Asthma

Cancer drug shows early promise for severe asthma


Imatinib, typically used to treat chronic myeloid leukaemia, has been shown to reduce airway hyper-responsiveness in patients with poorly controlled severe asthma.

The proof-of-principle study, published in NEJM and presented at the American Thoracic Society conference in Washington this week, also found imatinib reduced mast cell counts and a marker of mast cell activation.

While the US study included only 62 patients, it provides more support for the role of mast cells in the pathophysiology of severe asthma and a potential treatment for patients who do not have severe eosinophilic asthma.

Professor John Upham, group leader of lung and allergy research at the University of Queensland’s Translational Research Institute, said the receptor for stem cell factor, known as KIT, was important for mast cell function.

A clinical trial of oral imatinib, a known inhibitor of KIT activity as well as a number of other cellular pathways, was therefore of interest.

“In some people with severe asthma, their disease remains poorly controlled despite conventional treatment with inhaled steroids and long acting bronchodilators, so novel therapeutic options are needed. This study was undertaken to assess whether targeting airway mast cells might be of benefit in this situation,” Professor Upham said.

The randomised double blind trial compared 24 weeks of imatinib versus placebo as add-on treatment for people with asthma whose disease was inadequately controlled despite inhaled steroids and a second controller medication.

Patients treated with imatinib showed modest but statistically significant improvements in airway hyper-responsiveness as measured by a methacholine challenge test.

The reduction in hyper-responsiveness was inversely correlated with peripheral blood eosinophil counts. Serum tryptase levels also decreased significantly and spirometry improved with treatment.

“This pilot study provides an impetus for larger clinical trials of imatinib, in order to determine whether these initial observations can be translated into clinically important benefits for patients,” Professor Upham said.

Imatinib was generally well tolerated, though leg cramps and neutropenia were reported in some.

The researchers said mast cells could survive in tissues for months to years, so longer duration clinical trials were required.

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