Oral surveillance and JAK inhibitor safety: the theory of relativity

Abstract

The published results of the post-marketing ORAL Surveillance study, which compared the Janus kinase (JAK) inhibitor tofacitinib with anti-TNF therapy in older patients with rheumatoid arthritis who have cardiovascular risk factors, have led to changes in the recommendations for the use of JAK inhibitors. Although new safety signals have emerged for tofacitinib, namely malignancy and cardiovascular disease, it should be noted that these signals are relative to those seen with TNF blockers. The new data further raise our intrigue that venous thromboembolism might be a true risk related to JAK inhibition. Reassuringly, the totality of the findings from this newly published study and the other data collected to date suggest that JAK inhibitors can be used safely at approved doses by many patients with rheumatoid arthritis.

Fig. 1. Timeline of approved indications for Janus kinase inhibitors for rheumatic diseases.

In 2012 tofacitinib became the first Janus kinase (JAK) inhibitor to be indicated for a rheumatic disease, when the FDA approved its use in the treatment of rheumatoid arthritis (RA); EMA approval came in 2017. In addition to tofacitinib, other JAK inhibitors (baricitinib, upadacitinib and filgotinib) have also been approved for use in the treatment of RA, and the indications for JAK inhibitors have expanded to include psoriatic arthritis (PsA), ankylosing spondylitis (AS) and ulcerative colitis (UC). MTX, methotrexate.