A treatment-to-target approach is effective in reducing pain in patients with non-systemic juvenile idiopathic arthritis (JIA) regardless of the initial treatment strategy, according to a study published in Pediatric Rheumatology.1 Additionally, findings indicated several baseline-predictors for pain, which may identify patients with a high risk of developing chronic pain.

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JIA, which affects 33 per 100,000 children globally, often causes sleep disturbances, reduces quality of life, and disrupts school attendance. Although disease activity is a known factor of pain severity, it is not the only contributing factor. In fact, children with JIA have been shown to have a lower pain threshold when compared with healthy controls, even when they have no recognizable joint inflammation after treatment. Previous research has hypothesized that peripheral and central sensitization may contribute to a lowering of pain threshold in this patient population.2

“In JIA, treatment-to-target with clinical remission as a treatment goal has been widely recommended,” wrote lead investigator, Katinka Spekking, MS, associated with the Department of Pediatrics, Division of Pediatric Rheumatology, Willem-Alexander Children’s Hospital, Leiden, The Netherlands, and colleagues. “Treating JIA to target makes drug-free inactive disease a feasible outcome for an increasing number of children with non-systemic JIA. However, improved patient reported outcomes, such as less fatigue and pain, have not yet been confirmed for treat to target therapy.”

Pain scores in 3 targeted treatment strategies in patients with JIA, as well as the characteristics of predicting chronic pain, were evaluated in the BeSt-for-Kids-study, a Dutch multicenter, randomized, single-blinded trial. A total of 92 disease-modifying antirheumatic drug (DMARD)-naïve patients were randomized to receive initial sequential DMARD monotherapy, initial methotrexate/prednisone-bridging therapy, or initial methotrexate/etanercept therapy.

The differences in visual analogue scale (VAS) pain scores, defined as 0 – 100 mm, over time was compared between treatment strategies using linear mixed models with visits clustered among patients. A multivariable model evaluated the ability of baseline characteristics to estimate the chance higher pain scores during follow-up.

Pain scores reduced from a mean 55.3 mm at baseline to 19.5 mm at the 24-month mark. On average, pain scores decreased significantly with β -1.37 mm (95% confidence interval [CI] 1.726; -1.022) per month. No significant difference was observed between treatment strategies (interaction term treatment arm time [months] β [95% CI] arm 1: .13 [-.36; .62], arm 2: .37 [-.12; .86], and arm 3).

Several baseline characteristics predicted pain over time. A higher VAS pain score (β .44 [95% CI 0.25; 0.65]) and a higher active joint count (.77 [.19; 1.34]) were shown to be predictive of higher pain over time. However, low VAS physician (-.34 [-.55; -.06]), Child Health Questionnaire Parent Form 50 (CHQ-PF50) Physical (-.42 [-.72; -0.11]), and psychosocial summary score (-.42 [-.77; -.06]) predicted lower pain. The correction for sex and symptom duration revealed similar results.

Investigators noted the sample size of the study limited findings. Further, the study only evaluated pain intensity and did not take a potential response shift during the study period into consideration. Additionally, generalizability may have been limited as patients included in the BeSt-for-Kids-study only included patients with a symptom duration of ≥18 months.

Findings “emphasized the necessity of addressing patient related outcomes in addition to targeted treatment to reduce disease activity,” investigators concluded. “Several baseline predictors for pain over time were found, which could help to identify and support non-systemic JIA-patients with a high risk of pain in addition to a treat-to-target strategy treatment.


  1. Spekking K, Anink J, de Boer P, et al. Significant pain decrease in children with non-systemic Juvenile Idiopathic Arthritis treated to target: results over 24 months of follow up. Pediatr Rheumatol Online J. 2023;21(1):90. Published 2023 Aug 26. doi:10.1186/s12969-023-00874-z
  2. La Hausse de Lalouviere L, Ioannou Y, Fitzgerald M. Neural mechanisms underlying the pain of juvenile idiopathic arthritis. Nat Rev Rheumatol. 2014;10(4):205–11. doi: doi.org/10.1038/nrrheum.2014.4. [published Online First: 2014/02/05].

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