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Review
. 2020 Sep 14:13:519-531.
doi: 10.2147/JIR.S219586. eCollection 2020.

JAK Inhibitors in Rheumatoid Arthritis: An Evidence-Based Review on the Emerging Clinical Data

Robert Harrington #  1 , Shamma Ahmad Al Nokhatha #  1 , Richard Conway  1
Affiliations
Review

JAK Inhibitors in Rheumatoid Arthritis: An Evidence-Based Review on the Emerging Clinical Data

Robert Harrington et al. J Inflamm Res. .

Abstract

Janus kinase (JAK) Inhibitors are the latest drug class of disease-modifying medication to emerge for the treatment of rheumatoid arthritis (RA). They are a small molecule-targeted treatment and are the first oral option to compare favourably to existing biologic disease-modifying anti-rheumatic drugs (DMARDs). Tofacitinib, baricitinib and upadacitinib are the first 3 JAK inhibitors to become commercially available in the field and are the core focus of this review. To date, they have demonstrated comparable efficacy to tumour necrosis factor (TNF) inhibitors in terms of American College of Rheumatology (ACR) response rates and disease activity (DAS28) scores with similar cost to the benchmark adalimumab. This narrative review article aims to synthesise and distil the key available trial data on JAK inhibitor efficacy and safety, along with their place in the ACR and European League Against Rheumatism (EULAR) guidelines for RA. The novel mechanism of action of the JAK/STAT pathway is highlighted along with the potential effects of modulating each pathway. The rapid onset of action, role in attenuation of central pain processing and effect on structural damage and radiographic progression are also all examined in detail. We also explore the latest meta-analyses and comparative performance of each of the 3 available JAKs in an effort to determine which is most efficacious and which has the most favourable safety profile. Post marketing concerns regarding thromboembolism risk and herpes zoster infection are also discussed. Additionally, we review the cost-benefit analyses of the available JAK inhibitors and address some of the pharmacoeconomic considerations for real-world practice in the UK and US by detailing the raw acquisition cost and the value they provide in comparison to the benchmark biologic adalimumab and the anchor DMARD methotrexate.

Keywords: JAK inhibitors; immunosuppressive therapies; rheumatoid arthritis; targeted synthetic DMARD; tsDMARD.

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Conflict of interest statement

The authors report no conflicts of interest for this work.

Figures

Figure 1
Figure 1
Simplified representation of the JAK/STAT signalling pathway: 1. Ligand binding to the extra-cellular domain of the homodimer or heterodimer cytokines receptor, the latter is activated and auto-phosphorylation occurs, 2. STAT proteins bind to the activated receptor, 3. STAT proteins are phosphorylated followed by nucleus translocation and protein synthesis.
Figure 2
Figure 2
Forest plot comparing the JAKs to adalimumab.
Figure 3
Figure 3
Simplified overview of ACR 2015 and EULAR 2019 guidelines for management of RA.
See this image and copyright information in PMC

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