Peficitinib for the treatment of rheumatoid arthritis: an overview from clinical trials

Abstract

Introduction: The treatment of rheumatoid arthritis (RA), a chronic, systemic, autoimmune disease, has been greatly advanced by the introduction of biologic disease-modifying antirheumatic drugs (DMARDs); however, many patients still fail to achieve disease remission. Peficitinib, an orally bioavailable inhibitor of the Janus kinase (JAK) receptor family, was approved in Japan in 2019 and Korea in 2020 for the treatment of RA. Areas covered: This review provides an overview of JAK inhibitors currently marketed or in development; the pharmacodynamics and pharmacokinetics of peficitinib; and the efficacy and safety data for peficitinib from Phase 2b and 3 trials. Expert opinion: Peficitinib has proven clinical efficacy in Asian patients (Japan, Korea, and Taiwan) with RA who have an inadequate response to conventional DMARDs. In Phase 3 trials, clinical improvements and prevention of joint destruction were demonstrated for both 100 mg and 150 mg once-daily peficitinib versus placebo, and treatment for up to 52 weeks was well tolerated. Safety signals, in particular the increased incidence of herpes zoster-related disease, appeared in line with other JAK inhibitors. Post-launch monitoring will establish the long-term safety and effectiveness of this drug, and further studies are necessary to determine its potential use in non-Asian populations.

Impact of Different JAK Inhibitors and Methotrexate on Lymphocyte Proliferation and DNA Damage

“…In contrast, the FDA has rejected filgotinib for RA treatment, raising concerns, e.g., regarding its impact on sperm parameters and the risk-benefit profile of 200 mg dose [14,33]. In Asian countries, such as Japan and Korea, an additional pan-JAKi, peficitinib (Smyraf ® ), has also been approved for the treatment of patients with moderate RA [34,35].…”

“…Of note, IL-15 and IL-21 mediate proliferation and function of natural killer (NK) cells, which are essential for clearance of virus-infected and tumorigenic cells. JAKi treatment with tofacitinib and upadacitinib [17,[67][68][69][70][71], but not with baricitinib or filgotinib [35,72,73], was accompanied with mild to moderate decrease of circulating NK cell number and impaired NK cell function. Although, these effects were not associated with an increased risk of infectious diseases or lymphoma.…”

A Matching-Adjusted Indirect Comparison of Upadacitinib Versus Tofacitinib in Adults with Moderate-to-Severe Rheumatoid Arthritis

“…While the focus of the current study was to compare upadacitinib 15 mg versus tofacitinib 5 mg BID, future studies exploring upadacitinib’s comparative efficacy versus other approved JAK inhibitors such as baricitinib may help in further understanding of JAK profiles. Additionally, newer JAK inhibitors such as peficitinib (a pan-JAK inhibitor approved in Japan and South Korea) [ 27 , 28 ] and filgotinib (a JAK1 inhibitor approved in the EU and Japan) [ 29 ] may be approved in more global markets. Thus, the introduction of new therapies to the RA treatment landscape should warrant reevaluations of the comparative efficacy of all JAK inhibitors.…”

Comparative Efficacy and Safety of Peficitinib Versus Tofacitinib and Baricitinib for Treatment of Rheumatoid Arthritis: A Systematic Review and Network Meta-Analysis

“…Peficitinib (SmyrafÒ) is a pan-JAK inhibitor [7] that has demonstrated efficacy in phase 3 trials in Asia [9,10], with a similar safety profile to other JAK inhibitors [7,11]. It is approved for clinical use in Japan, Korea, and Taiwan, and is in late-stage clinical development in other Asian countries [7,12,13]. Tofacitinib (Xel-janzÒ) is an inhibitor of the JAK family that preferentially inhibits JAK1 and/or JAK3 over JAK2 [6,14], while baricitinib (OlumiantÒ) is an inhibitor of JAK1 and JAK2 [15].…”

“…JAKs transduce inflammatory cytokine signals from the cell membrane to the nucleus and are consequently implicated in the pathogenesis of RA [ 5 ]. At the time of this research, JAK inhibitors licensed for use (in any country) were tofacitinib [ 6 ], baricitinib [ 6 ], and peficitinib [ 7 ]; more recently, upadacitinib has also received approval [ 8 ].…”