Evaluating important change in cutaneous disease activity as an efficacy measure for clinical trials in dermatomyositis

Abstract

Background: Patients may experience improved quality of life (QoL) without complete clearance of skin disease. The Cutaneous Dermatomyositis Disease Area and Severity Index Activity (CDASI-A) score correlates with the Symptoms and Emotions subscales of Skindex-29, a measure of QoL, down to CDASI-A scores of 7 points (for Symptoms) and 10 points (for Emotions).

Objectives: Our goal was to define an important change in disease activity, as measured by the CDASI-A, that results in a meaningful change in QoL in patients with dermatomyositis.

Methods: In 103 patients, we assessed the percentage change and actual change in CDASI-A scores needed to achieve a meaningful improvement in QoL, using linear regression models.

Results: We found that meaningful improvement correlates with 7·86 points (P < 0·001) in Symptoms, and 10·29 points (P < 0·001) in Emotions, after correlating Skindex-29 to an established definition of meaningful change in the Dermatology Life Quality Index (DLQI). For patients with initial CDASI-A scores > 14 points, a 40% change in CDASI-A between the first two visits suggests a meaningful change in Skindex-29. In patients with moderate initial CDASI-A (15-26 points), the changes in CDASI-A resulting in meaningful changes in Symptoms and Emotions were 6 points (P < 0·001) and 7 points (P < 0·001), respectively. For initial CDASI-A scores in the severe range (27-35 points), an improvement in CDASI-A by 11 points (P = 0·030) and 9 points (P = 0·021) leads to a meaningful change in Symptoms and Emotions, respectively.

Conclusions: In patients with an initial CDASI-A score > 14 points, a 40% change in the CDASI-A score can be used to indicate a meaningful change in QoL in future dermatomyositis trials. What's already known about this topic? The Cutaneous Dermatomyositis Disease Area and Severity Index (CDASI) is a validated disease assessment tool used to capture the extent of cutaneous activity and damage. The Skindex-29 and Dermatology Life Quality Index are standardized and validated measures of quality of life (QoL) for clinical trials and correlate with CDASI Activity (CDASI-A) scores. What does this study add? We identified what change in Skindex-29 scores over two consecutive visits would indicate an important change (a minimal clinically important difference) in QoL. We determined which change in CDASI-A scores over two consecutive visits would lead to a meaningful change in QoL. For patients with an initial CDASI-A score > 14 points, a 40% change in the CDASI-A score over two visits is associated with a meaningful change in QoL. What are the clinical implications of this work? Clinical trials can consider using a 40% change in the CDASI-A score as an end point when assessing the clinical efficacy of drugs.

Figure 1:

Two patients with dermatomyositis. On left column: A 33-year-old female with a CDASI-A of 20 which indicates moderate disease. On the right column: A 73-year-old male with severe skin disease and a CDASI-A of 44.