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

• Published in: American journal of respiratory and critical care medicine 2006-10, Vol.174 (7), p.753
• Main Authors: Erin, Edward M, Leaker, Brian R, Nicholson, Grant C, Tan, Andrew J, Green, Linda M, Neighbour, Helen, Zacharasiewicz, Angela S, Turner, Jackie, Barnathan, Elliot S, Kon, Onn Min, Barnes, Peter J, Hansel, Trevor T
• Format: Article
• Language: English
• Subjects: Airway management; Asthma; Cytokines; Disease; Inflammation; Monoclonal antibodies; Patients; Rheumatoid arthritis; Sodium; Steroids; Tumor necrosis factor-TNF
• ISSN: 1073-449X; 1535-4970
• DOI: 10.1164/rccm.200601-072OC

Neutralization of tumor necrosis factor-alpha (TNF-alpha) is an effective antiinflammatory therapy for several chronic inflammatory diseases. 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 beta(2)-agonist usage using hand-held electronic devices. 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. 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.