JAK inhibitors, psoriatic arthritis, and axial spondyloarthritis: a critical review of clinical trials

ABSTRACT

Introduction

Psoriatic arthritis (PsA) and spondyloarthritis (SpA) are inflammatory arthritides associated with progressive damage, deformity and morbidity. Janus kinase (JAK) inhibitors block JAKs, cytoplasmic protein tyrosine kinases important in signal transduction and immune processes that are currently being studied as synthetic disease modifying anti-rheumatic drugs (tsDMARDs) in psoriatic arthritis and spondyloarthritis.

Areas covered

This review evaluates published phase 2 and 3 clinical trial data for JAK kinase inhibitors for psoriatic arthritis and spondyloarthritis. A literature search using PubMed was conducted using the following keywords: ‘psoriatic arthritis’, ‘ankylosing spondylitis’, ‘axial spondyloarthritis’, ‘non-radiographic axial spondyloarthritis’, ‘tofacitinib’, ‘baricitinib’, ‘filgotinib’ and ‘upadacitinib’. Mechanism of action, phase 2 and 3 clinical trial data, including efficacy and safety, are discussed.

Expert opinion

JAK inhibitors are important orally administered agents conferring different degrees of selectivity toward JAK1, JAK2, and JAK3 which may have implications on efficacy and safety in PsA and SpA. Phase 2 and 3 clinical trials in PsA for tofacitinib and upadacitinib and phase 2 for filgotinib confirmed efficacy comparable to biologic DMARDs. In SpA, phase 2 and 2/3 studies confirmed significant efficacy of tofacitinib, filgotinib and upadacitinib compared to placebo. Safety was comparable to clinical trial, long-term extension, and registry data for rheumatoid arthritis.

KEYWORDS:

• Ankylosing spondylitis
• filgotinib
• jak kinase inhibitor
• non-radiographic spondyloarthritis
• psoriatic arthritis
• axial spondyloarthritis
• tofacitinib
• upadacitinib

Declaration of interest

S Keeling has acted as a paid consultant/participant in advisory boards for AbbVie, Eli Lilly, Galapagos, Novartis, Pfizer, UCB, Maerck, Sandoz and has received educational grants from AbbVie, Pfizer, Sandoz, Merck. WP Maksymowych is chief medical officer of CARE arthritis limited, has acted as a paid consultant/participated in advisory boards for AbbVie, BMS, Boehringer Ingelheim, Celgene, Eli Lilly, Galapagos, Novartis, Pfizer and UCB; received research and/or educational grants from AbbVie, Novartis, Pfizer and received speaker fees from AbbVie, Janssen, Novartis, Pfizer and UCB. 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

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

Additional information

Funding

This paper was not funded.