Patients with symptomatic moderate asthma who were treated with anti-tumor necrosis factor alpha, an anti-inflammatory monoclonal antibody, experienced significantly fewer disease exacerbations than individuals taking a placebo.
This research appears in the first issue for October 2006 of the American Journal of Respiratory and Critical Care Medicine, published by the American Thoracic Society.
Trevor T. Hansel, M.D., Ph.D., of the National Heart and Lung Institute at Royal Brompton Hospital in London, and 11 associates infused 14 patients with infliximab, a monoclonal antibody that binds and neutralizes tumor necrosis factor alpha (TNFá). Eighteen patients received placebo during the eight-week double-blind study.
According to the investigators, both structured and inflammatory cells in asthmatics can release TNFá, which is an intercellular messenger protein, a cytokine, produced by white blood cells.
"Anti-TNFá therapy has been shown to be effective in patients with rheumatoid arthritis, ankylosing spondylitis, Crohn's disease and psoriasis, but ineffective in patients with chronic obstructive pulmonary disease (COPD)," said Dr. Hansel. "Preliminary reports of efficacy in asthma patients with concomitant rheumatoid arthritis have been encouraging. Small prospective studies of a soluble receptor directed against TNFá in severe refractory asthma have also shown improvements in lung function and airway hyperresponsiveness."
During the study, 13 of the 18 patients on placebo (72 percent) experienced exacerbations, as compared to only four out of 14 patients (29 percent) on infliximab therapy.
All patients in the study cohort continued to use inhaled corticosteroids for their asthma. Study protocol required them to be symptomatic during a two- to four-week run-in period.
After the run-in phase, infusions of either infliximab or placebo were administered at weeks zero, two and six.
"Treatment with infliximab reduced the number of moderate exacerbations in patients with asthma, as monitored by morning and evening use of an electronic spirometer incorporating a clinical diary," said Dr. Hansel. "Although infliximab therapy did not show significant efficacy for the primary endpoint of monitoring peak expiratory flow (PEF), it did produce a significant decrease in the diurnal (during the day) variation in the PEF rate."
(With PEF monitoring, patients take as deep as a breath as possible, then exhale as forcefully as possible into the mouthpiece of the PEF meter for three tests. As a gauge for pulmonary function, it is especially useful in patients older than age five who have persistent moderate to severe asthma.)
"None of the exacerbations we saw in our study warranted treatment with oral corticosteroids or hospitalization, so they cannot be considered to have been severe," said Dr. Hansel.
The researchers noted there were no adverse events associated with using the monoclonal antibody for treatment.
"Given that infliximab therapy was well-tolerated and appeared to reduce the incidence of asthma exacerbations, anti-TNFá therapy merits further study in larger clinical trials in patients with severe asthma," concluded Dr. Hansel.
Contact: Trevor T. Hansel, M.D., Ph.D., NHLI Clinical Studies Unit, Royal Brompton Hospital, Fulham Road, London SW3 6HP, United Kingdom
Phone: + 44 207 351 8974