McMaster University researchers have found patients with a very severe asthma benefit from injections of the antibody, mepolizumab.
The study by Dr. Param Nair and colleagues based at The Firestone Institute for Respiratory Disease, St. Joseph's Healthcare, found patients who require a lot of medication, including prednisone, to control their disease benefit from the injections.
The research published in the New England Journal of Medicine (NEJM), investigated asthmatics with a persisting type of airway inflammation with inflammatory cells called eosinophils. It is estimated there are 60,000 to 120,000 Canadians with this condition.
"Mepolizumab works by blocking the production of eosinophils," said the study's senior author Dr. Paul O'Byrne. "By preventing their production, we were able to improve asthma, reduce the need for prednisone and really show that eosinophils are important in causing asthma symptoms in these patients." O'Byrne is the E. J. Moran Campbell Professor in Respiratory Medicine and chair of the Department of Medicine at McMaster University, and executive director of the Firestone Institute of Respiratory Health at St. Joseph's Healthcare Hamilton.
Of three million asthmatics in Canada, about five to eight per cent are severe asthmatics. About half of these have severe asthma with persistent eosinophilia. Although these asthmatics are fewer in number, they represent huge costs to the health care system because frequent flare-ups which can require admission to hospital.
For their study, McMaster researchers recruited 20 mature asthmatic patients (56 – 58 years of age) who had been taking about 10 milligrams of prednisone for approximately nine years, along with other available asthma medication. For doctors, this is a difficult group to manage because of the many drugs they need to control their disease and the side-effects of prednisone which include weight gain, bone loss and an increased risk of diabetes.
During the six month randomized, double-blind, parallel-group trial, nine patients received mepolizumab and 11 were given a placebo.
Patients receiving mepolizumab "markedly reduced" their use of prednisone without their asthma getting any worse, O'Byrne said. By comparison, patients in the placebo group had their asthma flare up as prednisone was reduced.
At the beginning of the study, eosinophils in the sputum, or blood, were elevated in all patients. "But, mepolizumab reduced the number of eosinophils to the normal range and kept them at that level for the entire study," O'Byrne said.
O'Byrne cautioned mepolizumab is not appropriate for all patients with severe asthma. "Many patients with severe asthma would not get benefit from this treatment approach," he said, adding this antibody is only helpful for those with eosinophilic asthma.
Mepolizumab is an investigational drug and currently not approved for use in Canada.
A second study of 61 patients published in the same issue of the NEJM by British researchers also showed mepolizumab therapy effectively treats patients with very severe eosinophilic asthma.
In an accompanying editorial, Dr. Sally E. Wenzel, a specialist in internal and pulmonary medicine at the University of Pittsburgh Medical Centre, said that even though eosinophils have been identified as a prominent cell type in asthma for more than 100 years, their role as either an "effector" or "innocent bystander" was not confirmed until the publication of the two studies by McMaster and British researchers in the NEJM.
"These studies clearly confirm that in a sub-group of patients with eosinophilic asthma, eosinophils play a role in exacerbations," she wrote.
- Nair et al. Mepolizumab for Prednisone-Dependent Asthma with Sputum Eosinophilia. New England Journal of Medicine, 2009; 360 (1): 985-993
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