Efficacy and safety of a monoclonal antibody recognizing interleukin-8 in COPD: a pilot study.
OBJECTIVE
To investigate the efficacy and safety of a fully human monoclonal antibody recognizing the chemokine interleukin (IL)-8 in patients with COPD.


METHODS
Randomized, double-blind, parallel-group, placebo-controlled trial.


METHODS
Eighteen clinics/hospitals in the United States.


METHODS
One hundred nine patients with stable COPD.


METHODS
Three IV infusions of either monoclonal antibody recognizing IL-8 (800-mg loading dose; 400-mg subsequent doses) or active buffer solution administered monthly over a 3-month period.


RESULTS
The differences in the transition dyspnea index (TDI) total score, the primary outcome measure, between fully human monoclonal IgG(2) antibody directed against IL-8 and placebo were 0.8, 1.0, 0.8, and 0.3 at week 2 (p = 0.046) and months 1 to 3, respectively. At all time points, the proportion of patients achieving >/= 1 point improvement in the TDI was greater for the monoclonal antibody group compared with the placebo group: 28% vs 11% at week 2 (p = 0.028). There were no significant differences observed for lung function, health status, 6-min walking distance, and adverse events between groups.


CONCLUSIONS
The results of this phase 2 study suggest that neutralization of IL-8 with monoclonal antibody therapy may improve dyspnea in patients with COPD. These results support the further investigation of monoclonal antibody therapy targeting IL-8 for the treatment of this disease.
Mahler
Donald A
DA
Section of Pulmonary and Critical Care Medicine, Dartmouth-Hitchcock Medical Center, One Medical Center Dr, Lebanon, NH 03756-0001, USA. Donald.a.mahler@hitchcock.org
Huang
Saling
S
Tabrizi
Mohammad
M
Bell
Gregory M
GM
D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000009:adverse effects / Q000276:immunology; D061067:Antibodies, Monoclonal, Humanized; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004417:Dyspnea / Q000188:drug therapy / Q000276:immunology; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D016209:Interleukin-8 / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D018375:Neutrophil Activation / Q000187:drug effects; D010865:Pilot Projects; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy* / Q000276:immunology; D023062:Receptors, Interleukin-8A / Q000037:antagonists & inhibitors*; D012129:Respiratory Function Tests
C492798:ABX-Interleukin 8; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D016209:Interleukin-8; D023062:Receptors, Interleukin-8A