Upadacitinib for the treatment of rheumatoid arthritis

ABSTRACT

Introduction: Tofacitinib and baricitinib have recently been approved as second-line treatments for Rheumatoid arthritis (RA) though their maximum expected efficacy may be limited by dose-related toxicities. Upadacitinib selectively inhibits Janus Kinase 1 (JAK1) which could potentially reduce JAK2 and JAK3-related side effects.

Areas covered: In this paper, we review a newly developed oral selective JAK inhibitor, upadacitinib for the treatment of RA. The doses of upadacitinib extended-release 15 and 30 mg daily selected in phase III RA studies have shown a near-maximum efficacy in phase II studies. Upadacitinib inhibited radiographic progression and displayed rapid and sustained clinical and functional efficacy in RA when in combination with methotrexate (MTX), upadacitinib was superior to placebo in MTX-Inadequate Responders (IRs) and biologic disease modifying antirheumatic drugs-IRs while as monotherapy, it was superior to MTX in MTX-IRs and MTX-naïve patients. Upadacitinib was superior to adalimumab using ACR70, reduction of pain-VAS and improvement of HAQ-DI. The comparison with abatacept is still ongoing.

Expert commentary: Upadacitinib has displayed a rapid and favorable efficacy profile in RA but despite being a selective JAK1 inhibitor appears to have a similar safety profile to less-selective Jakinibs. Longer term safety data are awaited.

KEYWORDS:

• JAK inhibitors
• targeted synthetic DMARDs
• rheumatoid arthritis
• upadacitinib
• ABT-494

Declaration of interest

CJ Edwards has attended advisory boards, provided consultancy, been part of a speakers bureau or received research support from Abbvie, Biogen, BMS, Celgene, Fresenius, Gilead, GSK, Janssen, Lilly, MSD, Mundipharma, Pfizer, Roche, Samsung and Sanofi. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

One reviewer has disclosed that they have been a consultant to Pfizer, Hanmi Pharm and Green Croos Pharm. Another reviewer has disclosed that they have received speaking fees from Bristol-Myers, Pfizer, Eli Lilly, and Takeda. Peer reviewers on this manuscript have no other relevant disclosures.

Additional information

Funding

This paper was not funded.