Wednesday, 22 May 2019

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A New Era? JAK inhibitors in the Management of RA

ACR 2018 has come and gone. It was a conference filled with a number of highlights. One thing from this conference which really stood out was the continued plethora of data on JAK inhibitors. First in RA, and now in psoriatic arthritis and psoriasis.

There was a time when the gold standard of a new biologic in RA was hitting an ACR 20/50/70 of 60%, 40% and 20% respectively in a MTX IR population. In the new era of JAK inhibitors, the expectations are now higher, where we often see ACR scores of 70/50/30 in the for the ACR 20/50/70 scores respectively in the same population.

At this conference, the presentation of data for upadacitinib and filgotinib, both JAK-1 selective inhibitors, have continued push the case for the widespread use of these agents. For example, the SELECT COMPARE study, assessing the efficacy of upadacitinib 15mg OD versus Humira 40mg EOW or placebo showed that upadacitinib was similar to Humira in most efficacy domains, but in most cases were numerically superior, in addition to being statistically significant in achieving the all important ACR 50 response. This adds the the growing number of studies which show that JAKs are at least non-inferior to a TNF inhibitor, but may in fact be considered superior, depending on how much you scrutinize the methadological basis of such a claim.

Another thing that I find striking as I reviewed multiple posters about JAK inhibitors is how quickly they seem to work. In both the upacitinib and filgotinib phase 3 trials, most patients notice a significant improvement in pain, and quality of life by even 1 week. This is similar to previous data presented on tofacitinib and baricitinib. Therefore, I expect JAK inhibitors as a class in general to work very quickly.

Although we still define a primary failure to a biologic as a lack of optimal response by 6 months of initiating, I would argue that this rule does not apply to the JAK family. Those who will respond will likely respond early, and we are likely doing patients a disservice by waiting until the 6 months to switch inadequate responders. Perhaps for this class, even 3 months may be sufficient to be considered a primary failure to a JAK inhibitor? This is something that I will be incorporating into my own clinical practice and will try to assess my JAK patients sooner rather than later, after initiating treatment, and switching out earlier if needed.

I still remain part of the old guard, who still use a TNF inhibitor as first line after failing DMARDs. This stems more from old habits and greater comfort level from past experience that anything else. However, as an rheumatologist/epidemiologist who tries to incorporate best evidence into practice, it is becoming increasingly tough to justify these old habits. I still think the TNFs are a great class of molecules and don’t plan on abandoning them, but I think it may be time to share the spotlight here.

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