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 γδ and ThGM-CSF T-cell abundance with cT1 and PDFF. scRNAseq highlighted baseline transcriptomic signatures in MAIT cells associated with cT1 and PDFF. Naïve 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.

Key messages

• IL-17 inhibition was associated with a significant reduction in hepatic steatosis (PDFF) and liver inflammatory disease activity (cT1).

• Baseline γδ and ThGM-CSF T cell abundance was associated with cT1 and PDFF, and γδ T cells and cT1 and PDFF co-varied over follow up. Distinct gene expression signatures in MAIT and naïve CD4 T cells at baseline were associated with liver MRI parameters.

• Our results support larger mechanistic and clinical studies to test if IL-17 pathway inhibition improves liver disease in PsD, and whether treatment decision algorithms should account for metabolic liver disease.