http://bit.ly/WGyREh

Anti–Interleukin-5 Monoclonal Antibody to Treat Severe Eosinophilic Asthma — NEJM Editorial http://bit.ly/WGyXvM

Anti–Interleukin-5 Monoclonal Antibody to Treat Severe Eosinophilic Asthma | Now@NEJM http://bit.ly/Zh0WEy