Background: Retrospective reviews of clinical databases from two sites have identified strong relationships between patient-reported outcomes and skin activity in dermatomyositis (DM), as measured by CDASI-A. ^1,2 No studies validate these associations in a controlled setting. Additionally, the relationship between the PROMIS-29 Short Form and skin activity in DM has not been assessed. Previous investigations have demonstrated a correlation between IL-31 and itch in DM. ³ IFN-β and IFN-γ are known type I and II interferons, which are critical drivers of DM pathogenesis. ⁴

Objectives: To assess correlations between CDASI-A, quality of life (QoL), and biomarkers of disease activity in a double-blind, randomized, placebo-controlled clinical trial.

Methods: Data were retrospectively collected from five visits of a Phase 2 trial evaluating Lenabasum, a cannabinoid receptor type 2 agonist. Quality of life assessments extracted from the trial included Patient Global Assessment (PtGA) scores, PROMIS domains, and Skindex domains. Skindex question 10, regarding itch, was included in the analysis as a separate domain. Physician Global Assessment scores were also evaluated. Additionally, biomarkers derived from skin samples via IHC/PCR collected at visits 1 and 6 were assessed for predictors of CDASI-A response and association with disease activity. Analysis used linear mixed effect models to account for within subject-variability and repeated measures, where applicable. Analysis was performed without regard to treatment arm, as our goal was to correlate CDASI, QoL, and biomarkers among all subjects.

Results: Data from 22 subjects with DM and a combined total of 110 visits were included. Biopsies were collected from 12 subjects. Improvement in CDASI-A significantly correlated with Skindex-S, Skindex-E, Skindex-F, Skindex-Itch, PtGA global skin, PtGA global skin, PtGA global skin, and PtGA global skin, with p < 0.001. Improvement in PROMIS social role (p = 0.046) correlated with improvement in CDASI-A. Worsening of PROMIS fatigue (p = 0.019) and pain (p < 0.001) correlated with improvement in CDASI-A. Decreases in PGA overall disease, PGA skin activity, and PGA global skin all correlated with improvement of CDASI-A (p < 0.001). Change in IL-31 protein area positively correlated with change in disease activity (p = 0.047). A positive relationship between changes in IFN-β and IFN-γ protein area and disease activity trended towards significance.

Conclusion: In accordance with previous investigations from our group, well-established measures of QoL correlated significantly with CDASI-A. These findings support that CDASI-A reflects both clinical and patient-reported aspects of skin disease and is an appropriate outcome in DM clinical trials. Additionally, Skindex and PtGA scores may better relate to skin activity as measured by the CDASI compared to PROMIS domains. IL-31, a cytokine previously associated with itch in DM, ³ correlated significantly with CDASI-A in our study. Trends for IFN-β and IFN-γ reduction with disease improvement support their role in the pathogenesis of DM. This study helps define patient-reported outcomes and biomarkers that may be informative in DM trials.

REFERENCES:

[1]Goreshi R, et al. J Am Acad Dermatol . 2011;65(6):1107-1116

[2]Robinson ES, et al. Br J Dermatol . 2015;172(1):169-174.

[3]Patel J, et al. J Invest Dermatol. 2021;141(9):2151-2160.

[4]Wong D, et al. PLoS One . 2012;7(1):e29161

Disclosure of Interests: Joshua Dan: None declared, Jay Patel: None declared, Grant Sprow: None declared, Josef Concha: None declared, Rui Feng: None declared, Nilesh Kodali: None declared, Thomas Vazquez: None declared, DeAnna Diaz: None declared, Barbara White Shareholder of: Corbus Pharmaceuticals, Victoria Werth Speakers bureau: University of Pennsylvania, which owns the copyright for the CDASI, Grant/research support from: Corbus Pharmaceuticals