Infliximab for maintenance of glucocorticosteroid-induced remission of giant cell arteritis: a randomized trial

Ann Intern Med. 2007 May 1;146(9):621-30. doi: 10.7326/0003-4819-146-9-200705010-00004.

Abstract

Background: Tumor necrosis factor-alpha is present in arteries in giant cell arteritis.

Objective: To evaluate the efficacy of infliximab, an anti-tumor necrosis factor-alpha agent, in giant cell arteritis.

Design: Randomized, controlled trial.

Setting: 22 sites in the United States, the United Kingdom, Belgium, Italy, and Spain.

Patients: 44 patients with newly diagnosed giant cell arteritis that was in glucocorticosteroid-induced remission.

Intervention: Participants were randomly assigned in a 2:1 ratio to receive infliximab (5 mg/kg of body weight) or placebo. Sixteen patients were assigned to glucocorticosteroid plus placebo, and 28 patients to glucocorticosteroid plus infliximab.

Measurements: End points were measured through week 22, when an interim analysis resulted in early stopping of the planned 54-week trial. Primary end points were the number of patients who remained free of relapse through week 22 and adverse events. Secondary end points were time to first relapse, biomarkers, cumulative glucocorticosteroid dose, and the number of patients who remained relapse-free while the glucocorticosteroid dosage was tapered to 10 mg/d.

Results: Infliximab therapy did not increase the proportion of patients without relapse at week 22 compared with placebo (43% vs. 50%, respectively; difference, -7 percentage points [95% CI, -38 to 23 percentage points; P = 0.65), nor did it increase the proportion of patients whose glucocorticosteroid dosages were tapered to 10 mg/d without relapse (61% vs. 75%, respectively; difference, -14 percentage points [CI, -42 to 14 percentage points]; P = 0.31). The incidence of infection was 71% with infliximab and 56% with placebo (difference, 15 percentage points [CI, -14 to 45 percentage points]).

Limitations: The sample was too small to rule out modest effects of infliximab and included only patients with a new diagnosis. Only one dose of infliximab was evaluated, and the study was terminated early.

Conclusions: This trial is too small to draw definitive conclusions, but it provides evidence that using infliximab as maintenance therapy in patients in glucocorticoid-induced remission of newly diagnosed giant cell arteritis is of no benefit and may be harmful. If infliximab has benefit, it is unlikely to be great. ClinicalTrials.gov registration number: NCT00076726.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Anti-Inflammatory Agents / adverse effects
  • Anti-Inflammatory Agents / therapeutic use*
  • Antibodies, Monoclonal / adverse effects
  • Antibodies, Monoclonal / therapeutic use*
  • Blood Sedimentation
  • C-Reactive Protein / metabolism
  • Double-Blind Method
  • Drug Therapy, Combination
  • Female
  • Giant Cell Arteritis / blood
  • Giant Cell Arteritis / drug therapy*
  • Glucocorticoids / therapeutic use*
  • Humans
  • Infliximab
  • Interleukin-6 / blood
  • Male
  • Prednisolone / therapeutic use
  • Prednisone / therapeutic use
  • Remission Induction
  • Secondary Prevention
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors*

Substances

  • Anti-Inflammatory Agents
  • Antibodies, Monoclonal
  • Glucocorticoids
  • Interleukin-6
  • Tumor Necrosis Factor-alpha
  • C-Reactive Protein
  • Prednisolone
  • Infliximab
  • Prednisone

Associated data

  • ClinicalTrials.gov/NCT00076726