A prediction rule for polyarticular extension in oligoarticular-onset juvenile idiopathic arthritis.

OBJECTIVES: To search for predictors of polyarticular extension in children with oligoarticular-onset juvenile idiopathic arthritis (JIA) and to develop a prediction model for an extended course. METHODS: The clinical charts of consecutive patients with oligoarticular-onset JIA and ≥2 years of disease duration were reviewed. Predictor variables included demographic data, number and type of affected joints, presence of iridocyclitis, laboratory tests including antinuclear antibodies, and therapeutic interventions in the first 6 months. Joint examinations were evaluated to establish whether after the first 6 months of disease patients had persistent or extended course (i.e. involvement of 4 or less, or 5 or more joints). Statistics included univariable and multivariable analyses. Regression coefficients (ß) of variables that entered the best-fitting logistic regression model were converted and summed to obtain a "prediction score" for an extended course. RESULTS: A total of 480 patients with a median disease duration of 7.4 years were included. 61.2% had persistent oligoarthritis, whereas 38.8% experienced polyarticular extension. On multivariable analysis, independent correlations with extended course were identified for the presence of ≥2 involved joints and a CRP >0.8 mg/dl in the first 6 months. The prediction score ranged from 0 to 6 and its cut-off that discriminated best between patients who had or did not have polyarticular extension was >1. Sensitivity and specificity were 59.6 and 79.8, respectively. CONCLUSIONS: The number of affected joints and the CRP level in the first 6 months were the strongest predictors of polyarticular extension in our children with oligoarticular-onset JIA.

Analysis of arthritis flares after achievement of inactive disease with methotrexate monotherapy in juvenile idiopathic arthritis.

OBJECTIVES: To investigate the frequency of arthritis flare and factors affecting occurrence of flare in children with juvenile idiopathic arthritis (JIA) who achieved inactive disease (ID) with methotrexate (MTX) monotherapy. METHODS: A total of 217 patients were included. The modality of treatment discontinuation, time of MTX withdrawal, and disease course were examined retrospectively. For each patient, the first episode of ID after MTX start was evaluated. Patient follow-up was censored at occurrence of flare or at last visit with persistent ID. RESULTS: 170 patients (78.3%) had arthritis flare after a median of 1.6 years, whereas 47 (21.7%) maintained ID until last visit, after a median of 3 years. 54.2% of patients had discontinued MTX after ID, whereas 45.8% were still receiving MTX at the time of study censoring. Among patients who had MTX withdrawn, the median interval between ID and MTX stop was 1.5 years. Occurrence of flare was more common in patients who were still receiving MTX at study censoring than in those who had discontinued MTX (p<0.001). Most patients (78.8%) had MTX tapered over time by increasing the interval between doses. Tapering modality was comparable between patients with flare and persistent ID. Only 7.7% of the patients had a biologic DMARD started at the time of flare. CONCLUSIONS: Our results confirm that children with JIA who achieve ID with MTX monotherapy have a high risk of arthritis flare. The risk of flare was independent of withdrawal strategy. Most flare episodes were not treated with biologic therapy.

Glucocorticoids in juvenile idiopathic arthritis.

Glucocorticoid (GC) drugs are a potent and rapidly effective therapeutic option for the treatment of juvenile idiopathic arthritis (JIA). These medications are mainly used for the management of the extra-articular features of systemic-onset disease. A course of low-dose prednisone may be considered for achieving a rapid disease control in patients with severe polyarthritis refractory to other therapies or while awaiting the full therapeutic effect of a recently initiated disease-modifying antirheumatic drug or biologic agent. Short-term systemic GC administration may also be indicated for chronic iridocyclitis unresponsive to topical therapy. The general objective of GC therapy is to limit the maximum dose and exposure to the highest doses to what is needed to achieve disease control, and then to gradually taper the dose until the minimum level sufficient to maintain disease quiescence over time is reached. High-dose intravenous 'pulse' methylprednisolone administration is sometimes chosen to treat the most severe or acute disease manifestations of systemic JIA, particularly macrophage activation syndrome. Intra-articular GC injection is a safe and rapidly effective treatment for synovitis in children with chronic arthritis. Triamcinolone hexacetonide is the optimal GC preparation for pediatric patients. Local injection therapy is used most frequently to treat oligoarthritis, but the strategy of performing multiple injections to induce disease remission, while simultaneously initiating therapy with second-line or biologic agents, has also been proposed for children with polyarticular JIA. Administration of GCs is associated with potentially deleterious adverse effects, some of which can be irreversible. This highlights the need of a judicious use of these medications and careful monitoring of their toxicity. The recently published recommendations for the management of JIA provide useful guidance to the clinicians for the administration of GCs in children with chronic arthritis.

The conundrum of juvenile psoriatic arthritis.

