Julie A. Brevard, Mark Hurtt, Joanna Horobin, Olga Polyanskaya, James Baker, Victoria P. Werth, David F. Fiorentino
Objective: Skin inflammation is a universal characteristic of the multisystem inflammatory myopathy dermatomyositis (DM). About 35% of DM patients have a polycyclic or chronic disease course, usually due to active skin disease, despite standard of care therapy, demonstrating a significant unmet need for novel treatment options. To test the efficacy of novel therapeutics, feasible prospective clinical trials must be designed that employ quantitative endpoints. The Cutaneous Dermatomyositis Disease Area and Severity Index (CDASI) is a validated, reliable, and responsive measurement of cutaneous DM disease activity and damage. The primary objectives were to identify requisite design parameters (e.g., target trial population, duration, frequency of assessments, treatment difference, sample size) for a proofofconcept clinical trial of a novel therapy in patients with DM.
Methods: Trial simulations were conducted to determine sample size and statistical power. Simulation inputs were obtained from analyses of CDASI natural history data obtained from 115 adult DM patients followed at Stanford University.
Results: A population with baseline CDASI Activity scores ≥ 15 was simulated to eliminate a potential floor effect in patients with milder disease and to mimic a clinical trial population with moderate to severe skin disease. Given a 24 weeks trial with monthly disease assessments, simulations demonstrated that 45 patients per group were required to detect a 5 point treatment difference and 12 patients per group were required to detect a 10 point treatment difference with 80% statistical power using a 2 sided test.
Conclusion: This study provides evidence that the CDASI is a practical and feasible primary efficacy endpoint for DM clinical trials and lays out a framework for a clinical trial using CDASI as a primary endpoint.