State of the art: approved and emerging JAK inhibitors for rheumatoid arthritis

ABSTRACT

Introduction

Rheumatoid arthritis (RA) is the most common autoimmune inflammatory arthritis in adults. In the past decade, many treatments have emerged to expand the therapeutic armamentarium of rheumatologists. Among emerging treatments, Janus Kinase inhibitors (JAKi) are promising in treating RA and several other inflammatory conditions, such as psoriatic arthritis (PsA). The JAK/STAT signaling pathway is located downstream certain cytokines receptors that are known to be involved in RA pathogenesis. So far, three JAKi are approved for the treatment of RA, while other JAKi, are under investigation.

Areas covered

Herein, the authors review those JAKi approved and emerging for the treatment of RA and provide their expert perspectives on the subject area.

Expert opinion

JAKi represent an interesting alternative to other DMARDs when MTX has failed. Long-term extension studies are still ongoing, but one can assume that most of the major safety concerns have already come out. Switching from one JAKi to another DMARD has been little studied, but in such cases, preferring a treatment which does not interfere with the JAK/STAT pathway seems to be a reasonable choice.

KEYWORDS:

• JAK inhibitor
• rheumatoid arthritis
• tofacitinib
• baricitinib
• filgotinib
• upadacitinib

Article highlights’

• Rheumatoid arthritis is a chronic auto immune and inflammatory disease mainly involving the joints for which many therapies have been developed in the past two decades.

• Tofacitinib, baricitinib, and upadacitinib are the three approved and launched Janus kinase inhibitors as they demonstrated their efficacy either in DMARDs naïve patients or in case of failure of one or most cs- or bDMARDs.

• According to current guidelines, Janus kinase inhibitors can be prescribed as a second-line therapy at the same level as bDMARDs such as tumor necrosis factor inhibitors.

• They globally provide an interesting safety profile, but practitioners have to be aware of specific side effects such as the increased risk of serious infections, the increased risk of herpes zoster infections, and the increased risk of blood clots, especially for tofacitinib.

• Further studies are needed in order to assess long-term safety of other Janus kinase inhibitors than tofacitinib.

• Other Janus kinase inhibitors trials are currently underway in rheumatoid arthritis especially for filgotinib and peficitinib

Acknowledgments

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Declaration of interest

Y Jamilloux has received congress fees, participated on advisory boards and provided lectures for Swedish Orphan Biovitrum (SOBI), Novartis and AbbVie. P Seve has served on advisory boards for AbbVie and Novartis and provided lectures for LFB Pharmaceuticals, Roche, SOBI, AbbVie, and Pfizer. M Gerfaud-Valentin has also received congress fees from SOBI and Novartis. 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 referee declares employment from Pfizer. Peer reviewers on this manuscript have no other relevant financial relationships or otherwise to disclose.