ACR20 - Day 2.3 Save

This is the RheumNow podcast, and you're listening to highlights from the ACR twenty twenty virtual meeting. Our faculty reporters have been doing videos and recordings so that you could stay up to date. Hope you enjoy these and our panel discussions.

Hello, everyone. I'm Richard Conway from Dublin, Ireland, reporting from ACR twenty twenty, And I'm going to talk to you about a study presented by Doctor. Curtis on Saturday in plenary session two. This is abstract number nine thirty nine. And this was the SEEM Aure trial.

So this was a study of rheumatoid arthritis patients in remission, who were on combination therapy with etanercept and methotrexate. It was a double blind, randomised controlled trial. There were two fifty three patients included in the study. So at the start of the study, all of these patients were in remission on combination therapy with both etanercept and methotrexate. And they were then randomised into three different arms.

One arm continued combination therapy with etanercept and methotrexate. Second arm had their methotrexate stopped, so they just continued etanercept. And the third arm had their etanercept stopped, so they just continued methotrexate as monotherapy. And the authors assessed these patients after forty eight weeks, they use the ESTI, simplified disease activity index to do this. And what they found was that patients in combination therapy arm, fifty two point nine percent of those were in remission at week forty eight, In the etanercept arm, monotherapy arm, forty nine point five percent of patients were in remission at forty eight weeks and no significant difference between those two groups statistically.

And in the meditrexate monotherapy arm, twenty eight point seven percent of patients were in remission and that was statistically significantly less patients in remission on metatrexate monotherapy. There was also shorter time to disease worsening in patients who were treated with methotrexate monotherapy. And those patients who did relapse and had a flare of the rheumatoid arthritis, they reentered remission for the majority when treatments were reinstituted. So this for different groups, this was between seventy one and eighty percent. But again, not all patients re entered remission.

And that's something to be borne in mind. Most of those who weren't in remission had low disease activity, but some of them continued to have higher disease activity. So it would seem from this data that perhaps it's better to withdraw methotrexate than etanercept in patients who are in remission. And it would seem that withdrawing methotrexate and leaving patients on etanercept monotherapy does not seem to significantly worsen outcomes. There's a couple of caveats to this.

It's only forty eight weeks. We don't know what happens in the longer term. Metatrexate is significantly cheaper than etanercept. So there are cost implications to continuing the etanercept while stopping the metatrexate. And we don't know if this is true for other biologic agents and particularly other TNF inhibitors.

So etanercept doesn't typically cause the formation of neutralising antibodies where some of the other TNF inhibitors do. And methotrexate may potentially prevent that from happening. So theoretically, there may be more of an advantage to continuing methotrexate in those patients. Thank you very much. Follow me on Twitter at Richard P.

A. Conway. Tune into RheumNow for more updates from ACR twenty twenty.

Doctor. Catherine Dow reporting for RheumNow. All right, another abstract from ACR twenty twenty convergence meeting. So you really need to tell your patients to walk. It's not just for the benefits of exercise, but actually it could improve sleep.

Abstract 134, it's a pilot study exploring whether or not walking can improve your sleep. So what they did was they took 101 patients and they randomized them to either walking two to five times a week. And the goal is about 28 sessions over a period of eight weeks with one session a week that's supervised. So I know that some of you may not want to walk with your patients, but this is actually maybe assigning somebody like a family member to walk with them, just to give a motive. Now the other group was actually just given general exercise like, you know what, you would do really good exercising every day.

This is going help your joints and overall outlook in life. You know what we've been giving to our patients. So at the end of the study, what they had was patients fill out their sleep quality diary, okay, and sleep duration during this time. And not surprisingly, the group who had walked had improvements in both sleep duration and sleep quality compared to those who were just given general advice. And the amount of sleep that had improved one point six five hours.

Imagine what you can do if you got one point six five more hours of sleep every night. So put down your pen and don't write any more prescriptions for sleep aids. This is something that you can encourage the patients to do because it's not good just for their overall health, but it helps with sleep as well. Doctor. Catherine Dow reporting for RheumNow.

