What matters most to patients as we strive for remission in rheumatic diseases , and how is care evolving to meet those needs? Hear expert perspectives in symposium highlight clips from the 2025 American College of Rheumatology (ACR) Convergence in Chicago, Illinois, USA. Ronald van Vollenhoven (Amsterdam University Medical Center, Netherlands) chairs the discussion with Priya Reddy (Southwest Florida Rheumatology, Riverview, USA) and Frank Behrens (Goethe-University Frankfurt, Germany).
“All of what we do begins and ends with the patient in mind.” Priya Reddy breaks down the multifaceted patient journey in rheumatic diseases, the challenge of overlapping symptoms, and the key drivers behind diagnostic delay.
“We’re still seeing those significant lag times between diagnosis and initiation of treatment.” Priya Reddy shares what comes after diagnosis for people with a rheumatic disease and discusses current challenges.
What current unmet needs have the greatest impact on people living with rheumatic diseases? Frank Behrens explores key unmet needs across rheumatic conditions and how they shape patient outcomes, highlighting issues such as persistent symptoms, impact on quality of life, and incomplete disease control.
What difference can a treat-to-target strategy make in rheumatology? Ronald van Vollenhoven discusses target-driven care and how aiming for remission, low disease activity, or minimal disease activity may help to reduce the overall burden of rheumatic disease.
“If the patient has a sustained low disease activity or sustained remission, then all of the scores that reflect how they’re doing in daily life get better.” Ronald van Vollenhoven presents data on how remission influences patient quality of life and highlights the risk of permanent damage when rheumatic diseases remain uncontrolled.
Ronald van Vollenhoven, MD, PhD
Ronald van Vollenhoven is Professor of Rheumatology at Amsterdam University Medical Center, Netherlands. His research focuses on the development and systematic evaluation of biologic and immunomodulatory treatments for rheumatic diseases.
Disclosures: Research support from Bristol Myers Squibb. Support for educational programs from Alfasigma Global, AstraZeneca, Galapagos, Merck, Merck Sharp & Dohme, Novartis, Pfizer, Roche, Sanofi, and UCB. Consultancy and/or speaker fees from AbbVie, AstraZeneca, Biogen, Bristol Myers Squibb, Galapagos, GSK, Janssen, Pfizer, RemeGen, and UCB.
Priya Reddy, MD, FACR
Priya Reddy is a rheumatologist at Southwest Florida Rheumatology, Riverview, USA. She serves on the executive board of the Florida Society of Rheumatology, is founder and owner of Southwest Florida Rheumatology, and holds the roles of Secretary and Treasurer on the executive board of the American Women in Rheumatology Society.
Disclosures: Speaker and/or consulting fees from AbbVie, Amgen, Bristol Myers Squibb, Pfizer, Sanofi, and UCB.
Frank Behrens, MD
Frank Behrens is Professor of Translational Rheumatology, Immunology and Inflammation Medicine and Head of the Inflammation Clinic at University Hospital Frankfurt am Main, Germany, and Deputy Director of the Fraunhofer Institute for Translational Medicine and Pharmacology at Goethe University. His primary research interests focus on the pathophysiology of spondylarthritis, rheumatoid arthritis, and mixed connective tissue disease.
Disclosures: Research support from AbbVie, Chugai, Johnson & Johnson, Novartis, Pfizer, Roche, and UCB. Served as a consultant, speaker, or advisory board member for AbbVie, Affibody, AstraZeneca, Biotest, Boehringer, Bristol Myers Squibb, Celltrion, Celgene, Chugai, Fresenius, Genzyme, GSK, Johnson & Johnson, Lilly, Medac, MSD, MoonLake, Novartis, Pfizer, Roche, Sandoz, Sanofi, and UCB.
