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First Study of Infliximab Treatment in Patients with Chronic Obstructive Pulmonary Disease

Departments of Pulmonology and Allergology, University Medical Center Groningen, Groningen, the Netherlands

Correspondence and requests for reprints should be addressed to Nick H. T. ten Hacken, M.D., Ph.D., Department of Pulmonology, University Medical Center Groningen, P.O. Box 30.001, NL-9700 RB, Groningen, the Netherlands. E-mail: n.h.t.ten.hacken{at}int.umcg.nl

Rationale: Tumor necrosis factor- is believed to be important in the induction and maintenance of airway inflammation in chronic obstructive pulmonary disease. Objectives: We aimed to evaluate the effect of the anti–tumor necrosis factor- drug infliximab in patients with chronic obstructive pulmonary disease, with percentage of sputum neutrophils as the primary endpoint. Methods: We performed an exploratory single-center, double-blind, placebo-controlled, randomized, phase 2 trial in which 22 current smokers with mild-to-moderate chronic obstructive pulmonary disease participated. Fourteen patients received three infusions of infliximab (5 mg/kg) at Weeks 0, 2, and 6, and eight patients received placebo infusions. Sputum samples, respiratory symptoms, quality of life, exhaled nitric oxide, lung function parameters, bronchial hyperresponsiveness, resting energy expenditure, and side effects were evaluated. Measurements and Main Results: This study did not show a positive short-term effect of infliximab on airway inflammation, lung function, resting energy expenditure, or quality of life. Exhaled nitric oxide increased significantly at Day 2, Week 6, and Week 8 in patients receiving infliximab compared with those receiving placebo. Eight patients in the infliximab group (vs. none in the placebo group) reported increased coughing, but no serious adverse events or increase in respiratory infections were reported during 9 weeks of follow-up. Conclusions: In this short-term study, no clinically beneficial effects of infliximab were observed, and there were no significant safety issues. Definite conclusions concerning the effectiveness of infliximab treatment in chronic obstructive pulmonary disease await additional studies, including those with a larger number of patients with more advanced disease.

Key Words: chronic obstructive pulmonary disease • inflammation • tumor necrosis factor-

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