Weight May Influence Response to Asthma Treatments

February 28, 2006

Pharmaceutical Executive

Pharmaceutical Executive, Pharmaceutical Executive-02-28-2006, Volume 0, Issue 0

An analysis of Merck’s clinical trial data for Singular (montelukast) indicates that obese people may respond to asthma treatments differently than lean people. A University of Michigan professor explains his recently published paper.

Body weight may predict how a patient would respond to various asthma treatments, according to an analysis published in the March 1 issue of the European Respiratory Journal.

    The analysis, which draws on data from three clinical trials of Merck’s Singulair (montelukast), provides some evidence that body mass index (BMI) could be used to predict a patient’s response to asthma drugs, according to lead author Marc Peters-Golden. But Peters-Golden, a professor of internal medicine at the University of Michigan's medical school, stressed that these results are preliminary, since the data were collected for a different purpose, and retrospectively analyzed.

    “It raises potential new ideas for future study,” he said. “But it does not have the same level of conclusiveness as a brand new study designed to look at this.”

    Nonetheless, the study may point to some important links between obesity and asthma.

    The results indicate that obese people may respond better to asthma drugs that act against leukotrienes, molecules associated with inflammation and airway constriction, Peters-Golden said. Lean people respond better to inhaled steroids, which act on a variety of inflammatory molecules, but don’t have much effect on leukotrienes, he added.

    This information fits in to the growing understanding that asthma can be caused by a variety of problems, Peters-Golden explained. It’s not really a single disease, but more of a “wastebasket term” for a variety of problems that result in airway constriction.

    The European Respiratory Journal analysis may provide a link in developing the theory that asthma in obese people is related to higher-than-normal levels of leukotrienes, Peters-Golden said. Fat cells produce a hormone called leptin, which inhibits the appetite and promotes inflammation, according to Peters-Golden. It can also increase production of leukotrienes.

    If this theory is correct, it could explain why leukotriene-blockers, such as montelukast, were more effective at combating asthma in obese people.

    “Based on all the pieces of the puzzle that we know about,” Peters-Golden theorized. “Perhaps asthma in obese people is particularly driven by leukotrienes.”

    Further study should measure levels of leptin and leukotrienes in patients with varying BMIs both before and after treatment with inhaled steroids and leukotriene-blockers, Peters-Golden said. The studies should also examine a variety of asthma drugs that act against leukotrienes, either by blocking receptors or inhibiting production, he added.

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