- We know that many of the rheumatic diseases are of course autoimmune diseases, but they're also driven by cytokines and the specific cytokines that are involved in each of our diagnoses, they differ. But nowadays that is important because there are so many medications, treatments that specifically block or antagonize one or more of the cytokines. So it can help us to target the treatments more specifically and the word target is confusing because the target could be the molecule or it could be the target in what you want to achieve and I'll explain what I mean by that. Because the development of therapeutics for rheumatological diseases has taken such a great flight over the past two, three decades, there's also been a lot of discussions about treatment strategies and I will like to focus on that. So some treatment strategies that have been discussed and that have to some extent been implemented are the early intervention idea, the step up approach versus stepping down. Also dose reductions, which has been explored in studies and withdrawal of therapy in the best case where the patient doesn't need a treatment anymore. But the main treatment strategy that has been lifted to the forefront of our discussions is the treating to target paradigm. So here again, it states what the principles are. You identify the target, which is what you want to achieve, where you want the patient to be at a certain point in time, and you usually know if it's realistic to expect it after six weeks or after three months or after six months. So you say, okay, let's decide that whatever the situation is now, I'm giving you, let's say a medication. Now let's agree that you come back here in three months and I'm going to see how things are going. And then you do actually have the patient come back and you see how things are going, but here's the big point, you're committed to then also take the next step if needed. And this is where it often actually breaks down. If the patient says, well, you know, I've been taking this medication now for six months and you see that the disease is still active, but the patient says, well, you know, I would like to maybe wait because right now, I'm having a stressful period and that's maybe the reason it's not going so well. So I would like, and there's always a reason you could also postpone this. And sometimes it's legitimate, but many times it's also better to just say, no, no, we had agreed that now we have to take the next step. And it does involve shared decision making. So if the patient says, no way, that's another story, but in most cases, it's actually the physician who will have to take the lead in this and say, yes, we're going to do something to get the disease under better control than it is today. And so for this reiterative process, it's important to define what the goal is and usually it is a remission, but we can talk in a moment about what that is, and it could also be low or minimal disease activity. There are different options. So as I said, it has been applied to many different rheumatological diseases and I'm going to give you some specific examples. So in rheumatoid arthritis, which is where the TICORA study was done more than 20 years ago and where we learned that this actually does make an important difference. The definitions of all the disease states that are relevant have also been keeping pace. And so the Boolean remission is where you say that the patient cannot have more than one swollen or tender joint, and the CRP has to be low and the patient's assessment also has to be low. In the EULAR and the ACR did agree that that was the best definition, but then in that same task force, it was also concluded that you could instead use something called the SDAI, Simple Disease Activity Index, which is a simple addition of swollen and tender joint counts acute phase reactant and visual analog scale and then it has to be less than 3.3 and that gives you roughly the same patient population. There are other definitions of remission based on the DAS, on the CDAI, the main point is that you have to have some sort of an actual quantitative measure for remission and that will tell you where the patient should be, ideally after you have intervened. Now sometimes, a patient has a very severe and refractory disease, maybe has already had the disease for years or even decades and you know, as an experienced clinician that it's not realistic to expect a remission. And then it's okay to say that you will aim for low disease activity for which there are slightly less stringent criteria. Can sometimes be the best solution for the patient in that situation. Now for psoriatic arthritis, I'll let Frank Behrens be the judge if that's the correct target that is given here, but it seems to me that that is indeed in the literature, the very low disease activity where a whole series of criteria have have to be met, several criteria and it also has involves the DAPSA for the psoriasis and psoriatic arthritis. And then the alternative option for more minimal disease activity, which allows just a little bit more. For axial spondyloarthritis as you see below, it's mostly the ASDAS, the Ankylosing Spondylitis Disease Activity Score, that can indicate the inactive disease or the low activity disease. And of course there's lupus, systemic lupus erythematosus, where remission had not been defined until a few years ago and there were many, many different definitions in the literature. But now I think the field has consolidated around the so-called Doris definition, the definition of remission in SLE as DORIS. And so that actually works pretty well and it's now also being used in studies and clinical trials, but if the patient is very unlikely to ever achieve