Juvenile psoriatic arthritis (JPsA) has provided paediatric rheumatologists with a controversial topic for many years. The principal area of contention centres on the discordance between its treatment as a single diagnostic category in current classification schemes and the demonstration of its heterogeneous nature. A further point of debate is the distinctiveness of JPsA as an entity. Owing to these uncertainties, the concept of JPsA has evolved over the years and there have been several changes in its definition and diagnostic criteria. Recently, strong evidence has been provided that the spectrum of JPsA include at least two distinct subgroups, one that has the same characteristics as early-onset ANA-positive JIA, and another that is part of the spectrum of spondyloarthropathies and resembles the forms of psoriatic arthritis in adults that belong to the same disease family. These findings call for a revision of the classification of childhood arthritis, that refutes the assumptions that children with JPsA constitute a single homogeneous population and that JPsA should be considered an individual disease entity.

A new short and simple health-related quality of life measurement for paediatric rheumatic diseases: initial validation in juvenile idiopathic arthritis.

OBJECTIVE: To develop and validate a new short and simple measure of health-related quality of life (HRQL) in children with juvenile idiopathic arthritis (JIA). METHODS: The Paediatric Rheumatology Quality of Life Scale (PRQL) is a 10-item questionnaire that explores HRQL in two domains: physical health (PhH) and psychosocial health (PsH). Validation of the parent proxy report and child self-report versions of the instrument was accomplished by evaluating 472 JIA patients and approximately 800 healthy children. Validation analyses included assessment of feasibility, face and content validity; construct and discriminative ability; internal structure and consistency; test-retest reliability; responsiveness to clinical change; and minimal clinically important difference. RESULTS: The PRQL was found to be feasible and to possess both face and content validity. The PRQL score correlated in the predicted range with most of the other JIA outcome measures, thereby demonstrating good construct validity, and discriminated well between different levels of disease severity. Assessment of internal structure (factor analysis) revealed that the PhH and PsH subscales identify two unambiguously separated domains. The internal consistency (Cronbach's alpha) was 0.86. The intraclass correlation coefficient for test-retest reliability was 0.91. The PRQL revealed fair responsiveness, with a standardized response mean of 0.67 in improved patients. Overall, the PRQL appeared to be more able to capture physical HRQL than psychosocial HRQL. CONCLUSION: The PRQL was found to possess good measurement properties and is, therefore, a valid instrument for the assessment of HRQL in children with JIA. This tool is primarily proposed for use in standard clinical care.

A prediction rule for lack of achievement of inactive disease with methotrexate as the sole disease-modifying antirheumatic therapy in juvenile idiopathic arthritis.

BACKGROUND: To investigate the frequency of achievement of inactive disease (ID) in children with juvenile idiopathic arthritis (JIA) treated with methotrexate (MTX) as the sole disease-modifyng antirheumatic (DMARD) therapy and to develop a prediction model for lack of attainment of ID. METHODS: The clinical charts of consecutive patients started with MTX as the sole DMARD between 2000 and 2013 were reviewed. Patient follow-up was censored at first episode of ID or, in case ID was not reached, at last follow-up visit or when a biologic DMARD was prescribed. The characteristic at MTX start of patients who achieved or did not achieve ID were compared with univariate and multivariable analyses. Regression coefficients (ß) of variables that entered the best-fitting logistic regression model were converted and summed to obtain a "prediction score" for lack of achievement of ID. RESULTS: A total of 375 patients were included in the study. During MTX administration, 8.8% were given systemic corticosteroids and 44.1% intra-articular corticosteroids. After MTX start, 229 (61%) patients achieved ID after a median of 1.7 years, whereas 146 patients (39%) did not reach ID after a median of 1.2 years. On multivariable analysis, independent correlations with lack of achievement of ID were identified for the disease categories of systemic arthritis, enthesitis-related arthritis (ERA) and polyarthritis and C-reactive protein (CRP) >  1.4 mg/dl. The prediction score ranged from 0 to 3 and its cutoff that discriminated best between patients who achieved or did not achieve ID was > 0.5. The categories of systemic arthritis or ERA, both of which had a score greater than 0.5, were sufficient alone to predict a lower likelihood to reach ID. Polyarthritis and increased CRP, whose score was 0.5, assumed a predictive value only when present in association. CONCLUSION: A conventional treatment regimen based on MTX as the sole DMARD led to achievement of ID in a sizeable proportion of children with JIA. Our findings help to outline the characteristics of patients who may deserve a synthetic DMARD other than MTX or the introduction of a biologic DMARD from disease outset.

Juvenile Idiopathic Arthritis: Diagnosis and Treatment.