Follow me on Twitter at kdao2011.

Hi, this is Doctor. Artie Kavanagh and I'd like to welcome you to RWCS twenty twenty one. This will be our fourteenth meeting and it's going to be February. Now I know there's a lot of uncertainty. We are planning to have some part of the meeting live in Maui.

We think it's gonna be fantastic. We're just gonna go and day by day see how things are to make the safest and of course the best meeting we possibly can. I think RWCS really is the premier international academic rheumatology meeting. This year with the uncertainty, we're also gonna have a virtual component. So it'll be hybrid.

There'll be live RWCS, and we'd love to have you come there. There's also gonna be the hybrid online virtual version. We're calling it ERWCS. So look for more information about both of these. You can go to rwcs.com and get information and register.

So, we look forward to seeing you at RWCS twenty twenty one, February in Maui. Be there, aloha.

Hi, I'm Doctor. Janet Pope at RheumNow at ACR2020 or ACR20, the virtual meeting or convergence. I'd like to talk to you about abstract eight zero four. And the question here was why can't patients with RA maintain their ability to stay on their bio DMARDs? So in other words, it's about durability.

And this was a large Dutch study and what they did was they looked at patients, they removed patients who stopped their bio DMARDs for wanting pregnancy and they also removed patients who were in remission. And what they found were two features that decreased the ability to stay on therapy. Number one, ACPA positive, number two, monotherapy. So this brings up whether or not guidelines such as the EULAR guidelines in RA should be changed. Some of the guidelines say tapering therapy, obviously not always successfully stopping therapy but I do wonder if we should treat ACPA patients differently.

So I would say number one, when you're using an advanced therapy at least a Bio DMARD in RA consider background therapy even low dose methotrexate or leflunomide or even sulfasalazine, my opinion. Number two, if the patients ACPA positive leave well enough alone. So that's my take on this. I think the guidelines have to be put into perspective. Please go to RheumNow and the website as well to learn lots of updates.

Thank you.

Hello ACR Converge! I'm Doctor. Rachel Tate coming to you from my family's home office outside of Louisville, Kentucky. And today I wanted to discuss with you kind of an emerging topic that we see in rheumatology, treat to target, but not for RA, but for spondyloarthritis. So there were two interesting abstracts that I saw today that discussed this very issue, but from a feasibility standpoint in clinical practice.

So treat to target strategies within The Netherlands SPA Registry or SPANET were described in abstract number eight seventy nine. Patients were evaluated with an annual ASDAS score and those with an ASDAS score greater than or equal to 2.1 high disease activity were reevaluated at three, six, and twelve month intervals. And of course those who had a lower disease activity or less than 2.1 as the score were evaluated six and twelve months. This data was collected also regarding therapeutic changes within six weeks of a high as the score. So those numbers were also calculated.

We found that thirty eight percent of patients who achieved a low ASDAS score at the first visit. Twenty one percent of patients with high disease activity also had therapeutic changes within that six week window. But overall, the trend in patients who had high disease activity, it showed that only a few patients actually had treatment changes in total. So the follow-up scoring during the timeframe that was prescribed really wasn't achievable for this particular subset. So this actually suggests that treat to target while still being defined for SPA patients is really difficult to achieve in clinical practice.

Another abstract that also evaluates this feasibility of treat to target for SPA in outpatient clinics was abstract number eight ninety three out of Spain. Now this looked at BazDiS scores, C reactive proteins and ASDAS scores every six months for at least two years after the initiation of biologic therapy. Eighty percent of these patients achieved either remission or low disease activity at one visit. However, only forty percent remained at this level of disease control over time. So although the majority of patients actually achieved remission and low disease activity, which is what we are going for, while on biologic treatment, that percentage of patients who maintained this dropped significantly.

