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Enbrel May Offer Relief from Refractory Asthma

Enbrel (etanercept), a drug normally prescribed for rheumatoid arthritis and autoimmune diseases, may alleviate symptoms of asthma that does not respond to standard treatment, suggests a new study.

Enbrel acts by blocking the action of tumor necrosis factor alpha (TNF-alpha), a substance produced by activated white blood cells. TNF-alpha seems to be increased in people with refractory asthma, according to study authors Ian D Pavord, DM, and colleagues at the Institute for Lung Health.

The authors noted that the "rates of death and complications are high among patients with refractory asthma and account for a disproportionate amount of the health resource burden attributed to asthma," and that the range of treatment options available for these patients is limited.

The study was published in the February 16, 2006 issue of The New England Journal of Medicine (NEJM) and reported by MedPage Today on February 16.

Clinical Trial

In this study, the investigators measured markers of TNF-alpha activity in 30 people: 10 with refractory asthma; 10 with mild-to-moderate asthma and 10 with no asthma. They also studied the effects of Enbrel (25 mg, injected subcutaneously twice weekly) on the participants with refractory asthma in a placebo-controlled, double-blind, crossover study.

Results showed that the participants with refractory asthma had significantly increased expression in their peripheral white blood cells of membrane-bound TNF-alpha, TNF-alpha receptor 1, and TNF-alpha-converting enzyme, compared with participants in the other two groups.

After 10 weeks of treatment, participants receiving Enbrel improved by nearly one point (0.84) on the Juniper asthma quality-of-life scale, while participants receiving placebo experienced a decrease of 0.02.

Enbrel also appeared to ease breathing, as it was associated with a 0.32-liter increase in forced expiratory volume per second, compared with placebo; this difference became statistically significant at week five. Moreover, TNF-alpha-expression levels significantly decreased in participants taking Enbrel, an effect strongly associated with improved symptoms.

"The beneficial effects of etanercept-induced antagonism of TNF-alpha on markers of asthma control support the view that TNF-alpha contributes to the pathogenesis of refractory asthma."

However, they added that the study "involved small numbers of patients, and the results could have been compromised by missing data, the crossover design, or the imbalance in the treatment order. Thus, the clinical findings cannot be regarded as a directive for treatment."

In an editorial published in the same issue of NEJM, Serpil C Erzurum, MD, of the Cleveland Clinic, concurred:

"Despite the promise of early studies of anti-inflammatory therapy for asthma, it is prudent to await results of large, multicenter studies before applying such findings to individual patient care," he wrote. "Studies of TNF-alpha inhibitors in patients with asthma are ongoing, ensuring that we will not have to wait long for results.

"However, even if the results of larger trials are favorable, TNF-alpha inhibitor therapy will likely be used in combination with, not as a replacement for, standard treatment of refractory asthma," he added.

Enbrel is marketed jointly by Amgen and Wyeth and is approved by the US Food and Drug Administration (FDA) for moderate-to-severe rheumatoid arthritis, ankylosing spondylitis, moderate-to-severe juvenile rheumatoid arthritis and psoriatic arthritis. The drug companies did not support or play a role in this study, according to MedPage Today.

Enbrel May Help Patients With Refractory Asthma, MedPage Today, February 16, 2006.
Evidence of a role of tumor necrosis factor a in refractory asthma. Berry MA et al, The New England Journal of Medicine, volume 354(7), pages 697-708, 2006.
Inhibition of tumor necrosis factor a for refractory asthma. Erzurum SC, The New England Journal of Medicine, volume 354(7), pages 754-758, 2006.

Posted: February 2006