Background/Purpose: Patients with spondyloarthritis (SpA), a chronic inflammatory disease, have an increased cardiovascular risk, which is partly due to increased inflammatory activity in the arterial wall. IL-17A blockade with secukinumab is an effective treatment for SpA. The role of IL-17A in atherogenesis is controversial, some studies suggest that IL-17A is pro-atherogenic, while others indicate that IL-17A is athero-protective. The effect of secukinumab on arterial wall inflammation is unknown. Therefore, we assessed the effect of 3 months treatment with secukinumab on arterial wall inflammation in SpA patients. To assess the effect of 3 months treatment with secukinumab on arterial wall inflammation in SpA patients with peripheral disease (pSpA).

Methods:  20 SpA patients with peripheral disease (pSpA) were treated in a 12 week open-label trial. Treatment consisted of 300 mg secukinumab once a week during the first 4 weeks and then every 4 weeks thereafter. EULAR DAS response was used to define a responder/non responder state. To measure arterial wall inflammation we performed 18-fluorodeoxyglucose positron emission tomography with computed tomography (¹⁸F-FDG PET/CT) imaging in 18 patients at baseline and at week 12.

Results: Sufficient quality scans were available for analysis in 16 patients (age 44±12, 72% male, no previous cardiovascular events). Overall, three months treatment with secukinumab resulted in a significant improvement of disease activity, with 15 patients achieving a EULAR DAS response (9 good and 6 moderate responders). Correspondingly, CRP levels decreased significantly (baseline: 3.2[1.2–12.40] mg/dl vs. wk 12: 2.0[1.1-5.8] mg/dl, p= 0.011). Treatment with secukinumab did not affect cholesterol levels (LDL-c from 3.2±0.8 mmol/l to 3.5±0.9 mmol/l, p=0.219). Arterial wall inflammation as measured by PET-CT did not change over the course of the 12 weeks treatment with secukinumab (carotid  TBR_max baseline: 1.88±0.6 vs. wk 12: 1.76±0.4, p=0.067). Patients with a good response on secukinumab (n=9) showed a high TBR at baseline with a significant decrease of arterial wall inflammation, while there was a lower TBR in the patients with a moderate (n=6) or poor (n=1) response on secukinumab and there was no effect on arterial wall inflammation in these patients.

Conclusion: This pilot study in 16 patients with pSpA shows a successful clinical response upon secukinumab treatment for three months, with no change in arterial wall inflammation on group level. Sub analysis shows us a significant decrease of arterial wall inflammation in patients with a high TBR at baseline. Further research in larger patient groups, over a longer period of treatment remains warranted to fully elucidate the effect of secukinumab on vascular inflammation.