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Medicine Matters rheumatology

Dear colleagues, my name is Frank Behrens. I'm a rheumatologist here in Frankfurt, Germany. So indeed I'm in Frankfurt, despite the fact that the EULAR is now virtual and not being placed here in Frankfurt.

So with the SELECT-PsA 1 study, I think normally, it's a classical design of the study to understand whether upadacitinib is an active drug in psoriatic arthritis. Of course, this study wants to demonstrate whether upadacitinib is working in PSA with either 15 milligrams or 30 milligrams as a daily dose.

And interestingly, the design of this study was made in a specific way, not only to understand the value of upadacitinib versus placebo, which is a normal pivotal study design, but it's also designed to have an active comparator arm, which is adalimumab as a, let's say, standard, gold standard, for rheumatologists in PSA.

And it's not only a comparative arm. It's also powered against these kind of comparator arms, which means with this specific design, we are not only getting answer, but the upadacitinib in these different doses of 15 and 30 is working in PSA compared to placebo, but also it's to understand and directly compare it to adalimumab, which is one of the five arms of the study.

So we have a study which is designed with five arms. So we have two placebo arms. You have an adalimumab arm with 40 milligrams every other week. You have these upadacitinib arms, 30 milligrams and 15 milligrams, two doses, to understand whether upa is working compared to placebo, but also to find out whether the 30 milligram, it works better compared to the 15, or whether there is no difference between these doses.

And the interesting thing is, also, the study size. So we have these five arms, and you have, in total, more than 400 placebo patients, more than 400 adalimumab patients, and more than 400 patients in each individual upadacitinib arm, which is really a large study size, which gives us, really, confidence that we have, at the end, robust data.

It's randomized to 2, to 2, to 2, to 1, to 1, to these different five arms. You have a phase which is a randomized, double-blind, placebo-controlled treatment period until week 24, which is a typical design. And later on, all the placebos will be switching to an open-label extension period for period 2 until week 152. But now, at this EULAR, the data were presented on the first part of the study with this week 24 study design.

The primary endpoint of the study is the ACR20 response, but we have, also, a lot of key secondary endpoints, which gives us more insight in the value of upa in PSA. So in this clinical trial, the first question is, is upadacitinib working in active PSA based on the primary endpoint, what it was designed for?

And indeed, we have a clear answer that upa in both doses, 15 milligrams per day or 30 milligrams as an oral therapeutic option, has a proper response compared to placebo in active PSA. So we have nearly 80% ACR20 at week 12, with the non-responding imputation analysis for the 30 and 71% of the response rate for the 15 milligram compared to 36% in the placebo arm, which is highly significant.

So at the end, the primary endpoint is absolutely met, showing that upadacitinib is working in active PSA based on the ACR20 response, but also ACR50 and ACR70 are significant. So just to demonstrate, though, in the upa 30 arm, we have 25% achieving ACR70, which is really a high hurdle. So a 70% reduction in the composite score for arthritis is achieved at week 12, which is a relatively short period of time-- that's three months only-- compared to 2% in placebo arm and only 14% in the adalimumab arm.

So the first result and the main result is upa is working in both doses compared to placebo in active PSA for the ACR response criteria. And the response is rapid, a rapid onset. You have a clear, significant difference at week two and not only at a later stage. So after two weeks, you can clearly discriminate the upa arm from the placebo arm, which demonstrates a rapidness of response.

And in this kinetic of response, we see-- slightly-- superiority of the upa 30 compared to the 15. But the 15 is at least as good as the adalimumab comparator arm. So this is the main result of the primary endpoint. But as I mentioned, all the key secondaries are really interesting as well.

Yeah, coming to how it fits later on in our strategy and how to treat PSA. Yeah, so I think most if you were aware that the EULAR recommendations for treating PSA are updated just prior to the EULAR meeting and published right now. And if we have tried comparing different drugs, everybody is trying to squeeze out what is, exactly, the value comparing to the others.

So first of all, and based on the specific design-- and I mentioned the key secondary endpoint-- you were allowed in this study to analyze for non-inferiority of the upadacitinib arms, both doses, versus adalimumab. Which means you can clearly say, in this randomized clinical trial, that the upadacitinib as an oral treatment is definitely non-inferior to the SubQ adalimumab for the musculoskeletal domains for the ACR response. Which means we have an oral option which is as good as adalimumab for arthritis in PSA.

That's the first point. So the second point is, in the higher dose of 30 milligrams, you can also analyze within the study that upa 30 is superior to adalimumab in this setting for ACR response.

So this is the musculoskeletal domain. If you look for the skin domain, again, the upadacitinib oral treatment is at least as good as adalimumab in psoriasis. Which means we have now-- if it's licensed later in PSA-- an oral treatment which is as good as the standard treatment with adalimumab, which gives us a very convenient treatment option for PSA with an oral regime which is as effective as adalimumab, which is an important step forward in treating PSA patients.