Data source and study population
Data from an NIH funded clinical trial (NCT00792233) evaluating flare after discontinuation of anti-tumor necrosis factor (anti-TNF) therapy in pJIA were used [11]. This was a multi-center, prospective study with 2 phases conducted over a 14 month, on-protocol period. 137 patients with pJIA and clinically inactive disease were enrolled at tertiary pediatric rheumatology centers in the United States. For the first six months, patients who met the criteria for clinically inactive disease (CID) at enrollment (Wallace criteria [12]) were monitored while on stable therapy. For those who maintained CID for the entire six months, the anti-TNF agent was stopped and follow-up continued for eight more months. Other background therapy remained unchanged, and subjects were observed for the development of a protocol defined disease flare. Patients were monitored at 1, 2, 3, 4, 6 and 8 months after stopping the anti-TNF agent. The original study and this study were both approved by the institutional review boards. Patient consent for publication was obtained in the original study.
Study variables
PtGA scores of disease impact were assessed at every study visit, on a 10-mm visual analog scale (VAS) (scored 0–10), with the question, “Considering all the ways that arthritis affects you/your child, rate how you/your child is doing IN THE PAST WEEK.” Pain was assessed at every study visit, on a 10-mm VAS (scored 0–10), with the question, “How much pain do you think you/your child has had because of your/his/her illness IN THE PAST WEEK?” PhGA scores of disease activity were assessed at every study visit, on a 10-mm VAS (scored 0–10), with the question, “Mark the line to indicate the amount of JIA disease activity TODAY.”
Disease activity was also assessed by physical examination of 71 joints. All patients began the study with clinically inactive disease as measured by the ACR Provisional Criteria [12]. Active disease, or flare, was defined for this secondary analysis, as any active arthritis, using the ACR definition of active joint, when the active joint count had been 0 at the preceding study visit [13]. Inactive disease, or ‘no flare’, was defined for this secondary analysis as an active joint count of 0. PtGA–PhGA discordance was defined as a difference between the PtGA and PhGA scores.
Statistical analysis
Descriptive statistics were computed by ‘flare’ and ‘no flare,’ and student’s t-test, Wilcoxon rank-sum, and chi-square tests were used as appropriate. The change over time in PtGA, PhGA, and pain scores was calculated between every visit. For the first objective, Spearman’s correlation coefficients were calculated to determine the correlations and discordance between all of the global assessment scores, with the following interpretation: 0.2–0.39 ‘weak’, 0.4–0.59 ‘moderate’, 0.6–0.79 ‘strong’, and 0.8–1 ‘very strong’.
To explore whether the PtGA, PhGA and pain score was increased prior to overt flare, analysis was limited to data with a visit immediately prior to flare, defined as data recorded for the visit immediately prior to visit with flare. Finally, for patients who developed flare, a change score with the visit immediately prior to their flare and at baseline was computed. For patients who did not develop flare, we computed a change score with the last visit and at baseline. This change was used to model its association with flare status. Multivariable logistic regression was performed modeling flare as the outcome with the change in assessment score as an independent covariate, adjusting for the first visit assessment score. The area under the curve (AUC) is also reported to summarize the accuracy in delineating flare status based on change in scores, with AUC 0.5 suggesting no discrimination, 0.7 being acceptable, and 0.8–0.9 considered excellent. This was used to explore differences in the global assessment scores between study visits during remission and immediately prior to flare.