Crucial safety issues on Janus kinase inhibitors in rheumatoid arthritis might be associated with the lack of LDL-cholesterol management: a reasoned literature analysis

This point of view explores the safety concerns of Janus kinase inhibitors (JAK-Is), used in treating rheumatoid arthritis (RA) and other rheumatologic conditions. Increasing evidence shows that JAK-Is may elevate the risk of venous thromboembolism (VTE), especially pulmonary embolism. This fact has prompted the European Medicines Agency to advise cautious use of these drugs in patients over 65, smokers, and those at risk of cardiovascular issues or cancer. The paper analyses the evidence on the association between VTE risk and RA and whether different JAK-Is pose different risks. It also probes the link between VTE, lipids, and JAK inhibition, noting that JAK-Is can alter HDL and LDL levels. On the other hand, some evidence indicates that tighter LDL-cholesterol control could mitigate VTE risk, particularly pulmonary embolism. Moreover, data from trials show little attention to treating this main cardiovascular and VTE risk factor in rheumatological patients. Although the lipid paradox theory emphasizes the U-shaped relationship between LDL cholesterol and cardiovascular risk in patients with RA, uncontrolled levels of clinically relevant LDL cholesterol remain closely linked to cardiovascular and VTE risk. In conclusion, high-potency statins could help to manage the increased cardiovascular and VTE risk concomitant to JAK-Is treatment in rheumatologic patients without depriving them of the best therapeutic choice and, in addition, reducing the inherent risk associated with the disease.