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 beta(2)-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.