Giant cell arteritis: methotrexate reduces relapse on steroids

Clinical bottom line (level 1b)

  1. Patients with giant cell arteritis who take steroids and weekly methotrexate compared with steroids alone were lee likely to relapse.
  2. There was no clear difference in the rate of withdrawal due to adverse effects.
  3. Patients on methotrexate took on average 1100 mg less of prednisone.
Jover et al: Annals of Internal Medicine 2001; 134 : 106-114
Expires June 2005

The study

Double-blinded ?concealed randomised trial without intention-to-treat
Setting: clinic, university hospital, Spain

42 patients (aged mean 72, 69% female) with biopsy-proven giant-cell arteritis

Excluded if
  • history of chronic alcohol abuse (consumption of > 20g/day)
  • active chronic infection
  • history of neoplasm (unless successfully treated > 5 years before screening) or other clinical condition that might hinder follow-up
  • history of poor compliance with other medication
  • previous use of other immunosuppresive drugs
  • more than 2 weeks of high-dose steroid therapy (> 10 mg/d prednisone)
  • contraindications to methotrexate, such as known liver dysfunction or baseline elevation of serum aminotransferase levels to > twice normal
  • renal failure (baseline creatinine > 178 micromol/l)

    Control Group: (n = 21, 19 analysed): placebo
    Experimental Group: (n = 21, 18 analysed): oral methotrexate 10 mg once weekly
    All patients received oral prednisone 60 mg daily. This was gradually tapered by 10 mg per week to reach 40 mg at 1 month. Thereafter 5 mg per week, until 20 mg reached at 2 months. The rate of reduction could be adjusted depending on relapse or adverse effects. All patients received oral calcium and vitamin D. Patients with a history of TB received prophylaxis with isoniazid and folate.
    92% followed for 2 years
    Outcome notes:
    • any relapse : recurrence of symptoms of giant cell arteritis after definitive objective improval, followed by symptom reversal on resumption of or increases in prednisone dose.

    The evidence

    Outcome Time to outcome CER EER RRR
    (95% CI)    		 ARR
    (95% CI)    		 NN T
    (95% CI)
    any relapse 2 years 16
    (84.2%)    		 9
    (50.0%)    		 41%
    (2% to 64%)    		 34.2%
    (5.88% to 62.8%)    		 3
    (2 to 17)
    withdrew due to adverse effects 2 years 1
    (5.26%)    		 5
    (27.8%)    		 -430%
    (-4000% to 32%)    		 --22.5%
    (-45.5% to 0.485%)    		 -4
    (NNT = 210 to infinity;
    NNH = 2 to infinity)

    Outcome Control Group
    (SD)    		 Experimental Group
    (SD)    		 Mean Difference
    (95% CI)
    mean cumulative dose of prednisone (mg) 5365
    (1381)     		4249
    (1517)     		1116
    (210 to 2021)

    Comments

    1. Patients were randomly allocated in blocks of 6.
    2. Adverse effects from methotrexate included leukopenia, anaemia, and mucositis.
    3. The study is too small to show any difference in the rate of withdrawal due to adverse effects. However the overall rate and severity of adverse effects were similar between the 2 groups.

    Citation

    1. Jover JA, Hernandez-Garcia C, Morado IC, et al: combined treatment of giant-cell arteritis with methotrexate and prednisone: a randomized double-blind, placebo-controlled trial. Annals of Internal Medicine 2001; 134 : 106-114
    Search Terms: from Other Articles noted in ACP journal club
    Contributor: Chris Ball, June 2001
    Reviewer:

    Clinical Question.
    Patient giant cell arteritis
    Intervention or Exposure methotrexate
    Comparison placebo
    Outcome relapse
    		•