The safety and efficacy of infliximab in moderate to severe chronic obstructive pulmonary disease.
BACKGROUND
Chronic obstructive pulmonary disease (COPD) is a progressive, smoking-related, inflammatory lung disease in which tumor necrosis factor-alpha is overexpressed and has been suggested to play a pathogenic role.


OBJECTIVE
To determine if infliximab, an anti-TNF-alpha antibody, results in clinical benefit and has an acceptable safety profile in patients with moderate to severe COPD.


METHODS
In a multicenter, randomized, double-blind, placebo-controlled, parallel-group, dose-finding study, subjects with moderate to severe COPD received infliximab (3 mg/kg [n = 78] or 5 mg/kg [n = 79]) or placebo (n = 77) at Weeks 0, 2, 6, 12, 18, and 24. Efficacy, health status, and safety were assessed through Week 44.


RESULTS
Infliximab was generally well tolerated, but showed no treatment benefit as measured by the primary endpoint, Chronic Respiratory Questionnaire total score. Similarly, there was no change in secondary measures, including prebronchodilator FEV(1), 6-min walk distance, SF-36 physical score, transition dyspnea index, or moderate-to-severe COPD exacerbations. Post hoc analysis revealed that subjects who were younger or cachectic showed improvement in the 6-min walk distance. Malignancies were diagnosed during the study in 9 of 157 infliximab-treated subjects versus 1 of 77 placebo-treated subjects. No opportunistic infections were observed, and there were no differences in the occurrence of antibiotic-requiring infections, although the incidence of pneumonia was higher in infliximab-treated subjects. No infection-related mortality was observed. Higher proportions of infliximab-treated subjects discontinued the study agent due to adverse events (20-27%) than did placebo-treated subjects (9%).


CONCLUSIONS
Subjects with moderate to severe COPD did not benefit from treatment with infliximab. Although not statistically significant, more cases of cancer and pneumonia were observed in the infliximab-treated subjects. The impact of infliximab on malignancy risk in patients with COPD needs to be further elucidated.
Rennard
Stephen I
SI
University of Nebraska Medical Center, 985125 Nebraska Medical Center, Omaha, NE 68198, USA. srennard@unmc.edu
Fogarty
Charles
C
Kelsen
Steven
S
Long
William
W
Ramsdell
Joe
J
Allison
James
J
Mahler
Donald
D
Saadeh
Constantine
C
Siler
Thomas
T
Snell
Phillip
P
Korenblat
Phillip
P
Smith
William
W
Kaye
Mitchell
M
Mandel
Michael
M
Andrews
Charles
C
Prabhu
Rachakonda
R
Donohue
James F
JF
Watt
Rosemary
R
Lo
Kim Hung
KH
Schlenker-Herceg
Rozsa
R
Barnathan
Elliot S
ES
Murray
John
J
D000368:Aged; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage*; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D017079:Exercise Tolerance; D005260:Female; D006304:Health Status; D006801:Humans; D000069285:Infliximab; D008297:Male; D008875:Middle Aged; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy* / Q000503:physiopathology; D012129:Respiratory Function Tests; D012720:Severity of Illness Index; D016896:Treatment Outcome
D000893:Anti-Inflammatory Agents; D000911:Antibodies, Monoclonal; D000069285:Infliximab