Erin Balay-Dustrude

Objective: To assess the validity of the Patient‐Reported Outcomes Measurement Information System (PROMIS) Pediatric measures in patients with chronic nonbacterial osteomyelitis (CNO). Methods: Within the longitudinal patient registry of CNO, English‐speaking patients aged 8 years and older self‐reported PROMIS Pediatric measures of fatigue, pain interference (PI), pain behavior (PB), mobility, upper extremity (UE), physical activity (PA), and strength impact (SI), and external validation measures. Log‐transformed linear mixed‐effects models with random patient intercepts were used to assess PROMIS T‐score changes. Wilcoxon signed‐rank test was performed to determine the PROMIS T‐score changes among the improved, worsened, and unchanged groups. Spearman rank correlation test determined the relationship of PROMIS T‐scores with disease status reported by patients/families. Results: More than 1,000 clinical visits from 184 patients included PROMIS Pediatric measures entries. All PROMIS T‐scores correlated significantly ( P < 0.01) with patient‐reported variables and physician global assessment (PHGA). The correlation between function and mobility, PB, and PI was good (r = 0.4–0.6). The correlation of patient‐reported disease status was strong with PHGA (r = 0.75); moderate with mobility, PB, and PI; and weak with fatigue, SI, UE, and PA. The changes of PROMIS T‐scores over time for mobility, PB, PA, and PI compared with the self‐reported status change were significant ( P < 0.05). After effective treatment, when clinical disease activity score improved by at least three points (n = 18), the change of PROMIS T‐scores for mobility, PB, PI, and UE were significant ( P < 0.05). Conclusion: This study provided evidence supporting the use of PROMIS Pediatric mobility, PB, and PI measures for CNO clinical disease monitoring.

Objective: Multinational research is essential to improve recognition and management of systemic juvenile idiopathic arthritis (sJIA). Current cohorts vary in the clinical variables and outcome measures collected. Adult-onset Still disease (AOSD) and sJIA are widely considered to comprise a single disease spectrum; however, classification criteria and clinical tools differ between groups. This systematic literature review aimed to identify clinical features and outcome measures collected across sJIA and AOSD cohorts worldwide to guide the development of a minimal dataset for Still disease. Methods: A literature search was conducted from 2000 to 2024 using Ovid MEDLINE, Embase, and Wiley Cochrane Library (Trials). Included articles were in English and described sJIA or AOSD cohorts of ≥ 20 patients, reporting patient characteristics, clinical and laboratory features, and outcome measures. Results: A total of 240 articles were included (95 sJIA, 134 AOSD, 11 mixed), from 37 countries, describing 23,136 patients. International League of Associations for Rheumatology classification was used in 77.9% of sJIA studies, whereas 98.5% of AOSD studies used Yamaguchi criteria. There was no clear consensus on the definition of macrophage activation syndrome. Race and ethnicity were only reported in 11.7% of articles. Cohorts evaluated aligned on the most commonly collected laboratory items for both AOSD and sJIA, with some agreement among clinical features, whereas disease outcome measures used to evaluate and follow disease trajectory were variable. Conclusion: Data reporting across sJIA and AOSD cohorts for clinical characteristics and outcome measures is widely heterogeneous. Consensus on the identification of a standardized minimal dataset for Still disease cohorts is needed to foster future collaboration and improve patient outcomes.

