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Medicine Matters rheumatology

Hello. My name is Dr Philip Mease. I am a rheumatologist. I am from Seattle, Washington and have been very involved in research on psoriatic arthritis.

Upadacitinib is a selective JAK1 inhibitor. We are aware that it has very good effectiveness in rheumatoid arthritis. And so it was natural for us to want to understand its effectiveness in the treatment of psoriatic arthritis.

We've seen other JAK inhibitors show good efficacy, including tofacitinib and filgotinib. And this is an important mechanism of action which targets a number of key pathogenic cytokines in psoriatic arthritis. So we were very interested and curious to know how effective it would be in both a biologic naive population, which is the select PsA 1 study and a biologic experienced population, which is select PsA 2.

The main findings from select PsA 2, the bio DMARD inadequate responding population, were a very significant ACR responses. The primary endpoint was ACR 20. And with the 15 milligram dose of upadacitinib, we saw 57% of patients achieving ACR 20 versus 24% in placebo, and then, with the 30 milligram dose, 63.8%. And they were correspondingly good results with ACR 50 and 70 versus placebo.

But in addition, as you know, there are many different clinical domains of importance in psoriatic arthritis, including features such as enthesitis, dactylitis, skin and nail disease. And in these clinical domains as well, we saw very good results with a complete resolution of the enthesitis and dactylitis significantly, compared to placebo. And in terms of skin response, we saw that, with the 15 milligram dose, 52.3% of patients achieved a PASI75 75, 56.5% percent with the 30 milligram dose versus placebo of 16%. This is really quite good efficacy in the skin. We also saw significant improvements in patient reported outcomes, such as pain, fatigue, function, and quality of life.

The key take home message about safety was that the results were similar to what we've seen in the rheumatoid arthritis population with this medication. There were really no new signals. A slight increase in infection risk, for example, a few laboratory abnormalities. But by and large, the drug was very well-tolerated.

Many patients tell me that they would like to have an effective oral medication for the treatment of their psoriatic arthritis. This is because some people don't like to do injections or infusions. People who travel prefer to have a pill bottle rather than carrying needles and syringes through TSA. And in general, we also need a new mechanism of action other than some of the biologic agents for patients who either don't tolerate or have safety issues with the biologics or don't have full efficacy. And so if approved, this will be a welcome addition to our armamentarium of treatments for psoriatic arthritis and trying to gain the goal of putting a patient into remission or low disease activity, which was certainly seen in this particular trial.

In truth, I think any patient with psoriatic arthritis would be a candidate for upadacitinib treatment, including patients early in their disease course, patients later in their disease course, patients with predominantly arthritis, patients with significant skin disease. And so I think that this is really going to be able to be used for the broad range of psoriatic arthritis patients. One thing that I'm very interested in is looking at the sustained effectiveness.

One advantage of an oral medication is that we don't have the issue of immunogenicity. This is where a anti-drug antibody can be formed against a injected or infused protein. With an oral medication, this is not a problem. And so we are curious and interested in whether there could be a quite sustained benefit from the medication. So I'm looking forward to long term data, both from these trials, but also clinical registry data to help us understand that.