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Therapeutic Use of JAK Inhibitors in Rheumatoid Arthritis

Enrico Fasolato

Tofacitinib and baricitinib are the first orally accessible Janus Kinase (JAK) enzyme inhibitors to be licenced for the treatment of RA. Baricitinib is a selective, oral JAK1, 2 inhibitor with modest activity against TYK2 and much less activity against JAK3. Tofacitinib is a selective JAK1, 3 inhibitor with low activity against JAK2 and TYK2. In RA, both medicines have completed thorough phase III clinical studies and have shown rapid improvements in disease activity, function, and patient-reported outcomes, as well as disease change. The FDA approved tofacitinib 5 mg twice daily in 2012 for the treatment of RA in individuals who are intolerant or resistant to MTX. In 2016, the Federal Drug Administration approved an extended-release formulation for the treatment of RA. Tofacitinib 5 mg once daily in combination with MTX and baricitinib 4 mg and 2 mg once daily were authorised by the European Medicines Agency in 2017 for the treatment of moderate to severe active RA in adult patients who were intolerant or unresponsive to one or more traditional synthetic DMARDs.