ACR20 - Day 4.6 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.

Hi. This is doctor Eric Dine with RheumNow checking in from Baltimore, Maryland on the final day of ACR convergence. We've seen a lot of great reports over the whole conference that we've had so far. One question I think that was answered by a poster out of University of Miami is what to do with the patients with fatigue in rheumatoid arthritis and which patients do we expect to have benefits to have improvement when they come in complaining of fatigue in RA. So this study looked at one hundred and eleven patients with rheumatoid arthritis, and fifty two of them reported high fatigue scores at 12 with diagnosis.

So what were the factors that led to improvement in fatigue over time? In the univariate analysis, they found several predictors for improved fatigue. So female sex, non smokers, and increased baseline fatigue appeared to improve better with treatment of RA. Depression showed a trend toward significance but did not meet it in the univariate analysis. It's worth noting, this is just patients being seen with usual care of RA.

There is no specific intervention that was trialed for improvement of their fatigue. No interventions of any sort other than routine RA care. When we get to the multivariate analysis, they find really two odds ratios stand out quite dramatically. The first being non smokers were much, much likelier to improve with their fatigue. So the odds ratio was seven point six, that they're much more likely to get better fatigue as compared to the patients that were smokers.

Depression, on the other hand, opposite signal in the multivariate analysis that their odds ratio is 0.17, so much more unlikely to have improvement of their fatigue. So if a patient's a smoker and depressed, you're likely to see them continue to be fatigued. Whereas if they're a non smoker and they do not have mood difficulties, that's not a concern. Or they're much likely to do better. Exercise was subjectively measured through the activity questionnaires.

It was something I would have liked to see some more objective measures of exercise because I would have expected to see that play a role in fatigue in our patients. They asked about physical function, but not specifically about quantifying exercise and breaking it down by that. But I do think there are some very important notes for here that first, the impact of smoking. Smoking itself causes fatigue and that's something that's really important to adjust and modify for so many reasons in RA, but this is another thing that you can counsel your patient on to do better and to feel better. And thinking about mood disorders and if patients are fatigued, if it's related to the active RA inflammatory process, or if there's an underlying mood disorder that can also be addressed.

So I think this is exciting because it's a common problem. It's something that comes up, again, fifty two out of one hundred and eleven patients in this study, so almost half of your patients will complain of fatigue. And both smoking and mood symptoms are modifiable if you can get them into the right treatment options for both of those. So I think this is definitely something that could be translated into clinical practice. For Erythdine, this is RheumNow.

This is the final day of ACR convergence. And we've enjoyed looking at all the abstracts and presentations throughout the meeting. Take care.

Hi, I'm Jack Cush with RheumNow. We're here in the office of Doctor. Ken Segg, Chief of Rheumatology at the University of Alabama, Birmingham. I've asked Doctor. Segg to join us to talk about this new ReCePI trial.

So the ReCePI trial is aimed at treating patients with refractory gout with pig load a case and trying to use a DMARD as a way of suppressing the anti drug antibodies. You know these the peg is very immunogenic. It's kind of limited some of the efficacy and added to some of the toxicity associated with piglodecase. This is refrained a lot of people from using it. So there have been trials so far maybe using azathioprine or methotrexate and then mycophenolate.

And then Doctor. Saig stepped in and he designed this recipe trial wherein he chose mycophenolate. Ken, why did you choose mycophenolate?

Yeah, well Jack, thanks for the opportunity to talk about the study we refer to as ReCePI. And as you've noted, there's been a fair bit of work previously, mostly observational and somewhat anecdotal looking at different immunomodulatory drugs to try to attenuate the immunogenicity of pegyloticase, which as you pointed out is really the limiting factor in using this otherwise highly efficacious therapy. We talked to rheumatologists and we talked to immunologists and we said, well, do you see as sort of the pros and cons of different immunomodulatory drugs? And there's definitely pros and cons of mycophenolate, of methotrexate, of azathioprine. There is a large study underway looking at methotrexate, and I think that will be very interesting and some preliminary data has already been presented for that.

We had some concern that methotrexate, you know, a lot of the patients that we're thinking about treating have had non alcoholic steatohepatitis, some drink alcohol, methotrexate requires some gradual increase in dose. And so there was some potential safety concern about methotrexate, although arguably a drug that we're more familiar with and that we use in combination with our biologics in the inflammatory arthropathies, RA, spondyloarthritis, etcetera. So we thought that had a lot of potential and rheumatologists are familiar with using it. We have a lot of confidence and comfort using it based on our experience in lupus and vasculitis in particular.

