Randomized, double-blind, placebo-controlled, pilot trial of infliximab, a chimeric monoclonal antibody to tumor necrosis factor-alpha, in patients with moderate-to-severe heart failure: results of the anti-TNF Therapy Against Congestive Heart Failure (ATTACH) trial

Circulation. 2003 Jul 1;107(25):3133-40. doi: 10.1161/01.CIR.0000077913.60364.D2. Epub 2003 Jun 9.

Abstract

Background: Preclinical and preliminary clinical data have suggested that tumor necrosis factor-alpha (TNFalpha) may play a role in the evolution and progression of heart failure and that inhibition of TNFalpha may favorably modify the course of the disease. We evaluated the efficacy and safety of infliximab, a chimeric monoclonal antibody to TNFalpha, in patients with moderate-to-severe heart failure.

Methods and results: One hundred fifty patients with stable New York Heart Association class III or IV heart failure and left ventricular ejection fraction <or=35% were randomly assigned to receive placebo (n=49), infliximab 5 mg/kg (n=50), or infliximab 10 mg/kg (n=51) at 0, 2, and 6 weeks after randomization and were followed-up prospectively for 28 weeks. Neither dose of infliximab improved clinical status at 14 weeks, the primary endpoint of the study, despite suppression of inflammatory markers (C-reactive protein and interleukin-6) and a modest increase in ejection fraction in the patients receiving 5 mg/kg (P=0.013). Furthermore, after 28 weeks, 13, 10, and 20 patients were hospitalized for any reason in the placebo, 5 mg/kg infliximab, and 10 mg/kg infliximab groups, respectively. The combined risk of death from any cause or hospitalization for heart failure through 28 weeks was increased in the patients randomized to 10 mg/kg infliximab (hazard ratio 2.84, 95% confidence interval 1.01 to 7.97; nominal P=0.043).

Conclusions: Short-term TNFalpha antagonism with infliximab did not improve and high doses (10 mg/kg) adversely affected the clinical condition of patients with moderate-to-severe chronic heart failure.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Monoclonal / adverse effects
  • Antibodies, Monoclonal / blood
  • Antibodies, Monoclonal / therapeutic use*
  • Biomarkers / blood
  • C-Reactive Protein / analysis
  • Disease Progression
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Female
  • Follow-Up Studies
  • Heart Failure / drug therapy*
  • Heart Failure / immunology
  • Humans
  • Infliximab
  • Interleukin-6 / blood
  • Male
  • Middle Aged
  • Pilot Projects
  • Quality of Life
  • Recombinant Fusion Proteins / adverse effects
  • Recombinant Fusion Proteins / blood
  • Recombinant Fusion Proteins / therapeutic use*
  • Survival Analysis
  • Treatment Outcome
  • Tumor Necrosis Factor-alpha / analysis
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors*
  • Tumor Necrosis Factor-alpha / immunology

Substances

  • Antibodies, Monoclonal
  • Biomarkers
  • Interleukin-6
  • Recombinant Fusion Proteins
  • Tumor Necrosis Factor-alpha
  • C-Reactive Protein
  • Infliximab