Etanercept Therapy in Rheumatoid Arthritis. A Randomized, Controlled Trial

Ann Intern Med. 1999 Mar 16;130(6):478-86. doi: 10.7326/0003-4819-130-6-199903160-00004.

Abstract

Background: In a phase II study, etanercept (recombinant human tumor necrosis factor receptor [p75]:Fc fusion protein) safely produced rapid, dose-dependent improvement in rheumatoid arthritis over 3 months.

Objective: To confirm the benefit of etanercept therapy of longer duration and simplified dosing in patients with rheumatoid arthritis.

Design: Randomized, double-blind, placebo-controlled trial with blinded joint assessors.

Setting: 13 North American centers.

Patients: 234 patients with active rheumatoid arthritis who had an inadequate response to disease-modifying antirheumatic drugs.

Intervention: Twice-weekly subcutaneous injections of etanercept, 10 or 25 mg, or placebo for 6 months.

Measurements: The primary end points were 20% and 50% improvement in disease activity according to American College of Rheumatology (ACR) responses at 3 and 6 months. Other end points were 70% ACR responses at 3 and 6 months and other measures of disease activity at 3 and 6 months.

Results: Etanercept significantly reduced disease activity in a dose-related fashion. At 3 months, 62% of the patients receiving 25 mg of etanercept and 23% of the placebo recipients achieved 20% ACR response (P < 0.001). At 6 months, 59% of the 25-mg group and 11% of the placebo group achieved a 20% ACR response (P < 0.001); 40% and 5%, respectively, achieved a 50% ACR response (P < 0.01). The respective mean percentage reduction in the number of tender and swollen joints at 6 months was 56% and 47% in the 25-mg group and 6% and -7% in the placebo group (P < 0.05). Significantly more etanercept recipients achieved a 70% ACR response, minimal disease status (0 to 5 affected joints), and improved quality of life. Etanercept was well tolerated, with no dose-limiting toxic effects.

Conclusions: Etanercept can safely provide rapid, significant, and sustained benefit in patients with active rheumatoid arthritis.

Publication types

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

MeSH terms

  • Algorithms
  • Anti-Inflammatory Agents, Non-Steroidal / administration & dosage
  • Anti-Inflammatory Agents, Non-Steroidal / adverse effects
  • Anti-Inflammatory Agents, Non-Steroidal / therapeutic use*
  • Arthritis, Rheumatoid / drug therapy*
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Drug Administration Schedule
  • Etanercept
  • Female
  • Humans
  • Immunoglobulin G / administration & dosage
  • Immunoglobulin G / therapeutic use*
  • Male
  • Middle Aged
  • Patient Dropouts
  • Quality of Life
  • Receptors, Tumor Necrosis Factor / administration & dosage
  • Receptors, Tumor Necrosis Factor / therapeutic use*
  • Recombinant Proteins / administration & dosage
  • Recombinant Proteins / adverse effects
  • Recombinant Proteins / therapeutic use
  • Statistics as Topic

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Immunoglobulin G
  • Receptors, Tumor Necrosis Factor
  • Recombinant Proteins
  • Etanercept