Treat to target (drug-free) inactive disease in DMARD-naive juvenile idiopathic arthritis: 24-month clinical outcomes of a three-armed randomised trial

Abstract

QuestionWhich is the best strategy to achieve (drug-free) inactive disease in juvenile idiopathic arthritis (JIA)?MethodsIn a randomised, single-blinded, study in disease-modifying anti-rheumatic drug (DMARD)-naive patients with JIA, three treatment-strategies were compared: (1) sequential DMARD-monotherapy (sulfasalazine or methotrexate (MTX)), (2) combination therapy MTX + 6 weeks prednisolone and (3) combination therapy MTX +etanercept. Treatment-to-target entailed 3-monthly DMARD/biological adjustments in case of persistent disease activity, with drug tapering to nil in case of inactive disease.After 24 months, primary outcomes were time-to-inactive-disease and time-to-flare after DMARD discontinuation. Secondary outcomes were adapted ACRPedi30/50/70/90 scores, functional ability and adverse events.Results94 children (67 % girls) aged median (IQR) 9.1 (4.6–12.9) years were enrolled: 32 in arms 1 and 2, 30 in arm 3. At baseline visual analogue scale (VAS) physician was mean 49 (SD 16) mm, VAS patient 53 (22) mm, erythrocyte sedimentation rate 12.8 (14.7), active joints median 8 (5–12), limited joints 2.5 (1–4.8) and Childhood Health Assessment Questionnaire score mean 1.0 (0.6).After 24 months, 71% (arm 1), 70% (arm 2) and 72% (arm 3) of patients had inactive disease and 45% (arm 1), 31% (arm 2) and 41% (arm 3) had drug-free inactive disease. Time-to-inactive-disease was median 9.0 (5.3–15.0) months in arm 1, 9.0 (6.0–12.8) months in arm 2 and 9.0 (6.0–12.0) months in arm 3 (p=0.30). Time-to-flare was not significantly different (overall 3.0 (3.0–6.8) months, p=0.7). Adapted ACR pedi-scores were comparably high between arms. Adverse events were similar.ConclusionRegardless of initial specific treatments, after 24 months of treatment-to-target aimed at drug-free inactive disease, 71% of recent-onset patients with JIA had inactive disease (median onset 9 months) and 39% were drug free. Tightly controlled treatment-to-target is feasible.Trial registration number1574.

MRP8/14 and neutrophil elastase for predicting treatment response and occurrence of flare in patients with juvenile idiopathic arthritis

“…At baseline, all patient characteristics were acquired in a standardized manner, but clinical follow-up by the paediatric rheumatologist was not standardized and the investigators had no influence on the timing and data collection of follow-up. This limitation is compensated by cohort II, which consisted of patients participating in the trial; thus all data were prospectively acquired, following the standardized trial protocol [ 16 ], and our data show comparable results for both cohorts.…”

“…For example, regarding response to therapy, few patients could be categorized as responders to treatment in cohort I (10 out of 32 patients after 12 months of treatment), although in cohort II, 66 out of 81 patients were categorized as responders to therapy after 12 months. These numbers clearly demonstrate that the patients in cohort I and II were not similar: the latter cohort consisted of patients participating in a multicentre medication strategy trial [ 16 ]. These patients were younger in age, mainly from the poly-RF– subtype and had a shorter symptom duration and higher disease activity as compared with cohort I, which consisted of non-systemic JIA patients that were seen on our outpatient department and consented to participate in the study.…”

“…The second cohort consisted of 94 patients who participated in the investigator-initiated, multicentre single-blinded BeSt for Kids trial that investigated different treatment strategies in children with new-onset DMARD-naïve JIA [ 16 ]. Written informed consent was obtained from all parents and also from children, if ≥12 years of age.…”

No radiographic wrist damage after treatment to target in recent-onset juvenile idiopathic arthritis

“…We have recently performed a randomized clinical trial using the treatment-to-target approach in recent-onset JIA patients, comparing 3 strategy-arms with different initial and subsequent treatment steps, aiming at inactive disease, including tapering and stopping DMARD therapy [10, 11]. In this population we studied radiographic wrist damage using the Poznanski-score, at baseline and evaluated whether damage occurred or recovered with the abrogation of inflammation in the 3 strategy-arms.…”

Greetings from the editor 2019

“…A RD has also promised to provide readers with actual data for all data points in all figures in articles on clinical trials 1. This is in the process of implementation, as can be seen already in some trial papers published in recent months; the data are shown either directly in the publication (such as in ref 9) or in supplementary materials (such as in ref 10). We sincerely hope that in the future—thinking the thinkable—no publication on clinical trials in any journal will show figures without revealing the data for all data points.…”