The US FDA has approved the JAK inhibitor baricitinib (Olumiant, Lilly) for the treatment of moderate to severe rheumatoid arthritis.
Baricitinib – JAK Inhibitor
Indication: Moderate to severe rheumatoid arthritis unresponsive to biologic disease-modifying antirheumatic drugs (e.g., TNF-inhibitors)
Mechanism: Janus Kinase I (JAK1)/Janus Kinase 2 (JAK2) Inhibitor, inhibits downstream STAT transcription factor activation, reduces transcription of pro-inflammatory genes
Dosing: 2 mg PO QD
Efficacy: 1/2 of patients see improvement of symptoms after 12w of baricitinib vs. 1/4 of patients receiving placebo¹
Safety: 71% adverse event rate reported in treatment group vs. 64% in placebo, 4% serious adverse events in treatment group vs. 7% in placebo group
Common Side Effects: URI, herpes zoster, decreased neutrophils, increased creatinine, increased LDL, nausea
Considerations/Contraindications: increased risk of GI perforation, do not administer live vaccines, do not administer with strong immunosuppressants (e.g,, cyclosporine), other DMARDS, or other JAK inhibitors
- RA-BEACON Study: Phase III double-blinded randomized placebo-controlled trial, 174 patients in 2 mg group, 176 in placebo
- Approved in EU in 2017
What is a JAK Inhibitor?
Activation of JAK, a non-receptor tyrosine kinase, by extracellular cytokines induces the phosphorylation and dimerization of the transcription factor STAT, resulting in increased transcription of genes that contribute to the inflammatory response.² JAK inhibition prevents cytokine signal transduction in hematopoietic and immune system cells and thus dampens the inflammatory pathways responsible for rheumatoid arthritis progression.
What is rheumatoid arthritis?
Rheumatoid arthritis is a progressive inflammatory disease affecting primarily articular structures (joints). Rheumatoid arthritis causes significant pain and disability and is estimated to affect over 1.2 million people in the U.S.³
- Genovese, M. C. et al. Baricitinib in Patients with Refractory Rheumatoid Arthritis. N. Engl. J. Med. 374, 1243–1252 (2016)
- Wishart DS, Feunang YD, Guo AC, Lo EJ, Marcu A, Grant JR, Sajed T, Johnson D, Li C, Sayeeda Z, Assempour N, Iynkkaran I, Liu Y, Maciejewski A, Gale N, Wilson A, Chin L, Cummings R, Le D, Pon A, Knox C, Wilson M. DrugBank 5.0: a major update to the DrugBank database for 2018. Nucleic Acids Res. 2017 Nov 8. doi: 10.1093/nar/gkx1037
- Arthritis. Centers for Disease Control and Prevention. https://www.cdc.gov/arthritis/basics/rheumatoid-arthritis.html. Published April 3, 2018. Accessed June 6, 2018.