title: Long-term safety study of infliximab in moderate-to-severe chronic obstructive pulmonary disease.
abstract: BACKGROUND
  There was an increased number of malignancies in infliximab-treated (5.7%) over placebo-treated (1.3%) patients in a 44-week, phase 2 clinical study of 234 patients with moderate-to-severe chronic obstructive pulmonary disease (COPD).
  
  
  OBJECTIVE
  To collect malignancy and mortality data from completed clinical studies of infliximab in COPD treatment.
  
  
  METHODS
  The multicenter, observational Remicade Safety Under Long-Term Study in COPD (RESULTS COPD) collected malignancy and mortality data every six months for five years from patients who received ≥1 study-agent dose in a phase 2 study. Co-primary endpoints were the number of patients with malignancy and the number of deaths. Secondary endpoints included the number of patients with a malignancy according to malignancy type.
  
  
  RESULTS
  There was a gap period between the end of the phase 2 study and the initiation of RESULTS COPD, during which six malignancies and 14 deaths were reported spontaneously for the 107 (45.7%) of 234 patients with long-term safety information. Twenty-eight patients (overall 12.0%; placebo 10.4%, infliximab 12.7%) reported malignancies, including 12 patients during RESULTS COPD. Twenty-six patients (overall 11.1%; placebo 9.1%, infliximab 12.1%) died, including nine during RESULTS COPD. Lung cancer was the most common malignancy type (placebo n = 2; infliximab n = 10).
  
  
  CONCLUSIONS
  The greater proportion of malignancies observed with infliximab versus placebo in a phase 2 study diminished over the long-term follow-up. Due to the observational nature, limited patient participation, potential reporting bias from the interim spontaneous reporting period, and unblinding of all patients, more definitive conclusions cannot be drawn.
authors.affiliation: Division of Pulmonary, Critical Care, Sleep & Allergy, Internal Medicine, University of Nebraska Medical Center, 4111 Dewey Avenue, Omaha, NE 68198, USA. srennard@unmc.edu
authors.forename: Stephen I
authors.initials: SI
authors.lastname: Rennard
authors.forename: Susan K
authors.initials: SK
authors.lastname: Flavin
authors.forename: Prasheen K
authors.initials: PK
authors.lastname: Agarwal
authors.forename: Kim Hung
authors.initials: KH
authors.lastname: Lo
authors.forename: Elliot S
authors.initials: ES
authors.lastname: Barnathan
mesh_terms: D000368:Aged; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D000069285:Infliximab; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000139:chemically induced* / Q000401:mortality; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy* / Q000401:mortality; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors; D014481:United States / Q000453:epidemiology
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D000911:Antibodies, Monoclonal; D014409:Tumor Necrosis Factor-alpha; D000069285:Infliximab