RheumNow Podcast - ACR 2020 Retrospective (11 13 20) Save

It's the 11/14/2020. Hi, I'm Doctor. Cush. This is the RheumNow podcast. This is the ACR twenty twenty retrospective wherein I sort of looked back at what happened in the past week at ACR.

RheumNow was ever present during the meeting. We had a tremendous group of faculty. I think we had 11, no, 13 faculty members covering the meeting. We had a total of 11 big shot key opinion leaders doing perspective videos for us and leading different learning groups. We put out over 1,100 tweets.

We did over 160 videos. I think we did about 20 different podcasts. So there's no shortage of content to learn from the ACR and you don't even need to listen to me. You can go back and listen to those podcasts and really take it in from the people who were at all the sessions. But I'll give you a few of my highlights.

Number one, virtual is doable. It really was. I mean, I think that while there's a lot of hesitancy, by many to learn this way, my surveys of rheumatologists before the meeting and after the meeting say about 20% of you are totally disengaged on virtual and on ACR. And I don't know if it's virtual or ACR that you're disengaged from, but 80% are consuming it in one way, shape or another. 90% gave the ACR an A or a B grade, meaning they did very well.

ACR spent a lot of time planning this meeting and I think they did an exemplary job except for a few like technical glitches and downloads or not so much downloads actually in video and sound sometimes. But really it worked out really well. Everybody found a way around it. So the issue is, are you gonna do more of these virtual things? You're gonna wait to get back to flying and lugging posters and the real donut wall to take in the ACR the way you've always wanted it.

You know what? You better get used to virtual because this is going to go on for some time. You heard it here, maybe not first, but you heard it here again. I think the next big thing was LTF, hashtag LTF, listen to Fauci. We did listen to Fauci.

He gave us a one hour seminar on Saturday and it was great. If you haven't listened to Fauci's one hour lecture, you really should. It's A to Z. It says a lot of things about the COVID-nineteen that you may not know, especially the microbiology of it, the origins of it, and certainly the procedures to control it. I think it's a well worthwhile listen if you haven't done it.

In fact, everybody did it. Fauci broke the internet. It was really, there were tons of people who couldn't get on to watch it. It was that serious. And I think that Tony Fauci's address really speaks to what's going on still and that is COVID is still ever present.

While many of us want to hope this thing will go away, we're kind of burying our heads in the sand, trying to do our daily work, manage our families and whatnot, hoping that when we come up for air, we'll be able to go outside and go to a concert and eat at your favorite restaurant. But I think that the amount of COVID data that was presented, especially about its effects on practices was impressive. There were a lot of things that were kind of interesting. There was a Chinese abstract about monitoring patients with an app. I mean, there's plenty of reports like that, but this was like thousands, hundreds of thousands of data points collected by patients and showing for RA and for lupus that they were hitting their target measure of control 50 to 60% of the time except for when a holiday happened and then it dropped 10 points in disease control.

Things like that. Vivian Beikirk had a report about a Canadian tool for patient self assessment that could be used during telemedicine visits saying that patient's self exams are as good as your exams. And I think that that is probably true. Actually, someone said yesterday, Marty Bergman said at the extremes of assessment, meaning when it's really clear and when it's really obvious, both good and bad as far as disease activity measures, you can see it really well by televideo. It's in between that you probably need the face to face visits.

Next I like the TECOSPA. It's one of those tight controls, Ticora. There was one for RA, there was a tight control study for psoriatic arthritis. And now we have a tight control study for axial spondyloarthritis using an ASAS set of outcome measures. It was a study of 80 patients in both arms and one arm was treated with a protocol to achieve tight control every month.

And there was a protocol change until they got there. And the other arm was treated every three months with whatever the doc thought and without necessarily having a protocol change. Interesting thing was at the end of the study, which I believe was, I wanna say forty eight weeks. There was no difference in the two groups. While there was a numeric edge for those that were in the tight control group, it wasn't statistically significant.

And I'm not sure the result warranted all the assessments and interventions. Clearly that the tight control group got more biologics, but in the end they didn't do that much better. So that's I think a very interesting study. The next interesting study was a late breaking abstract L06. And this was the use of GCM CSF monoclonal antibody in the treatment of giant cell arteritis.

So the idea here was a phase two study of maverlimab using the drug or placebo in new onset or relapsing refractory GCA patients, only thirty five in each of those groups. They had that active disease and the drug was shown to be very, very effective. So, this is maybe yet another way of finding how to use less steroids and use a biologic to better control an often difficult disease. Next, the FAST study. This is a regulatory commitment study mandated by the EMA.

