RheumNow - EULAR 2018 - Day 3 Save

Hi. I'm Doctor. Jack Cush, executive editor of rheumnow.com, coming to you from Amsterdam and the site of EULAR two thousand eighteen. This podcast is part of our expanded coverage of EULAR. You can find us on our daily email from RheumNow or by going to the website, eular18.rheumnow.com.

Now the podcast. This is gonna be a collection of audio reports from RheumNow faculty, key opinion leaders, or abstract presenters from the meeting. I hope you enjoy the podcast, and be sure to tell your friends to tune in to RheumNow, to follow these podcasts, and to subscribe. Take care.

This is doctor Arty Cush, and I'm here at EULAR two thousand eighteen RheumNow. It's a good meeting, a lot of stuff going on, a lot of good topics being covered. The topic that has had a lot of interest over the past few years is biosimilars. And of course we look toward our European colleagues for a lot of the best and newest information about biosimilars because they have actual experience using these molecules more than we've had a chance to in The United States. A topic that has been of great concern, if you will, or interest to physicians, to patients, is the idea of multiple switches.

And that's been covered by a couple of abstracts here at EULAR in 2018. There are two one from Sweden, one from Denmark, where patients were on an originator biologic. They were switched to a biosimilar because it was less expensive. And then in these analyses, they looked at patients who switched back to the originator. It's an important topic and I looked for more information about these, but in these analyses it seemed that the patients who switched back and forth and back actually seemed to do pretty well clinically.

There's obviously a lot of patient input that's important for this. Some of the in the Danish cohort of patients what happened was the patients wanted to switch back and the patients and doctors chose to go from biosimilar back to the originator. So it raises the idea of the nocebo effect meaning patients may be on

a medicine and even if

that medicine is effective if they don't think it's going to be effective then it may impact how well they feel they're doing. So it's an important topic. There are about 30 abstracts on biosimilars at this meeting and a lot of other, up to date and interesting rheumatologic topics being covered here at EULAR. This is Arti Kavanaugh, EULAR twenty eighteen for RheumNow.

Hi, I'm Doctor. Jack Cush, executive editor of rheumnow.com coming to you from ULUR twenty eighteen. This afternoon I ended the day by going to a session by Gaylord Shet, a really interesting session. It was about bench to bedside and his particular lecture was called Does it matter to the clinician? Can pathophysiologic knowledge lead to better patient care?

Once he got over the shock of having to do that lecture, he sort of organized his thoughts around the concepts of pathophysiology, what we know about, disease and how it relates to psoriatic arthritis and risk in future therapy. It was a highly interesting session wherein he sort of laid out for us maybe some of the new thinking and how it could lead to some new changes in the management of psoriatic disease. First off, talked about a biomarker. Everyone loves a biomarker and he said that we should not lose sight of the fact that we have a biomarker in psoriatic arthritis and it's called psoriasis, meaning those are the people who are at risk. And we just now need to know what are the risk factors that can lead to the development of psoriatic arthritis.

First on his list was the idea of mechanical stress. He says that the psoriatic state being at risk for psoriasis whether it's genetically at risk or otherwise at risk is influenced by physical stress may be leading to skin disease but certainly leading to the articular manifestations. Everything from the enthesitis, the synovitis, the spondylitis, even the nail disease is felt to be due to mechanical stress. And one of the key elements that underlies this when one looks at the risk factors for developing psoriatic arthritis, many have been proposed, but one that you may not recognize is occupational heavy lifting. It's probably one of the only ones on the list that he showed us that was in fact significant, suggesting that that especially in males becomes a significant risk factor.

So he went through this, basically stating that there's obviously a preclinical phase where people can become, at risk, that there are risk factors like the usual ones, obesity and, lifestyle such as smoking, etc. But that can lead to, along with this mechanical stress, lead to immunologic activation. In fact, he supports that by showing data of psoriatic arthritis patients who stop their DMAR therapies and what is the risk for relapse of disease after one has stopped the taking the drugs and turns out that those who are greatest risk and by far and away way above the comparative group were males. Males were great risk for recurrence of their disease, and for flares, much more so than women. So that's important to take note of.

