A multicenter, randomized, double-blind, placebo-controlled trial of adjuvant methotrexate treatment for giant cell arteritis.
OBJECTIVE
To evaluate treatment with methotrexate (MTX) in patients with newly diagnosed giant cell arteritis (GCA) to determine if MTX reduces GCA relapses and cumulative corticosteroid (CS) requirements and diminishes disease- and treatment-related morbidity.


METHODS
This was a multicenter, randomized, double-blind study. Over 4 years, 16 centers from the International Network for the Study of Systemic Vasculitides enrolled patients with unequivocal GCA. The initial treatment was 1 mg/kg/day (<or=60 mg every day) prednisone, plus either 0.15 mg/kg/week MTX (increased to 0.25 mg/kg/week, for a maximum weekly dosage of 15 mg) or placebo. Two physicians, both blinded to treatment allocation, evaluated each patient at every trial visit. One physician was responsible for providing global medical care. The other assessed GCA status according to a standard protocol. Treatment failure was defined as 2 distinct relapses or persistence of disease activity after the first relapse, in spite of increased CS therapy.


RESULTS
Ninety-eight patients were enrolled. No significant differences between treatment groups were noted with regard to age, frequency of positive findings on temporal artery biopsy (placebo 87%, MTX 79%), or comorbidities at the time of enrollment. The median dosage of MTX was 15 mg/week. The incidence of treatment failure was comparable between groups after 12 months: 57.5% in the MTX group failed treatment (95% confidence interval [95% CI] 41.6-73.4%) compared with 77.3% in the placebo group (95% CI 61.9-92.8%) (P = 0.26). In a Cox regression analysis, MTX was not associated with a reduced risk of treatment failure (relative risk 0.72; 95% CI 0.41-1.28). There were no significant differences between groups with regard to abnormal elevations of the erythrocyte sedimentation rate following initial remissions, serious morbidity due to GCA, cumulative CS dose, or treatment toxicity. In the MTX group, there were fewer cases of GCA relapse heralded by symptoms of isolated polymyalgia rheumatica (1 case versus 5 in the placebo group; P = 0.05).


CONCLUSIONS
The results of this randomized, multicenter trial do not support the adjunctive use of MTX to control disease activity or to decrease the cumulative dose and toxicity of CS in patients with GCA.
Cleveland Clinic Foundation, Cleveland, Ohio 44915, USA. hoffmag@ccf.org
Gary S
GS
Hoffman
Maria C
MC
Cid
David B
DB
Hellmann
Loic
L
Guillevin
John H
JH
Stone
John
J
Schousboe
Pascal
P
Cohen
Leonard H
LH
Calabrese
Howard
H
Dickler
Peter A
PA
Merkel
Paul
P
Fortin
John A
JA
Flynn
Geri A
GA
Locker
Kirk A
KA
Easley
Eric
E
Schned
Gene G
GG
Hunder
Michael C
MC
Sneller
Carol
C
Tuggle
Howard
H
Swanson
J
J
Hernández-Rodríguez
Alfons
A
Lopez-Soto
Debora
D
Bork
Diane B
DB
Hoffman
Kenneth
K
Kalunian
David
D
Klashman
William S
WS
Wilke
Raymond J
RJ
Scheetz
Brian F
BF
Mandell
Barri J
BJ
Fessler
Gregory
G
Kosmorsky
Richard
R
Prayson
Raashid A
RA
Luqmani
George
G
Nuki
Euan
E
McRorie
Yvonne
Y
Sherrer
Shawn
S
Baca
Bridgit
B
Walsh
Diane
D
Ferland
Martin
M
Soubrier
Hyon K
HK
Choi
Wolfgang
W
Gross
Allen M
AM
Segal
Charles
C
Ludivico
Xavier
X
Puechal
D000368:Aged; D000369:Aged, 80 and over; D018501:Antirheumatic Agents / Q000008:administration & dosage*; D001799:Blood Sedimentation; D004311:Double-Blind Method; D005260:Female; D013700:Giant Cell Arteritis / Q000188:drug therapy* / Q000401:mortality; D006801:Humans; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage*; D008875:Middle Aged; D011237:Predictive Value of Tests; D012008:Recurrence; D017211:Treatment Failure
D018501:Antirheumatic Agents; D008727:Methotrexate