So this study concluded that younger and male patients were actually baseline predictors of maintenance of remission and low disease activity overall. So interestingly, there's another study out of China. This is abstract number eighteen ninety two, which showed that AS patients who completed self assessments actually had lower flare rates, higher treat to target rates overall, and they were termed proactive disease managed patients. So this reinforces the importance that we need to better define treat to target for this particular patient subset. We need to be sure we're educating and advocating for our patients.

And of course, we need to continue working hard to make sure that we are treating these patients early and aggressively. Stay tuned for this and more updates of ACR twenty twenty at roomnow.com and follow me at Twitter UpToTate.

Hi. This is doctor Robert Chow coming to you on RheumNow from ACR Convergence twenty twenty. I wanted to share with you two exciting abstracts today, both of which were oral presentations on the treatment of dermatomyositis. The first abstract was nine fifty five presented by Doctor. Agarwal.

This was the first placebo controlled randomized controlled trial of IVIG for the treatment of dermatomyositis. There were ninety five patients included with active disease and these patients were currently on either a standard immunosuppression or previously failed immunosuppression. These patients were then randomized one to one, either receiving IVIG or placebo. The primary endpoint was a minimal improvement of 20 points of the total improvement score, which includes muscle testing, physician and global assessment, the HAC enzyme levels and extra muscular disease activity. Seventy nine percent of the patients treated with IVIG met their primary endpoint versus only forty four percent of placebo.

The secondary endpoints were either moderate or major improvement in the total improvement score. And likewise, sixty eight percent versus twenty three percent met the moderate improvement and thirty two percent versus eight percent met a major improvement. Also, these findings persisted until week forty. The safety profile, the main adverse effects were headache, pyrexia, and nausea. There were three serious adverse effects compared to two in the placebo group and the serious adverse effects were thrombotic events, which we know are common related adverse effects from IVIG.

The second abstract is nine fifty eight. This abstract is also presented by Doctor. Agarwal. This was a Phase 2b double blinded controlled randomized, randomized controlled trial of tocilizumab in the treatment of dermatomyositis. Again, were randomized one to one receiving either tocilizumab or placebo.

These patients had refractory myositis. So either they had steroid failure or failure with at least one immunosuppressive agent. This patient only had 36. I mean, this study only had 36 patients with the primary endpoint again being the total improvement score. Unfortunately, this study did not meet the primary endpoints.

Twenty six percent of tocilizumab patients versus twenty nine percent had minimal improvement. There was no moderate or major improvement either. And furthermore, there was no significant change in steroid sparing effect. There was one serious adverse effect, which was infection with the tocilizumab group. I would say overall, these abstracts did provide promising and reassuring data on IVIg treatments, especially for this very complicated and difficult to treat disease.

But unfortunately there was no response as far as tocilizumab goes. However, it's still kind of unsure if we should use IVIG as a first line therapy, a second line, third line. Again, this study by Doctor. Agarwal, they use IVIG in concurrence with immunosuppression or previously failed immunosuppression. I would also like to know, can IVIG be tailored to specific dermatomyositis manifestations?

I would like to see data on IVIG especially related with extramuscular disease activity. As we know, dermatomyositis has a lot of extra muscular manifestations. I know that these studies will help me decide the way I practice and treat patients with dermatomyositis. I hope this was beneficial for you. Thank you for tuning in and follow RheumNow for full coverage of ACR twenty twenty.

And please follow me on Twitter DrRBC. Thanks.

Hi, I'm David Liu reporting once again for roomnow.com from ACI twenty twenty, the virtual conference. Wanted to tell you a little bit about a really interesting, abstract from the plenary which looked at warfarin use and end stage osteoarthritis, represented by knee and hip replacements. So knee and hip osteoarthritis. It was from Tia Nyogi's group at Boston University. And what they did was that they had a look at whether there's an association between these two things in a big UK primary care data set.

Now you ask you might be asking why might there be an association? Well, in fact, K, a lot of proteins and bone and cartilage are dependent on vitamin K as a cofactor. We know that some of the mutations that can occur and related to vitamin K can be associated with osteoarthritis. And we know it's whether vitamin K supplementation has trended towards less osteoarthritis in randomized control trials. So we haven't really been had the chance to examine this previously because patients who are on warfarin were on warfarin and they didn't have any other real choices for anticoagulation.