that, then you can also aim for the lupus low disease activity score developed in Australia. And it allows a little bit more activity, but still low and still pretty good for the patient. So I did already mention the TICORA study. Here you can see those results. That was the study where the Scottish doctors treated the patients with standard of care in black and I want to emphasize, those patients received good care. They were good doctors and they did their best and they were able to use all the medications they wanted. So that was not the limitation. But they didn't have that imperative, you have to do something if the disease not controlled. The patients in the purple, they had the tight control directive. And at the end of the day, that their result was much better. And that was for the clinical outcomes, which you can see here, but again, the point of of the study it was also reflected in radiographic damage and that was an important difference. And on the right side, you can see that this was also experienced by the patient as a clear improvement in all these patient reported outcomes. Now a similar study has been done in psoriatic arthritis. It's called TICOPA, so tight control in psoriatic arthritis and this study also made it clear that if you did the tight control schedule, the treating to targets schedule, that you would actually get much better results, 91% more likely to achieve the ACR20. The percentage were 62% and 44% and also on the right side, a lot of other outcomes that show how the patient's experiencing it, it indicates the BASDAI score and the BASFI score for the back aspects and then also the HAQ as a functional measure. And these all show a clear advantage for the tight control schedule. It's also been done for axial spondyloarthritis. Here again, you can see that the purple, which is the tight control schedule, will give you a better result in the patient proportion that achieves the big improvement in the ASAS. Also, how many patients achieving low disease activity in the middle or the very big 40 response. And on the right side, again, another set of outcomes that reflect more on the patients function as the BASFI is a functional measure. And also the EQ5D, which is this more comprehensive view at the patient's health related quality of life and that too showed a small but significant difference. So it was clear that in all these three diseases, treating to target or tight control was giving better clinical results, better functional results, also better experienced disease control by the patient. For lupus, this has not been proven. There is no trial that has been completed to show that that tight control or treating to target in systemic lupus erythematosus is more effective. There is a trial ongoing in Germany. I don't know if Frank if you participate in that trial?
- No, I'm no, I'm not.
- But it is led by Professor Matthias Schneider from Dusseldorf and it has already included, I believe 290 patients, but it's on its way to the 400 and it's again, they randomized. Some patients receive standard care, some patients receive care according to the treating to targets paradigm. And then the expectation is that that latter group will do better. But we cannot say it as evidence, we can just say that we think so and there's a fairly good amount of literature that would sort of support it. So in lupus we say we're using treating to target now, and it is actually also being embedded in the guidelines and recommendations from large organizations. The targets could be the DORIS remission as I mentioned or the low disease activity score as an intermediate target, or maybe in some patients it's the best we can do. And then there's a couple of other things in the general recommendations about lupus treatment, which I think many of you're familiar with, that if the patient is doing well, the glucocorticoids should be tapered and ideally also actually stopped. And the way at the right side of this slide is the very aspirational goal of being able to stop all the treatments. I think that is unfortunately for many patients with lupus still quite out of reach. There's of course some exciting data of very, very innovative therapies here also at this Congress, we're not going to talk much about that, but for the future, we always hope that there is an even better target possible. - So I've tried to convince you that treating to target or tight control is the way to go, that it will have your patient have a much better likelihood of achieving a remission, but maybe you're not convinced that a remission or low disease activity is such a good thing. So I want to show you some data that actually shows that if the patient has a sustained low disease activity or on the right side of sustained remission, that all the scores that reflect how they're doing in daily life get better. And that is shown here with something called the physical symptom score and the mental symptom score from the SF-36 instrument. It's a very well-standardized and highly established instrument for measuring how patients overall are doing. And this is coming from some drug trials, but it was clearly shown here that the good disease state by objective measures also translate in something that the patient experiences. Same thing you can say for the quality of life, the health-related quality of life, if you assess it with the ESSDAI, this is for patients with Sjögren's, the ESSDAI is a measure of the activity of the Sjögren's. It is composed of nine different aspects of that disease. And it turns out if the ESSDAI is lower, which is of course less activity of the disease, then the assessment of the patient's state of health with the SF-36 is better. And on the right side, it's not done with