The effect of infliximab plus methotrexate on the modulation of inflammatory disease markers in juvenile idiopathic arthritis: analyses from a randomized, placebo-controlled trial.
BACKGROUND
We evaluated the effect of infliximab on markers of inflammation in patients with juvenile idiopathic arthritis (JIA).


METHODS
In this randomized, placebo-controlled substudy, 122 patients with JIA received infliximab 3 mg/kg + methotrexate (MTX)(n = 60) or placebo + MTX (n = 62) at weeks 0, 2, and 6. At week 14, patients receiving placebo + MTX crossed over to infliximab 6 mg/kg + MTX; patients receiving infliximab 3 mg/kg + MTX continued treatment through week 44. Sera and plasma from eligible patients receiving infliximab 3 mg/kg + MTX (n = 34) and receiving placebo→infliximab 6 mg/kg +MTX (n = 38) were collected at weeks 0, 2, 14, 16, 28, and 52 and analyzed for inflammatory markers (IL-6, IL-12p40, ICAM-1, MMP-3, VEGF, TNF-α, and CRP).


RESULTS
At week 2, decreases from baseline in IL-6, ICAM-1, MMP-3, TNF-α, and CRP were greater with infliximab versus placebo treatment, and with the exception of CRP, these differences were generally maintained through week 14. The decreases from baseline to week 52 in IL-6, ICAM-1, VEGF, MMP-3, and CRP and increases in IL-12p40 levels were larger in patients receiving placebo→infliximab 6 mg/kg +MTX versus infliximab 3 mg/kg + MTX treatment. Patients receiving infliximab 3 mg/kg+MTX who achieved an American College of Rheumatology Pediatric 30 (ACR-Pedi-30) response had significantly larger decreases from baseline in ICAM-1 (p = 0.0105) and MMP-3 (p = 0.0253) at week 2 and in ICAM-1 (p = 0.0304), MMP-3 (p = 0.0091), and CRP (p = 0.0011) at week 14 versus ACR-Pedi-30 nonresponders.


CONCLUSIONS
Infliximab + MTX attenuated several inflammatory markers in patients with JIA; larger decreases in ICAM-1, MMP-3, and CRP levels were observed in ACR-Pedi-30 responders versus nonresponders.


BACKGROUND
NCT00036374.
Visvanathan
Sudha
S
IRCCS G, Gaslini and University of Genoa, Genoa, Italy. nicolaruperto@ospedale-gaslini.ge.it.
Wagner
Carrie
C
Marini
Joseph C
JC
Lovell
Daniel J
DJ
Martini
Alberto
A
Petty
Ross
R
Cuttica
Ruben
R
Woo
Patricia
P
Espada
Graciela
G
Gattorno
Marco
M
Apaz
Maria T
MT
Baildam
Eileen
E
Fasth
Anders
A
Gerloni
Valeria
V
Lahdenne
Pekka
P
Quartier
Pierre
P
Saurenmann
Rotraud
R
Travers
Suzanne
S
Mendelsohn
Alan
A
Xu
Stephen
S
Giannini
Edward H
EH
Ruperto
Nicolino
N
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