Juvenile idiopathic arthritis is a broad term that describes a clinically heterogeneous group of arthritides of unknown cause, which begin before 16 years of age. This term encompasses several disease categories, each of which has distinct presentation, clinical manifestations, and, presumably, genetic background and etiopathogenesis. Although none of the available drugs has curative potential, prognosis has greatly improved as a result of substantial progresses in disease management. The most important new development has been the introduction of the biologic medications, which constitute a valuable treatment option for patients who are resistant to conventional antirheumatic agents. Further insights into the disease pathogenesis and treatment will be provided by the continuous advances in understanding of the mechanisms related to the immune response and inflammatory process, and by the development of new drugs that are capable of selectively inhibiting single molecules or pathways.

Clinical outcome measures in juvenile idiopathic arthritis.

Juvenile idiopathic arthritis (JIA), as a chronic condition, is associated with significant disease- and treatment-related morbidity, thus impacting children's quality of life. In order to optimize JIA management, the paediatric rheumatologist has begun to regularly use measurements of disease activity developed, validated and endorsed by international paediatric rheumatology professional societies in an effort to monitor the disease course over time and assess the efficacy of therapeutic interventions in JIA patients.A literature review was performed to describe the main outcome measures currently used in JIA patients to determine disease activity status.The Juvenile Disease Activity Score (JADAS), in its different versions (classic JADAS, JADAS-CRP and cJADAS) and the validated definitions of disease activity and response to treatment represent an important tool for the assessment of clinically relevant changes in disease activity, leading more and more to a treat-to-target strategy, based on a tight and thorough control of the patient condition. Moreover, in recent years, increasing attention on the incorporation of patient-reported or parent-reported outcomes (PRCOs), when measuring the health state of patients with paediatric rheumatic diseases has emerged.We think that the care of JIA patients cannot be possible without taking into account clinical outcome measures and, in this regard, further work is required.

Defining criteria for disease activity states in nonsystemic juvenile idiopathic arthritis based on a three-variable juvenile arthritis disease activity score.

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.

Parent and child acceptable symptom state in juvenile idiopathic arthritis.

OBJECTIVE: To explore the parent and child acceptable symptom state in juvenile arthritis (JA-PASS and JA-CASS, respectively) and estimate the JA-PASS and JA-CASS cutoff values for outcome measures. METHODS: Children with juvenile idiopathic arthritis (JIA) and their parents completed a multi-dimensional questionnaire that included parent-reported and child-reported outcomes and a question about whether they considered the disease state as satisfactory. Additional assessments included demographic data, physician-reported outcomes, and acute-phase reactant levels. Stepwise logistic regression was used to assess contributors to JA-PASS and JA-CASS. Cutoff values of outcome measures that defined JA-PASS and JA-CASS were determined using both 75th percentile and receiver-operating characteristic (ROC) curve methods. Testing procedures included evaluation of discriminative and construct validity of the satisfaction question and assessment of reliability of JA-PASS and JA-PASS cutoffs. RESULTS: Of 584 parents, 385 (65.9%) considered their child in JA-PASS. Of 343 children, 236 (68.8%) considered themselves in JA-CASS. Significant contributors to being in either JA-PASS or JA-CASS were absence of active joints, better rating of overall well-being, and better physical function or health. Cutoff values yielded by 75th percentile and ROC curve methods were similar. Parent, child, and physician global ratings yielded the lowest percentage of false-positive misclassification and the best tradeoff between sensitivity and specificity. The satisfaction question showed good discriminative and construct validity and the JA-PASS and JA-PASS cutoffs were found to be stable over time. CONCLUSION: The acceptable symptom state is a relevant concept for children with JIA and their parents and constitutes a valid outcome measure that is potentially applicable in routine practice and clinical trials.

A new approach to clinical care of juvenile idiopathic arthritis: the Juvenile Arthritis Multidimensional Assessment Report.

OBJECTIVE: To develop and test a new multidimensional questionnaire for assessment of children with juvenile idiopathic arthritis (JIA) in standard clinical care. METHODS: The Juvenile Arthritis Multidimensional Assessment Report (JAMAR) includes 15 parent or patient-centered measures or items that assess well-being, pain, functional status, health-related quality of life, morning stiffness, disease activity, disease status and course, joint disease, extraarticular symptoms, side effects of medications, therapeutic compliance, and satisfaction with illness outcome. The JAMAR is proposed for use as both a proxy-report and a patient self-report, with the suggested age range of 7-18 years for use as a self-report. From March 2007 to September 2009, the questionnaire was completed by the parents of 618 children with JIA in 1814 visits and by 332 children in 749 visits. RESULTS: The JAMAR was found to be feasible and to possess face and content validity. All parents and children reported that the questionnaire was simple and easy to understand. Completion and scoring appeared to be quick, requiring < 15 minutes. There were very few missing data. Parents' proxy-reported and children's self-reported data were remarkably concordant. The JAMAR provided thorough information for the study patients about recent medical history and current health status. It performed similarly across different children's ages and characterized the level of disease activity and disability well. CONCLUSION: The development of the JAMAR introduces a new approach in pediatric rheumatology practice. This new questionnaire may help enhance the quality of care of children with JIA.