the ESSDAI, but with the ESSPRI, and that is fully based on the patient's own symptoms. And you, again, see the same differentiation. Now, this is a study from Austria where patients, again, were divided into those who had achieved a complete remission, this is in rheumatoid arthritis, patients who did not have a remission, but the low disease activity in the light green, or the patients who still had active disease in the gray. And as you can see that the outcomes that were measured here, they included the function, the physical function according to the HAQ, the EQ-5D as a measure of health, et cetera. You can see that in each case, the patient who is in remission does the best. And you think, "Okay, but, I mean, he already told us this." And I say, "Yes, I did just tell you that, but I wanted to show you the evidence," because it's not always clear that we believe these kind of numbers if we don't see that it also has a direct impact on the patient's own wellbeing in day-to-day life. And then there's another thing, the treating to target scenario does put a little bit of pressure on the physician. And that's also the point of it, as it tells you, if you're practicing, you cannot just say, "Oh, today I don't feel like making a lot of changes in the treatment of the patient. It's too much hassle." And I think we just heard from Dr. Reddy how much hassle it is in the United States to get the pre-approvals, right? And then in Europe we have a little bit less of that. But we have other things, which is that we have to also make sure that if the patient gets a new treatment, they may have to come for more controls and then they have to get blood tests. So there's always something. And so it may sometimes feel like aren't we making it also very difficult for ourselves as doctors? And then you can think, "Well, does a few months' delay make a difference? Do we have to hurry it up so much? So we're going to show you some data that says it actually makes a difference how fast you achieve all these things. Now, sometimes it's related to the duration of disease itself. This is a study that I think is important from rheumatoid arthritis. It turns out that the patients in this study were basically always achieved remission, but some achieved it very early on in disease and others achieved it later on in disease. And so the question is, does that make a difference? And the answer is yes, because if they had achieved the remission early on, it was very good for them to be in remission. Plus their function was excellent. Their HAQ values were very good. Whereas for the patients who had achieved the remission, but it had taken a long time, they were at remission, and that's good, but their function wasn't so good. And why not? Because the damage. And so the HAQ has clearly a reflection of the activity of the disease and also of the damage that has been caused by the disease over time. And that's something that you can't fix afterwards. And this was work by Professor Michael Ward who worked at the NIH for many years. And he sort of was able to analyze it mathematically in a very nice way that split the HAQ into the components where the function is impaired by inflammation and where it's impaired by damage. And that's what we've tried to avoid in that disease, in rheumatoid arthritis. But it also applies to the other diseases, in psoriatic arthritis, of course, also with damage to the joints and the bones also in the back with ankylosing spondylitis. And then with lupus and the systemic connective tissue diseases, the damage can be in all the different organs. And if you take the slightly slower approach, you may engender some damage. And that's the point that we want to try to avoid it altogether. The damage that can occur is listed here, a little bit schematically, and also to illustrate how many different things we as rheumatologists have to keep in mind. And I don't want to make everybody feel bad because it is very challenging, but we can do this. And it turns out that in the practical setting, we are able to achieve many of these goals. So I do want to point that out, because I think we have sometimes also the tendency to be a little bit down on ourselves. So, again, the timing of achieving an LLDAS, in this case, it's the low disease activity of lupus, is also clearly correlated with the overall results for that disease. And on the left side, you can see that if the patient achieved the LLDAS quicker and more persistently, then they had much fewer flares, which is also an outcome for the patient. Very important, patients with lupus say that what they hate is the fatigue and what they also hate is not knowing when the next flare is coming. The right side is also showing that if you do achieve a low disease activity, then it will eventually lead to more time in low disease activity and even remission, which was not shown in this analysis. But that's also why we think of low disease activity as an intermediate step in many cases. This is also about lupus, and it again shows that if the lupus low disease activity state is achieved, if the patient has low disease activity, then the probability of damage goes down and the probably of flare also goes down. So it's very advantageous for many points of view. And damage in lupus is, like I said, it's not just one organ as in rheumatoid, but it has to do with all the different organs that can be affected by the disease or by the treatment. So damage in lupus is actually about 50-50. Sometimes it's the disease, for example, think of a discoid skin involvement with scars, and the scars are the damage. But it can also be something related to the treatment. And the best example is perhaps osteoporosis from the glucocorticoids that are used