Cardiovascular risk in PsA greater for new users of IL-12/23, IL-17 vs. TNF inhibitors
Despite a low number of major adverse cardiovascular events overall, patients with psoriatic arthritis who newly start IL-12/23 or IL-17 inhibitors have a greater cardiovascular risk than those who begin TNF inhibitors, according to data.
“Biological disease-modifying antirheumatic drugs such as TNF, IL12/23 and IL17 inhibitors or targeted synthetic DMARDs (tsDMARDs) are recommended second-line therapies for moderate to severe PsA when standard treatments (including conventional synthetic DMARDs [csDMARDs]) fail to control disease or are not tolerated,” Laura Pina Vegas, a PhD student at Paris-Est Créteil University, in France, and colleagues wrote in Rheumatology. “Despite an established anti-inflammatory effect, their cardiovascular safety profiles in PsA remain uncertain.”
“Indeed, some studies report a lower risk of major adverse cardiovascular events (MACEs), and others show no significant risk,” they added. “Moreover, few studies have been conducted on more recently marketed bDMARDs, particularly IL12/23 or IL17 inhibitors, in PsA patients, and no real-world setting analysis is available. Thus, a large study is needed to quantify the comparative cardiovascular risk associated with second-line therapies among patients with PsA outside the restricted scope of randomized controlled trials.”
To analyze the risk for major adverse cardiovascular events in patients with PsA using various classes of biologic DMARDs and apremilast (Otezla, Amgen), Vegas and colleagues conducted a nationwide cohort study based on health administrative data from the French National Health Insurance. According to the researchers, the national health insurance system covers approximately 67 million people in France and is linked with the national hospital discharge database.
For their study, Vegas and colleagues included all adults with PsA who newly initiated biologic DMARDs or apremilast from 2015 to 2019, excluding those with previous cardiovascular disease. In all, the researchers included 9,510 patients newly starting a biologic DMARD — 7,289 using a TNF inhibitor, 1,058 using an IL-12/23 inhibitor and 1,163 using an IL-17 inhibitor — and 1,885 newly initiating apremilast. The primary endpoint was major adverse cardiovascular events, with the researchers using a time-to-event analysis with propensity score-weighted Cox and Fine-Gray models.
Follow-up ended Dec. 31, 2019.
According to the researchers, major adverse cardiovascular events occurred in 0.4% of included patients. After propensity score weighting, the risk for major adverse cardiovascular events was significantly greater in those starting IL-12/23 (HRw = 2; 95% CI, 1.3-3) and IL-17 (HRw = 1.9; 95% CI, 1.2-3) inhibitors, compared with TNF inhibitors. The data suggest no significant increased risk associated with apremilast (HRw = 1.3; 95% CI, 0.8-2.2). Vegas and colleagues reported similar results in the Fine-Gray competing-risks survival model.
“Given the relatively small number of events, our study provides reassuring data regarding the risk of MACEs in patients with PsA initiating a bDMARD or apremilast,” Vegas and colleagues wrote. “Our results suggest an increased risk of MACEs in new users of IL12/23 and IL17 inhibitors versus TNF inhibitors in PsA.”
“If these results are confirmed by further studies using other data sources,” they added, “they could encourage physicians to adapt the therapeutic journey of PsA patients by preferentially prescribing TNF inhibitors as the first second-line therapy, especially in patients at high cardiovascular risk, because they appear to have a better cardiovascular effect than other available IL inhibitors.”