Time to treatment as an important factor for the response to methotrexate in juvenile idiopathic arthritis.
OBJECTIVE
Methotrexate (MTX) is the most commonly used disease-modifying antirheumatic drug in juvenile idiopathic arthritis (JIA). Currently, individual response to MTX cannot be reliably predicted. Identification of clinical and genetic factors that influence the response to MTX could be helpful in realizing the optimal treatment for individual patients.


METHODS
A cohort of 128 JIA patients treated with MTX were studied retrospectively. Eleven clinical parameters and genotypes of 6 single nucleotide polymorphisms in 5 genes related to the mechanism of action of MTX were compared between MTX responders and nonresponders using a multivariate regression analysis.


RESULTS
The time from diagnosis to start of MTX treatment, physician's global assessment at baseline, and the starting dose were significantly associated with the response to MTX at 6 months after initiation. Patients with a shorter time from diagnosis to start of MTX and a higher disease activity according to the physician but with a lower MTX dose showed an increased response. The effect of the starting dose on MTX response seemed to be mainly due to the influence of the systemic JIA subtype. The time from diagnosis to start of MTX treatment and physician's global assessment at baseline were highly correlated. Therefore, the precise effect size of each independent variable could not be determined.


CONCLUSIONS
In children with JIA, the time from diagnosis to start of MTX appears to be an important factor for MTX response. Our results suggest that an earlier start of MTX treatment will lead to an increased response.
Albers
H M
HM
Leiden University Medical Center, Leiden, The Netherlands.
Wessels
J A M
JA
van der Straaten
R J H M
RJ
Brinkman
D M C
DM
Suijlekom-Smit
L W A
LW
Kamphuis
S S M
SS
Girschick
H J
HJ
Wouters
C
C
Schilham
M W
MW
le Cessie
S
S
Huizinga
T W J
TW
Ten Cate
R
R
Guchelaar
H J
HJ
D000293:Adolescent; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001171:Arthritis, Juvenile / Q000188:drug therapy* / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D004305:Dose-Response Relationship, Drug; D005260:Female; D005787:Gene Frequency; D006801:Humans; D007223:Infant; D008297:Male; D008727:Methotrexate / Q000627:therapeutic use*; D015999:Multivariate Analysis; D020641:Polymorphism, Single Nucleotide; D012189:Retrospective Studies; D013997:Time Factors; D016896:Treatment Outcome
D018501:Antirheumatic Agents; D008727:Methotrexate