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Stanley Cohen, MD: Hello. I'm Dr Stan Cohen. Welcome to Medscape's InDiscussion series on psoriatic arthritis (PsA). Today we will discuss a couple abstracts from the recent ACR 2022 Convergence meeting on psoriatic arthritis. We'll talk initially about switching therapies after a TNF inhibitor incomplete response and then discuss the issue of tight control in axial spondyloarthritis (axSpA). My guest today is Dr Alexis Ogdie. Dr Ogdie is associate professor of medicine, epidemiology at the Perelman School of Medicine. She's also director of the Center for Clinical Epidemiology and Biostatistics and director of the Penn Psoriatic Arthritis and Spondyloarthritis Program. Welcome, Alexis. Thanks for joining us today.
Alexis Ogdie, MD, MSCE: Thanks so much for having me.
Cohen: We talked about a year ago and had a wonderful discussion. Going through the presentations from the ACR meeting last fall, your research is quite prolific. You had multiple abstracts. We could have picked many to discuss, such as your work on comorbidities, central sensitization, delay in starting therapies, and so forth. But I thought it'd be interesting to talk about the role of therapies in treating psoriatic arthritis. I've done a lot of work in my career in rheumatoid arthritis, and over the last decade we have come to believe that switching mechanisms of action in rheumatoid arthritis may be better than cycling. I know you presented some data with Phil Mease and others from the CorEvitas Registry. Walk me through what you did and the findings you were able to present.
Ogdie: In this particular abstract, we took patients who had failed their first TNF inhibitor and saw them start their next therapy. We then followed them over 6 months, up to 2 years. We took those people and put them into two groups. One group was called "cyclers," so they went from one TNF to another TNF. The second group was called "switchers," and they went from a TNF to either an IL-17 inhibitor, IL-23 inhibitor, or one of the other mechanisms of action. Our question was: Is there really a difference between these two groups in terms of outcome? As you said, this has been demonstrated in rheumatoid arthritis, but there's been limited evidence in psoriatic arthritis, particularly when you examine a patient's physical exam. For example, one study suggested switching might be better in an administrative dataset. We found that it was approximately equal in terms of cyclers vs switchers. Out of almost 400 patients, 205 were cyclers and 189 were switchers. There were some similarities at baseline in terms of disease activity. For example, switchers tended to have a little more skin disease at the time they were switching their therapy, which makes sense because that's one of the reasons we sometimes switch away from a TNF inhibitor. At 6 months, we examined outcomes like minimal disease activity (MDA), very low disease activity, cDAPSA, as well as a range of individual outcomes and patient report outcomes. We found that patients who switched achieved MDA in about 19% of patients, and patients who cycled achieved MDA in about 16% of patients. It was not really that different, although when you adjust for other factors, the odds ratio is about 1.7, but it crosses one. So, it's not statistically significant, but it suggests maybe with more patients we would see an effect of switching.
Cohen: This was obviously observational registry data; it wasn't randomized, and you got very lucky that you had about the same number of cyclers and switchers. Did you have data on background conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) like methotrexate in the groups and so forth? Also, I know how the CorEvitas data works: You must have at least a 6-month visit, that's when they collect their data to see what the change may be vs primary or secondary failures to TNF inhibitors. Did you have any of that data?
Ogdie: In CorEvitas, we don't have a great sense of why people failed. We looked at what we had, and it was approximately equal in terms of stopping for efficacy vs safety. It seemed like about 60% stopped for efficacy, but we have no idea if that was primary or secondary failure. I think you're right that that's a really important factor and has also been seen in rheumatoid arthritis as an important factor for switching vs cycling. In terms of background csDMARDs, I realize that's not in our tables. Hopefully, when we get to the paper phase, we'll have that in there. We didn't have that in our baseline in terms of whether they were on methotrexate, for example.
Cohen: Methotrexate obviously has some benefit based on the data. But monotherapy with the biologics is just as good or better. You also found that when you looked at HAQ disability index (HAQ-DI) that physical function seemed to favor the switchers rather than the cyclers.