So it seems to be a good choice. It was a head to head of everybody getting pegylodecase and then half the group got the mycophenolate and the other half got placebo. The primary endpoint was sixteen weeks?

Primary endpoint was at twelve weeks. Twelve weeks. Then we followed patients off either placebo or off MMF for an additional twelve weeks to see about the durability. You know, whether if you use an immunomodulatory drug for a short period of time, would you sustain durability? Now, in mind, this is really a preliminary study.

It was largely designed as a pilot study. And while it turns out that the difference between MMF and placebo was statistically significant, know, frankly, we're a little bit surprised with such a small study design that we were able to observe that.

Yeah, in the short term, really impressive results. Eighty six percent on mycophenolate achieved uric acid less than six versus only forty percent that were on the placebo. And then you follow them all going forward off the mycophenolate and it'll be interesting to see how they do. I always thought that the benefit of this kind of trial would be really at long term outcomes and safety kind of stuff, which seems that there's already a benefit on that in the short term. But talk about both the efficacy and safety from your view.

Sure.

Yeah, well, I mean, the key with pegloticase is getting more of it. It works proportionate to how much you take. So I always tell patients, if you get one or two doses of this, that's better than nothing. But we'd really like to treat people for up to six months or so with this sort of, we see it as a debulking therapy. Somebody comes in, all these people in the study, and probably the experienced rheumatologist as well, is they nearly all have TOFI.

And so we're really trying to reduce the TOFI burden often and trying to treat people who have failed other therapies. And so these are really a difficult group of refractory patients. And so if you can get them on a longer course of pegloticase, you may benefit them more. And clearly twelve weeks is the starting point. You'd like to use it longer, but if, eighty plus percent of them can continue it that long, that's a good start.

I think this kind of data could should change some of the impressions and get move the hearts and minds to look into this because this is not just a debulking on those really horrific tophaceous people. You know, there are people that are going to benefit from this because uric is a uric acid deposition disease and does lots of damage. So again, congratulations on what I think is a really impressive result. What's the endpoint? I mean, is going to go on for

This study is concluded. And again, there's another study looking at methotrexate you

should be tuned for.

I think that'll be very interesting. But I suspect that over time, perhaps sooner rather than later, we may be moving towards using concomitant immunomodulatory drugs with pegloticase, particularly in people, younger people, perhaps people with significant obesity, people that we know from some of the observational data seem to be at higher risk of developing immunogenicity. And, we're going to really need to figure out who to consider this in, but, you know, it's nice to see an RCT that actually starts to provide the answer to that important question.

Ken, congratulations to you investigators and Doctor. Khanna, the lead author on this. Yeah, really great

team approach and, appreciate, Puja Khanna being the lead on this and, collaboration between UAB and Michigan with support from NIAMs as well as Horizon Pharma. So thanks to everybody and to all our patients who participated.

Back to work, there's more to do at the meeting,

That's right, enjoy ACR.

Alright, bye bye.

This is Doctor. Catherine Dow reporting for RheumNow. So I just attended the FDA updates at the ACR twenty twenty Virtual Conference coverage for the ACR Convergence. And so if you have been living under a rock or you're just not listening to the news, I'm going to update you on what the FDA changes have been made in twenty nineteen-twenty twenty since the last ACR meeting. Meeting.

And this has been a big year for approvals for pediatric rheumatology, which is great because, you know, therapeutics have been so limited, for our peds colleagues. So what the FDA did was they approved for patients with juvenile idiopathic arthritis over the age of two, galimumab. So this was approved on 09/29/2020, and they approved IV galimumab for both JIA as well as psoriatic arthritis in children. In addition to that, on 09/25/2020, they also approved tofacitinib for parleyarticular JIA. Now the tofacitinib dose is dose based on weight.

This is where you have to take out your calculators and calculate what you should give. But actually, there's an easier way to do that. You can look under, the websites for the FDA or you can actually go to the drug manufacturer's website. But here's the dosing. Tofacitinib dosing for JIA between ten to twenty kilograms is three point two milligrams BID, and if the child is twenty to forty milligrams, is four milligrams BID, and if the child is more than forty kilograms, you dose them just like you would an adult.

All right, the other labeling changes. So they did, remove a warning label for belimumab. So they took out mortality as, one of the warnings. And this is based on recent updates and post marketing research and reporting. They found that the risk for mortality in patients who have, been receiving it for lupus was no difference compared to placebo.

