ACR2018 Chicago Day4 Part2 Save

Hi. You are listening to ACR two thousand eighteen podcast. I'm Jack Cush, executive editor of RheumNow. This is a compilation of podcasts from the ACR two thousand eighteen meeting in Chicago wherein you'll hear daily reports from the experts, the KOLs, and people making the news. Hope you enjoy the recording.

Hi. I'm doctor Janet Pope. I'm a roving RheumNow reporter, I'm here at the RheumNow booth, ACR 2018 in Chicago. I wanted to talk to you about a very interesting abstract because I think there's a funny take home message. Abstract two eight seven o looked at 1,776 people with RA from the VA institution where they had had RA and their scores were done.

RAPIDS three, CDI, SDI, and other scores. And what's really interesting about this is that I think the scores are lacking face validity. Not going to tell you not to measure them, but what they found because it has implications for disease treatment is that the concordance of patients in low disease activity, remission, moderate high disease or high disease activity was not very concordant. So although these scores have very similar components, patients that were in remission on one score weren't in another. So the problem is if you're treating to a target, depending on varying your target, you could have far different treatment.

What I do think though is a real take home message is that the scores changing over time is still valid, so please measure, pick a score, and follow it. But if your neighbor's picking a different score, you might not agree on treatment. Thank you.

We're ready. Hello, this is Bill Scherge from Huntsville, Alabama, winding down at the ACR. But I want to talk about one very exciting program that I attended, and this is one that I think all of us in rheumatology need to focus on. It was the guidelines for reproductive health in all of our rheumatology patients. And, I'm always a little skeptical to hear these guidelines, but I was so impressed by the amount of work put into by the committee.

They reviewed over 12,000 articles that were put forth by obstetricians, maternal fetal medicine, endocrinologists, reproductive endocrinologists, along with rheumatologists and experts in the medicines that we utilize. They then whittled it down to roughly three twenty that were up to muster to be reevaluated. It's from these that the guidelines and suggestions have been proposed. This covers contraception, it covers drugs that we utilize, it covers what to do with flares. It's a very nice topic, but some of the highlights.

Very clearly, a point that came out was that the patient really views her rheumatologist as the prime provider of information. And there was a committee of patients that advised the panel, and they made it clear that they feel more comfortable with their rheumatologist than their gynecologist. And so we need to be familiar with this. We also need to bring up these, discussions early on and often as well because, as we all know, pregnancies can come at any time no matter what the best laid plans may be. And it's important for that, discussion to have taken place.

The idea with the medicines, certainly, we use the safest medicines for the patients. However, what has also been driven home is that this is not so much driven by what is dangerous to the baby, but more in keeping the mother healthy, keeping her disease under control, because that is what will allow the best outcome for the fetus. And so I urge you to look at some of these guidelines. The major ones were simply use the most effective contraception if the patient is looking for contraception. If a person is with active lupus or if they have a positive anti phospholipid antibody, you should not utilize estrogen based compounds.

But one interesting fact was that estrogens were deemed, safe for the postmenopausal lupus patient for symptoms in the same fashion of using the lowest effective dose. Clearly, if they have phospholipid antibody or if the disease is active, we would not recommend this. And looking at our RA patients, keep the disease under control. TNFs are generally felt to be safe. The recommendation and the guidelines is into the third trimester, and then consider removing them, although they did make point that our GI colleagues will frequently use TNFs throughout the entire pregnancy to keep inflammatory bowel disease under control.

So with that, I urge you to make yourself familiar with some of the other contents of the article. It will be hopefully coming out within the next year. These guidelines are available in abstract form, and I think another useful aspect of these would be to discuss them with your patients and also to discuss them with your colleagues, because we as rheumatologists need to be involved in the management of our pregnant patients. We don't want to let the control of our lupus patient who's pregnant strictly to the obstetrician. So it's a team effort.

Everyone needs to be on the same page. And with that, I say thank you and keep coming to the ACR.

Hi. I'm Jack Cush talking on psoriatic arthritis, and this is the best thing I saw today. It's a TYK2 inhibitor from BMS. It's got a long number instead of a name, BMS nine eight six one five. This is actually reported from the dermatology meetings and is actually in press at the New England Journal.

