Editors' ChoiceAsthma

One Size Doesn’t Fit All

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Science Translational Medicine  05 Oct 2011:
Vol. 3, Issue 103, pp. 103ec162
DOI: 10.1126/scitranslmed.3003257

“One size fits all” is a promise that is rarely kept, whether it is applied to clothing or to medical treatments. Most medical therapies administered to large groups of patients only help a subset of the patients; frequently, we do not know why a particular treatment did not work in a given patient. Indeed, common diseases can have many different causes, and the effectiveness of a particular therapy may depend on the specific disease pathology in an individual patient. Corren et al. provide a proof of this principle in the treatment of asthma, showing that a drug that blocks the cytokine interleukin-13 (IL-13) is particularly effective in the patient subgroup who have pretreatment evidence of increased production of periostin, a molecule that is up-regulated in response to IL-13 signaling.

Asthma is a disease of chronic airway inflammation that is punctuated by episodic airway constriction, which can result in potentially life-threatening difficulty in breathing. Current treatments have variable efficacy, and there is no cure. IL-13 is a secreted immune system signaling molecule that plays a major role in allergic inflammation; high production of IL-13 has been seen in asthma patients who are resistant to glucocorticoid therapy. The authors conducted a randomized, double-blind placebo-controlled trial of a monoclonal antibody to IL-13 (lebrikizumab) in 219 asthma patients who were not adequately controlled with inhaled glucocorticoid therapy. They found that patients with a high amount of periostin—a biomarker for IL-13 pathway activation—had significant improvements in airway mechanics after treatment with lebrikizumab. Those patients with lower amounts of periostin did not respond in a significantly different manner from placebo-treated subjects.

Although blocking a pathway would be predicted to be more effective in patients who demonstrate activation of that pathway, there are still very few examples of this rational approach in clinical medicine. This study provides a strong proof that findings from patient biomarker studies can and should be translated into clinical trial designs.

J. Corren et al., Lebrikizumab tretment in adults with asthma. N. Engl. J. Med. 365, 1088–1098 (2011). [Full Text]

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