August 29, 2012

Mepolizumab Reduced Severe Asthma Exacerbations by 50%

Leicester, UK—Treatment with the monoclonal antibody mepolizumab reduced by almost 50% percent severe exacerbations, emergency department visits, and hospitalizations in patients with severe asthma compared with patients given placebo.

That was the result of the largest study ever conducted in patients with severe asthma, involving 621 patients from 81 medical institutions in 13 countries between November 2009 and December 2011. It was published recently in a special issue of The Lancet on respiratory medicine.

“Mepolizumab is potentially an important advance because it seems to be a safe and effective treatment option for patients with eosinophilic asthma that is associated with frequent flare-ups, and may reduce the need for conventional treatment with oral corticosteroids that can have serious side effects including osteoporosis, high blood pressure, and impaired growth in children,” according to lead researcher Ian Pavord from University Hospitals of Leicester NHS in the United Kingdom.

Mepolizumab blocks the production of eosinophils, which can inflame lung airways. The drug previously was shown to reduce the frequency of asthma exacerbations and the need for steroids in two small proof-of-concept studies.

Study participants were randomly assigned to receive one of three dosages of intravenous mepolizumab —75 mg, 250 mg, or 750 mg—or placebo on a monthly basis for 12 months. After the end of that period, the rate of clinically significant exacerbations in the mepolizumab groups was around half that of the placebo group. The rates for patients receiving mepolizumab were 1.24, 1.46, and 1.15 per patient per year, from the lowest to highest dose, compared with 2.40 for those receiving placebo. Clinically significant exacerbations were defined as episodes requiring oral corticosteroids or admission or visit to an emergency department.

Mepolizumab was effective in reducing exacerbations, but it did not produce consistent improvements in symptoms or lung function, according to the authors, who added that “a dissociation between symptoms and risk of exacerbations probably exists in patients with severe asthma and suggests that they represent separate aspects of the disorder that require different management strategies.”

Adverse events, which included headache and nasopharyngitis, and were similar across all mepolizumab groups. Three deaths during the study were unrelated to treatment.

In comments that accompanied the article in The Lancet, Simone Hashimoto and Elisabeth Bel from the University of Amsterdam in The Netherlands note, “These effects are very promising, and raise hope for many patients for whom no effective drugs without significant adverse effects are available today.”

“The next step will be to assess the steroid-sparing effects of mepolizumab in a large population of patients who are oral corticosteroid-dependent….It would be ideal if anti-IL-5 treatment not only reduced the number of exacerbations, but also facilitated the tapering of oral corticosteroids, thereby preventing serious steroid-induced side effects,” Hashimoto and Bel add.

U.S. Pharmacist Social Connect