Of course now we have the novel oral anticoagulants, the direct acting oral anticoagulants, and that's really given us a chance to be able to try and compare the two. We've got enough data now and that's what's being looked at in this analysis of these GP primary care, primary care data from The United Kingdom. So looking at that, they had analysed whether there was an association in atrial fibrillation patients between warfarin and knee and hip replacements and NOACs and knee and hip replacements. They, of course, fought about confounders and corrected flows from the out. And really what they showed was that there was a strong association with warfarin and osteoarthritis in comparison to the patients on NOACs.

And that stood there even after things were adjusted for in the multivariable logistic regression, but also once it was considered about there might be practice to practice variation in the cluster analysis looking at that. The association was stronger for knee replacements, so knee osteoarthritis with adjusted odds ratio of one point four eight. So that's really something which really does provoke some questions. Should say as well that in this, the duration of warfarin usage led to incremental increases in risk for the total of knee and hip replacement. Really that gives us a sense of another pathway which might be really important in osteoarthritis.

I think there's obviously a question regarding warfarin use in osteoarthritis in general, especially when we've got choices. And if those choices are equal in certain groups, that's one thing in itself. Maybe this tells us a little bit more about osteoarthritis in general and the pathophysiological processes that underlie it. For more about osteoarthritis, pharmacoepi, and about everything that's happened at ACI twenty twenty, head along to rheumnow.com.

Hello. I'm Jonathan Kaye from the University of Massachusetts Medical School, and I'm here at ACR Convergence twenty twenty sitting in my home office where I've listened to presentations so far all day as well as all day yesterday. And I'm gonna talk today about a very interesting presentation and a very relevant presentation that Jeff Curtis gave at the Saturday plenary session where he presented the results of the SEEM trial, a trial looking at maintenance of remission after withdrawal of etanercept or methotrexate in patients with rheumatoid arthritis and sustained remission on combination therapy. This trial is very relevant and important in clinical practice because we're faced with the quandary of what to do about a patient whose disease is well controlled on the combination of a TNF inhibitor with methotrexate, do we withdraw the more expensive TNF inhibitor, or do we withdraw methotrexate, or do we continue them on the combination to prevent recurrent disease activity? There are two clinical trials that have been published which have addressed this question.

The PRESERVE trial, which was published in 2013 in The Lancet, Joseph Smolin was the first author, which looked at maintenance reduction or withdrawal of methotrexate after treatment with methotrexate and etanercept in patients with moderate rheumatoid arthritis. This trial, the PRESERVE trial, took patients with moderate active rheumatoid arthritis who were treated with methotrexate between fifteen and twenty five milligrams weekly for at least eight weeks, and they were randomized, or they were continued in an open label period to receive etanercept fifty milligrams subcutaneously in addition to weekly methotrexate. Those that had achieved sustained low disease activity with a dash 28 of 3.2 or less were then randomized into a subsequent double blind period of fifty two weeks, in which they were randomized one to one to one to receive either etanercept fifty milligrams plus methotrexate weekly, etanercept twenty five milligrams subcutaneously weekly plus methotrexate, or placebo plus methotrexate. The results of this study showed that patients who were assigned to receive either etanercept at fifty milligrams or twenty five milligrams plus methotrexate did better in maintaining low disease activity than did those who were treated with methotrexate alone. The next paper that's relevant was the publication in New England Journal of Medicine in 2014 of the PRIZE study.

