Tofacitinib and baricitinib, both Janus kinase (JAK) inhibitors, have distinct side effect profiles, particularly concerning gastrointestinal, hepatic, coagulation, and hyperlipidemia effects.
Gastrointestinal Side Effects:
Tofacitinib has been associated with gastrointestinal perforation events, which is a significant concern.[1] Baricitinib does not show a similar association with gastrointestinal perforation.
Hepatic Side Effects:
Both drugs can cause elevations in liver enzymes. The American Academy of Dermatology notes that tofacitinib can lead to increases in liver enzymes to more than three times the upper limit of normal.[2] Baricitinib also has potential hepatic effects, but specific comparative data are less detailed.
Coagulation Side Effects:
Both tofacitinib and baricitinib have been linked to an increased risk of venous thromboembolism (VTE). However, baricitinib appears to have a higher associated risk. A systematic review and meta-analysis indicated that baricitinib had a higher odds ratio for VTE events compared to tofacitinib.[3] Additionally, the WHO VigiBase analysis showed increased reporting odds for deep vein thrombosis and pulmonary embolism with baricitinib.[4]
Hyperlipidemia Side Effects:
Tofacitinib is known to cause dose-related elevations in lipid parameters, including triglycerides, total cholesterol, low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C).[2] Baricitinib also affects lipid metabolism, but the extent and clinical significance compared to tofacitinib are less well-documented. Real-world data suggest that both drugs can impact lipid profiles, but specific comparative data are limited.[5]
In summary, tofacitinib is more associated with gastrointestinal perforation and significant elevations in lipid parameters, while baricitinib has a higher risk of venous thromboembolism. Both drugs can cause hepatic enzyme elevations.
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References
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Adverse Events Associated With JAK Inhibitors in 126,815 Reports From the WHO Pharmacovigilance Database.
Hoisnard L, Lebrun-Vignes B, Maury S, et al.
Scientific Reports. 2022;12(1):7140. doi:10.1038/s41598-022-10777-w.
2.
Joint American Academy of Dermatology-National Psoriasis Foundation Guidelines of Care for the Management of Psoriasis With Systemic Nonbiologic Therapies.
Menter A, Gelfand JM, Connor C, et al.
Journal of the American Academy of Dermatology. 2020;82(6):1445-1486. doi:10.1016/j.jaad.2020.02.044.
3.
Risk of Venous Thromboembolism Associated With Tofacitinib and Baricitinib: A Systematic Review and Indirect Meta-Analysis.
Giménez Poderós T, Gallardo Borge S, Vazquez-Ferreiro P.
Pharmacotherapy. 2020;40(12):1248-1264. doi:10.1002/phar.2472.
4.
Thromboembolic Safety Reporting of Tofacitinib and Baricitinib: An Analysis of the WHO VigiBase.
Vallejo-Yagüe E, Weiler S, Micheroli R, Burden AM.
Drug Safety. 2020;43(9):881-891. doi:10.1007/s40264-020-00958-9.
5.
Real-Life Comparison of Four JAK Inhibitors in Rheumatoid Arthritis (ELECTRA-i Study).
Benucci M, Li Gobbi F, Damiani A, et al.
Journal of Clinical Medicine. 2024;13(6):1821. doi:10.3390/jcm13061821.