Being presented here at the ACR meeting, it's a a phase two, an early phase two dose ranging study only done in psoriasis, not a psoriatic arthritis trial. This is psoriasis trial. But, you know, TYK2 is part of the Janus kinase family, and this is a selective TYK2 inhibitor that's now making its way into inflammatory diseases and starting out in psoriasis and psoriatic arthritis. I believe trials are planned. In this particular trial, they did a dose ranging, and it turns out that the primary endpoint, a PASI 75, was achieved by, like, sixty nine to seventy five percent of patients at week twelve receiving either three milligrams or six milligrams.

I think there was a twelve milligram group in there too. So they are starting to narrow the dose. I don't think we they know it yet, but they've seen some very impressive results, as far as skin skin clearing. They had, good numbers of patients achieving a PASI 90, even a PASI 100 PASI 100. I don't know the numbers were as high as that seen with the IL-twenty three and some of the IL-seventeen inhibitors, but it's going to be a competitor.

So you're going to see more about TYK2 inhibition in diseases like psoriasis, psoriatic arthritis, and rheumatoid arthritis. The safety profile looked good and we need to see more data on this. That's it for RheumNow, tune in.

Hello. This is Bill Scherge from Huntsville, Alabama, winding down at the ACR. But I wanna talk about one very exciting program that I attended, and this is one that I think all of us in rheumatology need to focus on. It was the guidelines for reproductive health in all of our rheumatology patients. I'm always a little skeptical to hear these guidelines, but I was so impressed by the amount of work put into by the committee.

They reviewed over 12,000 articles that were put forth by obstetricians, maternal fetal medicine, endocrinologists, reproductive endocrinologists, along with rheumatologists and experts in the medicines that we utilize. They then whittled it down roughly three twenty that were up to muster to be reevaluated. And it's from these that the guidelines and suggestions have been proposed. And this covers contraception, it covers drugs that we utilize, it covers what to do with, flares. So it's a very nice topic, but some of the highlights, very clearly a point that came out was that the patient really views her rheumatologist as the prime provider of information.

There was a committee of patients that advised the panel, and they made it clear that they feel more comfortable with their rheumatologist than their gynecologist. And so we need to be familiar with this. We also need to bring up these, discussions early on, and often as well because, as we all know, pregnancies can come at any time no matter what the best laid plans may be. And it's important for that discussion to have taken place. The idea with the medicine, certainly we use the safest medicines for the patients.

However, what has also been driven home is that this is not so much driven by what is dangerous to the baby, but more in keeping the mother healthy, keeping her disease under control, because that is what will allow the best outcome for the fetus. So I urge you to look at some of these guidelines. The major ones were simply, use the most effective contraception, if the patient is, looking for contraception. If a person is with lupus or if they have a positive antiphospholipid antibody, you should not utilize estrogen based compounds. But one interesting fact was that estrogens were deemed safe for the postmenopausal lupus patient for symptoms in the same fashion of using the lowest effective dose.

Clearly, if they have phospholipid antibody or if the disease is active, we would not recommend this. And looking at our RA patients, keep the disease under control. TNFs are generally felt to be safe. The recommendation in the guidelines is into the third trimester, and then consider removing them, although they did make point that our GI colleagues will frequently use TNFs throughout the entire pregnancy to keep inflammatory bowel disease under control. So with that, I urge you to make yourself familiar with some of the other contents of the article.

It will be hopefully coming out within the next year. These guidelines are available in abstract form, and I think another useful aspect of these would be to discuss them with your patients and also to discuss them with your colleagues because we as rheumatologists need to be involved in the management of our pregnant patients. We don't want to let the control of our lupus patient who's pregnant strictly to the obstetrician. So it's a team effort. Everyone needs to be on the same page.

And with that, I say thank you and keep coming to the ACR.

Hi, I'm Jack Cush with RheumNow. We're here at the RheumNow booth in ACR twenty eighteen in Chicago. Great meeting so far. We're going to have a panel discussion, a group discussion about what's new and exciting in psoriatic arthritis here at the meeting. I'm very fortunate to have with me my friends Eric Ritteman from Chicago, Doctor.

Philip Meese from Seattle. Gentlemen, what's been the highlight for you? Philip, why don't you start with one highlight from this meeting that you'd like to talk about?

Well, one was obviously the data on filgotinib and psoriatic arthritis that was from Henry's lecture. The data showed that this very selective JAK1 inhibitor had good efficacy across all domains of psoriatic arthritis. Modest in skin, but very good in the musculoskeletal elements. And then in terms of the selectivity of of the molecule, what it's aiming for is not to have a JAK two effect on hematologic parameters. And indeed, the hemoglobin went up.

