Background/Purpose: Difficult to treat (D2T) psoriatic arthritis (PsA) presents a state of active inflammatory disease manifestations despite therapy with at least two biologic disease modifying anti-rheumatic drugs (bDMARDs) or targeted synthetic DMARDs (tsDMARDs) with two different mechanisms of action. Inflammation and angiogenesis are interlinked processes. EMMPRIN/CD147, a multi-functional protein that can induce the expression of the pro-angiogenic matrix metalloproteinases (MMPs) and vascular-endothelial-growth factor (VEGF), also regulates the expression of the anti-angiogenic factor endostatin.We aimed to assess the levels of pro- and anti-angiogenic factors in patients with D2T PsA patients compared to non-D2T PsA patients.

Methods: We determined the serum levels of the pro-angiogenic factors EMMPRIN/CD147, VEGF, MMP-9, MMP-9 activity, and the anti-angiogenic factors endostatin and Thrombospondin-1 (Tsp-1) in D2T PsA patients and in non-D2T controls who were stratified into two subgroups based on exposure to bDMARDs / tsDMARDS or to conventional DMARDs (biologic naïve) from a well-defined database. Each patient with D2T PsA was matched with at least one non-D2T patient of similar age and disease duration. The visit with the highest scores of articular and skin manifestations in the database was chosen for each patient. The serum levels of the biomarkers were evaluated using sandwich ELISA, and the MMP-9 activity was determined by the cleavage of its fluorescent substrate. The three patient groups were compared using Kruksal-Wallis ANOVA followed by Dunn’s multiple comparisons test.

Results: 23 patients with D2T PsA, accounting for 6.7% of the database population, were matched with 25 non-D2T bDMARDs /tsDMARDs-experienced PsA controls and to 25 non-D2T biologic naive patients. The mean age of the study groups was 62.32±15.48 years with a disease duration of 19.38±11.12 years. All patients had active disease, but the D2T group had higher scores of enthesitis compared to the non-D2T bDMARDs/tsDMARDs group and higher tender and swollen joint counts and HAQ scores compared to the non-D2T biologic naïve group. No significant differences were observed in the mean dactylitis or psoriasis area and severity index (PASI) scores, nor in other patient-related outcomes among the three groups. Comparing between the D2T patients, the non-D2T biologic experienced patients, and the non-D2T biologic-naïve patients, higher levels of EMMPRIN/CD147 (26.4±1.4, 19.4±0.88, 19.7±0.86 ng/ml, respectively, p< 0.001), endostatin (60.9±2.8, 52.1±1.56, 50.1±1.4 ng/ml, respectively, p< 0.048), and of MMP-9 activity (123,861±9,446, 90,067±5,620, 89,328±6,258 RFU, respectively, p< 0.017) were found in the DTT group. No statistically significant differences were found in the levels of VEGF and Tsp-1 between the three groups.

Conclusion: Higher level of CD147, and increased activity of MMP-9, which we have previously linked to the regulation of the anti-angiogenic factor endostatin, were detected in D2T PsA patients’ serum, suggesting their possible use as biomarkers, and indicating the complexity of the angiogenetic process in these patients, which merit further investigation.

« Back to ACR Convergence 2025

ACR Meeting Abstracts - https://acrabstracts.org/abstract/angiogenesis-markers-in-difficult-to-treat-psoriatic-arthritis-patients/