ACR/EULAR Response Criteria Approved for Adult, Juvenile Myositis

The ACR and EULAR have approved and released response criteria for adult and juvenile myositis, the result of a collaborative initiative that involved the International Myositis Assessment and Clinical Studies Group (IMACS) and the Paediatric Rheumatology International Trials Organisation (PRINTO). The decade-long collaboration was consensus driven, examined multiple clinical data sets and natural history studies, and used 1000Minds software for conjoint analysis.

The consensus documents—“2016 American College of Rheumatology/European League Against Rheumatism Criteria for Minimal, Moderate, and Major Clinical Response in Adult Dermatomyositis and Polymyositis” and “2016 American College of Rheumatology/European League Against Rheumatism Criteria for Minimal, Moderate, and Major Clinical Response in Juvenile Dermatomyositis”—were co-published in Arthritis & Rheumatology and Annals of Rheumatic Diseases in April 2017.

Joint Effort Helps Fill the Void
Rohit Aggarwal, MD, MSc, at the University of Pittsburgh and the project’s methodologic lead, says the effort was “comprehensive, diligent and data driven,” and “will fill the void that was in the field of myositis as related to clinical trials.” Notably, the process “was a confluence of rheumatologists, neurologists and dermatologists coming together to find consensus,” he says.

Lisa Rider, MD, at the National Institute of Environmental Health Sciences, National Institutes of Health in Bethesda, Md., and co-principal investigator, says that myositis has “largely been a field of failed clinical trials” given the lack of criteria for clinical response and data-driven outcome measures. “These criteria will advance our ability to detect clinical response in patients,” she says. The criteria development process was “a major undertaking and a major effort. It was truly an international effort … to get everyone working together and on the same page.”

Why the Need?
Composite response criteria were needed in myositis because of the heterogeneity of the disease and because no single core set measures adequately covered all the domains of myositis, according to the published criteria. For example, muscle enzyme levels can be normal in dermatomyositis (DM), and active muscle weakness in DM can occur without active rash.

Nicolino Ruperto, MD, MPH, at Istituto Giannina Gaslini in Genoa, Italy, and co-principal investigator, says the criteria “should be sensitive in detecting differences in improvement and in quantitating the degree of improvement either in current clinical practice or in future clinical trials.”

Juvenile vs. Adult Thresholds
The response criteria are the same for adult DM/polymyositis (PM) and juvenile DM, but higher thresholds are specified for juvenile DM than for adult DM/PM, because more responsiveness is seen in juvenile DM patients in clinical trials. Also, the juvenile DM response criteria allow for the possibility of using the IMACS or PRINTO core set measures and provide a more definitive threshold for major improvement.

The thresholds differ for adults and children. For each population, a total improvement score using a scale of 0–100 is intended to provide a quantitative assessment of degree of response for each patient. This score is the sum of improvement in each of the following six core set measures:

1. Physician global activity;
2. Patient global activity;
3. Manual muscle testing;
4. Health Assessment Questionnaire (HAQ);
5. Enzymes; and
6. Extramuscular activity in adults.

In juvenile DM, the six core set measures can be either from IMACS, as for adults, or from PRINTO:

1. Physician global activity;
2. Disease Activity Score (DAS);
3. Childhood Myositis Assessment Scale (CMAS);
4. Patient/parents’ global activity;
5. Physical summary score of the Child Health Questionnaire—Parent Form 50 (CHQ-PhS); and
6. Childhood HAQ.

In adults, a total improvement score of 20 or higher would be minimal improvement, 40 or higher would be moderate, and 60 or higher would be major. For juvenile patients, a total improvement score of 30 or higher would be minimal improvement, 45 or higher would be moderate, and 70 or higher would be major. According to the authors, these are hybrid response criteria where the same instrument can be used to define response vs. not as a categorical outcome, as well as the magnitude of response as a continuous measure.

Criteria for Everyday Use
Although these response criteria are intended for use in clinical trials, rheumatologists can apply them in day-to-day practice, Dr. Aggarwal says. A Web-based tool and downloadable calculator will be available later this year that will aid physicians in measuring a patient’s degree of response by entering the patient’s score on the core measures. “The Web-based instrument is primarily designed for clinical trials, but can be used by clinicians to assess response in their myositis patients in clinic,” he says.

“Proper quantification of the degree of improvement in clinical practice after therapy is administered to a patient is the cornerstone of any objective evaluation of treatment response,” Dr. Ruperto says. The availability of the criteria and the use of the Web-based tool will allow practicing rheumatologists to properly monitor the degree of response over time, and then discuss with the patient the continuation of or necessary changes to a personalized treatment plan, he says.

Dr. Rider says that the criteria “will advance our ability to detect clinical response in patients. Because we will all be using the same criteria, the same measures, we will be able to compare different trials and therapies. Hopefully different treatments for myositis will be developed that will help patients.”

Kathy Holliman, MEd, has been a medical writer and editor since 1997.