Objective: To develop and validate classification criteria for pediatric chronic nonbacterial osteomyelitis (CNO) jointly supported by EULAR and the American College of Rheumatology (ACR). Methods: This international initiative had 4 phases: (1) candidate items were proposed in a survey of pediatric rheumatologists, (2) criteria definition and reduction by Delphi and nominal group technique exercises, (3) criteria weighting using multicriteria decision analysis, and (4) refinement of weights and threshold score in a development cohort of 441 patients and validation in another cohort of 514 patients. Results: The new EULAR/ACR classification criteria for CNO require typical radiographic or magnetic resonance imaging findings and bone pain as an obligatory entry criterion and exclusion criteria of malignancy, infection, vitamin C deficiency, and hypophosphatasia, followed by additive weighted criteria in 5 clinical (site of bone lesions, pattern of bone lesions, age at onset, coexisting conditions, fever) and 4 pathology/laboratory domains (bone biopsy findings if done, anemia, C‐reactive protein level, and erythrocyte sedimentation rate). A total score ≥55 is required for classification as CNO. The new criteria had a sensitivity of 82% and specificity of 98% in the validation cohort. Conclusion: These new classification criteria for pediatric CNO developed with international input reflect current views about CNO, have high specificity and good sensitivity, and provide a key foundation for future CNO research.

Objective: This systematic search and review aimed to evaluate the available literature on discontinuation of adalimumab and other tumor necrosis factor inhibitors (TNFi) for patients with well-controlled chronic inflammatory arthritides. Methods: We conducted a publication search on adalimumab discontinuation from 2000–2023 using PubMed, CINAHL, EMBASE, and Cochrane Library. Included studies evaluated adalimumab discontinuation approaches, tapering schemes, and outcomes including successful discontinuation and recapture after flare, in patients with well-controlled disease. Studies included evaluated rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, and juvenile idiopathic arthritis (JIA). Results: Forty-nine studies were included. Studies evaluating adalimumab alone were limited, and many reported TNFi outcomes as a single entity. Studies on rheumatoid arthritis (RA) (32, 8 RCTs) reported flare rates from 33–87%. Flares with medication tapering were slightly lower than with abrupt stop, and successful recapture was generally high (80–100%). Studies on spondyloarthropathy (12, 4 RCTs), focused on tapering, noting lower flare rates in tapering rather than abruptly stopping, and high recapture rates (~ 90%). Studies on JIA (5) were observational and demonstrated modestly lower flare rates with tapering (17–63%) versus abrupt stopping (28–82%). There was notable variability in study design, follow-up duration, specificity for TNFi results, and controlled pediatric studies. Conclusion: The literature evaluating adalimumab and other TNFi discontinuation, flare rates, and recapture success within the inflammatory arthritis population demonstrated less flare when medications were tapered, over abrupt stop in the RA, spondyloarthropathy, and JIA populations. When medications were restarted after flare, recapture of well-controlled disease was generally high in RA and spondyloarthropathy, and generally favorable in JIA.

Objective: The physician global assessment of disease activity (PhGA) is a tool used nearly ubiquitously by pediatric rheumatologists for the assessment of patient disease activity status. However, this tool lacks standardization in its scoring. This survey aimed to identify score influencing factors, along with inclusion or exclusion of extra‐articular manifestations and imaging, when scoring the PhGA in juvenile idiopathic arthritis (JIA).Methods: Electronic surveys were sent to Paediatric Rheumatology International Trials Organisation and Pediatric Rheumatology Care and Outcomes Improvement Network members who completed a previous survey on scoring of the PhGA. Respondents were asked to rank their top seven factors for inclusion in the PhGA for nonsystemic JIA (nsJIA) and systemic JIA (sJIA), along with ranking extra‐articular manifestations and imaging for inclusion. Frequency and percentage of rank and Likert responses were analyzed, and geographic regions as well as level of experience were compared using the chi‐square test and Fisher's test.Results: A total of 276 respondents from 54 countries and six continents participated. For nsJIA, factors selected by >50% included number of swollen joints, active uveitis, duration of morning stiffness, and number of tender joints. For sJIA, factors selected by >50% were presence and duration of fever, laboratory tests, number of swollen joints, serositis, rash, hepatomegaly, lung disease, and lymphadenopathy. Agreement on the inclusion of extra‐articular factors, such as uveitis, macrophage activation syndrome, and sJIA‐associated lung disease, had >70% moderate or strong agreement for inclusion, whereas psoriasis had only 50.5% agreement for inclusion and imaging had 64.7% agreement for inclusion. Variations in rank between different geographic regions or level of experience were minor.Conclusion: This survey identifies factors that pediatric rheumatology providers find important for PhGA scoring of disease activity, documents varying agreement on inclusion of extra‐articular manifestations of disease, and lays the framework for further consensus work.

