VIDEO: Role of JAK inhibitors in RA treatment

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Certainly we've learned a lot about JAK inhibitors over the past, probably year and a half I would say, and there was a clinical trial called "ORAL Surveillance" that significantly changed our understanding of the risk of these molecules. We now have to come to grips with the fact that as compared to treatment with an important alternative class of medications, the TNF inhibitors, that JAK inhibitors are associated with a small but detectable increase in the risk of major adverse cardiovascular events, cancers, and infections. And there may also be a risk in that class in regard to blood clots. Those risks are small. But we consider the number of people with RA that we're treating, they are important risks and we now take them into account. The risk is especially prominent and in some studies almost limited to the group of people who have cardiovascular risk factors and/or who are older the age of 65 years of age. And so that's the group that is most at risk with those medications and where we have to be the most cautious in their use. I would say that nowadays, and if for rheumatoid arthritis, we would try methotrexate first as the first medication. When that is not sufficiently effective, we can either go to a TNF inhibitor. In some cases we may use combinations of multiple, that is three ORAL medications called triple therapy and that may be a reasonable option for some. And we would try a TNF inhibitor first and certainly before we would move on to a JAK inhibitor. I also think that we would try harder to think about alternatives in people who have failed a single TNF inhibitor. We might use a different biologic in another class such as abatacept or a IL6 receptor inhibitor before we would go to a JAK inhibitor. So, it has been, you know, we've become more aware of the risk and we still use them. And JAK inhibitors are effective medications for RA and work as fast or faster than any drug that's ever been developed. And that's an advantage. But we now have to recognize that they may be associated with increased risk at least as compared to TNF inhibitors. There's a lot of work going on in the space and there has been a fair amount of controversy about the data and how we interpret it. You know, for example, is it a class effect for all JAK inhibitors? And, you know, what is the true role nowadays? But I would say that in recent years, they have become relegated to probably after TNF inhibitors, at least one, if not more than one. And we are much more selective in using JAK inhibitors for treating people with RA older than 65 or those who have certainly cardiovascular risk factors or any significant risk factors or history of cancers.