Chest

Chest

Volume 126, Issue 3, September 2004, Pages 926-934
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Preliminary Reports
Efficacy and Safety of a Monoclonal Antibody Recognizing Interleukin-8 in COPD: A Pilot Study

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Study objective:

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

Design:

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

Setting:

Eighteen clinics/hospitals in the United States.

Patients:

One hundred nine patients with stable COPD.

Interventions:

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.

Measurements and results:

The differences in the transition dyspnea index (TDI) total score, the primary outcome measure, between fully human monoclonal IgG2 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.

Section snippets

Patients

Patients > 50 years of age with a diagnosis of COPD1 and a history of chronic bronchitis were recruited. Inclusion criteria were as follows: ≥ 20 pack-year smoking history; grade 1 or higher for breathlessness on the modified Medical Research Council scale19; and a baseline FEV1 ≥ 30% and ≤ 70% of predicted and < 70% of FVC. Exclusion criteria were as follows: an increase in FEV1 > 30% or > 300 mL, whichever was greater, at 30 min following two puffs (180 μg) of inhaled albuterol;

Patient Disposition

One hundred nineteen patients were randomized to one of two treatment groups (Table 1). Ten patients (7 patients receiving placebo, and 3 patients receiving ABX-IL8) withdrew from the study prior to the first scheduled administration of the study drug. These patients did not have a TDI assessment, and are therefore not included in the efficacy analyses. The remaining 109 patients constitute the modified intent-to-treat population. Overall, 99 patients (91%) received all three infusions of the

Discussion

There are no current guidelines or recommendations for selection of the most appropriate primary outcome measure for evaluating biological agents for the treatment of COPD. In a study of monoclonal anti-IgE antibody therapy in patients with asthma, Milgrom and colleagues36 used the asthma symptom score for assessing efficacy. These investigators found significant improvements in this outcome, but no significant change in FEV1 at 12 weeks with either a high dose or a low dose of the monoclonal

ACKNOWLEDGMENT

The authors thank the following investigators who participated in this trial (ABX-0209): Theodore Amgott, MD, Melbourne, FL; William Beliveau, MD, Johnston, RI; Richard Casaburi, MD, Torrance, CA; James Donohue, MD, Chapel Hill, NC; Richard Fei, MD, Lafayette, LA; Charles Fogarty, MD, Spartanburg, SC; Eric Kleerup, MD, Los Angeles, CA; Bernard Levine, MD, Phoenix, AZ; Michael Littner, MD, Sepulveda, CA; Imre Noth, MD, Chicago, IL; Stephen Rennard, MD, Omaha, NE; Gerardo San Pedro, MD,

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    • Cited by (0)

    Funding was provided by Abgenix, Inc.

    Dr. Mahler was a consultant to Abgenix on this study.

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    Copyright © 2004 The American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.