Janus Kinase and Tyrosine Kinase Inhibitors in Dermatology

A Review of Their Utilization, Safety Profile and Future Applications

Mojahed M.K. Shalabi, BS; Benjamin Garcia, BS; Kendall Coleman, BS; Alfredo Siller Jr., MD; Austinn Miller, MD; Stephen K. Tyring, MD, PhD

Disclosures

Skin Therapy Letter. 2022;27(1):4-9. 

In This Article

Adverse Effects and Safety Profile

The JAK inhibitors that are approved for autoimmune disease have an associated black box warning for the potential increased incidence of malignancy, serious infections, and thrombosis based on data from oral use in rheumatoid arthritis.[1] Tofacitinib and baricitinib have the most data on their safety and side effect profiles. However, the long-term safety of JAK inhibitors is still not completely understood. Current data suggests the safety of JAK inhibitors may be comparable to other biologics, and as investigations of this promising drug class continue, the safety profile should become more clear.[1] According to the literature, JAK inhibitors may potentially increase the risk of malignancies, as they could impair the immune system's surveillance mechanism to vet inconspicuous cells that could eventually become cancers.[1] The rate of serious infections in patients treated with JAK inhibitors is comparable to that of other biologic agents such as TNF-a,[1,20] though there is an increased risk of herpes zoster with JAK inhibitor usage.[1,21] Baricitinib, tofacitinib, ruxolitinib and upadacitinib all include warnings for potential deep vein thrombosis, pulmonary embolism, and arterial thrombosis.[1,18] Though these risks appear to be low and dose dependent, additional studies are needed to determine the exact mechanism behind it's pro-thrombotic effects.[1,37] Additional adverse effects include gastrointestinal perforations, hyperlipidemia, as well as impaired drug metabolism due to interaction with the CYP3A4 system.[1,42]

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