Hotline
Methotrexate for
Giant Cell Arteritis
Treatment with corticosteroids
(CS) is usually dramatically effective in the management of active giant cell
arteritis (GCA). Doses of prednisone equivalent of 40-60 mg a day are usually
used at the outset of treatment, with tapering of the dose according to symptoms
over an average of 2-3 years. A majority of patients have at least one relapse
during treatment, and side effects of long-term CS use in the doses required
for control of the disease are seen in 60-80% of patients, with attendant implications
for quality of life and need for medical services. In spite of this, most studies
of survivorship in GCA have not shown a diminished life expectancy in these
patients compared to the general population.
In an effort to reduce the
CS related side effects, numerous adjuvant therapies have been employed by physicians
treating this disease in an anecdotal fashion, particularly azathioprine and
methotrexate, without clear-cut evidence of their efficacy. This issue is of
great interest to practicing rheumatologist, and the subject of two recent studies.
At the 2000 ACR Annual Scientific Meeting in Philadelphia, results of two trials
of methotrexate (MTX) for this indication were reported. One of these, authored
by Jover and colleagues from Madrid, Spain, has since been published (Ann Intern
Med 2001;134:106-11). The other, a multicenter multinational trial authored
by Hoffman and colleagues, is in press.
Both studies were randomized
and placebo controlled. 98 patients with new onset GCA were enrolled in the
Hoffman trial (51 MTX + CS; 47 placebo + CS), and 42 (21 MTX + CS; 21 placebo
+ CS) patients with new onset GCA who had not received more that 10 mg prednisone/day
for the 2 weeks preceding enrollment were entered in the Jover trial. The initial
dose of prednisone was 60 mg/day in the Jover trial, and 1mg/kg/d, up to 60
mg/day in the Hoffman trial. Initial MTX dose in the Jover trial was 10 mg/wk;
this dose was maintained throughout the 24 month trial. The initial dose of
MTX in the Hoffman trial was 0.15 mg/kg/wk and increased to as much as 0.25
mg/kg/wk but not exceeding 15 mg/week total dose for the 12 month duration of
the trial.
In the Jover study, 12 relapses
occurred in 9 patients (43% by intent-to- treat analysis, but only 15 patients
actually completed the trial) in the MTX group, and 26 relapses occurred in
16 patients (76% by intent-to-treat; 18 patients completed the trial) in the
placebo group. Most relapses occurred within the first 30 weeks of treatment.
The mean cumulative dose of prednisone was 4187 + 1529 mg in the MTX group and
5489.5 + 1396 in the placebo group (a difference of 1302 mg, p = 0.009. The
authors reported that 3 patients were withdrawn for MTX related side effects,
and a total of 5 patients in the MTX group were withdrawn prematurely; 1 patient
in the placebo group was withdrawn prematurely. The rate of CS related side
effects was similar in both groups.
In contrast, the Hoffman
study found no difference between the number of relapses and treatment failures
(MTX 54%, placebo 68%; p=0.42), and there were no differences in cumulative
CS doses between groups. Like the Jover study, there was no difference between
groups in CS related toxicity, and the Hoffman study found no differences between
overall treatment toxicities between groups.
Both studies had similar
numbers of relapses in the MTX treated and placebo treated groups, although
the magnitude of difference was greater in the Jover study in this cohort of
a much smaller number of patients. The data about whether MTX has a steroid
sparing effect or efficacy in GCA are limited and underscore the need for more
well done clinical trials with an appropriate sample size to better resolve
this issue.
March 22, 2001
John J. Cush, MD; Eric Matteson, MD
Hotline Editors
Hotline is provided by the
ACR Communications and Marketing Committee as a service to members. This Hotline
reflects the views of the author(s) and does not represent a position statement
of the College.
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