Statin Use Key to Reducing CV Risk in Rheumatoid Arthritis Patients on Tofacitinib: ORAL Surveillance Analysis

The analysis emphasizes a concerning gap in cardiovascular preventive care within this population, marked by the suboptimal use of statins, medications known to reduce cholesterol and inflammation-related CV risks.

RA patients face an increased risk of cardiovascular disease (CVD) due to systemic inflammation and associated metabolic disturbances. The ORAL Surveillance study, a post-authorization safety trial comparing tofacitinib (5 and 10 mg twice daily) to TNF inhibitors (TNFi), reported a higher incidence of MACE with tofacitinib. Earlier analysis revealed this increased risk was primarily seen in patients with a history of atherosclerotic cardiovascular disease (ASCVD) and noted low baseline statin use.

Current guidelines recommend high-intensity statins for individuals with ASCVD or a high 10-year risk of MACE and moderate-intensity statins for those at intermediate cardiovascular risk.

In the post hoc analysis, Jon Giles, MD, MPH, of Cedars-Sinai Medical Center in Los Angeles, and colleagues sought to examine: (1) statin use based on baseline cardiovascular risk, (2) the effects of statins on lipid levels, and (3) the relationship between statin use and MACE risk among patients treated with tofacitinib versus TNFi in the ORAL Surveillance trial.

For this purpose, the researchers analyzed data from patients with rheumatoid arthritis (RA) aged 50 years or older, all of whom had at least one additional cardiovascular (CV) risk factor. Participants were assigned to receive either tofacitinib 5 mg (N=1,455) or 10 mg (N=1,456) twice daily (BID) or a TNF inhibitor (TNFi, N=1,451).

The use of statins was examined both at baseline and throughout the study, and treatment was categorized as high, moderate, or low intensity. Fasting serum levels of low-density lipoprotein (LDL) and high-density lipoprotein (HDL) were measured to evaluate lipid profiles.

To assess the association between statin use and the occurrence of major adverse cardiovascular events, the researchers calculated hazard ratios (HRs) using simple Cox proportional hazard models, focusing on the time to the first MACE event. This analysis aimed to clarify the impact of statin therapy on CV outcomes in patients treated with tofacitinib versus TNFi.

Key Findings:

• At baseline, 53.0% of patients with a history of ASCVD and 26.9% of those with high CV risk were using statins, though few were on high-intensity statins.
• Statin use was observed in 19.0% of patients with intermediate CV risk, primarily moderate-intensity statins.
• Baseline statin use was comparable between patients treated with tofacitinib and TNFi.
• Statin initiation during the study was relatively uncommon but occurred more frequently in patients receiving tofacitinib (11.8% for 5 mg BID and 12.2% for 10 mg BID) compared to TNFi (6.7%).
• Patients using statins at baseline had lower LDL levels and LDL ratios. LDL and HDL levels increased from baseline in both statin users and non-users, with larger increases observed in tofacitinib-treated patients compared to those on TNFi.
• MACE rates were similar in patients with or without baseline statin use across the study population and treatments.
• In tofacitinib-treated patients with a history of ASCVD, statin use at any time was associated with a lower risk of MACE compared to those not using statins (HR 0.49).
• In TNFi-treated patients with a history of ASCVD, statin use did not show a similar reduction in MACE risk.
• Among patients with ASCVD history and no statin use at any time, the risk of MACE was significantly higher with tofacitinib compared to TNFi (HR 4.07).
• For patients with ASCVD history using statins at baseline or at any time, there was no significant difference in MACE risk between tofacitinib and TNFi (HR 1.17).

"The post hoc analysis of ORAL Surveillance highlights a significant gap in cardiovascular preventive care for patients with rheumatoid arthritis, reflected in the underutilization of statins. In patients with a history of ASCVD, statin use appears essential in reducing the heightened MACE risk previously associated with tofacitinib compared to TNFi," the researchers concluded.

Reference:

Giles J, Charles-Schoeman c, Buch M, Dougados M, Szekanecz Z, Mikuls T, Ytterberg S, Koch G, Kwok K, Cadatal M, Menon S, Chen Y, Diehl A, Rivas J, Yndestad A, Bhatt D. Use of Statins and Its Association with Major Adverse Cardiovascular Outcomes with Tofacitinib versus TNF Inhibitors in a Risk-Enriched Population of Patients with Rheumatoid Arthritis [abstract]. Arthritis Rheumatol. 2024; 76 (suppl 9). https://acrabstracts.org/abstract/use-of-statins-and-its-association-with-major-adverse-cardiovascular-outcomes-with-tofacitinib-versus-tnf-inhibitors-in-a-risk-enriched-population-of-patients-with-rheumatoid-arthritis/. Accessed November 19, 2024.