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Researchers from the Netherlands compare three treatment options for patients with recent onset, non-systemic juvenile idiopathic arthritis.
Researchers from the Netherlands report that patients with recent onset, non-systemic juvenile idiopathic arthritis had greater clinical improvement with initial combination therapy of methotrexate and etanercept as compared to two other treatment options.
This study appears in the February 6 online issue of Pediatric Rheumatology.
Juvenile idiopathic arthritis is a diverse set of diseases with seven subtypes and is the most commonly diagnosed autoimmune disease in children, with the exception of systemic juvenile idiopathic arthritis, which many view as an auto inflammatory disease. There are a number of disease modifying anti-rheumatic drugs (DMARD), including biologicals, available for treatment, but there is little information on the use of these therapeutics in children. However, many studies - such as the BeST study of rheumatoid arthritis patients - have demonstrated that disease responds better to treatment when it is treated early.
Led by P.C.E. Hissink Muller, M.D., of Leiden University Medical Center in the Netherlands, this was a single-blinded trial of 94 newly diagnosed patients (67% girls, mean age nine years). Of the 94 patients, 38 percent were ANA positive (antinuclear antibody); 10 had oligo-articular disease; 68 polyarticular JIA; and, 16 had psoriatic arthritis. (Patients with rheumatoid factor-positive JIA, systemic JIA and enthesitis-related JIA were excluded from the study.) The data for this study was collected from the BeSt for Kids study.
Treatment and Findings
The patients were randomized into one of three treatment groups: Monotherapy (sulfasalazine or methotrexate); combination therapy with methotrexate and prednisolone; or, combination therapy with methotrexate and etanercept.
Patients in arm 1: Monotherapy of either sulphasalazine 50 mg/kg up to 2,000 mg per day or methotrexate 10 mg/m2 per week orally or subcutaneous (max 25 mg per week).
Patients in arm 2: Combination therapy started with methotrexate 10 mg/m2 per week orally or subcutaneous (max 25 mg per week) in combination with prednisolone orally 0,.5 mg/kg for four weeks, tapering by one week 0,25 mg/kg and one week 0,125 mg/kg, then stop.
Patients in arm 3: Combination therapy started with etanercept 0,8 mg/kg per week subcutaneous and methotrexate 10 mg/m2/ per week orally or subcutaneous (max 25mg).
After six weeks of treatment, patients in all three groups began to show improvement (ACR Pedi 30, 50 and 70%), which researchers attributed to bridging prednisone therapy, but improvements diminished after tapering and discontinuing prednisone. After three months, ACR Pedi 50 was reached by 10/32 (31%), 12/32 (38%) and 16/30 (53%) (p = 0.19). ACR Pedi 70 was reached by 8/32 (25%), 6/32 (19%) and 14/30 (47%) in arms 1-3 (p = 0.04).
28 percent of all patients experienced at least one adverse event with gastro-intestinal symptoms most frequently reported in 22, 44 and 28 percent of patients in arm 1, 2 and 3, respectively. Mild infections were second with 25, 19 and 43 percent of affected patients in arm 1, 2 and 3, respectively. There were three adverse event-related hospital admissions within the first three months (viral pneumonia from on sulphasalazine in arm 1, one patient with prolonged vomiting from methotrexate in arm 1, and, fever from one patient in arm two).
“During the first three months of the BeSt for Kids study, patients with newly diagnosed JIA who received initial combination therapy with methotrexate and etanercept, had significantly more aACR pedi 70 percent responses, comparable side effects and fewer medication changes as compared to methotrexate or sulfasalazine alone or methotrexate and six weeks prednisone bridging therapy,” wrote Dr. Hissink Muller and colleagues. “Long term follow up data on the extension of initial treatments aiming at inactive disease by a treat to target regime, are needed to relate to these initial positive results.”
This research was supported in part by Pfizer.
P. C. E. Hissink Muller, D. M. C. Brinkman, D. Schonenberg, et al. “A comparison of three treatment strategies in recent onset non-systemic Juvenile Idiopathic Arthritis: initial 3-months results of the BeSt for Kids-study,” Pediatric Rheumatology. Published online February 6, 2017. DOI: 10.1186/s12969-017-0138-4