So they did remove that label. In addition, they did add, to abatacept that angioedema and hypersensitivity reactions can occur, both in the sub q formulation as in and also in the IV formulation. So angioedema and hypersensitivity reactions that's added for abatacept. In addition to that, baricitinib, they did add hypersensitivity reaction, as part of, the label now for that. And then for gabapentin and pregabalin, what we've been prescribing for our patients who have fibromyalgia, they added respiratory depression as one of the warnings.

Okay, so this is with or without hydrocodone or other CNS suppressants. Gabapentin and Pregabalin can increase the risk for respiratory depression. And then in terms of approvals for adult, so in June, Kenakinumab was approved for adult onset Still's disease. And then in May 2020, ixekizumab for non radiographic axial spondyloarthritis, and that's at eighty milligrams every four weeks. And then they also approved, Nintandanib, for progressive ILD.

So that's actually a big win, especially for patients who have interstitial lung disease that's been progressive from autoimmune and connective tissue disease. And then they also did mention that, belimumab for their label, they removed that black and African American label where, may not be as efficacious that was removed. And then for secukinumab, they did get the secukinumab approval for non radiographic axial spondyloarthritis as well as ankylosing spondylitis at the higher dose. So that's going to change my practice actually, because, my patients with AS, they actually do do better when you use three hundred milligrams every four weeks. So now you can do it without having to relabel them.

Right? And then there's also several biosimilars that are approved too for adalimumab and they're basically word salad adalimumab AFZB and adalimumab FKJP. And then infliximab generic AXSQ and rituximab generic ABBS. So you'll be able to access generics, for your patients and might be a little bit more cost effective. So those are all the changes for the FDA in this 2020 meeting.

I hope you're having a great day. Follow me on Twitter, and then you can also access information about what I just spoken about on the FDA website. This is Doctor. Catherine Dow reporting for RheumNow.

So here we are, we're going to do our mid meeting recap and talk about spondyloarthritis. We're joined by John Rivel from Houston and Olga Petrina from New York. Welcome folks.

Thank you

for having us tonight.

Yes, it's great to be here. I've been on with the whole program and I share Eric's issues. I think there isn't a huge amount that's new to me that was being presented at this meeting. There's a lot of articles on treatment, and I think we're going to talk a bit about that. Pulling back, there are some very interesting things being presented on the microbiome, but really pulling back, I think the most striking theme that's coming out with this meeting, whether we're talking about treatment, whether we're talking about disease manifestations, or even genetic profiling, is the role of gender and the gender disparities that we're going to see, and I think that's some of the stuff that I'd like to, I don't know if Leanne focused on that last night, but that is what really struck me the most in going over all these abstracts, again, way, way back and looking at the overall picture here, probably, although there's not a lot new in that regard, Nonetheless, one of the most compelling things that comes from this meeting.

Interesting, and I think it really helps, I think, characterize patients and more we can characterize them, maybe the better we can treat them. Although maybe you should start by telling us something that you've seen so far in the first two days that really stood out for you.

Yeah, absolutely. And actually the matter of gender differences, that's something that stood out to me and that's the abstract that caught my attention interestingly enough. So there are two abstracts that I really wanted to to discuss and they all pertain to gender differences and the first one I will mention will seem like have nothing to do with it, but I will drag you into the woods of gender differences along the way. So the abstract thirteen oh three, which speaks initially about the prevalence of undiagnosed axial spondyloarthritis in patients with anterior uveitis and chronic back pain, starts out with the fact that a lot of patients have been referred to us from the ophthalmology clinic actually have symptoms of inflammatory back pain for a very long period of time and interestingly enough, from the most of the referrals who had recurrent arterial uveitis, eighty seven percent of the patients had inflammatory back pain way before they were referred to rheumatology. From those patients, about fifty three percent or more than fifty three percent of the patients meet the criteria for lower inflammatory lower back pain and close to thirty percent of them had radiographic findings that could be consistent with axial spondyloarthritis.

So as a result, about twenty three percent of the patients were eventually diagnosed with XBA, as they met the clinical criteria, and about forty in addition to that were requiring a follow-up with the suspicion of possible XBA and when we speak about this undiagnosed pool of patients what stands out the most to me is the gender issue. So what happens is all the patients female in male and male have similar distribution of HLA B27 positivity, duration of pain, severity of the disease and you name it all, but when it comes to the actual diagnosis in these studies thirty three percent of the male patients were given a diagnosis of ACT-five and only thirteen percent of the female patients were given the same diagnosis. So I'm wondering what's contributing to that. Is it the difference in the symptoms? Is it the difference in how patients relay their symptoms to their doctor or is there something phenotypically different about those patients?

