In June 2014, just prior to the Annual European Congress of Rheumatology in Paris, a special panel of rheumatology, neurology, and dermatology experts from across the globe came together to reach a consensus on new myositis response criteria for adult dermatomyositis and polymyositis and juvenile dermatomyositis.
This seminal work, seen as a step towards development of future therapeutics in myositis, was possible with the support of ACR and EULAR and built on the collaborative work of the International Myositis Assessment and Clinical Studies (IMACS) group and the Pediatric Rheumatology International Trials Organization (PRINTO), as well as numerous investigators and institutions around the world, including the National Institutes of Health (NIH) and myositis patient support groups. The panel reached consensus on composite response criteria to be used in myositis clinical trials, using core set measurements from IMACS and PRINTO.
In the Wednesday morning symposium New Adult and Juvenile Myositis Response Criteria, two members of the steering committee and consensus leaders from that landmark gathering in Paris will provide an overview of the new myositis response criteria, specifically describing how the criteria can be applied to the clinical setting and clinical trials.
“In myositis, there has been a paucity of clinical trials, partly due to lack of good response criteria, which has basically halted the progress of the field of polymyositis and dermatomyositis,” said Rohit Aggarwal, MD, MS, Assistant Professor of Medicine, Division of Rheumatology, University of Pittsburgh. “Efforts by the IMACS group led to the development of core set measures in the early 2000s. Subsequent to that, response criteria were proposed by IMACS, which was only partially validated and was considered preliminary.”
While there was some improvement after the development of those preliminary criteria, and a few clinical trials have been conducted since their development, there were several shortcomings of the criteria, most notably a lack of wide acceptance outside of the United States and outside the rheumatology specialty.
“In developing the new criteria, with the help of ACR and EULAR, we united the whole myositis community — adult and pediatric, different specialties, IMACS, and PRINTO — to work together on this project,” said Lisa G. Rider, MD, Deputy Unit Chief, Environmental Autoimmunity Group, Clinical Research Branch, National Institute of Environmental Health Sciences, NIH. “We used all the data sets available over the past ten years, all of the natural history study data sets and small clinical trials, as well as the larger randomized controlled trial data sets, including the Rituximab in Myositis trial and the PRINTO new onset JDM trial.”
The final response criteria are based on “conjoint analysis methodology,” Dr. Aggarwal said, in which each of the six core-set measures is evaluated in clinical trial and, based on a patient’s responses in the trial, a composite or “total improvement” score is generated.
“It’s a continuous measure on a scale of 0 to 100, with a higher score representing a higher magnitude of improvement,” he said. “Within that measurement, we established thresholds such that a patient with a score above 20 is considered minimally improved, moderately improved above 40, and significantly improved above 60. Similarly, we developed pediatric cut-offs of 30, 40, and 70 for juvenile dermatomyositis.”
Dr. Rider believes that the introduction of the new response criteria represents an important paradigm shift by providing a measurement system that reflects absolute percent change and a continuous improvement score rather than the relative percent change and dichotomous “improvement” or “no improvement” provided by the preliminary criteria. Importantly, she said, there are validated criteria not only for minimal clinical improvement but also moderate and major clinical responses.
“It’s a new way of looking at response criteria,” she said. “This should greatly improve the sensitivity and our power to detect different gradations of response, providing therapeutic endpoints for myositis therapeutic trials and clinical studies.”