‘No clear increased risk’ for CV events with tofacitinib in ORAL Surveillance post-hoc
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PHILADELPHIA — There is “no clear increased risk” for major adverse cardiovascular events associated with tofacitinib, according to a post-hoc analysis of the ORAL Surveillance trial presented at ACR Convergence 2022.
“ORAL Surveillance was a randomized, open-label, non-inferiority, post-authorization safety study that evaluated tofacitinib (Xeljanz, Pfizer) vs. TNF inhibitors in patients with active [rheumatoid arthritis] despite methotrexate therapy,” Maya H. Buch, MD, of the University of Manchester and the NIHR Manchester Biomedical Research Center, in the United Kingdom, told attendees. “The study population was enriched for cardiovascular risk to ensure enough events.”
Buch noted that this enriched population included individuals aged 50 years or older with at least one cardiovascular risk factor.
The study compared tofacitinib 5 mg and 10 mg twice daily with TNF inhibitors for the outcome of major adverse cardiovascular events (MACE) and venous thromboembolism (VTE). The initial results of ORAL Surveillance demonstrated that the MACE risk was increased in the tofacitinib arm.
In the current post-hoc analysis, Buch and colleagues aimed to expand on the three-point definition of MACE — a composite of cardiovascular death, non-fatal myocardial infarction (MI) and stroke — to include up to eight points that feature all cardiovascular events.
These events were sequentially added into the analysis and included hospitalization for unstable angina (MACE-4), coronary revascularization procedures (MACE-5), transient ischemic attack (MACE-6), peripheral vascular disease (MACE-7) and hospitalization for heart failure (MACE-8), as well as VTE (MACE-8 plus VTE).
There were 1,455 patients in the tofacitinib 5 mg group, 1,456 patients in the tofacitinib 10 mg group and 1,451 patients in the TNF inhibitor group.
According to the researchers, although the “totality” of cardiovascular risk associated with tofacitinib was elevated compared with TNF inhibitors, results showed that the risks for MACE-4 through MACE-7 were similar in the tofacitinib and TNF inhibitor groups.
“There is no clear pattern of risk,” Buch said.
Similarly, the risk for MACE-8 in both tofacitinib groups was comparable to the risk reported for TNF inhibition (HR = 1.08; 95% CI, 0.81-1.44).
“If you look at the totality of CV risk, MACE-8, which has the addition of heart failure, you see a picture with no clear increased risk of tofacitinib compared to a TNF inhibitor,” Buch said.
The picture is slightly different with regard to the risk for MACE-8 plus VTE, Buch added. In the 5-mg twice daily tofacitinib group, the risk was comparable to the risk associated with TNF inhibitors (HR = 1.12; 95% CI, 0.82-1.52). However, the 10 mg twice daily dose of tofacitinib carried an increased risk for MACE-8 plus VTE, compared with TNF inhibition (HR = 1.38; 95% CI, 1.02-1.85).
“It is clear that this is being driven by VTE,” Buch said. “There is a clear divergence with 10 mg tofacitinib twice a day to referent TNF inhibitors.”
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Buch MH. Abstract L06. Presented at: ACR Convergence 2022; Nov. 11-14, 2022; Philadelphia (hybrid meeting).
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