Well disease expression in women with spondylitis has always been problematic and quizzical to me. John, what's your take on that?

Well there's actually a lot of data being presented at these meetings, actually some from our group but some from a number of other groups, and that is the strikingly higher prevalence of peripheral manifestations in women with non radiographic and radiographic axial spondyloarthritis, including enthesitis, including peripheral arthritis, was also striking looking at some of the clinical trials. Now, there's only one that didn't show any difference between genders, but there was one, for example, Maria McGray presented from Metropolitan Hospital in Cleveland with execizumab, as well as a number of others, that have shown that women respond less well to biologic therapy than do men. There's an abstract being presented, I believe, on Monday. This is the same group, this is Lee and Matt Brown, they're looking at a different cohort, they're looking at the Swiss cohort, looking at eight fifty people from that, and what they're trying to do is to use that genetic risk profiling score that they presented as a plenary session at ACR two years ago. This time they applied it to a different cohort, the Swiss cohort, and lo and behold, if you look at women versus men with radiographic axial SpA or ankylosing spondylitis, there were no differences in the genetic score.

However, when they went to the non radiographics, the men with non radiographic axial SpA looked just like the men with radiographic axial SpA, using this polygenic risk score. The women, however, look like the general population, so striking differences there, which I think is real problematic as we're trying to make a diagnosis, and it all more the more underscores the gender disparity in this disease.

So we're about midway through the ACR meeting. John, you just touched on something that's coming up that's not been presented as of yet Olga. I know you have your schedule all planned out what are you looking forward to tomorrow what are looking forward to for the rest of the meeting in axial spondyloarthritis?

So I'm looking more, I'm expecting more data on again gender differences or baseline characteristics of the patients that are different that can actually help us predict how patients would respond to treatment based on not only gender could be other other characteristics so that's something that's interesting to me and let's speaking of again differences between the patients like this morning the the after was presented the pool data for exekinumab studies again talking about the gender difference at baseline patients who were female more likely to have higher VAST eye force just based on the higher nocturnal pain, peripheral joint pain and overall fatigue, while male patients tend to score higher on CRP and higher levels of GIL AB27 positivity observed there. So I think that where we start out is important because if patients have different pattern of the disease or the the picture of the disease, they may respond to treatment is different. So I would be curious to see more abstract on the treatment outcomes pertaining to different patient characteristics.

What else you mentioned?

And well as the data here do show that women tend to respond less well and that's clearly being seen in the current clinical trials. Correct.

Don, what are you looking forward to as far as reports or studies that may come out on Sunday or Monday?

There wasn't really a lot on Sunday, but Monday is chock full in the spotlight, especially in the poster session, with a lot of very interesting abstracts looking at different disease subsets like inflammatory bowel disease. Some interesting papers looking at the microbiome. One shows that the differences in the microbiome correspond to disease activity, another one looking at calprotectin levels, and showed that fecal calprotectin as a biomarker corresponds even in patients with AS with villous damage and blunting, So, these are things that I think to me are very interesting as far as pathogenesis is concerned.

How about the meeting overall, how's it affected you, john, you're notorious for, you know, being all over the meeting meeting people and learning your own style. How is this virtual thing affected you?

For better or for worse, it's a lot, it's sometimes it's hard to connect to sessions, sometimes the slides don't come regularly, but you what I really like about this is the ability to go back and review all the sessions, and so I'm going to predict that at the end of this meeting I'm going to learn a lot more, because I actually tend to get distracted by the networking. This way I'm having to focus on the science, and that's actually a pleasure.

Olga, what about you?

Well, what I like is the flexibility of it, and I must say I like it a lot lately, so I can be anywhere and still attend the live session if I wanted to and similarly I can just postpone some abstracts and posters for later on like knowing that they're pre recorded. What I hate about this meeting is this lack of human communication. I really enjoyed meeting my colleagues and having a little chat or a cup of coffee and talk about things live. I think that's a big minus for the virtual meeting.

Alright, folks, we'll wrap it up and thank you for joining our group discussion. This was a lot of fun. We want to thank our audience for watching. Tune in the room now for more videos, more stuff from ACR twenty twenty. Thanks.

Thank you.

Thank you, everybody.

So we're joined now by our RA faculty for our mid meeting recap. We're joined by John K from Massachusetts and Catherine Dow from Texas. Hi, folks.

Hello,

Jack. Hi, Artie.

So the perfunctory beginning of what do you think of the meeting so far, John?

