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Persistent inflammation refractory to standard antirheumatic therapy in children with juvenile spondylarthropathy (SpA) leads to morbidity and reduced quality of life. Tumor necrosis factor α (TNFα) plays an important role in the pathogenesis of synovitis and enthesitis. This study was undertaken to examine the impact of anti‐TNFα agents on juvenile SpA that is refractory to nonsteroidal antiinflammatory drugs (NSAIDs), disease‐modifying antirheumatic drugs, and corticosteroids.Ten juvenile SpA patients with a mean ± SEM age of 15.0 ± 0.7 years and disease duration of 4.4 ± 0.8 years, all of whom were HLA–B27 positive, were followed up for 1 year after initiation of either infliximab (n = 8) or etanercept (n = 2). Outcomes examined were within‐subject differences in the tender entheseal count (TEC) and active joint count (AJC), markers of inflammation, functional assessments (Childhood Health Assessment Questionnaire [C‐HAQ] score), and requirements for antirheumatic drugs.At baseline, all patients exhibited active arthritis and enthesitis that were resistant to NSAIDs (n = 10), methotrexate (n = 6), sulfasalazine (n = 8), corticosteroids (oral n = 6, intravenous pulse n = 3, and intraarticular n = 6), and bisphosphonates (n = 2). In 2 patients, sulfasalazine (n = 2), corticosteroids (n = 1), and bisphosphonates (n = 1) were stopped after initiation of the anti‐TNFα agent. In all patients, the arthritis and enthesitis significantly improved as evidenced by remission of the TEC and AJC by 6 months that was sustained during the 1‐year followup, markers of inflammation and C‐HAQ scores normalized, and there was a reduction in requirements for antirheumatic drugs (reduced dosage or discontinuation of NSAIDs n = 10, methotrexate n = 5, sulfasalazine n = 6, corticosteroids n = 4, and bisphosphonates n = 1).Anti‐TNFα therapy is a potential novel treatment for refractory juvenile SpA. Further prospective studies are required to examine the effectiveness and long‐term outcomes of anti‐TNFα therapy in this cohort. [ABSTRACT FROM AUTHOR]

To compare the safety and efficacy of parenteral methotrexate (MTX) at an intermediate dosage (15 mg/m2/week) versus a higher dosage (30 mg/m2/week) in patients with polyarticular‐course juvenile idiopathic arthritis (JIA) who failed to improve while receiving standard dosages of MTX (8–12.5 mg/m2/week). In the screening phase, 595 patients who were newly started on a standard dose of MTX were followed up for 6 months. Subsequently, the nonresponders, defined according to the American College of Rheumatology (ACR) pediatric 30% improvement criteria (pediatric 30), were randomized to receive an intermediate dose or higher dose of parenteral MTX for an additional 6 months. Improvement in the screening and randomization phase was defined by the ACR pediatric 30 response, as well as by the 50% and 70% response levels (ACR pediatric 50 and ACR pediatric 70, respectively). In the screening phase, after receiving standard doses of MTX, 430 patients (72%) improved according to the ACR pediatric 30, while 360 (61%) met the ACR pediatric 50 and 225 (38%) met the ACR pediatric 70; among these patients, 69 (12%) also met the definition of complete disease control. Of the 133 nonresponders, 80 were randomized to receive an intermediate dose or higher dose of MTX. In the randomization phase, the ACR pediatric 30 response rate was 25 of 40 children (62.5%) in the intermediate‐dose group versus 23 of 40 children (57.5%) in the higher‐dose group. An ACR pediatric 50 response rate was attained by 23 patients (57.5%) receiving an intermediate dose versus 22 (55%) in the higher‐dose group. An ACR pediatric 70 response rate was seen in 18 children (45%) receiving an intermediate dose versus 19 (47.5%) receiving a higher dose. Five children (12.5%) in the intermediate‐dose group versus 4 (10%) receiving the higher dose of MTX also met the definition of complete disease control. None of the intergroup differences in response rate were significant. There were no significant differences in the frequency of adverse events or laboratory abnormalities between the 2 randomized groups. This study shows that the plateau of efficacy of MTX in JIA is reached with parenteral administration of 15 mg/m2/week and that a further increase in dosage is not associated with any additional therapeutic benefit. MTX should be administered for up to 9–12 months to appreciate its full therapeutic effect. [ABSTRACT FROM AUTHOR]