Incidence of Major Cardiovascular Events Higher With Tofacitinib vs TNFi Therapy in High-Risk Patients With RA

heart attack, cardiovascular
Heart attack pain as a human cardiovascular organ with a painful cardiac inflamation with 3D illustration elements.
Researchers identified independent risk factors for major adverse cardiovascular events in high-risk patients with rheumatoid arthritis receiving treatment with tofacitinib vs TNF inhibitors.

The following article is a part of conference coverage from the American College of Rheumatology (ACR) Convergence 2021, being held virtually from November 3 to 10, 2021. The team at Rheumatology Advisor will be reporting on the latest news and research conducted by leading experts in rheumatology. Check back for more from the ACR Convergence 2021.


In patients with rheumatoid arthritis (RA), incidence of major adverse cardiovascular events (MACE) was higher with tofacitinib compared with tumor necrosis factor inhibitor (TNFi) therapy, according to study results presented at the American College of Rheumatology (ACR) Convergence 2021, held virtually from November 3 to 10, 2021.

In the current phase 3b/4 study (ORAL Surveillance; Identifier: NCT02092467), patients with RA receiving stable doses of methotrexate were randomly assigned to receive 5 mg tofacitinib twice daily, 10 mg tofacitinib twice daily, or TNFi therapy (40 mg adalimumab every 2 weeks or 50 mg etanercept every week).

The primary endpoint was MACE (defined as cardiovascular death except from pulmonary embolism, nonfatal myocardial infarction (MI), and nonfatal stroke). Incident rates (IRs) and hazard ratios (HRs) were calculated for fatal and nonfatal events and stratified for risk factors identified using univariate and multivariate Cox regression analyses.

A total of 4362 patients (n=1455 for tofacitinib 5 mg, n=1456 for tofacitinib 10 mg, and n=1451 for TNFi therapy) were included in the study. A total of 47, 51, and 37 patients receiving tofacitinib 5 mg, 10 mg, and TNFi therapy, respectively, reported MACE.

The IRs for major adverse cardiovascular events (total, fatal, and nonfatal) and MI (total and nonfatal) were higher with tofacitinib 5 mg and 10 mg compared with TNFi therapy. Across treatment groups, IRs for fatal MI and stroke (fatal and nonfatal) were similar. The HRs (tofacitinib vs TNFi therapy) were generally more than 1 for MACE, MI, and stroke.

Baseline covariates, identified as independent risk factors for MACE, included current smoking, aspirin use, age 65 years and older, and male sex (P <.0001, P =.004, P =.0011, and P =.0015, respectively). In the presence of 1 of these risk factors, IRs for MACE were higher among patients who received treatment with tofacitinib 5 mg and 10 mg compared with TNFi. In patients without these risk factors, IRs for MACE were similar across treatment groups; however, HRs for MACE were more than 1 among patients with or without risk factors who received tofacitinib vs TNFi therapy. 

Researchers concluded, “The incidence of MACE was numerically higher with tofacitinib vs TNFi treatment. Across treatment groups, the [baseline] covariates, current smoking, aspirin use, age 65 [years and older], and male sex were identified as independent overall risk factors in [patients] experiencing MACE; tofacitinib vs TNFi treatment in [patients] with any of these risk factors present was associated with numerically higher incidence of MACE.”

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


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Charles-Schoeman C, Buch M, Dougados M, et al. Risk factors for major adverse cardiovascular events in patients aged ≥ 50 years with RA and ≥ 1 additional cardiovascular risk factor: results from a phase 3b/4 randomized safety study of tofacitinib vs TNF inhibitors. Presented at: ACR Convergence 2021; November 3-10, 2021. Abstract 0958.