That's very different. I have not left my house. I've not left my office other than for dinner. I've not put the 10,000 steps on every day, but you can get from session to session very easily. The other nice thing is that you can see a session after it's occurred.

At the annual meeting when it's live, if you miss a session, tough luck. But here you can go in and look at it at your convenience again and again. There was a session today, Gerd Burmester talked about the history of biologics, and he had a slide about serendipity. And I miss the serendipity of walking through the exhibit hall, and not just meeting friends and other people whom I've not had the privilege of meeting before, but also passing by a poster that I didn't expect to look at and learning something and piquing my interest. So the fact that you're limited to seeing those things that you seek out limits the educational experience somewhat.

Catherine, what did you tweet today about serendipity?

Oh, that basically when you're trying something for one thing and it ends up you're finding out something else. It's kind of like you stumbling onto me.

Well, that's because you're petite and I stumbled over you actually on rounds one day.

That is true.

No, but I agree with John. I mean, actually like the virtual format, but next time I'm gonna get a hotel room and expense it to you because like my kids keep busting in they're like what's for lunch what's for dinner and I'm just like leave me alone leave me alone I'm in the middle of videoing.

Artie how are you handling that

with your boys? It's tough I mean it's everybody's doing much more stuff at home. And I guess the and the question I put to the panelist is, you know, you are announced they're gonna be hybrid. So would you all, you know, all things being equal now, would you would you say, you know what? This visual this this virtual is pretty good.

Or no I miss going post to the poster and just meeting old friends and stuff. What are you gonna do?

I'm old fashioned, I'd like to attend in person because I do like to give hugs. Like to, you know, get the freebies and I just not only that get this, I'm actually got vaccinated or I'm in the vaccine trial now for COVID-nineteen. Yeah and so hopefully I did get the real thing. I mean the first injection went well I haven't grown an extra head yet but I think so far so good. I'll get my second injection in a few weeks.

We'll be looking

for that.

Jonathan, were you going to go to EUL or are you going have this virtual thing hook you?

Oh, surprisingly, haven't been on an airplane since March 7, and I've forgotten what it's like to get frequent fire miles. It all depends on how safe or unsafe it is. But aside from that, the Europeans probably won't let us in. It'll depend on public health. Will travel bans still be in place?

My institution won't let us travel. If we travel outside of the country or even to an unsafe state or have to take an airplane flight, we have to quarantine for fourteen days on our own time.

Yeah, let's get into RA and you guys have been covering RA, there's been a lot happening at this meeting so far. Let's start with something that's really impressed you, Katherine.

Well, I think it started out with the great debate. We have Vivica Strand and then we have Michael Weinblatt. I mean, was a beautiful discussion and the audience actually, discussion was basically after methotrexate, failure in a patient with rheumatoid arthritis, what do you do next? Would you go straight for a JAK inhibitor or would you go for a TNF inhibitor, right? And so they each presented their case, you know, Vivica Strand was like, it's oral, you know, it's quick on quick off.

It has great efficacy. I mean, just as good of an efficacy as TNF inhibitors and yeah, it can cause shingles. Yeah, it can cause VTEs and MACE if you use a higher dose. And then here comes Weimblatt coming in, he's like one word, twenty two years of experience. And you know, I don't know whether that is trying to scare us because we're afraid of the new and we want to stick with the old, you know, but he has a point, you know, it's something that we're familiar with.

Yes, insurance is going to cover a TNF inhibitor before they're going to cover like a small molecule in certain states. You can use it in pregnancy, there's multiple indications, anything from rheumatoid arthritis, to uveitis, SPA to high adenitis and now immune adverse events from checkpoint inhibitor therapy. So I mean, yes, there's a lot of use. So that begs question, like, what would you do? And that's something that I kept in mind throughout the last few days that I've been at ACR come because I'm coming across these really good posters, you know, posters about like, you know, there's a meta analysis on head to head JAK inhibitors that have, they're looking at systematic reviews from UT Southwestern and they're talking about how, you know, they're comparing upa, berry, TOFA and filgotinib to, like the TNF inhibitors and they found that perhaps upa and up, okay, Jack, you got your hand raised.

You're way over forty five seconds.

I'm so excited about this. This is awesome.

I control I control the. But I wanna tell you one thing Michael at room now live that already and I run was asked on a panel that is with John O'Shea and other experts. What drug you're gonna give your mother or your sister, methotrexate a TNF inhibitor, Jack inhibitor. Everybody in the panel said a Jack inhibitor and they weren't necessarily, I can't reason why they would be forced to say that. But so I found it interesting that Michael's arguing the other point which really feeds into the rheumatologists who always want to use TNF inhibitors.

