How effective are JAK-inhibitors? Perspectives from clinical trials and real-world studies

ABSTRACT

Introduction

JAK-inhibitors have emerged as a new treatment option for rheumatoid arthritis, with five molecules currently available in different parts of the world: tofacitinib, baricitinib, upadacitinib, peficitinib, and filgotinib. These molecules have been the subject of numerous trials looking at their efficacy (how well they perform in controlled conditions) but also some observational studies from the general population to assess their effectiveness (how well treatment perform under real conditions). With each their own weaknesses and strengths, they give different but complementary information.

Areas covered

We will review what we can learn from trials and real-world studies on how effective JAK-inhibitors are in the treatment of rheumatoid arthritis.

Expert opinion

Trials of JAK-inhibitors have shown that JAK-inhibitors are efficacious for the treatment of rheumatoid arthritis. However, their main outcomes are not clinically meaningful as their aim is mainly the regulatory authorization of the product. Real-world studies are important as they evaluate the real-life effectiveness of the compounds, however, they are scarce at the moment, mainly evaluating tofacitinib and of variable quality. Future high-quality studies are needed to assess the real-world effectiveness of JAK-inhibitors in a more complete manner.

KEYWORDS:

• Comparative effectiveness
• jak-inhibitors
• janus kinase
• rheumatoid arthritis
• rheumatology
• trials

Article highlights

• This review shows that substantial trials have evaluated the efficacy of JAK-inhibitors.

• We learn from trials that JAK-inhibitors seems to be more efficacious than csDMARDs and placebo and as efficacious as adalimumab or etanercept for the treatment of rheumatoid arthritis.

• Trials conclusions are difficult to translate in the real world, as the patient population is different and the outcomes are not clinically meaningful.

• Only a few real-world studies have evaluated the effectiveness of JAK-inhibitors. Their outcomes are more relatable to routine clinical practice than trials. Of various quality and small sample size, overall these studies point to similar effectiveness of tofacitinib compared to bDMARDs.

• More high-quality real-world studies are needed to evaluate the effectiveness of JAK-inhibitors and their place in the treatment landscape of rheumatoid arthritis.

Reviewer disclosures

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

Correction Statement

This article has been republished with minor changes. These changes do not impact the academic content of the article.

Additional information

Funding

This paper is not funded.