Hypereosinophilic syndrome - mepolizumab

As well as combating infections, eosinophil white blood cells are involved in the control of mechanisms associated with asthma and allergy. The condition hypereosinophilia occurs when there are unusually high concentrations of eosinophils in the blood, and this is associated with numerous diseases such as asthma, allergic rhinitis, eczema and various malignancies.

There is currently no treatment other than attempting to reduce eosinophil levels and preventing organ damage, usually by giving prednisone in high doses, and drugs such as vincristine and cyclosporin or interferons if that does not work.

Interleukin-5 is involved in the maturation, growth and survival of eosinophils, and GlaxoSmithKline has developed a fully humanised monoclonal antibody, mepolizumab, that targets IL-5. It has been under-going trials to treat asthma, with disappointing results, but is showing more promise in hypereosinophilic syndrome, or HES, where eosinophil levels are above 1500 cells per microlitre of blood and there is no clear secondary cause of the elevated levels.

In one randomised, double blind, placebo-controlled trial, patients with HES who were being treated with prednisone monotherapy in doses of 20 to 60mg/day were given intravenous mepolizumab or placebo while the prednisone dose was tapered.¹ The primary end-point, of a reduction of prednisone dose to 10mg a day or less for at least eight consecutive weeks, was achieved by 84% of those given the antibody, compared with 43% of the placebo group, with no increase in HES symptoms.

It is also being assessed in refractory eosinophilic asthma, where eosinophilic inflammation of the airway is associated with the risk of exacerbations. A randomised, double blind, placebo-controlled, parallel group trial was carried out in 61 patients with this form of asthma, and a history of recurrent, severe exacerbations.² They were given infusions of either mepolizumab or placebo at monthly intervals for a year. Those given the antibody had significantly fewer severe exacerbations than those given placebo during the year - a mean of 2.0 compared with 3.4. They also had a significant improvement in qualitative quality of life measures. The only serious adverse events were hospitalisations for acute severe asthma.

Although it has proved ineffective in simple asthma, another trial has showed that it can allow prednisone doses to be reduced in a rare group of patients who had asthma with sputum eosinophilia.³ In a randomised, double blind, parallel group trial, 20 patients were given mepolizumab in monthly infusions for five months, or placebo. Of 10 patients who received placebo, there were 12 asthma exacerbations, compared with just one who had an exacerbation, and this one was not associated with sputum eosinophilia. Those given the antibody were able to reduce their prednisone dose much more substantially than the placebo group.