to control the disease. So we get the damage from both ends, but if we get the patient into a low disease activity state, then we get less damage. And that is a reason to also try to aim for that. And with remission, it's even better. So in rheumatoid arthritis, we already saw some data that if we can achieve the remission quickly, we get a better result. And this also underscores that from another study, that if the patient was able to achieve their remission soon after the diagnosis, then they had better patient-reported outcomes, better objective measures, such as the ESSDAI, and also less radiological progression, which is the SHS, left lower panel, and that's the radiographic damage, so that was also minimized. - Thank you so much. It is very, very nice to be here. And I want to thank my esteemed colleagues, as well as BMS, for bringing up what I think is a very relevant but often, you know, not covered topic, which is taking a step back as a rheumatologist and looking at the patient who has rheumatologic disease from sort of a global perspective. And so what I mean by that is, there are a lot of commonalities, I think, regardless of what disease state we wind up treating or diagnosing. And I hope that this introduction, as well as the conversation, keeps that sort of perspective in mind as we go through some of the slides. So I'm gonna start by discussing the idea of the patient journey. So at the end of the day, you know, all of what we do begins and ends with the patient in mind. And I think the patient journey in rheumatology is a unique one when we think about other specialties. And I'm gonna highlight some of that, and I hope that we engage in some robust discussion around it. Even though we're talking about onset of symptoms here, I love that the actual start of the patient journey is actually very likely to be before that, right? So we know the patients are probably starting to have either overt symptoms or not quite completely symptomatic, but maybe there are changes that are happening in their environment. What kind of socioeconomic status does a patient have? So there are definitely things that are gonna affect that journey before the full onset of what a patient recognizes as symptoms, or as maybe we even observe and collect from our history as symptoms. Then there is this entire part of the journey, which is the healthcare provider initial presentation of the patient, which includes the initial evaluation and treatment from that healthcare provider before the patient sees a rheumatologist. And we're gonna dig a little bit deeper into that part of the patient journey over the several slides, but we know that that part of the patient journey can be a considerably long one. And then here we are, you know, by the time the rheumatologist is seen, there are quite a number of things that have already happened. And I wanna stress too, to keep in mind what I said earlier, that the start of the patient journey can even be before the onset of symptoms. Because that's important for the rheumatologist, when they're faced with the patient, to also keep in mind when they're evaluating the patient. And of course, this is really this part of the journey once the rheumatology assessment takes place, is really what I think we spend, and I don't wanna be unfair, but I think we spend most of our time really in that space. We are thinking about how are we going to evaluate the patient, what is our diagnosis? What is the best treatment regimen and ongoing follow-up? And we spend a lot of time doing research and considering that particular part of the patient journey. And I like that we're going to talk a little bit about these other parts of it. So we know that whether a patient has psoriatic arthritis, lupus, RA, or Sjögren's disease, that these diseases have multi-system involvement. These are not diseases that we have the luxury of seeing present in one organ system, and therefore we get to be very, very focused. I tell my patients all the time I don't have the luxury of a cardiologist, and I can say that 'cause my father's one. But I don't have the luxury of being a cardiologist where, "Okay, here's my cath results. And look at that lesion, we know exactly where it is. You see that there's an occlusion and you know why you're having these symptoms." So it's a very concrete diagnosis, we don't have that sort of luxury. Our patients present with multi-system involvement. And the other thing that's really important is that there's a lot of overlap in the more non-specific symptoms throughout the different rheumatic diseases that we treat. And as you can see here on this slide, you're going to see fatigue throughout. I tell my patients when they say, "But doc, I have so much fatigue." I tell them, "Yes, it's coming from your rheumatic disease." But I can tell you that every single patient that walks in through my office is probably checking that box for a fatigue. That is such a ubiquitous presentation. Joint pain, we see in multiple disease states, obviously. And then we start to drill down on things like joint swelling, joint stiffness, where we're trying to take the pain from arthralgia to arthritis. And then if it's arthritis, is it inflammatory arthritis? And we start to hone in on our diagnosis. But this is one of the reasons that we have some challenges in diagnosing our patients. So what about that onset of symptom time period, where the patient is presenting to the healthcare provider outside of the rheumatologists office? We know by the time we take the history that there is a lengthy period of time before the patient is getting an accurate diagnosis. Sometimes we have the luxury of having a healthcare provider who, outside of rheumatology, already is very