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Ana-Maria Orbai, MD, FACR, MHS, explains how guselkumab improved PROMIS-29 scores in patients with psoriatic arthritis.
Rheumatology Network interviewed Ana-Maria Orbai, MD, FACR, MHS, on her study entitled, “Guselkumab-Treated Patients with Psoriatic Arthritis Achieved Clinically Meaningful Improvements in General Health Outcomes Measured with PROMIS-29 Through 52 Weeks: Results from the Phase 3 DISCOVER-1 Trial.” Orbai is Assistant Professor of Medicine in the Division of Rheumatology at the Johns Hopkins University School of Medicine, and founding director of the Psoriatic Arthritis Program.
Rheumatology Network: Can you tell me a bit about the DISCOVER-1 study design and the methods your team use to determine guselkumab efficacy in patients with psoriatic arthritis?
Ana-Maria Orbai, MD, FACR, MHS: DISCOVER-1 was a randomized control trial, comparing guselkumab with placebo. Guselkumab is a selective interleukin 23 inhibitor, which is FDA-approved for psoriasis and psoriatic arthritis based on its efficacy. In this phase 3 trial, the primary outcome is American College of Rheumatology (ACR) 20, which is quite standard for psoriatic arthritis clinical trials. But there were also psoriatic arthritis specific outcomes like the minimal disease activity, for example, in psoriatic arthritis, and health-related quality of life outcomes. And the subject of our discussion today is the Patient-Reported Outcomes Measurement Information System (PROMIS)-29 profile, which was also collected to gain additional information on the effect of guselkumab on health-related quality of life, instead of using the traditional measures you are accustomed to, like the 36-Item Short Form Survey (SF-36) and the health assessment questionnaire disability index (HAQ-DI) physical function measure. So, it's a step forward in trying to assess efficacy with newer measures such as the PROMIS profile.
RN: Why did you use the PROMIS-29 instruments in your analysis as opposed to other options?
AO: PROMIS-29 is a generic health instrument. It has several advantages over older measures. And for this reason, it's easy to interpret on the PROMIS scale. A score of 50 is the general population mean. So, if someone has a score of 50 for physical function, this means that they are at the average level in the United States. So then, if we look at scores in patients with a certain disease, or we want to see the effect of a treatment, we are able to see the scores around this 50 and how they are doing relative to the population mean. And the movement with treatment is easy to interpret as opposed to just having a dry score like we are used to with the other measures. Also, because it is a generic health instrument, we can compare the health-related quality of life and the health and function of people with psoriatic disease with other rheumatic diseases with the general population. It allows some generalizability and seeing data across diseases. Another advantage is that PROMIS-29 was generated from a database of questions that are used to assess each individual domain. And these questions were generated from interviews with patients and questions were tested to make sure they didn't perform differently for reasons other than what they are intended to measure. For example, if a question is not built with these considerations, with these scientific considerations in mind, you could easily pick an item that may perform differently in men and versus women just because of how the question is phrased or because of different concepts. So, it's a source of bias if you're not asking the question properly. These questions were tested in the general population to get rid of items or questions that would perform differently in special groups, for example, by sex or by age, and only the questions that were suitable from this perspective were selected to remain in the in the database assessing each of these domains. There is also another way of administering PROMIS instruments, for example, they can be administered as a computer adaptive test, where respondents would get the first question and then, depending on their response, they will get a subsequent question with various difficulty levels so that we can get a really precise score with a PROMIS-29 profile. It's the most simple form of these PROMIS instruments. And still, it performed very well in this clinical trial. It also takes care of concerns that, for example, with a computer adaptive test, you would get different questions every time depending on the patient's response, although that's not necessarily bad. But with the PROMIS-29, all participants got exactly the same questions for questions for each of these domains every time, so it’s identical between participants and identical when they receive the questionnaire the second and the third time.
RN: And what were the results of this study?
AO: The first finding in the study was that people with psoriatic arthritis has significantly worse scores than the general population on most PROMIS-29 domains, but particularly in physical function, social participation, fatigue, sleep quality, and a bit worse for depression and anxiety. Treatment with guselkumab versus placebo led to significant improvements in these domains. The primary outcome was at 24 weeks, so there was a statistically significant effect favoring guselkumab. So guselkumab can help patients improve their health-related quality of life scores by a third and a half of a standard deviation, which are considered to be clinically significant improvements. More so, our abstract looks at 52 weeks data. These improvements last throughout 1 year, where these outcomes were measured. So, significant improvement, clinically significant improvements, and these lasted through 52 weeks through 1 year after people started treatment.
RN: And what is the clinical significance of these results?
AO: We already know that from the primary outcomes of the clinical trials that guselkumab improves the manifestations of psoriatic arthritis and that it does so across the spectrum of the disease, including skin, joint disease activity, arthritis enthesitis dactylitis, as well as patient-reported outcomes like pain. It is always useful to show that not only disease outcomes are improved, but that the patient's symptoms and health-related quality of life is improved. If you're making my psoriatic arthritis better, I also expect that my fatigue, physical function, and pain will improve. And this is what has now been demonstrated with a PROMIS-29 profile. I should mention that it was also demonstrated with the SF-36 and with HAQ-DI. And we see that that we can triangulate that the effect of guselkumab can also be seen with this measure with significant improvements in fatigue, physical function participation, pain, interference, and so on.
RN: What does this mean for rheumatologists?
AO: I'll tell you what this means for me for my clinic. So in in the Johns Hopkins psoriatic program, as well as in many other clinics across the United States, PROMIS-29 measures are collected not only as a part of research studies, but as well as clinical care, at least in our case. So, patients come to clinic, and they complete PROMIS questionnaires before each visit. We are not only able to see the disease activity that we measure during routine care using the joint counts, the enthesitis counts, the skin assessment, and other clinical assessments, but now we also have the patient's perspective, using the PROMIS measures. And knowing that this treatment improves the patient-reported measure as well is very useful. We also have a timeline on when we should expect some of these improvements. We know that as early as week 4, pain, physical function, and all of these outcomes start to improve and then there's buildup across as people stay on treatment longer. So I think it's helpful that patients can tell us if they improve and we can use this course to track early responses to treatment, which are always encouraging and are good motivation to stay to stay on treatment because our treatments can take longer, sometimes weeks or months, to work. It's very useful to have a measure that can tell early on that this is doing something because we're going to continue to see improvement.