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JAK Inhibitor Selectivity


Experts discuss the selectivity of Janus Kinase (JAK) inhibitors and considerations when selecting treatment for atopic dermatitis (AD).

Christopher Bunick, MD, PhD: Ruth Ann, you said something really important earlier when you talked about the rheumatoid arthritis [RA] population, that when you compare the upadacitinib data vs the tofacitinib data, it showed that the event rates for upadacitinib were lower than the pan–JAK [Janus kinase] inhibitor of tofacitinib. And I think that this gets to the concept of JAK selectivity. So what I mean by that is we know that tofacitinib is a pan–JAK inhibitor, it’s inhibiting multiple JAK family kinases. But when we look at the baricitinib, which is more of a JAK-1 selective therapy, and we look in this RA population, what we’re seeing with the lower event rates with upadacitinib may speak directly to the fact that JAK selectivity actually matters. And there is a paper published this year by Burmester and colleagues looking at upadacitinib safety. It looked at over 6000 patients and 15,000 patient-years of upadacitinib exposure and showed exactly what you mentioned, Ruth Ann, about the safety of upadacitinib vs tofacitinib and RA patients. I was wondering if there’s anything else you could add about that, specifically with regard to the JAK selectivity?

Ruth Ann Vleugels, MD, MPH, MBA:I think it is just pertinent to this discussion we’re having today since we’re really focusing on atopic dermatitis [AD], even though I love speaking about all the rheumatic diseases. It’s interesting because, yes, upadacitinib showed lower [rates] of those adverse events in RA cohorts but then, interestingly, when we then go into upadacitinib in AD, there are lower rates yet as compared to RA patients receiving the same drug, upadacitinib. So [this is] really interesting because I think it then again [shows] us to be a little bit fortunate in dermatology; this AD cohort is a healthier cohort than a typical RA cohort. So you have the advantage of potentially the more selective JAK inhibitor; we also have the advantage of a different cohort than in a RA cohort, which in a rheumatology community is considered one of our sicker cohorts, if that makes sense. So I think that’s a really, really great question.


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