But let's move on. John, what did you like that so far at the meeting?

There have been a whole bunch of interesting things. I think that it's the year of the lung. You've got a couple of abstracts about rheumatoid arthritis interstitial lung disease. Jeff Sparks presented an abstract that showed that ILD was more prevalent among older patients with rheumatoid arthritis. He also presented an oral presentation where anticyclid and filigrain antibodies seem to be a biomarker for the development of interstitial lung disease.

A talk that I'm looking forward to tomorrow at the plenary session looks at citrulline reactive B cells in the lungs of patients with early rheumatoid arthritis and at risk rheumatoid arthritis. So the lung is sort of the alpha and the omega. It's the organ in which rheumatoid arthritis might start, and it's the end result of established rheumatoid arthritis. So the lung is really becoming a rather prominent topic at this meeting.

Jeff, he did last year at ACR, his own brass review showing a lot of lung stuff and ILD. And this was a claims based review where he showed all that stuff where lung is seen it was five percent of the population claims data, but it was associated with death and infectious death, cancer death, but most of all respiratory deaths. So it's a really bad player.

Absolutely. Abstract today by Jeff and I think both of you may have hopefully saw that the RAC, the tapering etanercept and that generated a lot of interest. Some of it about what background Jeff was using, what Woodcastle was the formation of the background for his Zoom call. But what did you all, did you all get to see that? What did you think?

Tapering methotrexate versus tapering etanercept and people on combination. That was, I think really a very definitive study on tapering, which is a very important topic.

Absolutely. Did a video for RheumNow today, so I'll give a plug for that if people want a more in-depth discussion of that abstract. Tapering is a theme at this meeting. On Monday, there's the Norwegian study which looked at stable versus tapered TNF inhibitors in patients with rheumatoid arthritis who

are in

remission. Jeff's study sort of follows on the PRESERVE trial and the PRIZE trial, which looked at tapering versus discontinuing either etanercept or methotrexate. Jeff's study was different from those. Those studies looked at patients with low disease activity or remission rheumatoid arthritis. Jeff's study looked at patients who were in STI remission, stable STI remission.

The definition of the activity was patients with very well controlled rheumatoid arthritis. There wasn't a strict definition of control at the time of entry. But he showed very nicely that getting rid of the methotrexate was the better way to go that if you stop methotrexate, the etanercept continuation as monotherapy seemed to control remission or continuation of both, but much better than if you stopped the more expensive etanercept. So the bias is always to try to stop the more expensive drug. But here the better outcome comes when you stop methotrexate.

Well, you look at patient ends too, I mean, what would they prefer? Most of my patients prefer to stay on etanercept and stop their methotrexate because you know, it's convenient it has less side effects they're not losing their hair they're not having like some of the oral, side effects nausea vomiting and having to have their blood monitored every three to four months.

Well my patients like it because they can drink alcohol.

Oh, my patients don't drink. They're good.

Well, they're Texans.

So it's about, a couple of minutes left. This I know you all have your schedules planned out thoroughly. What are you very excited about seeing in the remaining couple of days of the meeting?

Well, there's more to see than there's time to see it. Certainly the ACR Rheumatoid Arthritis Management guidelines, are going be presented on Monday, are gonna be very interesting. It's not necessarily gonna be novel, but it's gonna be a synthesis of past knowledge. There's a session on Monday about predictors of rheumatoid arthritis responses, where there's Mayo Clinic study that used machine learning to look at pharmacogenomics to come up with an algorithm for methotrexate response. This is a theme where machine learning is being used to do a lot of things.

There was a great abstract on Friday looking at machine learning to read hand x rays and look at joint space narrowing, really very elegant study out of Taiwan that might actually give us the sharp scores that radiologists are reluctant to do because of the lack of time. 's another abstract on Monday using machine learning to determine the rule to predict response to cirilimab, Ernest Choi. Peter Taylor's looking at whole blood transcriptional changes following filgotinib administration. And then as I mentioned before, there's that tapering study out of Norway that's gonna be presented. So there's lots of good stuff.

And on Sunday, the plenary abstract about citrulline reactive B cells in the lung. And then interesting session at 3PM where Ron Van Vohlenhoeven, Peter Taylor, and Mike Hollers are gonna talk about resetting immune tolerance to prevent rheumatoid arthritis. So really, we've come a long way since the first ACR meeting that I attended in 1986, where we didn't have biologics and we certainly weren't talking about remission and we weren't talking about prevention. So it's a very exciting world that we're entering.