When febuxostat was approved, especially when febuxostat was approved with some worry about cardiac outcomes. And the FAST study was a study that was done in Europe. It was over six thousand patients who were on allopurinol for their gout. And then they were then randomized to receive either allopurinol, continued allopurinol or fuboxifestat doses of eighty and it could be escalated to one hundred and twenty, but really almost everybody was on eighty milligrams a day. Five year study, very few dropouts, six percent.

Minority of disease flares equal in both groups as you would expect. And in the end, febuxostat group was not any different than allopurinol group when it came to one, lowering uric acid. In fact, febuxostat was better. Two, cardiovascular events that was like MI and other MACE events were equal between the groups and with an edge febuxostat. And also no differences in cardiac deaths.

So that's important. I think that this sort of tells us a few things. We know that there have been multiple signals in the past where febuxostat looked like it might be worse than allopurinol in patients having cardiac events. But then there are other studies where it wasn't. And I think this speaks to the complexity of managing and treating and studying gout.

There's a high comorbidity burden here, especially when it comes to cardiovascular risk. These are complex, poorly controlled patients often with many of the features of the metabolic syndrome And uric acid complicates things even more so than metabolic syndrome will. And then trying to make changes in the face of all that, a lot of things are gonna happen which can be ascribed to one drug or another. This begs the question whether or not fabuxtat needs to have a box warning. I don't think it's gonna change the need to use allopurinol first and fabuxtat second.

I think it will change whether or not you should worry more about fabuxtat in patients who may be at cardiovascular risk. Next, the SEEM RA study. This is a plenary session presentation by Doctor. Jeff Curtis. Got a lot of discussion at the meeting.

The CMRA study is basically a study of withdrawal. Patients with rheumatoid arthritis who are in solid remission for more than six months with a SDAI score of less than 3.3. That's the same as a CDAI score of less than three or my clinic of gas of less than three. It's strong measure of remission for more than six months on etanercept and methotrexate in RA. And then once you have been in remission six months, you have a randomized withdrawal.

Either you stay on the combo or you stay only on methotrexate or only on etanercept. And guess what? The combo did much better, like fifty seven percent. The patients on etanercept did much better than those who stayed on methotrexate, where it was like, I don't know, fifty percent versus twenty seven percent. Don't hold me those numbers, but it's just basically saying the bottom line is you do worse just being on methotrexate.

You do pretty darn good being on either etanercept or etanercept and methotrexate, which says that they're kind of equal. But in this six month follow-up study, it didn't matter whether you stayed on both or stayed on etanercept. It's a strong statement for stopping the methotrexate, which is actually in line with the ACR guidelines, but opposed to the UR guidelines for the management of RA. So a lot of talk about that. I don't know if that's gonna change my therapy, but I think it's an impressive study and well done.

Next, another JAK inhibitor hits the marketplace in rheumatology and it's not a JAK, but it's in the Janus kinase family. It is a TYK2 inhibitor. Ducravacitinib is a new TYK2 inhibitor. It's been studied in psoriasis, looks pretty good and now it's being studied in psoriatic arthritis where the results there were very, very good. Psoriatic arthritis looked very good when they were given this TYK2 inhibitor.

It's an early phase two study, so it looks great. We'll see how it does in phase three. Congratulations to them. Next I think was to talk about ACR, guidelines. I did a video and I think it became part of the podcast during the meeting.

If you wanna see my take in my rant on the ACR guidelines and believe me, got a seven minute long, crazy rant on this where I call it red flags and speed bumps or red flags and detours is the name of the video. But the bottom line is, ACR has codified its treatment regimens for us to look at, adhere to, discuss. This is an update of twenty fifteen guidelines and since then we've had, several new drugs approved including cerilumab, two JAK inhibitors in baricitinib and ipadacitinib, and adding them to the mix. But a lot of the things in there were, spot on, treat to target, minimize use of corticosteroids, use methotrexate as an anchor drug. Had a few things that I thought were absolutely goofy, actually recommending sulfasalazine over methotrexate for patients with mildly active disease who are DMARD naive, makes no sense to me.

I use my best drug first, whether you have mild disease or moderate or severe disease. And then they said, you're having methotrexate toxicity on oral methotrexate, they recommended switching to split oral dosing or parenteral sub q methotrexate as a way of managing that or increasing folic acid. Sorry, Charlie, all of those are wrong. It's not really even a guideline. That's like a wish.