honed in. Sometimes I like to think from some of the notes that I send back to my specialists who refer patients or the primary care doctors who refer patients, that they're learning rheumatology from some my notes and they're asking some questions about inflammatory arthritis, and they're a little step ahead, but that does not always happen. And patients are often getting a misdiagnosis which, as they go from that healthcare provider to maybe not getting the right answer to another healthcare provider, whether it's still a primary care provider or another specialist, they're getting another misdiagnosis. And we know that this delay in diagnosis, and of course, the misdiagnosis is going to lead to some adverse effects and poor clinical and functional outcomes. This is something that we know very well. Now look at some of the different specialists that our psoriatic arthritis patients will see, right? They may see an orthopedist, and we say about the surgeon, you know, if you have a hammer, everything is a nail, and surgeons are ready to go in there and operate. I've had a lot of axSpA patients who've already had large joint surgeries, which probably they did not need if that diagnosis was done early and patients had appropriate treatment. Certainly, they see the urgent care providers. If you've got PsA patients with dactylitis sausage digit, they are thinking that it's gout and maybe it's an acute flare of gout. We also see that patients with Sjögren's disease are seeing the dentists and the oral surgeons for those oral sicca manifestations. So they're seeing multiple providers. And this is also going to contribute to that significant delay. And if we look here, this is, I think, something to really sort of look at these numbers and think about, right? We kind of know this, but when we actually look at some of these studies, if you're looking at lupus or Sjögren's, about 50% of patients, it's taking 18 months longer, or 24 months or longer, depending on the disease state, to actually get diagnosed. You're seeing 50% of patients in RA are having six months or longer for diagnosis. And the time between seeking medical attention for a PsA patient and getting a diagnosis is six months or more in about 66% of patients. But if we look at the amount of misdiagnosis, now this was sobering to me, that 96% of patients in this study that looked at 203 PsA patients, 96% of them were initially misdiagnosed. And while it's sobering, and while I'd love to say that somebody else is misdiagnosing the patient, I know that I'm guilty too, of seeing patients and thinking, is this really psoriatic arthritis or is this seronegative RA? And finally finding that psoriasis, either in the navel or in the gluteal cleft, and you know, finally being able to see it behind the ear. So this is not something that is just outside of rheumatologists alone. And then in this other study we're seeing for lupus patients is a larger number of patients, 2,000 plus. We're seeing 47% of them. And the other interesting fact that's on here is, 35% of patients met the primary criteria for Sjögren's in a group of patients who had RA, lupus, or systemic sclerosis. So we wanna also think about our diagnosis and patients already diagnosed with other rheumatic disease as well. - We know that there are poor outcomes. We know that the likelihood of patients getting to minimal disease activity or low disease activities affected by a delay in diagnosis, more likely to have treatment failures and unlikely to have control or progression to disability. And while we know the clinical and functional outcomes, let's not forget the psychological impact of having longstanding ongoing inadequately treated disease, this takes a toll. I know all of you have seen that patient in your office who you see the depressed affect. They've got active psoriatic skin disease, they're having pain in their joints. And when you say, how bad is the pain? I mean, it's always, it's a little heartbreaking. You know, I have to say, when the patients say, oh, it's probably about a four or five, and I'm seeing very inflamed peripheral arthro, you know, peripheral joints, I'm seeing enthesopathy and I'm like, really, you know, you're quite tender. And they say, well, I've had this so long, I've just got used to the pain. I think really our patient's baseline level of pain over such a long period of time is pretty significant. And we know that has to have that psychological impact. Of course, with psoriatic skin disease when it starts in their youth or through adolescence, that's got to be very, very difficult to handle that. So it's really important to consider the psychological impacts as well. And then finally, as I mentioned, when we get back to our part of what we look at in terms of determining what's the right treatment and ongoing follow up, we know that this, we've not cracked the code on this, right? We don't, we've got a lot of guidelines that I'll go into. We have a lot of working groups that are really trying to perfect this art. But this is a challenge. We know that even after patients are diagnosed that, you know, we need to figure out what is the correct treatment regimen. And there is lag time as well here, even in this, you know, arena and sort of time where we have multiple treatment options available. I think one of the most exciting things about rheumatology is the ongoing explosion. I think of potential therapies across different disease states. And even though we have a lot of different options and you're seeing them listed there, whether they're adjunctive therapies, conventional synthetic DMARDs, and of course now targeted synthetic as well as biologic DMARDs, we're still seeing those significant lag times between diagnosis and