Kathryn, what are you looking forward to?

Well, tomorrow, I mean, early in the morning they have the thieves market poster and you know, I'm like a sucker for good titles. They have titles like disease of the soul, Think Beyond the Obvious and Practice What You Preach. I mean come on that's that's such a grabber. And then afterwards I want to attend this lupus lecture actually. It's the state of the art lecture The Future is Now, presented by Doctor.

Mary Crow. They also have a conflict around that same time about the EULAR treatment recommendations for RA psoriatic arthritis, and whether or not you should follow algorithms in your clinical practice. And then on Monday I'm going to definitely attend the guidelines for RA JIA and also the FDA update on safety.

You know there's a lot of stuff that is going to be presented. Is there anything that you wish was going be presented that's not on the program. One ten second answer for either you.

Is John still there? Did he

He's still here. Left me speechless. There's not a lot on biosimilars this year, but I'm not sure how much more there would be to present about biosimilars given the reluctance of The United States to allow us to use them.

It's going down every year. Arty and I have just been tracking it.

It's 19 this year, from about 25 last year abstracts.

Yeah.

All right folks we want to thank john k and Catherine Dow for joining us. Hi, everyone. I'm Jack Cush with RheumNow. And this is my big opportunity to rant on the new 2020 ACR guidelines for the treatment of rheumatoid arthritis. They were presented today.

I I think there's been a lot of discussion about them so far. It's a long document, a lot of recommendations. The process was long and arduous, I'm sure. 81 PICO questions. This is a revision of the twenty fifteen guidelines.

And the reason to revise them is because thinking is always changing. And certainly we have new drugs. I think there's five new drugs including ceruleumumab, two JAK inhibitors, baricitinib and apadacitinib. So they came up with new guidelines. I want to start by saying congratulations to the committee for their effort.

These are good friends, smart people who've done a good job trying to place into some formula how we should manage RA, which is really difficult and takes a lifelong of learning to know how to in fact do. So codifying it in a few pages is almost impossible, which is now my great opportunity to step all over it. I got nothing but red flags and detours on this thing. So I wait before I start my rant, let me just get dressed for this. So hold on a second.

Stole this from Costco the other day. They didn't seem to miss it. Okay, here we go. All right, I think I'm ready. I think everyone gets the message.

How do I look, mom? All right, so I'm gonna try to do this fast. Here's my rant. You can go through it on your own pace, but you should note number one, there's a total of 44 recommendations and 37 of which are conditional. Meaning it was sort of like this, we had a vote, this is the best we came up with, we couldn't say it's strong, it's conditional or they're lacking evidence.

So that's number one, a lot of these are conditional, it's expert opinion. And you may not agree with the experts. Number two, the language is medieval, my goodness, conditional this strongly recommend that if not long, then short. Mean, it's really when you read it, or when you have someone else read it to you, it's just painful to listen to. Third, know, DMAR naive patients who have moderate to high disease activity, I got no problem with their choices there.

It's the usual things methotrexate and then moving on. I got a problem with however low disease activity so DMARD naive patients who have low disease activity, they recommend first hydroxychloroquine. Second, conditionally, course, sulfasalazine and sulfasalazine before methotrexate and methotrexate before leflinamide. You may like that idea. That's all about safety.

It's not about what works best. Shouldn't you use, especially in DMAR naive patients, your best drug first? Is hydroxychloroquine and sulfasalazine your best drug first? Or is this all about safety? And of course, there's absolutely no data on these choices.

This is all about preference. It may be patient preference, and that always trumps physician preference and we know that. So I got a gripe with that. Methotrexate dosing, they had a lot on this and this just drove me crazy. So they certainly recommend you should use PO dosing over sub q or parenteral dosing.

However, if the patient has signs of toxicity, they recommend that you should either go to split dose oral or parenteral sub q or increase the dose of folate. By the way, the first two options are idiotic. If the patient's having intolerance by going to sub q or any other parenteral form or oral split dosing, you're delivering more drugs, you're gonna get more toxicity, not less. So I'm not sure where these guys came up with that one. The third choice of increasing folic acid, we do it because we don't ever have anything else to do.

But that's not shown to work for anything other than drug discontinuations and maybe lowering LFTs. And that's about it. Look at the Cochrane review on that. So anyway, that drives me crazy. Of course, they want you to do those things before you switch to another DMARD.