Paul Emery was the first author on this study, and this looked at patients with early active rheumatoid arthritis who were naive both to methotrexate and biologic therapy. These patients were treated for one year in an open label phase with etanercept fifty milligrams subcutaneously weekly and methotrexate weekly. And then those who had achieved low disease activity or remission were randomly assigned between weeks thirty nine 50 two to receive either continued etanercept at a dose of twenty five milligrams instead of fifty milligrams weekly with methotrexate, methotrexate alone, or placebo for thirty nine weeks. So in this study, methotrexate and etanercept were withdrawn, or etanercept was withdrawn, or the dose of etanercept was reduced. And the endpoint was looking to see whether patients would remain in low disease activity or remission.

And the study found that patients who continued to receive etanercept and methotrexate, or atanercept at a reduced dose and methotrexate did better in terms of continued low disease activity compared to those who were withdrawn from therapy completely. The study that Jeff Curtis presented looked at patients who were in very good rheumatoid arthritis disease control. So this was a term that was used to define patients who were eligible for the study, and they had to be in this very good rheumatoid arthritis disease control for at least six months, according to the investigator. At the time of screening, they had to be in S di remission of 3.3 or less, and they had to have been treated with etanercept for at least six months, and stable doses of methotrexate ten to twenty five milligrams weekly for at least six months, with a stable dose for at least eight weeks prior to the run-in. The primary endpoint of the study was S dye remission, S dye of 3.3 or less at week forty eight, comparing those patients who were treated with etanercept monotherapy to those on methotrexate monotherapy.

The study design took patients who were on the combination of etanercept and methotrexate, and they were randomized two to two to one to either etanercept fifty milligrams subcutaneously weekly alone with methotrexate withdrawn, methotrexate ten to twenty five milligrams weekly with etanercept withdrawn, or etanercept fifty milligrams subcutaneously weekly, continuing with the methotrexate as combination therapy. Rescue therapy was allowed if patients met specific criteria, and the criteria were if they had moderate to severe disease activity at any time, low disease activity on at least two separate visits, or if at the two consecutive visits they had either low disease activity or moderate disease activity. So, what did they find? The groups were relatively well balanced. And at week forty eight, in terms of S diuremission without disease worsening, twenty eight point seven percent of those treated with methotrexate therapy monotherapy, compared to forty nine point five percent of those on etanercept monotherapy were in ester remission.

So almost twice as many patients remained in ester remission without disease worsening at week forty eight if they were continued on etanercept with methotrexate withdrawn, but fewer remained in ester remission if etanercept was withdrawn and they were continued on methotrexate monotherapy. The proportion of patients who remain in ester remission on the combination of etanercept and methotrexate was fifty two point nine percent, which was very close to the forty nine point five percent of those on etanercept monotherapy. So, this study showed that etanercept monotherapy with methotrexate withdrawal in patients in ester remission was as effective as continuing patients on the combination. So, in terms of time to disease worsening, patients tended to worsen sooner if they were on methotrexate monotherapy than if they were on either etanercept monotherapy or the combination, and recapture of disease control after rescue therapy was comparable in all groups. So, the study showed that similar proportions of patients maintained remission with etanercept monotherapy as with continuing the combination of methotrexate and etanercept.

The patients who flared, they were able to recapture low disease activity or remission with rescue therapy. And in terms of safety, the safety was comparable across the three groups. So, this study suggests in a trial design similar to the TEMPO trial, where you compare monotherapy with methotrexate, monotherapy with etanercept, or the combination of etanercept and methotrexate, in this case withdrawing one of the two treatments in patients in remission, not low disease activity or remission, but ester remission, that ester remission is best maintained with withdrawal of methotrexate and continuation of etanercept, the TNF inhibitor, compared to withdrawal of the TNF inhibitor and continuation of methotrexate. So in clinical practice, this study suggests that the best approach, if you have a patient on the combination of etanercept and methotrexate, is to withdraw the methotrexate and continue the biologic agent to maintain excellent disease control. Now, the remaining question is how can you predict who will best maintain remission or who might lose remission if you withdraw one or the other of the two drugs.

So genetic or other biomarker predictors of remission maintenance will be appropriate to study in the future. This presentation was excellent. Jeff is to be commended not only on the study, but also on his typical excellent presentation style. I look forward to seeing more studies, not only Jeff's, but others, at ACR Convergence. And I look forward to seeing you all again on RheumNow.

