Objective. To determine cutoff values for defining remission, minimal disease activity, and parent and child acceptable symptom state in juvenile idiopathic arthritis (JIA) using the Juvenile Arthritis Disease Activity Score (JADAS).Methods. For the selection of cutoff values, data from a clinical database including 609 children with JIA were used. Optimal cutoff values were determined against external criteria by calculating the 75th percentile of cumulative score distribution and through receiver operating characteristic curve analysis. External criteria included formal definitions of inactive disease and minimal disease activity, subjective rating of remission by physicians, parents, and children, and rating of acceptable symptom state by parents and children. The choice of cutoffs was made based on clinical and statistical grounds. Cross-validation was performed using 4 JIA patient samples that included a total of 1,323 patients, and was based on assessment of construct, discriminant, and predictive validity.Results. With all versions of the JADAS, the cutoff score for classifying a patient as having inactive disease was 1, whereas the cutoff for classification of minimal disease activity was 2 for oligoarticular JIA and 3.8 for polyarticular JIA. Cutoffs for physicians', parents', and children's subjective rating of remission ranged from 2 to 2.3. Cutoffs for acceptable symptom state ranged from 3.2 to 5.4 for parents and from 3 to 4.5 for children. Results of cross-validation analyses strongly supported the selected cutoff values.Conclusion. Cutoff values for classifying various disease states in JIA using the JADAS were developed. In cross-validation analyses, they proved to have good construct and discriminant validity and ability to predict disease outcome.
Objective. To determine cutoff values for defining the states of inactive disease (ID), low disease activity (LDA; or minimal disease activity), moderate disease activity (MDA), and high disease activity (HDA) using the clinical (3-variable) Juvenile Arthritis Disease Activity Score (cJADAS). Methods. For selection of cutoffs, data from a clinical database including 609 children with juvenile idiopathic arthritis (JIA) were used. Optimal cutoffs were determined against external criteria by calculating the 75th and 90th percentile (for ID and LDA) and 10th and 25th percentile (for HDA) of cumulative score distribution and through receiver operating characteristic curve analysis. External criteria included definitions for ID and LDA cutoffs and therapeutic decisions for HDA cutoffs. MDA cutoffs were set at the score interval in-between LDA and HDA cutoffs. Crossvalidation was performed using 2 JIA patient samples (n ؍ 485) and was based on assessment of construct and discriminant validity. Results. The selected cutoffs were as follows: <1 for ID in both oligoarthritis and polyarthritis; <1.5 and <2.5 for LDA in oligoarthritis and polyarthritis, respectively; 1.51-4 and 2.51-8.5 for MDA in oligoarthritis and polyarthritis, respectively; and >4 and >8.5 for HDA in oligoarthritis and polyarthritis, respectively. In crossvalidation analyses, the cutoffs showed a strong ability to discriminate between disease activity states defined subjectively by physicians and parents, levels of pain, and presence/absence of functional impairment and disease damage. Conclusion. Cutoff values for classifying various disease states in nonsystemic JIA using the cJADAS were developed. The cutoffs revealed good measurement characteristics in crossvalidation analyses and are suited for application in clinical practice and research.
Cutoff values for classifying HDA in JIA using the JADAS were developed. In cross-validation analyses, they proved to have good construct and discriminant validity and ability to predict disease outcome.
Systemic juvenile idiopathic arthritis (sJIA) is the form of childhood arthritis whose treatment is most challenging. The demonstration of the prominent involvement of interleukin (IL)-1 in disease pathogenesis has provided the rationale for the treatment with biologic medications that antagonize this cytokine. The three IL-1 blockers that have been tested so far (anakinra, canakinumab, and rilonacept) have all been proven effective and safe, although only canakinumab is currently approved for use in sJIA. The studies on IL-1 inhibition in sJIA published in the past few years suggest that children with fewer affected joints, higher neutrophil count, younger age at disease onset, shorter disease duration, or, possibly, higher ferritin level may respond better to anti-IL-1 treatment. In addition, it has been postulated that use of IL-1 blockade as first-line therapy may take advantage of a “window of opportunity,” in which disease pathophysiology can be altered to prevent the occurrence of chronic arthritis. In this review, we analyze the published literature on IL-1 inhibitors in sJIA and discuss the rationale underlying the use of these medications, the results of therapeutic studies, and the controversial issues.
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