The safety and efficacy of infliximab in moderate to severe chronic obstructive pulmonary disease

Stephen I. Rennard, Charles Fogarty, Steven Kelsen, William Long, Joe Ramsdell, James Allison, Donald Mahler, Constantine Saadeh, Thomas Siler, Phillip Snell, Phillip Korenblat, William Smith, Mitchell Kaye, Michael Mandel, Charles Andrews, Rachakonda Prabhu, James F. Donohue, Rosemary Watt, Hung Lo Kim, Rozsa Schlenker-Herceg & 2 others Elliot S. Barnathan, John Murray

Research output: Contribution to journalArticle

307 Citations (Scopus)

Abstract

Rationale: Chronic obstructive pulmonary disease (COPD) is a progressive, smoking-related, inflammatory lung disease in which tumor necrosis factor-α is overexpressed and has been suggested to play a pathogenic role. Objectives: To determine if infliximab, an anti-TNF-α 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. Measurements and Main 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 FEV1, 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.

Original languageEnglish (US)
Pages (from-to)926-934
Number of pages9
JournalAmerican Journal of Respiratory and Critical Care Medicine
Volume175
Issue number9
DOIs
StatePublished - May 1 2007

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Chronic Obstructive Pulmonary Disease
Safety
Placebos
Pneumonia
Infliximab
Neoplasms
Opportunistic Infections
Infection
Dyspnea
Lung Diseases
Health Status
Disease Progression
Anti-Idiotypic Antibodies
Tumor Necrosis Factor-alpha
Smoking
Anti-Bacterial Agents
Mortality
Incidence
Therapeutics

All Science Journal Classification (ASJC) codes

  • Pulmonary and Respiratory Medicine
  • Critical Care and Intensive Care Medicine

Cite this

The safety and efficacy of infliximab in moderate to severe chronic obstructive pulmonary disease. / Rennard, Stephen I.; Fogarty, Charles; Kelsen, Steven; Long, William; Ramsdell, Joe; Allison, James; Mahler, Donald; Saadeh, Constantine; Siler, Thomas; Snell, Phillip; Korenblat, Phillip; Smith, William; Kaye, Mitchell; Mandel, Michael; Andrews, Charles; Prabhu, Rachakonda; Donohue, James F.; Watt, Rosemary; Kim, Hung Lo; Schlenker-Herceg, Rozsa; Barnathan, Elliot S.; Murray, John.

In: American Journal of Respiratory and Critical Care Medicine, Vol. 175, No. 9, 01.05.2007, p. 926-934.

Research output: Contribution to journalArticle

Rennard, SI, Fogarty, C, Kelsen, S, Long, W, Ramsdell, J, Allison, J, Mahler, D, Saadeh, C, Siler, T, Snell, P, Korenblat, P, Smith, W, Kaye, M, Mandel, M, Andrews, C, Prabhu, R, Donohue, JF, Watt, R, Kim, HL, Schlenker-Herceg, R, Barnathan, ES & Murray, J 2007, 'The safety and efficacy of infliximab in moderate to severe chronic obstructive pulmonary disease', American Journal of Respiratory and Critical Care Medicine, vol. 175, no. 9, pp. 926-934. https://doi.org/10.1164/rccm.200607-995OC
Rennard, Stephen I. ; Fogarty, Charles ; Kelsen, Steven ; Long, William ; Ramsdell, Joe ; Allison, James ; Mahler, Donald ; Saadeh, Constantine ; Siler, Thomas ; Snell, Phillip ; Korenblat, Phillip ; Smith, William ; Kaye, Mitchell ; Mandel, Michael ; Andrews, Charles ; Prabhu, Rachakonda ; Donohue, James F. ; Watt, Rosemary ; Kim, Hung Lo ; Schlenker-Herceg, Rozsa ; Barnathan, Elliot S. ; Murray, John. / The safety and efficacy of infliximab in moderate to severe chronic obstructive pulmonary disease. In: American Journal of Respiratory and Critical Care Medicine. 2007 ; Vol. 175, No. 9. pp. 926-934.
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abstract = "Rationale: Chronic obstructive pulmonary disease (COPD) is a progressive, smoking-related, inflammatory lung disease in which tumor necrosis factor-α is overexpressed and has been suggested to play a pathogenic role. Objectives: To determine if infliximab, an anti-TNF-α 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. Measurements and Main 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 FEV1, 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.",
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AU - Fogarty, Charles

AU - Kelsen, Steven

AU - Long, William

AU - Ramsdell, Joe

AU - Allison, James

AU - Mahler, Donald

AU - Saadeh, Constantine

AU - Siler, Thomas

AU - Snell, Phillip

AU - Korenblat, Phillip

AU - Smith, William

AU - Kaye, Mitchell

AU - Mandel, Michael

AU - Andrews, Charles

AU - Prabhu, Rachakonda

AU - Donohue, James F.

AU - Watt, Rosemary

AU - Kim, Hung Lo

AU - Schlenker-Herceg, Rozsa

AU - Barnathan, Elliot S.

AU - Murray, John

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N2 - Rationale: Chronic obstructive pulmonary disease (COPD) is a progressive, smoking-related, inflammatory lung disease in which tumor necrosis factor-α is overexpressed and has been suggested to play a pathogenic role. Objectives: To determine if infliximab, an anti-TNF-α 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. Measurements and Main 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 FEV1, 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.

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