Select Your GCA Therapy Save

David Lu here from EULA twenty twenty four in sunny ish Vienna, and here to talk a little bit about one of the most anticipated abstracts, the Select GCA study, which was presented as a late breaking abstract today, PBALBA0001. So the late breaking abstract was for the study that looked at upadacitinib versus placebo in giant cell arteritis. And we'd already heard that there was a positive result in a press release about two months ago. And so, everyone was really interested to see what the actual results looked like. So this study looked at two different doses of upadacitinib.

Seven point five milligrams, that's half of our normal rheumatoid arthritis dose, and fifteen milligrams daily. And in fact, the seven point five milligrams daily just missed out on hitting the primary endpoint. So the p value was 0.057. So just missed out on that. But the fifteen milligram well and truly hit the primary endpoint, which was the proportion of patients achieving sustained remission from week twelve through to week fifty two.

And we saw that at forty six percent in the upadacitinib fifteen percent group versus twenty nine percent in the placebo group. So, I think that's quite- that's quite a nice result. I mean, it's certainly of the magnitude that maybe we would have expected from tocilizumab as well. They did a whole lot of secondary endpoints and you can see actually that the steroid spared is about over the course of the fifty two weeks. They gave opadacin of a twenty six week taper versus a fifty two week taper and placebo.

And that saves about one point two grams of of prednisolone. And I think critically, what everyone was looking for was about the safety. Because all the And inevitably, there was a question about, well, given the regulatory safety warnings, should we be And thinking about the kind of disease that GCA is with relatively high median age, is this the kind of thing where we should be using it, using a JAK inhibitor? So firstly to say, within this twelve month period of time, of all the types of things that you might be concerned about, actually, upadacitinib came out really well. So major adverse cardiovascular events were two in the study, both of which in the placebo arm.

Serious infections were actually lower in the upper groups versus placebo groups, probably because of the steroid. And I think it's a good opportunity to remind ourselves steroid is what drives a lot of this in terms of a problem. And actually, wasn't really much of a zoster signal either. Malignancy, we didn't really see much, although it's too short of a period of time as well. Nevertheless, I think it makes a really interesting point and one actually that came up in my debate with Janet yesterday, which is really about trying to, in terms of when we try to assess JAK inhibitor safety, we've got to think about what disease we're looking at and what the comparator is.

And frankly, when the comparator is glucocorticoid, then that's a problem. And I think we've got to also think that maybe tocilizumab, which is the other currently approved alternative ipadasympneum for giant cell arteritis, That there's increasing questions about whether that's doing enough overall to truly suppress the disease, and especially at a vascular level, and whether it will actually truly wash out to prevent as many ischaemic complications and vascular remodeling issues as we might think it- might hope it would do otherwise. So really a lot of space here for OOPA. Some really exciting results there. Obviously, I'd like to see the full paper in due course, I'd like to see extension data, like to see structural outcomes and long term safety.

But also, I think we're getting to the point that now if we're starting to see more agents, really love to see a head to head between upadasubmib, tocilizumab, maybe secukinumab if it washes out in GCAPTIN. Plenty plenty more work to watch in this space. So plenty more on all of EULA 2024, roomnow.com.