initiation of treatment. So this is still an issue. The final aspect of it is we have a diagnosis. We have to personalize that treatment to that patient. We follow the guidelines, but we have multiple therapies available, but our patients are cycling through multiple treatments. If we look here on your left, there was a study here, 725 patients, we're seeing 40% had three or more therapies, four or more therapies in 23%, 13% had five. So there's a lot of disease drugs out there, but they are cycling through one after another. This is another indicator that we have not hit the targets that we want. And same here when we're talking about rheumatoid arthritis or we're talking about lupus, we have a considerable amount of agents available in patients. There's definitely cycling through. So wouldn't it be great if with the very first drug choice we made, we hit that target right at the beginning? And sometimes it happens, but more often than not, we are adding therapies or cycling through. So to sort of summarize, you know, I hope that I've sort of driven that message home that there are lots of embedded delays in the rheumatology patient journey. And this is not unique to one disease state. It is really across all of our disease state. And this is, you know, this is due to and impacted by the diversity and disease presentation, symptom overlap, for example, as well as this prolonged time that we take in getting that right drug choice for that patient that will, you know, manage their symptoms. - Here we have a research in PsA and ask for self-reported severity, and you see the purple one are mild disease, the gray one are moderate disease, and the green one are severe. And if you look to the bar of advanced therapies prior to treatment on the left side and advanced therapies after induction of advanced therapy means targeted synthetics, biologics, et cetera, and ask the patients how frequently you have still a severe or moderate disease activity. The good news is, severe disease is really only below 10% after inducing a proper treatment. But interestingly, more than 50% of the patient in US, also in EU demonstrated still active disease beyond mild disease, despite the fact that we have already induced proper treatment in this individual patient cohorts. What are the most important symptoms reported by the patient despite the fact that they were treated in up to 90% with biologics or targeted? In RA, it is still pain. We have already discussed it, it's fatigue. But it's also stiffness still. It's aspects we are not often asking. I don't know how frequently you are asking whether about sexual wellbeing in your individual patients and they will not spontaneously report these signs. It's their only chance is to get a questionnaire to find it out, whether it's well captured. Also, the independency from other family members is an important question and the mental wellbeing as well. If you go to axial SpA, it's roughly the same. And you see on the left hand, if you have patients with an ASDAS scoring below 1.3 though means remission, you still have 45 patients who are reporting symptoms from their disease. So they're not symptoms free because this is the definition of remission. So if you have no symptoms anymore from your disease, and this has not happened also in ASDAS below 1.3, you see a lot of pain, back pain, of course, stiffness, arthritis, enteritis, all these things are reported by the patient despite the fact that they are according to our objective disease activity measures in remission. Comorbidities and associated diseases. What is the differences? So maybe you are aware that in all treatment recommendations for axial SpA and PsA, uveitis and IBD are now no longer listed as comorbid conditions on, but they are listed as associated disease. What does associated disease mean? Associated disease means that there is a pathophysiological overlap between the index disease and associated disease. For example, PsA as index disease, plus IBD as associated disease. There's such a huge overlap on the pathophysiological concept that the presence of the associated disease will have an impact on the choose of the mode of action for the index disease. That's the main topic. That means you have to have in mind whether these or one of the other comorbid condition is present by the selection of the mode of action for your individual treatment for the index disease. And that's a difference, while a comorbid condition is just the consequent of an untreated or uncontrolled primary disease or it's a consequence of the treatment itself. For example, osteoporosis in steroid use in RA or cardiovascular risk in uncontrolled RA, for example. These are typical comorbids. So we will not are taking into account specific mode of actions based on presence or non-presence of cardio like risk factors, for example. So risk for organs damage or structural damage. So I mentioned already in my introduction that we have both structural damage in the arthritic domain driven diseases and we have organ damage risk in those with vascular disease and mixed connective tissues, diseases like lupus. And you see that specifically on the left hand side in lupus, a classical disease where we are treating not only to control signs and symptoms but specifically to protect them from getting organ damage in the long run of the chronic disease. And to see the incidence of organ damage among patients with lupus are roughly 40%. And of course, it's our job, first of all, to early diagnose and then to make a treatment which protects them to get organ damage in a way. And you see here the kind of hierarchic order, you see neuropsychiatric disorders, renal disorders are of importance and the damage in this organ system, of