JAK3-selective inhibitor peficitinib for the treatment of rheumatoid arthritis

ABSTRACT

Introduction: Rheumatoid arthritis (RA) is a chronic progressive autoimmune disease characterized by synovitis as well as symmetric and destructive arthropathy. Although several disease modified antirheumatic-drugs (DMARDs) have widely used in clinical practice, certain patients are nonresponsive to or cannot take such medications due to adverse reactions. It is evident that Janus kinase (JAK) inhibitors have the potential to provide a significant breakthrough in the treatment of RA. These potent, orally administered, JAK inhibitors simplify the treatment options for patients.

Areas covered: We discuss the pharmacodynamics, pharmacokinetics, efficacy, and safety of peficitinib for the treatment of RA.

Expert opinion: Peficitinib is a novel JAK3 inhibitor potently inhibiting JAK3 enzymatic activity and JAK1/3-mediated cell proliferation. Its selectivity for JAK family kinases is similar to that of tofacitinib, but slightly less potent for JAK2. It is currently being evaluated by the FDA to treat adult patients with moderately to severely active RA who show inadequate response to or are intolerant of methotrexate. It can be used either as monotherapy or combination therapy with methotrexate, or other DMARDs. However, we think that more cautious consideration and measurement for adverse events are needed, after considering the safety results of ongoing clinical studies of peficitinib.

KEYWORDS:

• Janus kinase inhibitors
• rheumatoid arthritis
• peficitinib
• JAK3-selective inhibitor
• pharmacokinetics

Article Highlights

• JAK3 is a key target molecule for the treatment of RA.

• Peficitinib is a JAK3-selective inhibitor that blocks the signal transduction and then suppresses immune responses.

• Peficitinib and tofacitinib have comparable potency for JAK1 and JAK3, but peficitinib is slightly less potent for JAK2, whereas it is approximately threefold more potent for TYK2 than tofacitinib.

• Peficitinib is recommended to treat adult patients with moderately to severely active RA who show inadequate response to, or are intolerant of methotrexate, monotherapy or combination therapy with methotrexate, or other DMARDs.

Declaration of interest

The authors have no 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. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.