International Consensus on Preliminary Definitions of Improvement in Adult and Juvenile Myositis

National Institute of Environmental Health Sciences, NIH, Bethesda, Maryland 20892, USA.
Arthritis & Rheumatology (Impact Factor: 7.76). 07/2004; 50(7):2281-90. DOI: 10.1002/art.20349
Source: PubMed


To use a core set of outcome measures to develop preliminary definitions of improvement for adult and juvenile myositis as composite end points for therapeutic trials.
Twenty-nine experts in the assessment of myositis achieved consensus on 102 adult and 102 juvenile paper patient profiles as clinically improved or not improved. Two hundred twenty-seven candidate definitions of improvement were developed using the experts' consensus ratings as a gold standard and their judgment of clinically meaningful change in the core set of measures. Seventeen additional candidate definitions of improvement were developed from classification and regression tree analysis, a data-mining decision tree tool analysis. Six candidate definitions specifying percentage change or raw change in the core set of measures were developed using logistic regression analysis. Adult and pediatric working groups ranked the 13 top-performing candidate definitions for face validity, clinical sensibility, and ease of use, in which the sensitivity and specificity were >/=75% in adult, pediatric, and combined data sets. Nominal group technique was used to facilitate consensus formation.
The definition of improvement (common to the adult and pediatric working groups) that ranked highest was 3 of any 6 of the core set measures improved by >/=20%, with no more than 2 worse by >/=25% (which could not include manual muscle testing to assess strength). Five and 4 additional preliminary definitions of improvement for adult and juvenile myositis, respectively, were also developed, with several definitions common to both groups. Participants also agreed to prospectively test 6 logistic regression definitions of improvement in clinical trials.
Consensus preliminary definitions of improvement were developed for adult and juvenile myositis, and these incorporate clinically meaningful change in all myositis core set measures in a composite end point. These definitions require prospective validation, but they are now proposed for use as end points in all myositis trials.

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Available from: Hermine I Brunner, Sep 30, 2014
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    • "We used the proposed definition by IMACS to define improvement in disease activity during the intervention period [32]. To be a responder, a patient should improve ≥20% in ≥50% of IMACS core measures with no more than two worse by ≥25%, which could not include measures of muscle function (MMT). "
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    ABSTRACT: This randomized, controlled study on patients with polymyositis or dermatomyositis was based on three hypotheses: Patients display impaired endurance due to reduced aerobic capacity and muscle weakness, endurance training improves their exercise performance by increasing the aerobic capacity, and endurance training has general beneficial effects on their health status. In the first part of this study, we compared 23 patients with polymyositis or dermatomyositis with 12 age- and gender-matched healthy controls. A subgroup of patients were randomized to perform a 12 week endurance training program (exercise group, n=9) or to a non-exercising control group (n=6). We measured maximal oxygen uptake (VO2 max) and the associated power output during a progressive cycling test. Endurance was assessed as the cycling time to exhaustion at 65% of VO2 max. Lactate levels in the vastus lateralis muscle were measured with microdialysis. Mitochondrial function was assessed by measuring citrate synthase (CS) and beta-hydroxyacyl-CoA dehydrogenase (beta-HAD) activities in muscle biopsies. Clinical improvement was assessed according to the International Myositis Assessment and Clinical Studies Group (IMACS) improvement criteria. All assessors were blinded to the type of intervention (i.e. training or control). Exercise performance and aerobic capacity were lower in patients than in healthy controls, whereas lactate levels at exhaustion were similar. Patients in the exercise group increased their cycling time, aerobic capacity and CS and beta-HAD activities, whereas lactate levels at exhaustion decreased. Six of nine patients in the exercise group met the IMACS improvement criteria. Patients in the control group did not show any consistent changes during the 12 week study. Polymyositis and dermatomyositis patients have impaired endurance, which could be improved by 12 weeks of endurance training. The clinical improvement corresponds to increases in aerobic capacity and muscle mitochondrial enzyme activities. The results emphasize the importance of endurance exercise in addition to immunosuppressive treatment of patients with polymyositis or dermatomyositis. Trial registration: Identifier NCT01184625.
    Full-text · Article · Aug 2013 · Arthritis research & therapy
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    • "The dosing regimen used with these patients was based on previous studies of ACTH gel in patients with exacerbations of muscle sclerosis and nephrotic syndrome.10,11 Manual muscle testing, recommended in the assessment of treatment outcomes in patients with dermatomyositis and polymyositis, was performed using the Medical Research Council scale at baseline and at 3 months.12–14 A Medical Research Council manual muscle testing scale score of 2 reflects an inability to produce active movement against gravity, a score of 3 reflects active movement against gravity but not resistance, a score of 4 reflects active movement against gravity and resistance, and a score of 5 reflects normal power. "
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    ABSTRACT: Effective and tolerable treatment options for patients with dermatomyositis and polymyositis are limited. This retrospective case review describes treatment with adrenocorticotropic hormone (ACTH) gel in five patients who experienced a disease exacerbation and either failed or were unable to tolerate the side effects of previous therapy with steroids, intravenous immunoglobulins, and steroid-sparing drugs. Patients received ACTH gel subcutaneous injections of 80 U (1 mL) twice weekly (four patients) or once weekly (one patient) over the course of 12 weeks for short-term treatment of symptom exacerbations. Manual muscle testing using the Medical Research Council scale was assessed at baseline and at 3 months. Improvement was seen in all patients, including improved muscle strength, decreased pain, and resolution of skin involvement. All patients tolerated the treatment well, and no significant side effects occurred. The treatment of dermatomyositis and polymyositis is an approved use for ACTH gel, and these anecdotal reports would suggest consideration of ACTH gel as a therapeutic option. Further investigation is warranted.
    Preview · Article · Jun 2012 · Drug Design, Development and Therapy
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    • "The Delphi approach has been widely used in the pediatric rheumatology field, both alone and in combination with the Nominal Group Technique; a structured group-meeting format where meeting participants generate, clarify, and methodically vote for ideas until achieving consensus. [9] These processes have yielded criteria for clinical remission in some categories of juvenile idiopathic arthritis [10], core sets of measures for disease activity and damage in juvenile dermatomyositis and juvenile systemic lupus erythematosus [11], definitions of improvement in juvenile [12] and adult rheumatoid [13] arthritis, definitions of improvement in adult and juvenile myositis, [14] and to develop guidelines for trials of therapies in idiopathic inflammatory myopathies. [15] "
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    ABSTRACT: North American pediatric rheumatologists have created an investigator-initiated research network (the Childhood Arthritis and Rheumatology Research Alliance - CARRA) to facilitate multi-centre studies. One of the first projects undertaken by this network was to define, by consensus, research priorities for the group, and if possible a first group-sponsored clinical trial in which all members could participate. We determined consensus using the Delphi approach. This approach has been used extensively in health research to reach consensus in large groups. It uses several successive iterations of surveys eliciting ideas and opinions from specialists in the field. Three surveys were designed based on this method and were distributed to members of CARRA to elicit and rank-order research priorities. A response rate of 87.6% was achieved in the final survey. The most highly ranked research suggestion was to study infliximab treatment of uveitis unresponsive to methotrexate. Other highly ranked suggestions were to study i) the treatment of systemic arthritis with anakinra and ii) the treatment of pediatric systemic lupus erythematosus with mycophenolate mofetil. The Delphi approach was an effective and practical method to define research priorities in this group. Ongoing discussion and cooperation among pediatric rheumatologists in CARRA and others world-wide will help in developing further research priorities and to facilitate the execution of clinical trials in the future.
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