And that actually reflects a lot of practice which is wrong. If you switch from oral methotrexate that's giving you side effects and toxicity to split oral dosing, you get more drug delivered and guess what, you get more toxicity. The same is said for parenteral methotrexate, you get more drug delivered and more toxicity. So I don't understand the switch other than to confuse the patient. And then more folic acid is a pipe dream about getting better.

Folic acid has been shown to reduce the number of drug discontinuations and reduce LFTs. But other than that, it doesn't help oral ulcers in any substantial way or proven way. There are also guidelines put out for JIA. They're unique in that they talked about oligoarthritis, TMJ management and systemic JIA management. Look those up.

We wrote about them during the meeting. Michelle Petrie had some interesting observations at the meeting. I'll summarize it by, and she'll look at the video that I did with her, where she says that lupus anticoagulant is the most predictive of the anti phospholipid clotting test that we do in our lupus patients. Most predictive for predicting arterial and venous thrombosis. It is superior to the anti phospholipid panel, it's superior to the beta-two glycoprotein-one IgA, although that is also her second best choice.

And it's better than double positivity and triple positivity in predicting these events. I thought that was really important. That's abstracts twelve sixty one, twelve sixty two. There was a lot of stuff the meeting about machine learning. And I've written a blog that I really like called Moneyball.

The idea being, give me tons and tons of data and help me be smarter about my guests like decisions. My decisions are very highly informed, but let's face it, I am guessing when I'm going to stop someone who's on etanercept and move on to another drug. Is there another TNF inhibitor? Is it gonna be another MOA? Am I gonna go oral with another small molecule?

It's a guesswork, it's preference. It's sometimes patient preference. Sometimes it's guided by concern over particular toxicity, which would be less with choice number three. But why not use big data to help us figure it out? Well, there's a lot of stuff on machine learning.

Most of it is dizzying and confusing and really not applicable in the real world at this point. I encourage people to do more of machine learning, artificial intelligence to help us make better decisions. But at this point, I can only really endorse some of the studies that look at, using machine learning to better analyze x rays, whether it's looking at peripheral x rays or axial x rays in the spondyloarthropathy patients. So other than that, this is machine learning gone mad at this meeting. They will save cost.

They're not gonna be useful till they have predictive value, but nonetheless interesting. Also interesting, studies on metabolomics and proteomics really with some impressive data, I think it's a little early for their application. For instance, Doctor. Fava in Boston had a plenary session talk on IL-sixteen as a urinary proteomic biomarker that correlates highly with, glomerulonephritis, especially type class three and class four. Also with the activity of the histology, not the chronicity, and it also changes as the patient improves.

And there's a lot of IL-sixteen, it's the second most common cytokine found in the kidney. So a really impressive work done by Fava and colleagues on that plenary session talk. Three more things. TOFA, has been shown to work in end closing spondylitis, a sixteen week result, using ASAS 20 as a response outcome, 56 versus 29 against placebo, ASAS 40 more stringent outcome. Those on top had a forty percent response versus 12% placebo.

That's abstract L11 looked really good. The select PSA study, the select studies are all on upadacitinib showing again it works really well in upadacitinib fifteen or thirty milligrams had better results than placebo, especially when looking at patient reported outcomes. That was abstract thirteen forty one. And then lastly, know, actually I should say two other abstracts, both by Doctor. Khanna, different Doctor.

Khanna's. Doctor. Khanna from the University of Michigan presented the results of a recipe study wherein they studied patients who were going on peglodipase and use mycophenolate as a way of abrogating the immunogenicity of the PEG molecule, which sometimes limits the efficacy and safety of the drug. Well, again, this was a really impressive study. Twenty four week outcomes, their primary endpoint was lowering serum uric acid.

It was sixty eight percent versus thirty percent in placebo. That was abstract number nine fifty two. But again, it looked really good. It gave much better clinical responses, it looks like it's gonna have more durability, and I think that was impressive. Dinesh Khanna presented a new phase two trial, of a new auto taxin inhibitor in patients with early cutaneous scleroderma that also looked highly impressive.

Again, I would encourage you to look at that report as well. That's it for this week on the podcast. Go to our website, find a lot of stuff about the coverage of the meeting. Other things that we did in the meeting besides the podcast and all the videos, we have another feature on our website called ACRIQ. You can do a little exam as to what you learned at the ACR, sort of self score yourself and see how you did.

And I think you can also sign up for topic reports where you can get emails of your favorite if you follow lupus or JAK inhibitors or TNFs or scleroderma, RA, gout, etcetera. You can get a download of all the things that were reported from the past week at the meeting. That's it. We'll talk to you next week. Bye bye.