Dermatomyositis (DM) is a rare and debilitating inflammatory disease associated with muscle weakness and skin manifestations. As with all rare diseases, clinical trials in DM are challenging due to the small number of patients available for study, and DM patients may even present with skin- or muscle-predominant disease. A Phase 2 study of an anti-interferon-beta monoclonal antibody (dazukibart) in DM was recently completed. Most trial data were collected in skin-predominant DM patients, measuring the Cutaneous Dermatomyositis Disease Area and Severity Index (CDASI); the Total Improvement Score (TIS) was only measured in a small subset of muscle-predominant DM patients. Because TIS is a more holistic endpoint, planning for further dazukibart development depended on a robust understanding of TIS response. This analysis aimed to develop an exposure-response model for dazukibart in DM patients. The model was intended to describe the timecourses of all relevant clinical responses, including CDASI and TIS, using the available data to collectively inform the exposure-response relationships. The model provided evidence for a TIS response in DM patients treated with dazukibart that was consistent with the observed data and supportive of further development. The model used here could be applied directly to model-based meta-analysis of other DM trials, and the general approach can be used in rare diseases with multiple endpoints. Trial registration numbers: NCT03181893, NCT02766621.
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