Recent developments for new investigational JAK inhibitors in psoriatic arthritis

ABSTRACT

Introduction

Psoriatic arthritis (PsA) is a chronic inflammatory disease affecting about one-third of subjects with psoriasis. Several treatment modalities targeting Janus Kinase pathways and intracellular inflammatory cascade are now available and under clinical investigation to treat this disease.

Areas covered

This review describes ongoing and recently completed phase 2 and 3 randomized clinical trials (RCTs) evaluating the efficacy and safety of approved JAK (Tofacitinib and Upadacitinib) and investigational JAK inhibitors (JAK1 inhibitors: Filgotinib and Ivarmacitinib (SHR0302); TYK2 inhibitors: Brepocitinib (PF-06700841) Deucravacitinib (BMS-986165), and NDI-034858) in PsA through February 2023.

Expert opinion

Current standard of care has significantly improved the quality of life in PsA. Recently approved JAK inhibitors for PsA have addressed many of the unmet needs of PsA, particularly of those with severe phenotypes. Preliminary results from several RCTs have reported good and fast efficacy and an acceptable safety profile of investigational JAK inhibitors in PsA. Additional clinical trials and long-term outcome data on these agents are necessary for increasing available therapeutic options for PsA.

KEYWORDS:

• Brepocitinib
• deucravacitinib
• filgotinib
• ivarmacitinib
• JAK inhibitors
• psoriatic arthritis
• tofacitinib
• upadacitinib

Article highlights

• Recently, the understanding of the pro-inflammatory intracellular pathways mediated by Janus Kinase (JAK1, 2 and 3 and TYK2) has addressed the development of their antagonists, JAK inhibitors.

• Approved JAK inhibitors for PsA, tofacitinib and upadacitinib, have addressed many of the unmet needs of PsA, particularly of those with severe phenotypes.

• Preliminary results from several Randomized Clinical Trials have reported good and fast efficacy and an acceptable safety profile of investigational JAK1 inhibitors in PsA.

• Preliminary results from several Randomized Clinical Trials have showed that oral allosteric and selective TYK2 inhibitors, brepocitinib and deucravacitinib, are associated with an acceptable safety profile and efficacy across numerous PsA disease domains.

• Additional clinical trials and long-term outcome data on investigational JAK inhibitors can be useful for increasing available therapeutic options for PsA.

• Increasing knowledge of immunoinflammatory JAK-mediated pathways could expand the PsA therapeutic armamentarium, improving the opportunity for tailored and personalized therapy.

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.

Additional information

Funding

This paper was not funded.