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ICYMI: Who gives a ‘JAK’ why and how they work, as long as they do!

Several abstracts have studied the mechanism of action of JAK inhibitors (JAKi) in various diseases. JAKi alter many other mediators affected by the JAK STAT pathway. For instance, T cell signature in blood that is proliferative was associated with a response in RA. The problem is that we don’t know if this signature is unique to JAKi response, or to any treatment in RA (abstract 0013).

What to use after failure of csDMARDs in RA? 

This RCT performed in Europe is contrary to FDA guidelines which recommend that JAKi are to be considered AFTER TNFi. This realworld pragmatic trial compared any TNFi as first advanced therapy vs. barictinib (abstract 0450). At 12 weeks the ACR50 was non-inferior (i.e. pretty darn similar). So although there was not superiority of baricitinib in RA patients failing csDMARDs, the responses seemed to be equal using either choice. So, in clinical practice, it may depend on access, patient preference and safety. Interestingly, the RA BEAM trial1 showed superiority in MTX inadequate responders who were treated with baricitinib 4 mg daily vs. adalimumab, and the current pragmatic trial presented at #ACR23 did not show differences. The diverse findings may be explained by trial design, and the pragmatic nature of the study where any TNFi therapy could be used and there was no blinding and the study was only 12 weeks and differences in background treatment. 

We may or may not learn if VTEs are different in high risk RA patients with active disease who are treated with baricitinib or a TNFi when the large FDA mandated trial that is event driven is completed. 

So, who to prescribe a JAK in and their mechanism of action depends on what you look at; there are many targets that can be affected with JAKi and it may also depend on the disease studied.

References

1. Taylor PC, et al. Baricitinib versus placebo or adalimumab in rheumatoid arthritis. N Engl J Med. 2017;376:652-62

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