There were no grade two, three, or four changes. So that suggests that there was something about the biology that was true to form. So, this drug is now going on into phase three, and it will be, hopefully another JAK, an oral agent taken once a day that can be effective for psoriatic press.

So what did you think of, again, is an early trial. It's a hundred and thirty patients. It's their first phase two. Then results were great. Eighty versus thirty three in ACR twenties.

That really is the safety profile was either understated or just really it is that safe. So they had very few SAEs, very few, you know, events.

I I think it's too early to say. Just too few patients, short period of time. My guess is that on many of the side effects, it's going to show up further zoster, cholesterol, just some LFTs. But on that on that team stuff, think that was very interesting and very cool.

Eric, what was the highlight for you at this meeting?

You know, I think, honestly, upfront, one the big highlights was the number of controlled trials that we're seeing in the psoriatic early space. And one of them was a trial of a molecule called pemikizumab. Know we've had IL-seventeen inhibitors, but IL-seventeen inhibitors is a broad category. The two drugs that we've had to date, secukinumab and isekizumab, inhibit IL-17A, a specific monomer of IL-seventeen. Bemekizumab is an interesting molecule that inhibits both IL-17A and IL-17F, which may potentially bring added benefit.

In preclinical data, particularly for skin, there's a suggestion if you block both, you actually get a greater response than just blocking IL-17A. And we previously had it, we saw a trial actually in psoriasis. It was an early trial that maybe showed that it wasn't clear. So here we had a phase two trial in psoriatic arthritis and the key question was, do you get more mileage out of blocking both IL-17A and IL-17F? And the answer was not clearly yes.

It looked kind of like the other IL-17A inhibitors. It was a phase two study. Is from a limited number of patients, but broadly there was not a sense that there was this huge uptake in response relative to what we're used to seeing in IL-17A inhibitors in psoriatic arthritis. Safety didn't seem different. Again, it's phase two and like Phil said in the Filgotinib study, you don't want to make too many safety calls on a

phase two level in smaller patients. But it didn't look

like blocking both molecules and in a safety concern. I'm just not sure it added a efficacy benefit. We'll see as they go into later stage products.

So if you think this says anything about the importance of blocking IL-17F, I mean, go after A, isn't it correct? Yes. And the question is, is f important in this equation?

So based on I'll I'll echo what Eric said. Based on some translational studies looking at heat maps of inhibition of expression of inflammatory molecules. It looked like there is some benefit to F addition to A.

The proof is going to be pudding in

the phase three proof.

So I I I think it I

I would completely echo Eric's comment. So you you asked me to comment on the the thing that I one item, but I have to say that there was another trial that really was a fundamentally important trial for all of us as rheumatologists to take care of psoriatic arthritis patients, and that was the SEEM trial.

SEEN, absolutely. So this was a

trial in which we took patients very early in disease, median duration of disease six months, and they were methotrexate and we put them on either methotrexate alone, etanercept alone or on the combination of the two.

Modeled after the TEMPO study of rheumatoid arthritis. Exactly.

So what did we learn from TEMPO? We learned that methotrexate was similar to monotherapy atanercept and that the combination of the two was clearly superior in all of the arthritis domains and X rays and so forth. And so what did we learn from the SEEM trial? As it turns out, methotrexate did very well. There was a good set of ACR responses.

It worked in penthesitis and bactulitis, bacterovitis, which we had not previously known. It had decent skin scores. The one area that had sort of fell down was that there were some progressors in the X-ray arena. So there was some structural damage progression.

Only only on methotrexate? Only on methotrexate.

There wasn't a lot of people,

though. No.

It wasn't

a lot of careful about A

very very small number of people, but at least there was a trace of a signal. The Tannercept did better than methotrexate, but not by a whole lot. But it was clearly superior. And when you wove in the issue of side effects, which were nausea, etcetera, with methotrexate, I think patients, if they had a choice, would prefer being on a TANERCEPT monitor. But the real difference from the TEMPO trial was by taking etanercept and methotrexate together, it

really didn't add benefit over what we saw the high So in relatively early RA, adding methotrexate to a standard of at standard of didn't mean much, but because it was relatively early, you probably maxed out your methotrexate response. You probably had really good methotrexate responses, which is, again why you don't have big separation between all these arms that itanercept was better and the combination was better than methotrexate. But, Ericks, what's your impression of the trial?