Objective: Identification of characteristics associated with active disease in juvenile idiopathic arthritis (JIA) could inform early disease treatment strategies. This study evaluated characteristics associated with active disease at 12 and 24 months after JIA diagnosis in the era in which biologic disease‐modifying antirheumatic drugs (DMARDs) became available for JIA.Methods: This single‐center retrospective study from 2004 through 2018 assessed characteristics associated with active nonsystemic categories of JIA at 12 and 24 months after diagnosis. Relative prevalence (RP) of disease activity was evaluated in relation to prespecified characteristics. Using RP, the effect of increasing biologic DMARD availability on these predictors was assessed at 12 months.Results: A total of 1,151 patients with JIA were included. At 12 months, a 40% to 45% higher point prevalence of active disease was noted in older children (>5 years). Patients with active disease at 3 months had a greater prevalence of active disease at 12 months (RP 1.5, 95% confidence interval [CI] 1.2–1.8) and 24 months (RP 1.3, 95% CI 1–1.6). Compared to oligoarticular JIA, polyarticular RF‐negative, psoriatic, and enthesitis‐related JIA had a greater prevalence of active disease at 12 and 24 months. At 24 months, a greater prevalence of active disease was observed in children ≥10 years. RP of active disease was 25% lower in the late cohort (2013–2018) than in the earliest cohort (2004–2008; RP 0.75, 95% CI 0.62–0.92) when more biologic medications were available, but disease activity predictors were broadly similar over time.Conclusion: Patients with JIA with active disease at 12 and 24 months were older at diagnosis, categorized as polyarticular RF‐negative, psoriatic, or enthesitis‐related JIA. Active disease at 3 months after diagnosis was associated with worse outcomes at 12 and 24 months.

Juvenile idiopathic arthritis (JIA) is a common chronic illness in childhood and comprises seven categories based on the International League of Associations for Rheumatology (ILAR) criteria. Accurate assessment and measurement of the clinical, functional, and quality of life outcomes of patients with JIA are paramount for understanding the disease course and formulating effective treatment strategies. Interest in the development and use of outcome measurements specifically focused on rheumatologic conditions has greatly expanded over the last two decades, adding to and improving upon the established disease measures. Furthermore, many of these measures have been validated using the widely accepted Outcome Measures in Rheumatology (OMERACT) core principles of instrument validation, allowing researchers and clinicians to gain confidence in these tools. This review summarizes the current validated disease outcome measures in JIA, including clinical, imaging, patient-reported, and functional outcome measurement tools, and highlights ongoing work that continues to refine and improve upon the available tools. The clinical disease outcome measures discussed in this review include physician global assessment (PhGA), American College of Rheumatology (ACR, Wallace) criteria for clinical inactive disease and clinical remission, juvenile arthritis disease activity scores (JADAS), juvenile spondyloarthritis disease activity index (JSPaDA), juvenile arthritis damage index (JADAI), and the ACR pediatric response scores. The imaging outcome measures discussed include the Dijkstra composite scores, childhood arthritis radiographic score of the hip (CARSH), and Poznanski Score. The patient-reported disease outcome measures discussed include patient global assessment (PtGA), patient-reported outcome measurement information system for JIA (PROMIS), juvenile arthritis parent/child centered disease assessment index (JAPAI, JACAI), juvenile arthritis multidimensional assessment report (JAMAR), and the Pediatric quality of life inventory rheumatology module (PedsQL). The functional outcome tools discussed include the Childhood Health Assessment Questionnaire (CHAQ), juvenile arthritis functionality scale and index (JAFS and JASI), and Juvenile Arthritis Functional Assessment Report and Scale (JAFAS and JAFAR).