Intra-articular corticosteroids versus intra-articular corticosteroids plus methotrexate in oligoarticular juvenile idiopathic arthritis: a multicentre, prospective, randomised, open-label trial.
Little evidence-based information is available to guide the treatment of oligoarticular juvenile idiopathic arthritis. We aimed to investigate whether oral methotrexate increases the efficacy of intra-articular corticosteroid therapy.



We did this prospective, open-label, randomised trial at ten hospitals in Italy. Using a concealed computer-generated list, children younger than 18 years with oligoarticular-onset disease were randomly assigned (1:1) to intra-articular corticosteroids alone or in combination with oral methotrexate (15 mg/m2; maximum 20 mg). Corticosteroids used were triamcinolone hexacetonide (shoulder, elbow, wrist, knee, and tibiotalar joints) or methylprednisolone acetate (ie, subtalar and tarsal joints). We did not mask patients or investigators to treatment assignments. Our primary outcome was the proportion of patients in the intention-to-treat population who had remission of arthritis in all injected joints at 12 months. This trial is registered with European Union Clinical Trials Register, EudraCT number 2008-006741-70.



Between July 7, 2009, and March 31, 2013, we screened 226 participants and randomly assigned 102 to intra-articular corticosteroids alone and 105 to intra-articular corticosteroids plus methotrexate. 33 (32%) patients assigned to intra-articular corticosteroids alone and 39 (37%) assigned to intra-articular corticosteroids and methotrexate therapy had remission of arthritis in all injected joints (p=0·48). Adverse events were recorded for 20 (17%) patients who received methotrexate, which led to permanent treatment discontinuation in two patients (one due to increased liver transaminases and one due to gastrointestinal discomfort). No patient had a serious adverse event.



Concomitant administration of methotrexate did not augment the effectiveness of intra-articular corticosteroid therapy. Future studies are needed to define the optimal therapeutic strategies for oligoarticular juvenile idiopathic arthritis.



Italian Agency of Drug Evaluation.
Istituto Giannina Gaslini, Genoa, Italy; Università degli Studi di Genova, Genoa, Italy. Electronic address: angeloravelli@gaslini.org.
Angelo
A
Ravelli
Istituto Giannina Gaslini, Genoa, Italy.
Sergio
S
Davì
Università degli Studi di Genova, Genoa, Italy.
Giulia
G
Bracciolini
Istituto Giannina Gaslini, Genoa, Italy.
Angela
A
Pistorio
Istituto Giannina Gaslini, Genoa, Italy; Università degli Studi di Genova, Genoa, Italy.
Alessandro
A
Consolaro
Istituto Giannina Gaslini, Genoa, Italy.
Evert Hendrik Pieter
EHP
van Dijkhuizen
Azienda Ospedaliera Universitaria Ospedali Riuniti Salesi Children's Hospital, Ancona, Italy.
Bianca
B
Lattanzi
Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.
Giovanni
G
Filocamo
Università degli Studi di Genova, Genoa, Italy.
Sara
S
Verazza
Istituto Gaetano Pini, Milan, Italy.
Valeria
V
Gerloni
Istituto Gaetano Pini, Milan, Italy.
Maurizio
M
Gattinara
Istituto Gaetano Pini, Milan, Italy.
Irene
I
Pontikaki
Ospedale Pediatrico Bambino Gesù, Rome, Italy.
Antonella
A
Insalaco
Ospedale Pediatrico Bambino Gesù, Rome, Italy.
Fabrizio
F
De Benedetti
Azienda Ospedaliera Cardinale G Panico, Tricase, Italy.
Adele
A
Civino
Azienda Ospedaliera Cardinale G Panico, Tricase, Italy.
Giuseppe
G
Presta
Ospedale Policlinico, Chieti, Italy.
Luciana
L
Breda
Ospedale Policlinico, Chieti, Italy.
Valentina
V
Marzetti
IRCCS Burlo Garofolo, Trieste, Italy.
Serena
S
Pastore
Ospedale Pediatrico Bambino Gesù, Rome, Italy.
Silvia
S
Magni-Manzoni
Università degli Studi di Palermo, Palermo, Italy.
Maria Cristina
MC
Maggio
Ospedale degli Infermi, Biella, Italy.
Franco
F
Garofalo
Università Cattolica Sacro Cuore e Fondazione Policlinico Universitario A Gemelli, Rome, Italy.
Donato
D
Rigante
Istituto Giannina Gaslini, Genoa, Italy.
Marco
M
Gattorno
Istituto Giannina Gaslini, Genoa, Italy; Università degli Studi di Genova, Genoa, Italy.
Clara
C
Malattia
Istituto Giannina Gaslini, Genoa, Italy.
Paolo
P
Picco
Istituto Giannina Gaslini, Genoa, Italy.
Stefania
S
Viola
Istituto Giannina Gaslini, Genoa, Italy.
Stefano
S
Lanni
Istituto Giannina Gaslini, Genoa, Italy.
Nicolino
N
Ruperto
Istituto Giannina Gaslini, Genoa, Italy; Università degli Studi di Genova, Genoa, Italy.
Alberto
A
Martini
D000305:Adrenal Cortex Hormones; D001171:Arthritis, Juvenile; D006801:Humans; D007270:Injections, Intra-Articular; D007558:Italy; D008727:Methotrexate; D011446:Prospective Studies; D016896:Treatment Outcome
D000305:Adrenal Cortex Hormones; D008727:Methotrexate