A total of 29 experts in myositis (15 in the adult form and 14 in the pediatric form) participated in a 2-day workshop to define clinical improvement in myositis clinical trials. A presentation of each of the core set assessment measures for myositis disease activity - including Physician and Patient Global Disease Activity, muscle strength assessment (using manual muscle strength testing), functional assessment (using Health Assessment Questionnaire), muscle enzymes, and extra-muscular assessment - was made that included a review of the validity and performance of the measure in four NIAMS adult idiopathic inflammatory myopathy (IIM) clinical trials and in a multi-center juvenile IIM natural history study, as well as the use of the measure in published prospective IIM trials. Following this presentation, participants completed a survey regarding the amount of change in each core set measure that in their judgment was clinically significant, for the development of a myositis disease activity index. Both adult and juvenile myositis experts voted for a median improvement of 15% in muscle strength and physical function, 20% improvement in physician, parent/patient global assessments and in extra-muscular activity, and 25-30% improvement in any of the muscle enzymes as the clinically significant improvement in each measure. Both groups rated muscle strength and physician’s global assessment as most important for inclusion in a disease activity index, and muscle enzymes as least important. Both adult and juvenile groups voted for a median improvement in 3 measures in order to rate the patient overall as improved, and both were able to ignore worsening in 1 measure to still consider the patient improved, allowing up to 20% worsening in that measure.

Participants next rated a total of 120 paper patient profiles during 6 separate sessions, in which data for each core set measure was presented at baseline and follow-up. Following silent rating of the profiles, nominal group technique was used to reach consensus on those profiles in which consensus did not exist (defined as 70% agreement). After the nominal group technique format for discussion, consensus in the ratings was achieved for 107 adult paper patient profiles and 111 pediatric paper patient profiles. The ratings of these profiles will be used to analyze definitions of improvement that incorporate the findings of the survey, and to develop the sensitivity and specificity of each of the possible definitions of improvement.

An open discussion of the workshop content was also held at the conclusion of the 2nd day. Recommendations of this discussion included the strong sentiment that absolute changes in the core set measures also be analyzed to establish definitions of improvement, in addition to examination of percentage change in the measures, to establish a disease activity index. There was caution in examining MMT, in that the units of measure had no clinical validity established, and some participants expressed preferences for using alternative measures of strength testing, including quantitative myometry and the Childhood Myositis Assessment Scale. It was recommended that measures starting at 0 or within normal limits not be included as a measure that would count as clinically improved, even though that measure may meet criteria using percentage change (e.g., improvement within the normal range of a muscle enzyme was not considered to be a clinically important change). It was agreed that if one core set measure was absolutely required in a definition of improvement, that it should not be allowed to worsen (whereas several other parameters may worsen by a set amount and the patient could still be rated as improved). Finally, the inability of many core set parameters to distinguish activity from disease damage was considered an urgent issue, and there was felt to be a strong need to develop additional objective measures of activity that would be able to make this distinction.

The workshop concluded with a presentation of the Myositis Damage Index. Data would be retrospectively obtained from the adult and juvenile IIM patients over the course of the coming year, and results of analysis regarding their change in damage, as well as results for the potential definitions of improvement, will be presented at the second workshop next year.

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