The early recognition is obviously an important part and that may be because of the threshold for identification is different in that skin's easy to see, joints not so much, so there is an early threshold that one has to go through. That all becomes important and leads to factors such as nail disease and nail disease is as we know a risk factor for developing psoriatic arthritis but that's part of that mechanical stress that needs to be present that leads to an increased risk of disease. Turns out that when you look for evidence of enthesitis, another sign of mechanical stress, this also becomes something that portends the onset of disease and if you look at those who have abnormal MRIs or abnormal ultrasounds as features of mechanical stress, it looks like that that too predicts the disease. So it is a systemic disease, it was one that needs to be controlled, it is not driven by IL-six and CRP. Instead, it seems to be largely driven by IL-twenty three and IL-seventeen and possibly IL-twelve.

And you know, he used his bedside to bench slide that actually shows that really really well. IL-seventeen obviously is a key player and therefore why it is a new target in developing disease. He made a point that in addition to the enthesopathy, there's the arthritis but often the arthritis is overstated in clinical trials that in practice it's probably a lot fewer joints that are involved. The oligoarticular disease, asymmetric polyarticular disease is far more common than the very polyarticular patients who are enrolled in trials. And enthesopathy is often involved in practice and may not often be appreciated.

And so what has been seen is that the more interesting new data is that IL-twenty three, whether individually like guselkumab or in combination with twelve twenty three inhibition, really hasn't fared all that well, when it comes to managing things like axial disease and enthesitis and whatnot. Enthesitis responds more like the skin than the joints in some trials that were shown especially with ustekinumab So, that's an interesting factor that he presented. He's going forward looking at fingerprinting patients developing profiles, of gene expression that may be important in identifying, those at risk. So again, what makes this unusual disease is the combination of enthesitis and synovitis, and its effect on growing new bone. But the disease needs to be considered maybe in a different manner that there may be risk which can be modified by lifestyle and then immunology which can be modified by therapeutics.

So lifestyle would be avoiding mechanical stress, avoiding obesity and smoking and then dealing with some of the magnifiers of disease in the comorbidities, whether it's managing hyperuricemia, cardiovascular risk or depression. These are a lot of the concepts that were covered. It was a very stimulating, intellectually stimulating session run by Professor Georg Chet. We wanna thank him for that. That's it.

Tuning in from EULAR and Amsterdam. Enjoy your room now.

Hello, everyone. This is Olga reporting from the annual EULAR meeting here in Amsterdam. I would like to tell you about the study presented by doctor George from University of Pennsylvania, where they observed patients who underwent total knee arthroplasty while on biologic therapy, and they assessed for infectious complications after surgery. Patients who enrolled in this study were on biologic therapy for at least one year. And for those who received the Rituxan, they they had to have their infusion at least sixteen weeks before before surgery.

And outcomes that were measured were infections, hospitalizations within thirty days, readmissions within thirty days, and one year prosthetic joint infections. It has been shown in this study that patients while on biologics have comparable outcomes in terms of infection except for patients on tocilizumab where infection risk was much higher. Although, authors noted that, they had very few patients on tocilizumab and that could have affected the result. Also, across all, biologic groups, risk of infectious complications, readmissions, or prosthetic joint infections were higher in patients who received concomitant prednisone treatment, particularly prednisone in a dose more than ten milligram daily. It is, been concluded in the study that prednisone may increase the risk of, infectious complications in patients on biologics, and it is recommended that we lower or try to lower prednisone dose prior to surgery regardless of their biologic therapy.

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Hello, I'm Peter Lipsky and I'd like to tell you about a trial we've been carrying out with peglodecase. One of the issues about peglodecase is that even though it's a very effective molecule, patients have a tendency to develop anti drug antibodies. And we looked at the initial pharmacokinetics of this molecule from the previously published randomized controlled trials. And as you can see, after the initial dose, by two weeks the blood level is quite low, the circumstance which favors the development of anti drug antibodies. So we propose that by giving an extra dose one week after the first dose, would avoid this trough level of zero and would have, much higher levels and be in to the range when we would expect high dose high zone tolerance and less, anti drug antibody formation.

In fact, the results of the trial showed some, improvement in the sense that more people could respond, but we still had a number of people who failed to have persistent response. But we looked at individuals one week after the administration of peglodecase here at a time when their uric acid levels were very low. Well, we could see that they divided into two groups based upon the mean level of serum peglodecase. There was a group that had higher levels and a group that had lower levels. And in fact, this was the group that had a persistent response.

