A randomized, placebo-controlled trial of infliximab plus methotrexate for the treatment of polyarticular-course juvenile rheumatoid arthritis.
OBJECTIVE
To evaluate the safety and efficacy of infliximab in the treatment of juvenile rheumatoid arthritis (JRA).


METHODS
This was an international, multicenter, randomized, placebo-controlled, double-blind study. One hundred twenty-two children with persistent polyarticular JRA despite prior methotrexate (MTX) therapy were randomized to receive infliximab or placebo for 14 weeks, after which all children received infliximab through week 44. Patients received MTX plus infliximab 3 mg/kg through week 44, or MTX plus placebo for 14 weeks followed by MTX plus infliximab 6 mg/kg through week 44.


RESULTS
Although a higher proportion of patients in the 3 mg/kg infliximab group than in the placebo group had achieved responses according to the American College of Rheumatology (ACR) Pediatric 30 (Pedi 30) criteria for improvement at week 14 (63.8% and 49.2%, respectively), the between-group difference in this primary efficacy end point was not statistically significant (P = 0.12). By week 16, after the crossover from placebo to infliximab 6 mg/kg when all patients were receiving infliximab, an ACR Pedi 30 response was achieved in 73.2% of all patients. By week 52, ACR Pedi 50 and ACR Pedi 70 responses had been reached in 69.6% and 51.8%, respectively, of patients. Infliximab was generally well tolerated, but the safety profile of infliximab 3 mg/kg appeared less favorable than that of infliximab 6 mg/kg, with more frequent occurrences of serious adverse events, infusion reactions, antibodies to infliximab, and newly induced antinuclear antibodies and antibodies to double-stranded DNA observed with the 3 mg/kg dose.


CONCLUSIONS
While infliximab at 3 mg/kg and 6 mg/kg showed durable efficacy at 1 year, achievement of the primary efficacy end point at 3 months did not differ significantly between infliximab-treated and placebo-treated patients. Safety data indicated that the 6-mg/kg dose may provide a more favorable risk/benefit profile. These results warrant further investigation in children with JRA.
Ruperto
Nicolino
N
IRCCS, Istituto G. Gaslini, Genoa, Italy. nicolaruperto@ospedale-gaslini.ge.it
Lovell
Daniel J
DJ
Cuttica
Ruben
R
Wilkinson
Nick
N
Woo
Patricia
P
Espada
Graciela
G
Wouters
Carine
C
Silverman
Earl D
ED
Balogh
Zsolt
Z
Henrickson
Michael
M
Apaz
Maria-Teresa
MT
Baildam
Eileen
E
Fasth
Anders
A
Gerloni
Valeria
V
Lahdenne
Pekka
P
Prieur
Anne-Marie
AM
Ravelli
Angelo
A
Saurenmann
Rotraud K
RK
Gamir
Maria Luz
ML
Wulffraat
Nico
N
Marodi
Laszlo
L
Petty
Ross E
RE
Joos
Rik
R
Zulian
Francesco
F
McCurdy
Deborah
D
Myones
Barry L
BL
Nagy
Kalman
K
Reuman
Peter
P
Szer
Ilona
I
Travers
Suzanne
S
Beutler
Anna
A
Keenan
Greg
G
Clark
Jason
J
Visvanathan
Sudha
S
Fasanmade
Adedigbo
A
Raychaudhuri
Aparna
A
Mendelsohn
Alan
A
Martini
Alberto
A
Giannini
Edward H
EH
D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000009:adverse effects; D018501:Antirheumatic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D001171:Arthritis, Juvenile / Q000188:drug therapy*; D002648:Child; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D000069285:Infliximab; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage* / Q000009:adverse effects
D000911:Antibodies, Monoclonal; D018501:Antirheumatic Agents; D000069285:Infliximab; D008727:Methotrexate