How Does Risk for CV Events Differ Between Tofacitinib and TNFi in RA?

Risk for certain cardiovascular events may not differ between treatment with tofacitinib and TNF inhibitors.

The risk for a composite of all ischemic cardiovascular (CV) events and heart failure (HF) may not differ between treatment with tofacitinib and tumor necrosis factor inhibitors (TNFis), according to results of a post hoc analysis presented at the American College of Rheumatology (ACR) Convergence 2022, held from November 10 to 14, in Philadelphia, Pennsylvania.

Results of the ORAL Surveillance study ( Identifier: NCT02092467) showed a higher risk for major adverse CV events (MACE) and venous thromboembolism (VTE) with tofacitinib vs TNFis. Further, a post hoc analysis of the ORAL Surveillance study reported a higher risk for MACE with tofacitinib compared with TNFis among individuals with a history of atherosclerotic CV disease (ASCVD).

The current analysis expands on a 3-point MACE (MACE-3; a composite of CV death, nonfatal myocardial infarction [MI], and stroke) by assessing the risk for all adjudicated CV events as part of extended MACE endpoints in the ORAL Surveillance study with tofacitinib vs TNFis.

Researchers enrolled patients 50 years and older with at least 1 additional CV risk factor who received treatment with tofacitinib 5 mg twice daily, tofacitinib 10 mg twice daily, or a TNFi. All extended MACE endpoints, which were based on MACE-3, sequentially added adjudicated ischemic CV events (ie, hospitalization for unstable angina [MACE-4], coronary revascularization procedures [MACE-5], transient ischemic attack [MACE-6], and peripheral vascular disease [MACE-7]), hospitalization for HF (MACE-8), and VTE (MACE-8 plus VTE).

A total of 1455, 1456, and 1451 patients received tofacitinib 5 mg, 10 mg, and a TNFi, respectively.

Hazard ratios (HRs) for MACE-4 to MACE-7 with tofacitinib vs TNFi were similar to HRs for MACE-3. Further, the risk for MACE-8 was similar with combined tofacitinib doses vs TNFi (HR, 1.08; 95% CI, 0.81-1.44).

The risk for MACE-8 plus VTE was similar with tofacitinib 5 mg vs TNFi (HR, 1.12; 95% CI, 0.82-1.52), but the risk was higher with tofacitinib 10 mg vs a TNFi (HR, 1.38; 95% CI, 1.02-1.85).

The risk for MI appeared to be higher with tofacitinib compared with TNFi (HR, 1.74; 95% CI, 0.89-3.41, combined doses); however, the risk for other individual adjudicated CV events was generally similar with both treatments. Across all extended MACE definitions, the risk seemed to be higher with tofacitinib vs TNFi in individuals with a history of ASCVD.

The study authors concluded, “These data highlight the need for a better understanding of risk [for] individual CV events in [patients] with RA.”

Disclosure: This research was supported by Pfizer. Some of the study authors have declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.


Buch M, Bhatt DL, Charles-Schoeman C, et al. Risk of extended major adverse cardiovascular event endpoints with tofacitinib vs TNF inhibitors in patients with rheumatoid arthritis: a post hoc analysis of a phase 3b/4 randomized safety study. Presented at: ACR Convergence 2022; November 10-14; Philadelphia, PA. Abstract #L06.