乌鸦传媒

Treatment with guselkumab (Tremfya) showed early clinical improvements by week 8 in adult patients with active psoriatic arthritis (PsA) for most measures, including joint and skin disease, enthesitis, and dactylitis. These improvements were associated with a meaningful increase in health-related quality of life from year 1 through year 2 in a post-hoc analysis of the phase III DISCOVER-2 study, which was presented at the American College of Rheumatology (ACR) annual meeting.

In this exclusive 乌鸦传媒 video, , of the University of Washington School of Medicine and the Swedish Medical Center in Seattle, discusses the various abstracts from the meeting.

Following is a transcript of his remarks:

A number of very interesting abstracts from the DISCOVER-2 trial, which was a trial of use of guselkumab in two different doses in patients with psoriatic arthritis who had not been exposed to biologic DMARDs [disease-modifying antirheumatic drugs] previously.

We're seeing the 2-year data, so 100 week. And what's very interesting is that most of the analyses that I'm going to be talking about were an NRI analysis, meaning non-responder imputation. So the strictest, most conservative, way of analyzing data.

Key abstract was the overall 2-year data that showed sustainment of efficacy in ACR responses, enthesitis and dactylitis improvement, obviously skin disease with excellent improvement, as well as patient-reported outcomes such as fatigue, quality of life, and physical function. Really no new safety signals came out either. Very low rates of serious infection, and we're not seeing signals for other problems like inflammatory bowel disease, herpes zoster, major adverse cardiovascular events, and so forth. So a very safe safety profile.

There were several other abstracts that were included, including, for example, looking specifically at the issue of fatigue. Fatigue is one of the most critical issues that patients describe when they have inflammatory arthritis. And we saw that there was significant benefit for fatigue. In fact, the FDA said you can actually promote on this, you can include it in your label. And there was sustainment of effect over a 2-year period.

Another abstract looked at whether or not there were predictors of long-term good response. One of the predictors was improvement of enthesitis, and skin disease early on was correlated with down the road having improvements in multiple composite measures such as minimal disease activity, DAPSA [Disease Activity in Psoriatic Arthritis] scores, and so forth. So, interesting that early improvement in certain clinical domains could predict long-term sustained benefit.

There's been a lot of interest in the effect of IL-23-inhibiting medications on the axial component of disease, because there was a failed trial with one of the IL-23 inhibitors in ankylosing spondylitis patients, a small phase II trial.

In DISCOVER-2, we have shown that patients with axial PsA, which represents about 30% of the patients in that trial, had very significant improvement of clinical symptoms of back pain, for example, and other measures of spine disease, in patients that had evidence of sacroiliitis at baseline.

And so, we saw further sustainment of that benefit in the 2-year data, but also an interesting look at genetic and cytokine differences between the axial PsA patients and the PsA patients who didn't have axial disease. For example, there was much less in the way of HLA-B27 positivity, more HLA-B8 positivity in the axial PsA population. Subtle differences in other factors. And so this is something that I think we're going to be watching for, with the results from the STAR trial, which is currently underway, how guselkumab performs in axial PsA.

There was one other very interesting abstract I found, which suggested that there might be differences in binding of the molecule to a CD4 molecule, the Fc receptor portion that might differentiate the drug from other IL-23 inhibitors and maybe have some impact on efficacy.

And, lastly, an abstract showed that patients who achieved minimal disease activity in the long run, as well as complete clearance of skin disease, complete clearance of dactylitis, that those patients, no matter how severe they were at baseline in various aspects -- for example, skin disease, joint disease, and so on -- all of those patients were able to achieve these very high-threshold outcomes. So, we don't have to be in the position of saying, well you have too severe disease to really expect optimal improvements.

So, all in all, a very complete data package to show us the sustained efficacy for guselkumab over time in multiple clinical domains of psoriatic arthritis, and a very good safety profile.

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