Early exposure-response modeling of an interferon-beta monoclonal antibody (dazukibart) in adults with dermatomyositis
Abstract
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.
How strong is the evidence?
Evidence Hub reads this as a randomized trial, done in people. Its evidence level is 2 of 5 (High · randomized trial). Randomized trials of a reasonable size are the strongest single-study design.
Read the paper
Related studies
- eggNOG 5.0: a hierarchical, functionally and phylogenetically annotated orthology resource based on 5090 organisms and 2502 viruses
- Online Survival Analysis Software to Assess the Prognostic Value of Biomarkers Using Transcriptomic Data in Non-Small-Cell Lung Cancer
- OptiType: precision HLA typing from next-generation sequencing data
- Nicotinic Cholinergic System and COVID-19: In Silico Identification of an Interaction between SARS-CoV-2 and Nicotinic Receptors with Potential Therapeutic Targeting Implications
- Saccharomyces cerevisiae cells have three Omega class glutathione S-transferases acting as 1-Cys thiol transferases
- Hemolysis at low blood flow rates: in-vitro and in-silico evaluation of a centrifugal blood pump
Go deeper in Evidence Hub
Evidence Hub adds a study data sheet (design, sample size, evidence level, key numbers), an AI summary and a chat grounded in the paper's text.