Background In the BeSt for Kids (a three-armed treatment strategy study in juvenile idiopathic arthritis (JIA)) time to inactive disease, time to flare after Disease Modifying Anti Rheumatic Drug (DMARD) discontinuation, ACRpedi scores, functional ability, safety, and radiological damage are compared. Follow up will be 2 years. Here we present the 3 months clinical outcomes of initial treatments.
Methods Recent onset, DMARD naïve JIA patients (Rheumatoid Factor-negative polyarticular, oligoarticular or with psoriasis (ILAR-criteria), <18 months symptom duration) were randomized (per center, variable blocks) to 3 treatment strategies: 1. sequential DMARD-monotherapy (starting with sulfasalazine (SSZ) 50mg/kg/day or methotrexate (MTX) 10mg/m2/week, based on physician's preference), 2. combination therapy: MTX 10mg/m2/week and 4 weeks prednisolone-bridging 0.5mg/kg/day, in 2 weeks tapered to nil, and 3. combination therapy with MTX 10mg/m2/week and etanercept 0.8mg/kg/wk.
NSAIDs and intra-articular steroids are permitted in all patients. MTX was combined with folic acid 5mg/week. Treatment adjustments were made every 3 months after assessment by a trained, blinded examiner. Target was ACRpedi50 after 3 months and inactive disease from 6 months and onwards.
Results From October 2009 to April 2014, 95 children, of which 33% boys, were enrolled: 32 in arm 1, 32 in arm 2 and 31 in arm 3. Baseline median (IQR) age was 8,6 (4,5-12,9) years. 38% were ANA positive, 12 patients had oligoarticular disease, 68 patients oligoextended/polyarticular JIA and 15 patients had JIA with psoriasis. Baseline median (IQR) ACRpedi scores: VAS physician 49 (40-58) mm, VAS patient 54 (37-70) mm, ESR 6,5 (2-14,8) mm/hr, number of active joints 8 (5-12), number of joints with limited range of motion 3 (1-5), CHAQ score 0,88 (0,63-1,5). In arm 1, 17/32 had started with MTX, the others with SSZ. One patient in arm 1 (lost to FU) and 1 in arm 3 (uveitis) dropped out before 3 months.
By 3 months ACRpedi50 was reached by 10/32 (31%),12/32 (38%) and 16/30 (53%) (p=0,19) and ACRpedi70 was reached by 8/32 (25%), 6/32 (19%) and 14/30 (47%) in arms 1-3, respectively (p=0.04).
Toxicity (mainly gastrointestinal complaints) was similar in the treatment arms. Three short hospital admissions (serious adverse events) were reported. In 2/32, 1/32 and 2/30 patients MTX dose was reduced or switched to subcutaneous and 3/15 patients stopped SSZ after 6 weeks because of nausea, malaise, headache.
Conclusions After 3 months of initial treatment in a three-armed strategy trial, patients with recent onset JIA achieve more clinical improvement (significantly more ACRpedi70) on initial combination therapy with MTX and etanercept than on initial MTX or SSZ monotherapy. Numerically, response to initial treatment with MTX and prednisolone bridging seems more effective than monotherapy and less effective than combination with etanercept, but these differences were not statistically significant.
Disclosure of Interest P. Hissink Muller Grant/research support from: Pfizer, D. Brinkman: None declared, D. Schonenberg: None declared, Y. Koopman-Keemink: None declared, J. van den Berg: None declared, P. Bekkering: None declared, M. van Rossum: None declared, L. van Suijlekom-Smit: None declared, C. Allaart: None declared, R. ten Cate: None declared