New Antibody-Based Treatment for Severe Asthma
A new antibody-based drug could improve symptoms for some patients with severe asthma without the long list of debilitating side effects associated with traditional steroid-based treatments, according to a new study in the New England Journal of Medicine.
Many patients with severe asthma require very high doses of corticosteroids, which can pose serious side effects, such as mood swings, diabetes, bone loss, skin bruising, cataracts, and hypertension.
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“We now may have an option to replace prednisone to treat severe asthmatics—this is the first class of drugs that has been shown to help patients reduce the dose of prednisone,” says study investigator Parameswaran Nair, MD, PhD, staff respirologist at the Firestone Institute for Respiratory Health at St. Joseph’s Healthcare Hamilton and professor of respirology at the Michael G. DeGroote School of Medicine at McMaster University in Ontario, Canada.
One of the ways steroids help patients with asthma is by decreasing the number of eosinophils in the blood and in airways. A protein called interleukin-5 (IL-5) is largely responsible for bringing eosinophils into the lungs.
“Mepolizumab and a number of other drugs in the same class currently being evaluated block IL-5 and, therefore, should be a substitute for the high doses of steroids,” Nair explains. “Currently, we do not know how long these patients ought to be on these drugs. We think that an injection of the drug would benefit for about 2 to 3 months. The treatment is likely to be life-long; thus, it is not a cure of asthma in the strictest sense of the word.”
Nair was the lead investigator of the Steroid Reduction with Mepolizumab Study (SIRIUS) trial in Canada. He and his colleagues recruited the largest number of participants for the global study, funded by GlaxoSmithKline. It included 135 patients with severe eosinophilic asthma, who were randomized to 100 mg of subcutaneous mepolizumab or placebo, every 4 weeks for 20 weeks.
In patients who required daily oral glucocorticoid therapy to maintain asthma control, mepolizumab had a significant glucocorticoid-sparing effect, reduced the annualized rate of exacerbations by about 32%, and improved asthma symptom control.
Nair says patients who are likely to benefit from the drug have a history of improving quickly with steroids (prednisone) and who have high levels of eosinophils in their blood (greater than 300/microlitre) or sputum (> 3%).
“While there are drugs like omalizumab that may help patients with allergic asthma, this new class of drugs would work in those who are allergic and non allergic, provided they have eosinophils in their sputum and/or blood,” he says. “My own research suggests that those with the highest levels in sputum are the ones who are likely to benefit the most—these patients are considered to have ‘eosinophilic asthma.’”
Along with researchers in other labs around the world, Nair and his colleagues are evaluating a number of new drugs that block IL-5 and other proteins that may be relevant in patients with eosinophilic asthma.
“We are also investigating mechanisms of why some patients require high doses of steroids in the first place and to understand mechanisms why steroids may not work in these patients, why they are susceptible to recurrent bacterial bronchitis, and if these infections may, in some way, contribute to the steroids not working properly,” he says.
—Colleen Mullarkey
Reference
Bel EH, Wenzel SE, Thompson PJ, Prazma CM, Keene ON, Yancey SW, et al. Oral glucocorticoid-sparing effect of mepolizumab in eosinophilic asthma. N Engl J Med. 2014 Sep 8. [Epub ahead of print].