So for further information about this and other studies, go to the RheumNow website, and I'll see you again soon. I'm Jonathan Kaye.

Hello, this is Doctor. Eric Dine from Baltimore, Maryland checking in with RheumNow at ACR Convergence Day two. I wanted to chat today about some interesting studies from the poster session this morning in regards to rheumatoid arthritis. I'm going to talk about abstract seven sixty, which is a study out of The UK by Doctor. Dimateo.

And in this study, they looked at x-ray bone erosions in patients with anti CCP positivity, but without any with musculoskeletal symptoms, but without any clinical synovitis. How often is it? What do you do about it? Does it predict the risk of development of inflammatory arthritis? So this has been, I think, topic of conversation during the meetings throughout as to subclinical arthritis or positive antibodies without evidence of arthritis.

How do you manage these patients? Do you start them on early treatment? Kind of the clinical holy grail of how do we prevent patients from getting worsening disease at the very early stages. So in this study, they looked at four eighteen patients that were evaluated for musculoskeletal symptoms, arthralgias, with positive CCP antibodies. All patients involved in the study had a baseline radiographs of their hands and their feet, And they included patients with bone erosions that were measured by musculoskeletal radiologists and confirmed by a second independent musculoskeletal radiologists.

What they found were in this CCP positive arthralgia group. Bone erosions were quite rare. So seventeen out of the four eighteen patients or four point one percent had bone erosions. Where are these erosions likely to be found? Most frequently in the feet.

So remembering to not only look at the x rays of the hands, also look at the x rays of the feet, particularly the standing radiographs. In these four percent of patients, did they go on to develop inflammatory arthritis? In the study that they show the data, it showed not many, not a significant difference at least compared to the patients without bone erosions. So in total, there were one hundred and twenty three of the almost four hundred patients that progress to inflammatory arthritis. That's a total value of thirty one percent will progress to inflammatory arthritis.

And specifically, patients that start with bone erosions, forty one percent versus thirty one percent without bone erosions. This is an odd ratio of one point six, but it's not significantly significant. That odds ratio crosses one, the p value is zero point three seven. When you do the multivariable analysis, the odds ratio comes out to exactly one point zero. So about patients that had repeat x rays?

They only had seventy three patients with repeat x rays that showed for progressing to develop bony erosions. How do you interpret this? How do you use this for clinical study for clinical use? I say that, you know, I think overall, it says that in this group of patients, bony erosions were pretty uncommon overall in patients without clinical synovitis. So that's pretty reassuring before you get the imaging that if they don't have synovitis on exam, they've never had synovitis, they're probably unlikely to have bone erosions.

In seropositive patients, you know, it looked like four percent from this study. Is it not predictive, as they say for inflammatory arthritis? I think my takeaway from this study is that patients do progress to inflammatory arthritis. And again, in relatively short interval, we see that nearly half of them did progress to inflammatory arthritis when they had CCP positivity. And as to the finding that bony erosions do not progress, I think it's hard to say because there are only seventeen patients that have bony erosions, so we're talking about a small sample size.

And I wonder if we had more patients that showed early erosive disease, if they might have shown a trend that they do not do as well. I think it's interesting to correlate this with the abstract that we talked about yesterday, four eighty one, which talked about the role of imaging for subclinical synovitis. I think these are patients that I might do an ultrasound or do MRI to see if they have some subclinical synovitis to help us guide that next step in therapy. Overall, I think it's very interesting. I think it'll be very interesting as we continue to get lots of more studies throughout the ACR convergence, looking at these patients that have high concerns for development of inflammatory arthritis with positive serologies, but do not have inflammatory arthritis, what do we do?

Who do we aggressively treat early without overtreatment? So lots of information throughout this convergence, lots of information throughout on RheumNow. I'm Eric Diana, I'm good to meet Rob for the meeting and looking forward to talking with you further. Thank you very much. Take care.