Impact of disease-modifying therapies in adults with concomitant psoriatic and metabolic liver disease with integrated immunoprofiling

Psoriatic disease (PsD) is associated with metabolic dysfunction-associated steatotic liver disease (MASLD), but the hepatic effects of biologic therapies are unclear. We evaluated paired liver MRI and multi-modal immunoprofiling in PsD patients initiating new systemic therapy. COLIPSO is a prospective cohort of adults with moderate-to-severe psoriasis or psoriatic arthritis (PsA) starting a new conventional synthetic or biologic disease-modifying antirheumatic drug (DMARD). Liver MRI was performed at baseline and ~6 months. A subset of participants with PsA underwent peripheral blood flow cytometry and single-cell RNA sequencing (scRNAseq). Primary outcomes were within-subject change in quantitative MRI measures of liver disease activity and fat content (iron-corrected T1 [cT1] and proton density fat fraction [PDFF]). Bayesian models were used. Thirty-five participants (mean age 50 +/- 13 years; 61% male) were followed for ~29 weeks. Baseline disease activity was moderate (mean DAPSA 29) and 40% had MASLD. IL 17 inhibitors (IL-17i) improved PDFF (-1.58 +/- 1.61%) and cT1(-43.6 +/- 52.7ms), whereas TNFi showed little change. Compared with csDMARD, IL 17i improved PDFF (probability of direction [pd] 89%) and cT1 (pd 93%), which was not seen with TNFi. Flow cytometry (n=17) linked baseline gamma delta T-cell and ThGM-CSF T-cell abundance with cT1 and PDFF. scRNAseq highlighted baseline transcriptomic signatures in MAIT cells associated with cT1 and PDFF. Naive T-cell RNA signatures at baseline were associated with MRI improvements. In PsD, only IL-17i were associated with improved liver disease in addition to improving clinical PsD outcomes. T-cell subtypes bridging innate and adaptive immunity were associated with liver disease features.