Increased Risk for Major Adverse Cardiovascular Events Among Patients With PsA Receiving IL vs TNF Inhibitors

Patients with psoriatic arthritis (PsA) have a greater risk for major adverse cardiovascular events (MACEs) with use of interleukin (IL)-12/23 and IL-17 vs tumor necrosis factor (TNF) inhibitors, according to study results published in Rheumatology.

Psoriatic arthritis has been linked to increased risk for cardiovascular disease (CVD) and cerebrovascular diseases. Studies have shown that inflammation coupled with insulin resistance results in endothelial cell dysfunction and atherosclerosis. Biologic disease-modifying antirheumatic drugs (bDMARDs), including TNF inhibitors and IL-12/23 and IL-17 inhibitors, and targeted synthetic DMARDs (tsDMARDs), such as apremilast, have shown anti-inflammatory effects for patients with PsA; however, the cardiovascular safety profile of these drugs remains unclear.

To evaluate the risk for MACEs in patients with PsA receiving bDMARDs, the researchers examined health administrative data from the French National Health Insurance. Patients with PsA with at least 1 prescription for bDMARDs or apremilast and those who were bDMARD- and apremilast-naive were included in the current cohort study. The bDMARDs included were etanercept, infliximab, adalimumab, certolizumab, and golimumab as TNF inhibitors, ustekizumab as an IL-12/23 inhibitor, and secukinumab and ixekizumab as IL-17 inhibitors. Index date was defined as the date of the first reimbursement of a bDMARD or apremilast during the study period.

Primary endpoint was occurrence of a MACE, defined as a composite outcome combining acute myocardial infarction and ischemic stroke, which was identified by a hospital discharge diagnosis.

Of the 66,456 patients with PsA, 9510 (83%) were new bDMARD users, including 7289 (77%) initiating a TNF inhibitor, 1058 (11%) an IL-12/23 inhibitor, 1163 (12%) an IL-17 inhibitor, and 1885 (17%) apremilast. A total of 51 MACEs were identified, with the median time-to-event of 12 months (interquartile range [IQR], 5-22 months) in the bDMARD group and 3 months (IQR, 2-14 months) in the apremilast group.

Risk for MACEs was significantly higher (P <10^-4) with the IL-12/23 (weighted hazard ratio [HRw], 2.0; 95% CI, 1.3-3.0) and IL-17 inhibitors (HRw, 1.9; 95% CI, 1.2-3.0), but not with apremilast (HRw, 1.3; 95% CI, 0.8-2.2), vs TNF inhibitors. Researchers suggested that increased risk for MACEs with IL inhibitors may be due to the protective role of TNF inhibitors or an adverse effect of the IL-12/23 and IL-17 inhibitors, or a combination of both.

An additional prespecified subgroup analysis was performed among patients without skin psoriasis requiring topical therapies and among patients without comorbidities related to CVD. Results did not differ for patients without skin psoriasis; however, risk for MACEs was significantly higher (P <.01) with IL-17 inhibitors (HRw, 1.6; 95% CI, 1.1-2.8), but not with apremilast (HRw, 0.7; 95% CI, 0.4-1.5), vs TNF inhibitors.

Study limitations included the inability to determine adherence rates, individual risk factors for MACEs, disease activity, and dose of medication used. Researchers were also unable to determine the cumulative lifetime cardiovascular toxicity.

“…Encourage physicians to adapt the therapeutic journey of patients [with PsA] 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,” the researchers concluded.

Disclosure: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.

Reference

Pina Vegas L, Le Corvoisier P, Penso L, Paul M, Sbidian E, Claudepierre P. Risk of major adverse cardiovascular events in patients initiating biologics/apremilast for psoriatic arthritis: a nationwide cohort study. Rheumatology. Published online July 9, 2021. doi:10.1093/rheumatology/keab522