And that may be your only choice. You know, the next recommendation was if you're not a target, then do treat the target. That's an old recommendation. They thought they had to bring that one out. They say if you're on maximum doses of methotrexate, they recommend that you switch to a biologic or you add in a biologic or a targeted synthetic as opposed to adding in sulfa salazine and hydroxychloroquine and going with triple D Mart therapy.

What they want you to go more expensive rather than cheaper. Does Jim Odell know about any of this? I don't think he's on the committee. Obviously, cost effective measure would be to use simpler therapies. That's actually what's recommended in the UR guidelines.

They want you to go with the things that work best. Yes, I think that they may work best. But the evidence of that is, oh, this is all conditional recommendation. There is no evidence for any of that. Next, if you're on a biologic or targeted synthetic and you're not doing well, they suggest you switch to another class.

Shouldn't you be allowed to use IL-six inhibitor twice, a TNF inhibitor twice, even a JAK inhibitor twice before you're switching to another class. That guideline didn't seem to make any allowance for that. They have a guideline of tapering which makes sense. They then go to what they call special populations. This is really special if you know what I mean.

God bless their heart. Nodules, they recommend methotrexate first. Well, that's really special. And if not methotrexate, then another non methotrexate DMARD. There's no evidence of any of this.

Again, all of us don't know how to treat nodules honestly, but to codify it in a recommendation, think was kind of a little bit risky. What about pulmonary disease? Any kind of stable pulmonary disease, they come out and say methotrexate is okay. That's brilliant. That's what really should be in there because the risk of methotrexate is a risk for hypersensitivity pneumonitis not worsening of ILD.

Then they talk about heart failure. Class III and IV heart failure should be given what treatment? They say a non TNF biologic. Again, absolutely no evidence for any of that. None.

I mean, it's been studied. Patients with RA with heart disease can take TNF inhibitors just fine. It all comes from the very old Enbrel trial back in about 2002, 2003, the Renaissance study and whatnot, where there were marginal signals there. Use your best drug first. Clearly, if someone is on a TNF inhibitor and develops heart failure, yes, switch to another class of medicine.

That does make sense. Lymphoproliferative disorder, say, yes, rituximab, it's an indication of rituximab. That does make sense. They got that one right. Another one they got right was hepatitis B.

And these are very smart recommendations. Antiviral therapy is recommended for hepatitis B patients who are hepatitis B core antibody positive and going on rituximab. Doesn't matter what their hep B surface antigen is. Core antibody with a negative Hep B surface antigen is a low risk situation. But if you're going on rituximab, it becomes a high risk situation.

On the other hand, if you have patients who are B surface antigen positive, they need to be on antiviral therapy no matter what or not take the biologic. And the ones where you can use biologics and targeted synthetics with very low risk like two percent are patients who are B surface antigen negative and who have epi core antibody positivity plus or minus hep B surface antibody positivity. Next, if you have an NFA LD, non alcoholic fatty liver disease, it's Okay to take methotrexate if they are in fact stable. If you are on rituximab and you have hypogammaglobulinemia and you've not had infection, you can continue the rituximab. So I like that.

They got two that I don't necessarily like. One is I've changed to my notes are on the side here. A prior serious infectious event, they recommend that you use a conventional synthetic DMARD to treat such patients. If they're already on a conventional synthetic DMARD, they suggest you use another conventional synthetic DMARD or add on another as opposed to going to biologic. There's no evidence for that.

Here you're in a very difficult situation. Patient has a serious infectious event or more than one and they have active disease. The use of biologic where this is worrisome of infections. And remember, infections is related to number one inflammation and then the disease. Then maybe lastly, the drug.

So at some point, you might have to take a risk with a more aggressive therapy, targeted synthetic or biologic in people who are not responding to conventional synthetic DMARDs with the hope that you can control inflammation and lessen infectious risk. Very difficult situation, they've tried to put it to paper, maybe the actual manuscript will have more granularity on that very difficult management situation. And then lastly, there's no provision in any of the guidelines for risk factors, You are guidelines still do have poor prognostic risk factors that changes the treatment options, meaning if you're high titer seropositive, if you have extra articular manifestations, if you have erosions, you failed multiple prior therapies, that's not in these guidelines because there in fact is some evidence to say that the poor prognostic factors are not quite as meaningful as we make them out to be. Nonetheless, it is a difference between the ACR guidelines and the recently published twenty nineteen your guidelines. I know I'm gonna get into trouble for this one, but that's why I'm wearing this bulletproof safety vest.

Hope you enjoyed it. Tune in for more.