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Published ahead of print on July 13, 2006, doi:10.1164/rccm.200601-072OC
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American Journal of Respiratory and Critical Care Medicine Vol 174. pp. 753-762, (2006)
© 2006 American Thoracic Society
doi: 10.1164/rccm.200601-072OC

Original Article

The Effects of a Monoclonal Antibody Directed against Tumor Necrosis Factor-{alpha} in Asthma

Edward M. Erin, Brian R. Leaker, Grant C. Nicholson, Andrew J. Tan, Linda M. Green, Helen Neighbour, Angela S. Zacharasiewicz, Jackie Turner, Elliot S. Barnathan, Onn Min Kon, Peter J. Barnes and Trevor T. Hansel

Clinical Studies Unit, National Heart and Lung Institute, and Department of Thoracic Medicine, Imperial College, London; Department of Nephrology, Royal Free Hospital, London; Department of Respiratory Medicine, St. Mary's Hospital, London, United Kingdom; and Centocor, Inc., Malvern, Pennsylvania

Correspondence and requests for reprints should be addressed to Trevor T. Hansel, F.R.C.Path., Ph.D., NHLI Clinical Studies Unit, Royal Brompton Hospital, Fulham Road, London SW3 6HP, UK. E-mail: t.hansel{at}imperial.ac.uk

Rationale: Neutralization of tumor necrosis factor-{alpha} (TNF-{alpha}) is an effective antiinflammatory therapy for several chronic inflammatory diseases.

Methods and Objectives: We undertook a double-blind, placebo-controlled, parallel-group design study in 38 patients with moderate asthma treated with inhaled corticosteroids but symptomatic during a run-in phase. Infliximab (5 mg/kg) or placebo was administered by intravenous infusion at Weeks 0, 2, and 6. We assessed clinical response by monitoring lung function, symptoms, and inhaled beta2-agonist usage using hand-held electronic devices.

Results: The primary endpoint, change in morning PEF at Days 50–56 compared with the last 7 d of the run-in, was not significantly different on treatment. However, infliximab was associated with a decrease in mean diurnal variation of PEF at Week 8 (p = 0.02; 95% confidence interval [CI], –8.1 to –0.72). Furthermore, there was a decrease in the number of patients with exacerbations of asthma (p = 0.01; 95% CI, 4.4 to 52.7) and an increased probability of freedom from exacerbation with time (p = 0.03) in patients on infliximab (n = 14) compared with placebo (n = 18). In addition, infliximab decreased levels of TNF-{alpha} (p = 0.01) and other cytokines in sputum supernatants. There were no serious adverse events related to the study agent.

Conclusions: Treatment with infliximab was well tolerated and caused a decrease in the number of patients with exacerbations in symptomatic moderate asthma. The promising preliminary findings underscore the need to evaluate therapy directed against TNF-{alpha} in larger trials enrolling patients with more severe asthma.

Key Words: asthma • monoclonal antibody • pharmacology • tumor necrosis factor-{alpha} •




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