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.
Hoffman
Gary S
GS
Cleveland Clinic Foundation, Cleveland, Ohio 44915, USA. hoffmag@ccf.org
Cid
Maria C
MC
Hellmann
David B
DB
Guillevin
Loic
L
Stone
John H
JH
Schousboe
John
J
Cohen
Pascal
P
Calabrese
Leonard H
LH
Dickler
Howard
H
Merkel
Peter A
PA
Fortin
Paul
P
Flynn
John A
JA
Locker
Geri A
GA
Easley
Kirk A
KA
Schned
Eric
E
Hunder
Gene G
GG
Sneller
Michael C
MC
Tuggle
Carol
C
Swanson
Howard
H
Hernández-Rodríguez
J
J
Lopez-Soto
Alfons
A
Bork
Debora
D
Hoffman
Diane B
DB
Kalunian
Kenneth
K
Klashman
David
D
Wilke
William S
WS
Scheetz
Raymond J
RJ
Mandell
Brian F
BF
Fessler
Barri J
BJ
Kosmorsky
Gregory
G
Prayson
Richard
R
Luqmani
Raashid A
RA
Nuki
George
G
McRorie
Euan
E
Sherrer
Yvonne
Y
Baca
Shawn
S
Walsh
Bridgit
B
Ferland
Diane
D
Soubrier
Martin
M
Choi
Hyon K
HK
Gross
Wolfgang
W
Segal
Allen M
AM
Ludivico
Charles
C
Puechal
Xavier
X
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