SOHO 2026 | Looking beyond JAK inhibitor efficacy in myelofibrosis: side effects, safety, and dosing

Yeah, absolutely agree. So like we were saying, you know, JAK inhibitor use with the four agents is just inherently a very nuanced subject. And I think this is a great topic you touch on because, you know, they all have unique side effects, right? With rux, you get weight gain, you can get shingles, you can get, you know, non-melanoma skin cancers, elevated cholesterol, blood pressure. So you’ve got to look at the cardiovascular implications, for example, of using rux with momelotinib, which I believe is the second most commonly used JAK inhibitor. You know, you have, you know, this early hypotension slash dizziness, some thrombocytopenia, some diarrhea, but then also rarely neuropathy, rarely liver enzyme problems. So it’s very important to be aware of, you know, the side effect profiles of each. You know, pacritinib, you know, brings its own set of issues, if you will. I mean, this diarrhea early on, but importantly, you’ve got to be very careful about concomitant blood thinners or QT prolonging drugs, which are generally, you know, you should avoid. So there’s a lot of things, you know, fedratinib, you give everybody thiamine so that you don’t run into the dreaded Wernicke’s encephalopathy. And it also has nausea, diarrhea issues early on. So I think knowing the side effect profile is very important. Dosing, as you touched on, is also critical, especially with rux, because, you know, momelotinib, pacritinib, and even fedratinib, there’s not that much variation in dose. I think that one is more, you know, you, okay, if you have side effects, you look at the package insert is more that, that, that type of thing. But with rux, we know it’s such a dose-dependent drug. I mean, you just don’t get the same benefits unless, you know, if you’re not able to give an optimal dose. So I think thinking about that, knowing when to switch, when to add on something for anemia so that you can give a better dose of rux. You know, these are things that one absolutely has to consider. And then, you know, like you said, there are patients who will be on these for years. You know, this is after all a chronic disease, even though it is worse than PV and ET, but still, you know, median survival six to seven years across the board and some patients actually much longer, right? And some unfortunately shorter. But I think to think about the, you know, other implications beyond efficacy, as you said, is important. For example, infections with rux. I have seen, I mean, we all have seen some very unusual infections on rux in some patients. And we know it’s a very potent immunosuppressive agent. And so this is going to happen now and then. You know, it’s not a common thing, but it’s going to happen sometimes. So, you know, unusual infections have been reported in the literature on rux so just staying vigilant for that type of thing. So yes it’s a lot of stuff beyond just efficacy for sure

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