This was the group that tended to make anti drug antibodies. And if you look at these groups in more detail, you can see that those who got above the threshold level of peglodecase in that group about seventy five percent were responders, whereas those who didn't get into that or didn't achieve that level, only thirty percent were respondents. So this has now given us a target level of peglodecase that we can aim for. And we're now expanding this trial by giving a loading dose of sixteen milligrams with the anticipation that we'll get more people into the higher level of peglodecase activity and as a result have less anti drug antibody and more tolerance to the drug.

Hello, everyone. This is Olga Petrina reporting from the EULAR meeting here in Amsterdam. Today, I wanted to tell you about the study on pregnancy outcomes in secukinumab treated patients. It is an Italian study presented by doctor Moroni as a poster where she observed six patients who conceived while on secukinumab treatment while receiving hundred and fifty milligram of secukinumab after loading schedule for at least forty five weeks from the start of therapy. Patients were able to continue treatment for another seven to eight to eight weeks until their pregnancy test became positive.

And at that start time, medication was discontinued. In this study, they did not see any fetal malformations in in in in these patients, and all pregnancy were uneventful with no negative pregnancy outcomes. All babies who were born in the studies were presented with Apgar score of more than eight at birth, and mothers were able to stay in low disease activity score with disease activity scores of less than four. So far, the medication seems to be safe, but, of course, the the the amount of patients very small and more additional studies or data collection will be required to continue proving safety of sacucunumab in pregnant patients. Thank you.

Have a nice day. If you want to know more, please follow us on RheumNow.

Hi. I'm Philip Romsen from the University of Queensland in Brisbane, Australia, and I'm here in the beautiful city of Amsterdam for EULA two thousand and eighteen. And I wanted to tell you about the session that I've just come from. It's a crystal arthritis session. There were a number of great abstracts, but I want to tell you about three or four today.

The first one is a study from Fernando Perez Ruiz from Spain. He took six fifty crystal arthritis patients who had CPPD, demonstrated it on aspirate, and then looked for severity markers and what the predictors were. He saw that having hemochromatosis genotypes was associated with more severe disease. And also cases had higher ferritins. So that's certainly interesting and that's one of the biggest studies of crystal demonstrated CPPD.

Hopefully we'll see more research in this under researched area. The other thing was there was a great analysis of some pegylodecase trials. They looked at the people who were responders and the responders who were treated monthly were more likely to have flares and that's probably because the see sawing nature of the uric acid that you see that you didn't see with the two weekly responders. So the take home from that is to use it two weekly and non monthly. There was another interesting study from Brazil where they did CT scans on a whole lot of gout patients and saw that thirty percent of them had stones.

Now when you ask them, only sixteen percent said they had stones. So the take home from that is twice the number of people who say they have stones do have stones. And not necessarily urate stones, maybe that's for another study. And finally, there was a really interesting study that replicated the result of the Cares study recently published in the New England Journal. It was a propensity study, a matching study from South Korea that used 50,000 patients and showed there was an increase in death when you took febuxostat compared to allopurinol.

So that means that a number of studies now showing that result. So I'm Philip Robinson from the University of Queensland and I'm here now in the beautiful city of Amsterdam. And if you want more information, go to roomnow.com.

Hi, I'm Roman Cavanagh. I'm a rheumatologist from Galway and I'm at Uilar in Amsterdam this year. I was at a session on scleroderma this morning and I wanted to talk to you about an abstract, an oral presentation that I heard this morning. I have to say normally this clinical research is something that I would probably walk on past, but it's about digital ulcers in scleroderma, which I find extremely difficult to treat. And this is a study of the use of autologous adipose graft transplant for the treatment of digital ulcers in scleroderma.

And the basic principle is that the authors take some adipose tissue from the abdominal wall and spin it down with the centrifuge, take the cells out and inject it into the base of the affected digit. They took a population and they compared that to a sham placebo injection with saline. So they took a group of patients with scleroderma with non healing digital ulcers and they randomized them. And in one group they treated twenty five patients with the autologous fat transplant and in a smaller group of 12 patients they used the saline injection. And the primary endpoint was the prevalence of healed ulcers at a four week and eight week time point.

And secondary outcome measures were pain and the number of dilated capillaries seen on video capillaroscopy.