Mepolizumab prevents some ER visits in people with a severe form of asthma
An experimental drug called mepolizumab can prevent severe asthma attacks in people with an uncommon form of the disease that responds poorly to standard steroid medications, researchers report in two studies in the March 5 New England Journal of Medicine.
Scientists from Britain and Canada also find that a simple test of sputum (coughed up matter) can reveal which patients would most likely benefit from mepolizumab. Thus the drug might help some people with asthma reduce the use of steroids such as prednisone, which have side effects, says Ian Pavord, a pulmonologist at Glenfield Hospital and University of Leicester in England and coauthor of one of the studies.
Asthma is a chronic disease in which the airways become inflamed, constricted, scarred and laden with mucus. The wheezing and shortness of breath that asthma causes — and the frightening struggle for air felt in a severe asthma attack — can be brought on by allergens, fumes, stress and even exercise or cold air.
An immune system overreaction to these triggers underlies the disease. Mepolizumab quells the reaction by neutralizing the effect of interleukin-5, an immune protein that activates circulating immune cells called eosinophils and recruits new ones from nascent cells in the bone marrow. The normally trustworthy eosinophils run amok in 50 to 60 percent of people with asthma.
Fortunately, most people with eosinophil-based asthma respond well to steroid treatment delivered by inhalers, says Paul O’Byrne, a physician at McMaster University in Hamilton, Ont., who coauthored the Canadian study.
But in about one in 10 of these patients, steroids eventually lose their punch. “These people are really difficult to treat,” O’Byrne says. Since mepolizumab targets eosinophils specifically, it made sense to test the drug in these patients.
Both new studies recruited people who continued to have severe asthma attacks despite ample inhaled steroids or regular prednisone pills.
In the Canadian study, O’Byrne and his colleagues enlisted 20 such adults and randomly assigned nine to receive monthly injections of mepolizumab over several months. The others got placebo injections.
None of those getting mepolizumab had an emergency episode attributable to eosinophil-based asthma during the trial or in the two months afterward. But nine such episodes occurred in the placebo group. Patients getting mepolizumab also required less and less steroid medication during the study.
In the British trial, Pavord and his colleagues randomly assigned 29 people with severe asthma to get monthly injections of mepolizumab and 32 others to receive placebo injections. Those receiving the drug had a total of 57 emergency asthma attacks over 11 months, while the placebo recipients had 109 episodes.
Eosinophil levels in sputum were much higher in asthma patients who were getting the placebos. The numbers were close to normal with mepolizumab use.
Mepolizumab, also called Bosatria, is made by GlaxoSmithKline, which provided funding for both studies.
Using sputum to test eosinophil levels was pioneered by the Canadian researchers. It could help doctors identify patients who would benefit most — if regulators approve the drug, says physician Parameswaran Nair, a coauthor on the Canadian paper who is also at McMaster.
“This might prevent some emergency room visits,” says pulmonologist Sally Wenzel of the University of Pittsburgh Medical Center. “But it’s not a panacea,” she says, since it didn’t eliminate all emergency asthma attacks.
Meanwhile, a big question remains: Why are some patients’ eosinophils no longer susceptible to the dampening effects of steroids? “We don’t know,” O’Byrne says.
Haldar, P., et al. 2009. Mepolizumab and exacerbations of refractory eosinophilic asthma. New England Journal of Medicine 360(March 5):973-984.
Nair, P., et al. 2009. Mepolizumab for prednisone-dependent asthma with sputum eosinophilia. New England Journal of Medicine 360(March 5):985-993.
Flood-Page, P., et al. 2007. A study to evaluate safety and efficacy of mepolizumab in patients with moderate persistent asthma. American Journal of Respiratory and Critical Care Medicine. 176:1062-1071.
Leckie, M., et al. 2000. Effects of an interleukin-5 blocking monoclonal antibody on eosinophils, airway hyper-responsiveness, and the late asthmatic response. Lancet 356:2144-2148.
Wenzel, S.E. 2009. Eosinophils in asthma — closing the loop or opening the door? New England Journal of Medicine 360(March 5):1026-1028.