course, musculoskeletal, cardiovascular, endocrine, pulmonary, et cetera, all these should be prevented. And on the right hand side, we have a typical arthritic domain driven disease like axial SpA, ankylosing spondylitis. And you see that an increase was seen in the mSASSS or in the radiographic changes despite the effect of control. And you know that we have still the discussion about the sequence of osteoproliferation and newborn formation in axial SpA. Nowadays, we believe that inflammation control leads to fatty degeneration and after fatty degeneration, there's a kind of misrepair with osteo class activity with osteoblast activation and osteoproliferation. And this is not fully controlled right now despite the fact that this kind of disease process is well known and cannot be completely up regulated by the different treatment modalities. And of course, we have the impact on quality of life. We discussed it sometimes disease activity is fine, but quality of life is not. Sjögren's disease is a typical topic where we have a huge discrepancy between how we address Sjögren's syndromes in the majority of rheumatologists and the patient feel about the disease. You see the impact in physical domain but also in mental domains and the mental wellbeing, anxiety, depressive symptoms are frequent in those diseases independent from the severity of the Sjögren's syndrome or the Sjögren's disease. And this has to be taken into account when we do different treatment decisions. Yeah, I mentioned already that we're talking about biomarkers, AI driven analyzes of as many features as we can use in PsA. This is an example. There's a huge European consortium called HIPPOCRATES, leaded by our colleagues in Dublin. And there is a huge collection of genetic markers, transcriptomic markers, proteomics marker, lipidomic markers, metabolomic markers. And the idea is not to find specific... Ah, the other way around. Yeah, it's not the main idea to identify specific disease specific markers to learn more about the disease and to identify new targets for treatment. The idea is to find cluster, to find cluster across different biomarkers, to identify groups with different behavior across with respect to progression, with respect to response to treatment, et cetera. And you can only do these in large cohorts. This is why we are using, in this case a lot of investigator initiative research data sets, but also data and biomarkers from randomized clinical trials from different companies who agree to be part of these consortium. Are the patients happy with the treatments we have? Are we happy with the treatments? And you mentioned it, it's so great to have so many therapeutic options. And here you see on the left hand side again, PsA. Did I mention already that I love PsA? Though, and Lorna for you it's on the right hand side, the lupus data as well. So the questions to the patient, are you happy with your treatment? And the next question is did you ever experience, some adverse reaction side effects? And what do you like or dislike on your individual treatment? And you see half of the patient on the left hand side with classical oral treatments experience adverse reactions. They don't like to be monitored and you have to go to your doctor, either GP or rheumatologist to be tested with a blood in a frequent way. They have to make compromises based on the fact that he has to take some medication. Difficult to remember, it depends on the frequency of administration. You all know once daily is the ideal thing to don't forget it. If you do it three times per day and no one will take it. Based on the fact that in the middle of the day, no one will take a tablet because you are in your job or in school and some. These are all things who might influence adherence and compliance. If you look for the biologics, and that's the interesting thing though, the rate of experience adverse reaction is much lower, 25% only. But of course, they don't like the injections. They have other challenges with the freezer and having all these things in the freezer and not your food. Yeah, it's inconvenient, of course, when you travel, et cetera. So, and on the right hand side, you see the lupus patients. And of course, the lupus patients are not happy with the steroids. They have a huge fear for the long-term adverse reactions because we as doctors mention it, of course, that you have to be careful with the high steroids and half of them also experience side effects of steroids. Despite we believe that steroids are easy to use for the patients, for classical immunosuppressants. Again, half of the patients experienced adverse reactions and they had still, the patient have a challenge with these idea that may be not only the disease but also the treatment might increase the risk for getting organ damage. For example, liver, renal system, et cetera. And so, all these shows you the challenges we have with our daily practice. And finally, that's what I mentioned at the beginning, that we are still dealing with increased mortality in our diseases and I think we can't accept it to be honest. So it couldn't be that patients will die earlier based on their rheumatic conditions because it's our job to normalize these mortality. Of course, we are dealing with delayed diagnosis and all these things, but I think as soon as they are in our hands, we have to do everything to control inflammation and to normalize mortality in these patients. This is Sjögren's disease and PMR. This is PsA in Toronto cohort, in Ontario cohort. And you see, despite the fact mortality is dropping down over time, but the gap is not closed yet. And I think this is up to us to close this gap between the normal population and some psoriatic disease patient.
