The Paediatric Rheumatology International Trials Organisation Provisional Criteria for the Evaluation of Response to Therapy in Juvenile Dermatomyositis

Paediatric Rheumatology International Trials Organisation, Genoa, Italy.
Arthritis care & research 11/2010; 62(11):1533-41. DOI: 10.1002/acr.20280
Source: PubMed


To develop a provisional definition for the evaluation of response to therapy in juvenile dermatomyositis (DM) based on the Paediatric Rheumatology International Trials Organisation juvenile DM core set of variables.
Thirty-seven experienced pediatric rheumatologists from 27 countries achieved consensus on 128 difficult patient profiles as clinically improved or not improved using a stepwise approach (patient's rating, statistical analysis, definition selection). Using the physicians' consensus ratings as the "gold standard measure," chi-square, sensitivity, specificity, false-positive and-negative rates, area under the receiver operating characteristic curve, and kappa agreement for candidate definitions of improvement were calculated. Definitions with kappa values >0.8 were multiplied by the face validity score to select the top definitions.
The top definition of improvement was at least 20% improvement from baseline in 3 of 6 core set variables with no more than 1 of the remaining worsening by more than 30%, which cannot be muscle strength. The second-highest scoring definition was at least 20% improvement from baseline in 3 of 6 core set variables with no more than 2 of the remaining worsening by more than 25%, which cannot be muscle strength (definition P1 selected by the International Myositis Assessment and Clinical Studies group). The third is similar to the second with the maximum amount of worsening set to 30%. This indicates convergent validity of the process.
We propose a provisional data-driven definition of improvement that reflects well the consensus rating of experienced clinicians, which incorporates clinically meaningful change in core set variables in a composite end point for the evaluation of global response to therapy in juvenile DM.

Download full-text


Available from: Ricardo Russo
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: To investigate the longitudinal association of nailfold capillary density (NCD; as a potential marker of activity) with various other clinical measures of disease activity and to evaluate baseline NCD as a predictor of disease outcome in children with JDM. Data from 809 clinic visits from 92 JDM patients were prospectively collected at each clinic visit over a time period of 5.5 years. The number of capillaries per millimetre at the distal nailfold was scored using a stereomicroscope. Disease activity was determined using the Childhood Myositis Assessment Scale (CMAS) and a modification of the validated disease activity score (DAS), which included three skin (SDAS) and three muscle (MDAS) criteria. An inception cohort subgroup (n=28) with a baseline visit at diagnosis was analysed separately. Both DAS subscores, MDAS (β = -0.04437, P < 0.0001) and SDAS (β = -0.1589, P < 0.0001), as well as the CMAS (β = 0.02165, P < 0.0001) were significantly associated with loss of end row nailfold capillary over time (multiple regression mixed-model analysis). All patients in the inception subcohort showed a reduced baseline NCD (diagnostic sensitivity = 100%) that improved as the disease improved, but this did not predict longer term outcome or course of disease. NCD is a marker of skin and muscle disease activity, and is an important measure of disease activity changes from visit to visit. Determination of capillary density may be useful when making treatment decisions. A decrease in NCD may be considered for inclusion in the diagnostic criteria due to its high sensitivity.
    Full-text · Article · Dec 2010 · Rheumatology (Oxford, England)
  • [Show abstract] [Hide abstract]
    ABSTRACT: Networking is key to overcoming the logistical, methodological and ethical problems related to the implementation of paediatric studies. The adoption of legislation to encourage paediatric clinical trials by the American and European regulatory agencies has opened a new era in the assessment of drug safety and efficacy in children. Two very large international trial networks--the Pediatric Rheumatology Collaborative Study Group (PRCSG) and the Paediatric Rheumatology International Trials Organisation (PRINTO)--have played a critical role in the implementation of this legislation and have facilitated several successful controlled studies on the safety and the efficacy of new and old drugs in paediatric rheumatic diseases. The PRINTO and PRCSG networks can be seen as a model for international co-operation in other paediatric subspecialties.
    No preview · Article · Feb 2011 · Archives of Disease in Childhood
  • [Show abstract] [Hide abstract]
    ABSTRACT: Juvenile dermatomyositis (JDM) is a rare, often chronic autoimmune disease with onset during childhood. It is characterized by weakness in proximal muscles and pathognomonic skin rashes. Although the etiology remains unclear, it has been proposed that JDM is caused by a vasculopathy within the muscle tissue and multiple other organ systems of genetically susceptible individuals, possibly in response to environmental triggers. The goals of treatment include control of the underlying inflammatory myositis and prevention and/or treatment of complications (eg, contractures and calcinosis). Delayed treatment may lead to poorer outcome in terms of disease course and calcinosis. The course in JDM is variable. Monocyclic disease occurs in about one third of patients. These patients have a good response to standard therapy. Early recognition and aggressive immunosuppressive treatment result in improved prognosis.
    No preview · Article · Feb 2011 · Current Rheumatology Reports
Show more