As described above, a clinical trial in patients with rheumatoid arthritis reported an increased risk of MACE (defined as cardiovascular death, myocardial infarction, or stroke) for patients receiving tofacitinib compared with those receiving TNF blockers [38]; this led to the inclusion of a boxed warning on all JAK inhibitors indicated for the treatment of arthritis and other inflammatory conditions. Here, TNF is linked to rheumatoid arthritis.