ASH 2020 | Real-world data analysis of ruxolitinib in myelofibrosis

For ruxolitinib, we all are very familiar with the COMFORT studies. COMFORT-I and COMFORT-II, where ruxolitinib was pitted against either a placebo or best available therapy in a controlled trial setting. As we all know that controlled trial settings tend to get the best results and patients really seem to go a long time, because there’s some selection bias, right? You’re picking the patients who are going to stay on study for a long time. There are inclusion criteria, there’s all these restrictions, basically cherry picking the population. So in the COMFORT studies, we know that the median duration of treatment is right around three years. We know the proportion of patients, somewhere 20 to 40% of patients will have spleen volume reductions at 35%. And in those studies, in terms of dosing, we see that the dosings are pretty stable for all patients. Not a lot of dose reductions, they all started on the same dose as per protocol.

So it was very manufactured almost, results. And this is not what we see everyday in clinic. It’s not the real world necessarily. And so to better understand what is going on in the real world in terms of dosing of ruxolitinib and how long patients are on treatment and what type of benefit they’re deriving, we aim to take a different look. In patients who, through these claims databases and these large EMR-based databases, understanding what was going on with these folks treated with ruxolitinib. Then I think the major take home points are one, many patients are on a kind of a suboptimal dose of ruxolitinib. From other studies we know that doses when you get above 10 twice a day or higher, they tend to have a much better chance of having spleen volume reduction and symptom burden improvement. And as the doses get lower, there’s maybe less benefit there, really a dose response curve.

And in quote unquote, this real-world database, we found a significant number of patients who were suboptimally dosed based on either their platelet count or whatever was going on. So that’s kind of a first take home point. The second take home point, really which I think is the most impressive is the duration of treatment. So the time that patients were on ruxolitinib on average was much lower in the real world database, this analysis that we did, compared to the COMFORT studies.

Again, we always quoted these big talks we give and when we’re comparing against new clinical trials, this median time on treatment of about three years, but we’re seeing about a year and a half with these real world analyses when you look kind of across the board. It’s not just this one that we presented, but a lot of the different ones that have been presented over the last couple of years. So really the duration of treatment is much shorter. So not only are patients on a much lower doses with potentially less benefit, but they’re also on it for a much shorter period of time. And really looking at that it says, well, we need better medications. We need more medications and better medications because although ruxolitinib has dramatically changed the way we take care of patients with myelofibrosis, it is by no means a perfect drug. And really this is the basis for saying, “We need to do better.”