Combined treatment of giant-cell arteritis with methotrexate and prednisone. a randomized, double-blind, placebo-controlled trial

Ann Intern Med. 2001 Jan 16;134(2):106-14. doi: 10.7326/0003-4819-134-2-200101160-00010.


Background: Corticosteroids remain the cornerstone of therapy for giant-cell arteritis, but relapse during dose tapering and corticosteroid-related adverse events often complicate management of this condition. Although several approaches, including combined therapy with cytotoxic agents, have been suggested to overcome these problems, no study has clearly shown benefits of alternate treatments.

Objective: To analyze the safety and efficacy of combined therapy with corticosteroids and methotrexate in giant-cell arteritis.

Design: Randomized, double-blind, placebo-controlled trial.

Setting: University-based clinic.

Patients: 42 patients with new-onset giant-cell arteritis according to biopsy.

Intervention: High initial doses of corticosteroid were given; the dose was then tapered quickly until therapy was completely withdrawn. Methotrexate or placebo was given weekly from the start of corticosteroid therapy for 24 months.

Measurements: Number of relapses, cumulative dose of corticosteroid, and number of adverse events were assessed on completion of follow-up.

Results: Compared with combined prednisone and placebo therapy, treatment with prednisone and methotrexate reduced the proportion of patients who experienced at least one relapse (45% vs. 84.2%; P = 0.02) and the proportion of patients who experienced multiple relapses (P = 0.004). The mean cumulative dose of prednisone was 4187 +/- 1529 mg in the methotrexate group and 5489.5 +/- 1396 mg in the placebo group (mean difference, 1302 mg [95% CI, 350 to 2253 mg]; P = 0.009). Overall, the rate and severity of adverse events were similar between groups. Treatment was discontinued in 3 patients in the methotrexate group who experienced definite drug-related adverse events. In sensitivity analysis that included patients lost to follow-up, differences between groups in number of relapses and cumulative dose of prednisone were significant.

Conclusions: Treatment with methotrexate plus corticosteroid is a safe alternative to corticosteroid therapy alone in patients with giant-cell arteritis and is more effective in controlling disease.

Publication types

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

MeSH terms

  • Adrenal Cortex Hormones / adverse effects
  • Adrenal Cortex Hormones / therapeutic use*
  • Aged
  • Double-Blind Method
  • Drug Administration Schedule
  • Drug Therapy, Combination
  • Female
  • Follow-Up Studies
  • Giant Cell Arteritis / drug therapy*
  • Humans
  • Immunosuppressive Agents / administration & dosage
  • Immunosuppressive Agents / adverse effects
  • Immunosuppressive Agents / therapeutic use*
  • Male
  • Methotrexate / administration & dosage
  • Methotrexate / adverse effects
  • Methotrexate / therapeutic use*
  • Placebos
  • Prednisone / administration & dosage
  • Prednisone / adverse effects
  • Prednisone / therapeutic use*
  • Recurrence
  • Sensitivity and Specificity
  • Statistics, Nonparametric


  • Adrenal Cortex Hormones
  • Immunosuppressive Agents
  • Placebos
  • Prednisone
  • Methotrexate