In the Oral Rheumatoid Arthritis Trial (ORAL) Surveillance study, a randomized safety endpoint trial which involved active rheumatoid arthritis (RA) patients who were 50 years of age or older with the presence of at least one cardiovascular risk factor and that compared combined tofacitinib doses (5 mg BID and 10 mg BID) and TNF inhibitor, the incidences of MACE (death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke) were higher in the tofacitinib groups than TNF inhibitor (HR: 1.33; 95% CI: 0.91–1.94) (103). This evidence concerns the gene TNF and Stroke.