Upadacitinib tartrate in rheumatoid arthritis.

In rheumatoid arthritis (RA) there is an unmet therapeutic need, as a substantial proportion of patients does not achieve low disease activity or remission despite the use of conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) and/or biological DMARDs (bDMARDs). The Janus kinase (JAK) inhibitors are the most recently added drug category in the therapeutic armamentarium in RA. Upadacitinib tartrate (Rinvoq), a selective and reversible JAK1 inhibitor, inhibited interleukin (IL)-6 and IL-7 and ameliorated adjuvant-induced arthritis in preclinical studies. In phase III randomized controlled trials (RCTs), upadacitinib, as monotherapy or in combination with csDMARDs, showed efficacy in RA patients with inadequate response to csDMARDs or bDMARDs. In a head-to-head RCT, upadacitinib 15 mg once daily was superior to adalimumab in achieving remission and in patient-reported outcomes. Upadacitinib has a good safety profile but it may increase the risk for herpes zoster, and as a substrate of cytochrome P450 (CYP) enzyme CYP3A4 it should not be coadministered with strong CYP3A4 inducers. Upadacitinib is contraindicated in patients with active tuberculosis, serious infections, active malignancy and in patients with severe liver impairment. Upadacitinib has been approved for the treatment of moderate to severe RA.