Jaime Calvo-Alén, Spain | June 2021
The first JAK inhibitor was approved as a treatment option in inflammatory diseases nearly 10 years ago,1 and since then the role of JAK inhibitors has expanded. JAK inhibitors are now included as a treatment option in the EULAR recommendations for patients with inadequate response to CSDMARDS and represent an oral therapy option for patients living with rheumatoid arthritis (RA).2 At this moment, in my view, it is possible to find many different patient scenarios in clinical practice where the use of JAK inhibitors may be the most suitable.
At the same time, together with IL-6 inhibitors, JAK inhibitors should be a strong option for patients who are going to be treated with monotherapy due to intolerance of or contraindication to a CSDMARD.
EULAR 2021 contained many interesting presentations and discussions regarding JAK inhibitors. An exciting session on tsDMARD therapies in RA focused specifically on JAK inhibitors, discussing many aspects such as mechanism of action, specificity, emerging data, etc.3 The presentation then turned its focus to real-world data, a topic I discuss further below.
Multiple studies presented at EULAR 2021 reported on treatment retention rates. In a Canadian study, researchers found that JAK inhibitors had greater durability than BDMARDS after CSDMARD failure, with improved retention rates for JAK inhibitors.4 In the same sense, data from 1805 patients in the Swiss registry SCQM-RA showed higher retention rates in patients treated with a JAK inhibitor compared with either TNF inhibitors or with BDMARDS with other mechanisms of action due to efficacy. Discontinuations with a JAK inhibitor were similar to TNF inhibitors but higher than bDMARDs with other mechanisms of action due to intolerance. This oral presentation also pointed out that in patients who took a JAK inhibitor, those receiving combination JAK inhibitor therapy achieved numerically higher rates of retention than those receiving TNF inhibitor monotherapy.3 A Swedish study reported similar retention rates at 1 year with JAK inhibitors (65%) vs BDMARD (58%-80%) depending on the type of bDMARD. It is important to note, however, that in the Swedish study patients often received JAK inhibitors as a later line of therapy (after bDMARDS) and methotrexate was less frequently used as a combination therapy with JAK inhibitors vs bDMARDS, complicating comparisons. The study also noted that comorbidities occurred less often with JAK inhibitors, while RA activity was similar.5 Similar results were presented in a Spanish study using the BIOBADASER registry. The authors reported similar survival rates at 3 years for patients taking JAK or TNF inhibitors, although in this case, patients receiving JAK inhibitor treatment had more comorbidities. They were also older than patients taking TNF inhibitors and had a longer disease duration.6 Another study, conducted in Japan, suggests that, in addition to all of the settings described above, JAK inhibitors may also be considered when treating patients living with difficult-to-treat RA. The study found JAK inhibitors to be effective in patients with difficult-to-treat RA, with drug retention rates of 51% to 66% at 1 year.7 While this was a small, single center study.7 it supports the use of JAK inhibitors for patients with difficult-to-treat disease.
Finally, an additional real-world study assessed disease activity and patient reported outcomes in patients switching between IL-6 receptor inhibitors and JAK inhibitors using data from the real-world Corrona RA registry. In general, efficacy measures were substantial regardless of which order patients received the 2 inhibitor therapies. These results show JAK inhibitors to be at least on par with IL-6 receptor inhibitors and suggest that individual patient characteristics should play a role in treatment decisions.
BIODASER, Spanish Registry for Adverse Events of Biological Therapy in Rheumatic Disease; bDMARDS, biologic disease-modifying antirheumatic drugs; csDMARDS, conventional synthetic disease-modifying antirheumatic drugs; EULAR, European League Against Rheumatism; IL-6, interleukin 6; JK, Janus kinase; RA, rheumatoid arthritis; SCQM-RA, Swiss Clinical Quality Management in RA; TNF, tumor necrosis factor; tsDMARDS, target synthetic disease-modifying antirheumatic drugs.
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