Candidate Biomarkers for Response to Treatment in Psoriatic Disease.

Abstract

Objective: To determine whether biologic therapy alters serum C-X-C motif chemokine ligand 10 (CXCL10), matrix metalloproteinase 3 (MMP3), S100 calcium-binding protein A8 (S100A8), acid phosphatase 5 (ACP5), and C-C motif chemokine ligand 2 (CCL2) levels in patients with psoriatic arthritis (PsA) and cutaneous psoriasis without arthritis (PsC), and whether baseline levels of these proteins predict response to treatment for PsA.

Methods: We included (1) patients with PsA taking tumor necrosis factor inhibitors (TNFi), interleukin 17 inhibitors (IL-17i), methotrexate (MTX), and those who were untreated with bDMARDs or csDMARDs; (2) patients with PsC taking bDMARDs; and (3) matched patients with PsC who were not treated with bDMARDs or csDMARDs. Serum samples at baseline and at the 3- to 6-month follow-up visit were retrieved from the biobank. Protein levels were quantified using a Luminex multiplex assay. We compared follow-up vs baseline protein levels within groups and change in levels between groups. For the predictive potential of the biomarkers, we developed logistic regression classification models. Response to treatment was defined as (1) achieving low disease activity or remission (according to the Disease Activity Index for Psoriatic Arthritis); (2) ≥ 75% reduction in Psoriasis Area and Severity Index; and (3) ≥ 50% reduction in actively inflamed joint count.

Results: In PsA, TNFi reduced serum levels of all 5 proteins, IL-17i increased ACP5 and CCL2, and MTX reduced MMP3. Changes in MMP3 and S100A8 levels were significantly different between untreated PsA and matched biologic-treated PsA (P < 0.05). There were no significant differences between treated or untreated patients with PsC. Baseline levels of CXCL10, MMP3, S100A8, and ACP5 had good predictive value (area under the curve > 0.80) for response to biologics in patients with PsA.

Conclusion: Treatment with biologics and MTX affect serum CXCL10, MMP3, S100A8, ACP5, and CCL2 levels in patients with PsA. MMP3, S100A8, ACP5, and CXCL10 have potential use as serum biomarkers to predict response to treatment for PsA.