Background 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. So, it is not known wat the effect is of treatment with IL-17A blockade on inflammatory activity in the arterial wall.
Objectives To assess the effect of 3 months treatment with secukinumab on arterial wall inflammation in SpA patients with peripheral disease (pSpA).
Methods We included 20 patients with clinical pSpA 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 a 18-fluorodeoxyglucose positron emission tomography with computed tomography (18F-FDG PET/CT) imaging in 18 patients at baseline and week 12, which is a validated method to quantify arterial wall inflammation. Arterial wall inflammation is measured in both the ascending aorta and carotids, maximal FDG uptake is shown as the maximal target-to-background ratio (TBRmax).
Results 18 patients with pSpA (age 44±12, 72% male) and without a previous cardiovascular event underwent imaging. Overall, three months treatment with secukinumab resulted in a significant improvement of disease activity with 17/18 patients achieving a EULAR DAS response (9 good and 8 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). Importantly, treatment with secukinumab did not affect cholesterol levels (total cholesterol baseline: 5.1±1 mmol/l v.s wk 12: 5.5±1 mmol/l, p=0.167; LDL-c baseline: 3.2±0.8 mmol/l v.s wk 12: 3.5±0.9 mmol/l, p=0.219). Additionally, arterial wall inflammation as measured by PET-CT did not change over the course of the 12 weeks treatment with secukinumab (aorta TBRmax baseline: 3.3±0.9 vs. wk 12: 3.3±0.7, p=0.861; carotid TBRmax baseline: 1.88±0.6 vs. wk 12: 1.76±0.4, p=0.067).
Conclusions This pilot study in 18 patients with pSpA without any preexisting CV events showed that treatment with secukinumab for 3 months has no effect on arterial wall inflammation as measured by PET-CT. Further research in larger patient groups, over a longer period of treatment, and with different measurements remains warranted to fully elucidate the effect of IL-17A blockade on vascular inflammation.
Acknowledgements This study was funded by an unrestricted grant from Novartis.
Disclosure of Interest L. Van Mens: None declared, S. Verweij: None declared, A. van Kuijk Grant/research support from: UCB, Pfizer, MSD, Janssen, Consultant for: Novartis, Celgene, E. Stroes Speakers bureau: Amgen, Sanofi, Merck, D. Baeten Grant/research support from: Pfizer, MSD, AbbVie, Novartis, UCB, Janssen, Boehringer Ingelheim, Consultant for: Pfizer, MSD, AbbVie, Novartis, UCB, Janssen, Boehringer Ingelheim, Eli Lilly, Roche, BMS, Glenmark, Employee of: UCB
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