440 CDASI-activity vs IGA scores for dermatomyositis in the lenabasum phase 3 trial

Dermatomyositis(DM) is an autoimmune disease with skin and muscle involvement to varying extents. With its recalcitrance to standard-of-care treatments for some, more treatment options are needed. Clinical trials use outcome measures to assess disease activity, such as the CDASI-activity(CDASI-A) or Investigator’s Global Assessment(IGA) scores for cutaneous disease in DM. To be clinically useful, measures must demonstrate responsiveness to change. We evaluated CDASI-A and IGA scores from the DM lenabasum phase 3 trial. Our study population included both amyopathic(n=22) and classic subtypes(n=145). We assessed physician-reported degrees of improvement in cutaneous disease and corresponding mean changes in CDASI-A and IGA scores from baseline, at weeks 16, 28, and 52. Of note, improvement was defined as 1) no vs yes and 2) if yes, slight vs moderate vs major. Mean changes for no, slight, moderate, and major improvement in CDASI-A include: -4.8; -5.0; -8.6; -12.0 (Week 16), -1.9; -5.5, -8.6, -17.1 (Week 28), and 0.5; -6.2; -13.4; -17.5 (Week 52). Mean changes in IGA include: 0.03; -0.4; -0.9; -1.1 (Week 16), -0.2; -0.4; -0.6; -1.3 (Week 28), and -0.6; -0.8; -1.0; -1.7 (Week 52). CDASI-A mean changes increased for each degree of improvement, with significantly greater improvement than the previous degree(p<0.05). IGA mean changes reflected a 1-1.7 point change corresponding to major improvement, and could only discriminate between no vs yes improvement. Mean score change for slight improvement represents the minimal clinically significant change. This value is close to a 5-point change for CDASI-A, which is consistent with previous research. For IGA, this value is less than a 1-point change and is smaller than the currently used 2-point change threshold for meaningful change. This study is a novel assessment of the CDASI-A and IGA outcomes from the investigator’s perspective in the largest DM study, and suggests preferential use of CDASI-A scores in future DM trials.