Ogdie: Some individual outcomes were different. For example, HAQ-DI. Enthesitis count was much different, and then body surface area (BSA) was different. Switchers had an improvement in 47% to less than 3% BSA vs 33% in those who cycled. There may be some specific reasons, but for most of the outcomes, it was just a little bit better for swollen joint counts. I think a larger study is needed. We are just about to launch a trial in this area. Keep an eye out at EULAR for our study plans on that. We have a study that will hopefully be opening in May that also addresses the switching vs cycling question.
Cohen: You're launching a strategy trial?
Ogdie: Yes, it's a randomized controlled trial among patients who have failed the first TNF inhibitor, and it will be stratified based on primary vs secondary failure.
Cohen: That's great. Is this going to be a pharma-sponsored trial? National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) or National Institutes of Health (NIH)? What kind of trial is it going to be?
Ogdie: It's a collaborative trial with pharma. We're running it out of Penn and Utah, and there's a multi-site trial.
Cohen: That's exciting because obviously that's what we need. Looking at the new Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) guidelines, I didn't see anything that endorsed cycling vs switching at this point.
Ogdie: Right. In the ACR guideline from 2018, there was a suggestion to try a second TNF inhibitor first, but that was right when the IL-17 inhibitors were coming out. There wasn't a lot available aside from ustekinumab at the time. We only had early data on IL-17 inhibitors. I think that could change down the road. At this moment, there's not strong evidence to suggest one way or another. It's not in the guidelines.
Cohen: I'm excited to hear that there's going to be the proper protocol pursued to try to answer this question. Let's talk about a lecture that you gave at the meeting. We've had data for many years in rheumatoid arthritis that supports tight control and treat to target with the TICORA data very early on, and now other studies, the BeSt study and then the psoriatic arthritis group has the TICOPA study targeting an ACR20 response. You gave an overview of a paper that was presented last year along with other data looking at the TICOPA study where they were targeting low disease activity and axial spondyloarthritis (axSpA). Walk me through the clinical trial design and what the findings were, and your thoughts on the message from this study.
Ogdie: This was a cluster randomized trial among patients with axial spondyloarthritis. They were randomized to either a tight control arm or a standard-of-care arm. In the tight control arm, they were aiming for an Ankylosing Spondylitis Disease Activity Score (ASDAS) low disease activity (LDA) as a target. The interesting thing about this trial was that the outcome at 48 weeks was an ASAS Health Index. They used ASDAS-LDA as the target and then quality of life improvement as the outcome. I think many of us who treat axSpA know how intertwined quality of life is with disease activity, but that can encompass different things. At the end of this trial, they found that there was not a statistical difference between the ASAS Health Index in people in the tight control arm vs the standard-of-care arm. There was a difference in the ASDAS-LDA between the two arms, as makes sense. If you're targeting this target, you're changing therapies in order to get there, and you are generally going to get to a lower place if you're actually targeting it. It worked, but then it was a negative trial. It was a confusing study. It is particularly difficult in axial spondyloarthritis, where we're using fully clinical intuition to treat a patient, as imaging was not incorporated in this trial.
Cohen: In reviewing the paper, I was impressed by the difference in the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI 50). In the tight control group, it was quite robust and not as good in the usual care group. In fairness to the trial, all of these investigators were spondyloarthropathy experts. Even in the usual care group, they would be aggressive in managing the disease. It looked to me that when they did their powering, they looked at the ASAS Health Index and figured that only 20% of people would meet the improvement grade — a 30% improvement — when it really was 30%-35% in the usual care. My experience has been that with the spondyloarthropathies, at least with the initial treatments, you can pick off a large number of patients who do very well. My thought was maybe the study, unfortunately, was underpowered.
