New anti-arthritis therapy proves effective in treating severe asthma
Researchers at the University of Southampton's School of Medicine believe they have made a major breakthrough in the treatment of severe asthma that remains troublesome despite the use of steroid anti-inflammatory and bronchodilator drugs. The researchers, headed by Professor Stephen Holgate, MRC Clinical Professor of Immunopharmacology at Southampton, have shown that a small inflammatory protein-tumour necrosis factor alpha (TNFa)-is generated in very high levels by the lungs of severe asthmatics despite their high use of available asthma treatments.
This observation led to a pilot study, involving 15 asthmatic patients, to block the inflammatory protein with the biological agent etanercept (Enbrel) that binds to TNFa and presents its actions. The findings are due to be published in the journal Thorax.
"The clinical response we achieved with etanercept was truly remarkable," said Professor Holgate. "Many of the patients voluntarily stopped their regular nebulised bronchodilator and all gained considerable improvements in asthma symptoms, lung function and quality of life. On completing the trial, patients wanted to continue with the therapy.
"This study is the first to demonstrate a key role for TNFa in chronic asthma which had previously been considered as a largely allergic disorder. The remarkable clinical benefit achieved with etanercept mirrors that achieved with this therapy in other chronic inflammatory disease such as rheumatoid arthritis, inflammatory bowel disease and psoriasis.
"Etanercept along with humanised blocking antibodies is finding wide use in patients with severe debilitating inflammatory diseases. Chronic asthma can now be added to these. One of the most important abnormalities in asthma is the "twitchiness" of the airways that narrow with the least provocation. This hyperresponsiveness was dramatically reversed by the 12-week etanercept treatment.
"Although our study was uncontrolled, a recent placebo-controlled study in Leicester has replicated the findings. Large international multicentre studies are now underway in phase 3 clinical trials being conducted by Wyeth and Amgen, the producers of etanercept," he added.
Asthma affects approximately 30 million people in Europe alone (1). Approximately one fifth of the asthma population has severe disease (2). According to Professor Holgate, what is particularly exciting about this study is that patients with or without allergic features associated with their asthma benefited equally to TNFa blockade with etanercept.
"Statistics show that 10 per cent of the asthma population accounts for approximately 50 per cent of the total health costs for this disease. Severe asthma is a major risk factor for death from this disease, of which 1500 occurred in the UK last year. A once or twice weekly injection that could offer hope to people at risk of dying from this disease would be a major breakthrough," said Professor Holgate.
While there is considerable cause for optimism, the Southampton team acknowledge the need for large scale trials in this at-risk population of asthma sufferers. However, Professor Holgate adds, "Just as has been the case for other chronic inflammatory disorders, blocking the effects of TNF in patients with severe asthma in whom treatment options are limited, is likely to be of real benefit."
The Southampton team's research has been supported by the Medical Research Council as well as medical research charities including their own charity AAIR (Asthma, Allergy and Inflammation Research).