Sviluppo e validazione di nuove misure di valutazione dello stato di malattia nella dermatomiosite giovanile

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Innovative Research Design to Meet the Challenges of Clinical Trials for Juvenile Dermatomyositis

Purpose of Review: This paper aims to provide a summary of the recent therapeutic advances and the latest research on outcome measures for clinical trials in juvenile dermatomyositis (JDM). Recent Findings: Recent randomized controlled trials (RCTs) have demonstrated the superiority of the combination of prednisone with methotrexate over other conventional therapies and the potential effectiveness of rituximab in refractory cases. A multinational project has led to develop new criteria for the definition of minimal, moderate, and major improvement in future JDM clinical trials. This effort has been paralleled by the establishment of criteria for clinically inactive disease. The validation of the first composite disease activity score for JDM is in progress. Summary: The new outcome measures will increase the reliability of assessment of clinical response in JDM clinical trials and foster future multinational RCTs aimed to investigate novel treatment strategies for refractory forms of JDM

Experience with the use of mycophenolate mofetil in juvenile idiopathic inflammatory myopathies

Objective The objective of this study was to evaluate the efficacy and safety of MMF in juvenile idiopathic inflammatory myopathies (JIIMs). Methods Patients diagnosed with JIIM and treated with MMF enrolled in the Juvenile Dermatomyositis Research Group (JDRG) in the UK or followed at the Giannina Gaslini Institute in Genoa, Italy, were included. The following information was collected retrospectively at MMF initiation, at 3, 6 and 12 months after treatment start, and at last follow-up visit: clinical manifestations, laboratory data, physicians' subjective assessment of disease activity, standardized outcome measures of muscle strength/endurance, cutaneous disease activity, physical function, global disease activity, cumulative damage, and ongoing treatment. Results Of the 29 patients included, 23 had juvenile DM and 6 had overlap myositis. During administration of MMF, improvement in measures of muscle strength, skin disease activity, and overall disease activity was seen, with an increase in the frequency of normal scores for Manual Muscle Test-8 from 50.0% to 83.3%, Childhood Myositis Activity Score from 53.5% to 88.9%, muscle component of DAS from 55.2% to 84.2%, skin component of DAS from 31.0% to 42.1%, visual analogue scale for skin disease activity from 25.0% to 47.4%, and visual analogue scale for overall disease activity from 7.1% to 42.1%. The number of patients with inactive disease increased from 10.3% at baseline to 68.5% at last follow-up. CS dose was significantly reduced, from 0.3 to 0.1 mg/kg/day. No relevant side effects were reported. Conclusion Our experience suggests that MMF is a valuable therapeutic option for the management of JIIM

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

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

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

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

Development and testing of reduced versions of the MMT-8 in juvenile dermatomyositis

Objective To develop and test shortened versions of Manual Muscle Testing-8 (MMT-8) in juvenile dermatomyositis (JDM). Methods Construction of reduced tools was based on retrospective analysis of individual scores of MMT-8 muscle groups in three multinational datasets. The 4 and 6 most frequently impaired muscle groups were included in MMT-4 and MMT-6, respectively. Metrologic properties of reduced tools were assessed by evaluating construct validity, internal consistency, discriminant ability, and responsiveness to change. Results Neck flexors, hip extensors, hip abductors and shoulder abductors were included in MMT-4, whereas MMT-6 also included elbow flexors and hip flexors. Both shortened tools revealed strong correlations with MMT-8 and other muscle strength measures. Correlations with other JDM outcome measures were in line with predictions. Internal consistency was good (0.88-0.96) for both MMT-4 and MMT-6. Both reduced tools showed strong ability to discriminate between disease activity states, assessed by the caring physician or a parent (p < 0.001), and between patients whose parents were satisfied or not satisfied with illness course (p < 0.001). Responsiveness to change (assessed by both standardized response mean and relative efficiency) of MMT-4 and, to a lesser degree, MMT-6, was slightly superior to that of MMT-8. Conclusion The metrologic performance of MMT-4 and MMT-6 was overall comparable to that of the other established muscle strength tools, which indicate that they may be suitable for use in clinical practice and research, including clinical trials. The measurement properties of these tools should be further tested in other patient populations evaluated prospectively

Development and testing of a hybrid measure of muscle strength in juvenile dermatomyositis for use in routine care

To develop and test a hybrid measure of muscle strength for juvenile dermatomyositis (JDM), which is based on the combination of the Manual Muscle Testing 8 (MMT8) and the Childhood Myositis Assessment Scale (CMAS), but is more comprehensive than the former and more feasible than the latter

Development and validation of a composite disease activity score for measurement of muscle and skin involvement in juvenile dermatomyositis

Objective. To develop a composite DAS for JDM and provide preliminary evidence of its validity. Methods. The Juvenile DermatoMyositis Activity Index (JDMAI) is composed of four items: physician's global assessment of overall disease activity; parent's/child's global assessment of child's wellbeing; measurement of muscle strength; and assessment of skin disease activity. The score of the JDMAI is the arithmetic sum of the scores of each individual component. Six versions of the JDMAI were tested, which differed in the tools used to assess the third and fourth items. Validation procedures were conducted using three large multinational patient samples including a total of 627 patients. Results. The JDMAI was found to possess face and content validity, good construct validity, satisfactory internal consistency (Cronbach's alpha = 0.58-0.89), fair responsiveness to clinically important change (standardized response mean = 0.82-3.12 among patients improved) and strong capacity to discriminate patients judged as being in the state of inactive disease or low, moderate or high disease activity by the physician (P<0.001) or whose parents were satisfied or not satisfied with the course of their child's illness (P<0.001). Overall, the six versions of the JDMAI showed similar metrological performances in validation analyses. Conclusion. The JDMAI was found to possess good measurement properties in a large population of patients with a wide range of disease activity, and is, therefore, suitable for use in both clinical and research settings. The final version of the JDMAI will be selected after its prospective validation