Research Identifies Potential Biomarkers for Treatment Response in PsA

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Biologics and methotrexate (MTX) treatment for psoriatic arthritis (PsA) affect serum CXCL10, MMP3, S100A8, ACP5, and CCL2 levels, some of which may have potential use as biomarkers in predicting response to PsA treatment.¹

“Several biomarkers that may aid in the prediction of treatment response of PsA have been proposed. Among them, C-X-C motif Chemokine 10 (CXCL10) was significantly higher in psoriasis patients that develop PsA compared to those that do not. Matrix Metalloproteinase 3 (MMP3) serum levels are higher in PsA patients compared to healthy controls. S100 Calcium Binding Protein A8 (S100A8) showed predictive ability of response to TNFi in synovial tissue of PsA patients. Acid phosphatase 5 (ACP5, also known as Tartrate-Resistant Acid Phosphatase [TRAP]) is differentially expressed between TNFi responders and non-responders. Chemokine ligand 2 (CCL2) is increased in PsA patients and promotes the migration of T cells into the synovium contributing to the joint damage seen in PsA,” lead investigator Rachel Offenheim, Psoriatic Arthritis Research Program, and Schroeder Arthritis Institute, and Krembil Research Institute, University Health Network, Toronto, Canada, and colleagues wrote.¹

Offenheim and colleagues analyzed data from a biobank from patients with PsA treated with TNF inhibitors (TNFi), Interleukin-17 inhibitors (IL-17i), and MTX, compared with patients with PsA untreated with biologic disease-modifying antirheumatic drugs (bDMARDs) or conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) and patients with psoriasis on bDMARDs and matched untreated.² They analyzed serum samples at baseline and at 3-6 months follow-up and quantified protein levels using a Luminex multiplex assay. They developed logistic regression classification models for the predictive potential of the biomarkers. They defined response to treatment as achieving low disease activity or remission according to Disease Activity in PSoriatic Arthritis (DAPSA) Scores, a 75% reduction in Psoriasis Area and Severity Index (PASI) scores, and a 50% reduction in actively inflamed joint count.¹

The investigators found that in participants with PsA, TNFi reduced serum levels of CXCL10 (P <.001), MMP3 (P <.001), S100A8 (P <.001), ACP5 (P <.001), and CCL2 (P <.05, IL-17i increased ACP5 (P <.01) and CCL2 (P <.05), and MTX reduced MMP3 (P <.05). Changes in MMP3 (P <.01) and S100A8 (P <.05) levels were significantly different between patients with untreated PsA and matched patients with biologic-treated PsA. There were no significant differences between patients with treated or untreated PsC.¹

Offenheim and colleagues found that high baseline levels of ACP5 (area under the curve [AUC], AUC = 0.80) in patients with PsA treated with biologics and low baseline levels of MMP3 (AUC=0.80) in patients not treated with biologics were predictive of DAPSA response. High baseline levels of CXCL10 (AUC=0.87) and S100A8 (AUC=0.88) in patients with PsA treated with biologics, while high baseline levels of MMP3 (AUC=0.93) and ACP5 (AUC=0.93) and low baseline levels of S100A8 (AUC=0.86) in patients with PsA not treated with bDMARDs or csDMARDs were predictive of a PASI response. High baseline levels of MMP3 (AUC=0.82) and S100A8 (AUC=0.84), and low baseline levels ACP5 (AUC=0.90) were predictive of a response in actively inflamed joint count in patients with PsA treated with biologics.¹

“In this study, we determined the effect of biologic treatment (TNFi and IL-17i) and MTX on serum CXCL10, MMP3, S100A8, ACP5, and CCL2 in psoriatic arthritis (PsA) patients,” Offenheim and colleagues concluded.¹ “Our results highlight that MMP3, S100A8, ACP5 and CXCL10, have potential use as serum biomarkers to predict response to treatment in PsA patients.”

REFERENCES
1. Offenheim R, Cruz-Correa OF, Ganatra D, Gladman DD. Candidate Biomarkers For Response To Treatment In Psoriatic Disease. J Rheumatol. 2024. 51(9). doi: 10.3899/jrheum.2024-0396
2. Singh JA, Guyatt G, Ogdie A, et al. Special Article: 2018 American College of Rheumatology/National Psoriasis Foundation Guideline for the Treatment of Psoriatic Arthritis. Arthritis Rheumatol. 2019; 71:5-32