Janus kinase versus TNF inhibitors: where we stand today in rheumatoid arthritis

ABSTRACT

Introduction

In recent decades, Rheumatoid arthritis (RA) treatment landscape has evolved with the induction of new biological and targeted therapies that provide significant therapeutic benefits in patients with sustained disease.

Areas covered

Tumor necrosis factor inhibitors (TNFi) were the first biologics used in the treatment of RA. Although they present a significant efficacy, an insufficient response of some patients led to further research and discovery of targeted therapies, such as Janus kinase inhibitors (JAKi), which act at a molecular level, regulating many cytokines. Clinical benefits have been seen with both TNFi and JAKi as monotherapy and combined with conventional synthetic disease-modifying antirheumatic drugs. Still, some significant side effects have been reported with JAKi, and several questions remain about their safety and selectivity in action. This review summarizes the current knowledge on the mechanism of action, the clinical efficacy, and safety of TNFi vs. JAKi.

Expert opinion

TNFi and JAKi are particularly useful in treating inflammatory arthropathies. Both drug categories are recommended by ACR and EULAR institutions in RA patients suffering from moderate to severe disease. Safety data in long-term studies are required to determine the optimal benefit to the risk profile of JAKi use.

KEYWORDS:

• Rheumatoid arthritis
• treatment
• JAK kinase
• TNFa
• efficacy
• side effects

Abbreviations

ABA, abatacept; ACR, American College of Rheumatology; ADA, adalimumab; bDMARD, biologic disease-modifying antirheumatic drug; CZP, certolizumab pegol; csDMARDs, conventional synthetic disease-modifying antirheumatic drugs; bid, ‘bis in die’ (twice a day); EMA, European Medicines Agency, ETN, etanercept; EULAR, European League Against Rheumatism; HZ, Herpes zoster; GCs, glucocorticoids; GM-CSF, granulocyte–macrophage colony-stimulating factor; GLM, golimumab; IL, interleukin; INF, infliximab; IV, Intravenous; JAK, Janus kinase; MACE, major adverse cardiovascular events; MMP, matrix metalloproteinases; MCP1, Monocyte Chemoattractant Protein-1; MTX, Methotrexate; NSAIDs, nonsteroidal anti-inflammatory drugs; RA, Rheumatoid arthritis; Sc, Sub-cutaneous injection; sTNFa, soluble TNFa; tmTNF, transmembrane TNF; STAT, signal transducer and activator of transcription; tsDMARD, targeted synthetic disease-modifying antirheumatic drug; TNF, tumor necrosis factor; TNFi, Tumor necrosis factor inhibitors; TNFR, TNF receptor; TYK2, tyrosine kinase-2.

Article highlights

• TNFi have demonstrated a clinical benefit and sustained remission with an acceptable toxicity profile in randomized controlled studies, extensional and observational studies.

• TNFi remain the bDMARDs of choice in RA patients with inadequate response to csDMARDs.

• JAK regulate many cytokines involved in RA pathogenesis.

• JAKi showed a good clinical response in MTX naïve, or patients with inadequate response to MTX or TNFi, and no inferiority to TNFi use, with superiority in some cases to other bDMARDs.

• Safety data in long-term studies are required to determine the optimal benefit-risk profile of JAKi.

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.