Ogdie: I think there's a few things. One is that it probably was underpowered for that particular outcome. If you had more patients, there would be a numerical difference between the two outcomes. With enough patients, you would see a statistical difference. I agree that many patients can respond for a while and then don't respond as well anymore. I think for our axSpA patients, we do see a lot of pain — 30% have central sensitization by current estimates. More than that, all kinds of things happen. Back pain is so common anyway. For example, I had a patient who had really bad axial spondyloarthritis and did beautifully on adalimumab. We had to titrate his dose a little bit, but he was doing great. He was running a marathon and training for another marathon when he ended up having some severe back pain. He was convinced that the back pain was his axial spondyloarthritis coming back, and he was very anxious and scared about what was going to happen. He'd done so well on this therapy. With imaging, we found a disc herniation, which makes sense with all the running he was doing. I think one of the difficult pieces about axial spondyloarthritis is that you can still have mechanical back pain. You can still get all the regular things that adults get. Separating those two out is important, and if you just use the ASDAS, you would overtreat patients at times. You could also end up undertreating patients who are poor reporters of disease activity. I think it's a challenging mix. With RA and even PsA, we can feel what's going on — we can see the swollen joints. When we're talking about treat to target, we're targeting something that we can see in front of us. I think that's the difference with axSpA that makes it much more challenging.
Cohen: I agree. Degenerative disc disease begins in your early 30s and complicates the scenario. Am I correct that EULAR, which is very prolific as well, is coming up with treatment recommendations to improve their impact factor in their journals? Do they recommend a treat to target in the spondyloarthropathies?
Ogdie: They have it framed a specific way. This treatment should be guided according to a predefined treatment target. I think they word it specifically that way. But then they have an additional paragraph that says the task force emphasizes that the treatment target should be used as guidance but only result in intensifying immunosuppressive treatment if the physician and patient are convinced that the presence of residual inflammatory activity and other contextual factors do not impede such an intensification. There was one line that says essentially treat to target but with caveats. Wrap in all those things that I just talked about that make it difficult to fully assess what's going on sometimes.
Cohen: Sounds like they brought a lawyer in.
Cohen: — Is the ASAS Health Index replacing the other measures of physical function and disability in the spondyloarthropathy realm?
Ogdie: Within axSpA, ASQoL was previously one of the disease-specific quality-of-life measures. The ASAS Health Index is replacing that. It is not necessarily replacing function, for example, but there are questions on function. It captures a full range of things — there are 17 different items, including sexual activity, fatigue, and sleep.
Cohen: Let me ask you about another abstract that you had about trying to predict who is going to develop psoriatic arthritis from a population of folks. I'm actually working with a company that's using machine learning and artificial intelligence — the future of the world — to try to look retrospectively at clinics for general practitioners (GPs) of patients who haven't been diagnosed with psoriatic arthritis but actually have psoriatic arthritis. You were doing a similar exercise looking back at chart review and demographic features. Can you talk about what you found in that particular study?
Ogdie: We took patients who were seen in three of our institutions: Penn, Utah, and MetroHealth, and identified all patients with axial spondyloarthritis arising in one particular time frame. We were looking at the treatments, but then we wanted to look back and see how people were being treated from a primary care physician vs only seeing a rheumatologist. In terms of the machine learning part and looking back at risk factors, this is something that our group has done a lot of, and I think what we have learned is there are many caveats to that. While machine learning is really exciting, it's not actually about the methods — it's about the data. One of the things that we frequently don't have is enough data from the patients prior to their development. They have to first go to the doctor, and then the doctor actually has to record the right information. For example, when we looked at this in psoriatic arthritis, we did that exact same thing. We found that if you look at what dermatologists are coding in the 6 years prior to psoriatic arthritis diagnosis, it's things like skin rash or psoriasis. And then there's this tiny sliver of inflammatory arthritis or joint pain codes or anything related to joint pain. They essentially don't code that at all. They only code what was related to their specialty, whereas the GPs do a much better job of that. Maybe they are the target as opposed to dermatologists, for example. But even then, the GP needs to recognize what is actually happening and put in the right codes, like is this Achilles enthesitis or is it ankle pain? Depending on the code, the machine learning may look at that. So, while having those codes does predict later psoriatic arthritis, the question is, as you're sitting in front of the patient and watching things add up, at what point should you be alerted that this patient is developing psoriatic arthritis? There are many caveats to those data, especially using administrative or electronic medical record data.
Cohen I saw another abstract you had, which is interesting, suggesting that multiple morbidities or comorbidities may increase the risk of developing psoriatic arthritis in patients with psoriasis. I thought that was fascinating as well.
Ogdie: Yes, that was by Paras Karmacharya, and he's had a couple abstracts and papers looking at multimorbidity. The concept is that as you add additional comorbidities, you are at increased risk for mortality, which we know from the general population from rheumatoid arthritis. The other question is does adding comorbidities increase your risk for psoriatic arthritis? We know that obesity is a risk factor for PsA, and hyperlipidemia and other metabolic conditions. There's been a variety of comorbidities associated with development of PsA. The question is does it matter which ones, or is it just adding each individual comorbidity? He did find a trend suggesting that the number of comorbidities was associated with increasing risk for PsA. This is similar to something that Lars Kristensen presented from their data in Denmark, in which they examined comorbidities in the preceding years prior to PsA. I think this is a general concept. How would you implement this in practice? I think we need to understand what the specific comorbidities are, how many need to add up, and when to throw up that flag for the clinician to say, "This patient probably needs to see a rheumatologist, or you need to do X, Y, or Z to prevent PsA."
Cohen: In the RA field, we're very interested in pre-RA prevention and struggling with that, knowing we don't have a uniform definition at this point. But [for] the 10%-30% who develop PsA from psoriasis, it would be very important if we could prevent that. This has been great. You're doing a wonderful job — just keep it up. I look forward to the actual clinical trial to try to answer the question about switching vs cycling. Thanks very much for being with us today.
Ogdie: Thanks so much for the opportunity. Have a great rest of day.
Cohen: Today we talked about some fascinating presentations in psoriatic arthritis. Thank you so much for joining us again. This is Dr Stan Cohen for InDiscussion.
Listen to additional seasons of this podcast.
1600: The Impact of Second-Line Therapeutic on Disease Control After Discontinuation of First Line TNF Inhibitor in Patients With PsA: Analysis From the CorEvitas Psoriatic Arthritis/Spondyloarthritis Registry
Cycling or Swap Biologics and Small Molecules in Psoriatic Arthritis: Observations From a Real-life Single Center Cohort
Baseline Disease Activity Predicts Achievement of cDAPSA Treatment Targets With Apremilast: Phase III Results in DMARD-naïve Patients With Psoriatic Arthritis
Etanercept and Methotrexate as Monotherapy or in Combination for Psoriatic Arthritis: Primary Results From a Randomized, Controlled Phase III Trial
EULAR 2023. European Congress of Rheumatology
GRAPPA Treatment Recommendations: 2021 Update
Special Article: 2018 American College of Rheumatology/National Psoriasis Foundation Guideline for the Treatment of Psoriatic Arthritis
Effect of a Treatment Strategy of Tight Control for Rheumatoid Arthritis (the TICORA study): A Single-blind Randomised Controlled Trial
Aiming at Low Disease Activity in Rheumatoid Arthritis With Initial Combination Therapy or Initial Monotherapy Strategies: The BeSt Study
Long-term Follow-up of Patients in the TIght COntrol of Inflammation in Early Psoriatic Arthritis (TICOPA) Trial
Efficacy of a Tight-control and Treat-to-target Strategy in Axial Spondyloarthritis: Results of the Open-label, Pragmatic, Cluster-randomised TICOSPA Trial
ASAS Health Index: The "All in One" for Spondyloarthritis Evaluation?
Central Sensitization Has Major Impact on Quality of Life in Patients With Axial Spondyloarthritis
ASAS-EULAR Recommendations for the Management of Axial Spondyloarthritis: 2022 Update
Treatment of Ankylosing Spondylitis by Primary Care Physicians and Rheumatologists: A Retrospective Study in Three Health Systems
Multimorbidity in Psoriasis as a Risk Factor for Psoriatic Arthritis: A Population-Based Study
Comorbidities, Pain and Fatigue in Psoriatic Arthritis, Psoriasis and Healthy Controls: A Clinical Cohort Study
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Cite this: New Research on Switch vs Cycle in Psoriatic Arthritis - Medscape - Mar 28, 2023.