No, very much saw that and I think, you know, the intriguing part was that it was different than what we've in RM, the second, adding the methotrexate to the biologic. The challenge is how do you then translate this into clinical practice, right? So the two questions that come up is, so does this trial say we shouldn't be using methotrexate or because methotrexate worked really well? Maybe that's, you know, absent the tolerability issues, this trial actually more than anything we've seen to date said methotrexate is a really effective drug, so then it's sort of a glass half full, glass half empty. Should we be using more methotrexate based on this?

Yes, Tantaset was better, but it's way more expensive. Okay? And the other issue was, it was clear that adding methotrexate to utanercept didn't make any difference. Is that just an etanercept thing or is that a TNF issue? And we can't tell if that's the next question of this because in RA across all the TNF molecules, adding methotrexate gives you better response and psoriatic arthritis doesn't with tantacet.

With tantacet, I don't know unfortunately about the other molecules.

So let's wrap up with a little commentary from two of you about this TIC inhibitor. I mean, that's sort of novel and not seen by our community yet. Who wants to take a stab at that?

I'll I'll start by just commenting that so this is a drug that has an interesting mechanism of action. It very selectively binds to a portion of the tick molecule that is, quote, not conserved. So it is not promiscuous across JAK domains. It's very specific for TIC two. And and so what they're going for, is specific inhibition of interleukin 23, which signals, through TIC two.

And it showed very they they showed data from a psoriasis trial in which there were PASI 75 responses in the high sixty percent range. So not dissimilar

from what we've seen with the monoclonal TNF inhibitors.

I think pretty good. Not necessarily as high as the IL-seventeen or IL-twenty three inhibitors Right. But still very good. And the safety profile was pretty darn good. Interestingly, at higher doses, a little bit of acne was noticed.

But the they did a novel thing. They asked patients at the beginning of the trial, Do you have musculoskeletal pain centers? And then they measured the MDS response in those patients. There were about thirty percent of patients that had pain at baseline, so that could have been at least largely a psoriatic arthritis complication. They didn't specifically ask about PSA, and they found a very significant drop in pain.

So it gave them a little bit of a signal about the possibility of of testing it in PSA. And and as I understand it, they are going forward with the trial and its way out of the place.

Exciting. Eric, what do do there? I I it is interesting. I think it was more interesting in concept than what we actually showed. I actually was a little disappointed.

So, you know, we spent a lot of time talking about over the last few years the various Jack isoforms JAK1, JAK2, JAK3, and TIC2 is sort of the fourth in that group. And we've seen pretty clearly in all the data we've had that inhibiting the different JAKs gives you fairly similar clinical response. We've talked a lot about it. It doesn't seem much different. This is the first data we've seen with inhibiting the fourth member of that family.

So I thought that was really interesting. And as Phil pointed out, the hook for this ideally would be IL-twenty that three, which we know is an incredibly important molecule in skin psoriasis particularly, signals through TYK2 and not through any of the other members of the family so that maybe you can isolate the IL-twenty three. But the trial didn't really show that and I think that's a really key point is that when you looked at the skin, this was a skin trial, it's a psoriasis trial, when you looked at the skin results, it didn't look like an IL-twenty three inhibitor. Looked more like TNF inhibitor, as Philips had IL-seventeen. So, you know, the promise of this would be an oral drug that works like an IL-twenty three inhibitor which we've seen is really the sort of pinnacle of what we've got treating psoriasis.

We don't know yet psoriatic arthritis where they're gonna go. I don't think it answered that promise.

But it's still a new molecule and it's exciting

It's to sensitive. It's very cool and I want see more with it.

Absolutely. Gentlemen, thank you very much for your very instructive comments. I think it's really educational.

Thank you.

Thank Jack.

Tune in. Pleasure. Bye.

This is Artie Cavanagh for RheumNow Live, which is a new meeting that's coming up. You're watching me on RheumNow, but we're taking that to the next step. And Jack Cush and I, we're gonna have this meeting in Dallas, gonna be, the March 2019. It's brand new and it's gonna be a great learning experience for rheumatologists to share our expertise with each other and learn about some of the newest developments, some of which we've seen here at ACR twenty eighteen. So we'll see you at RoomNow live in Fort Worth in March.

This is Artie Cavanagh. I'm in room now live, and I'm here at ACR twenty eighteen. Just wanna invite you all to come to the Rheumatology Winter Clinical Symposium, RWCS. It'll be February 1639. We'll get to discuss a lot of the hot topics in rheumatology.

Be there. Aloha. This is Arti Kavanaugh at the ACR two thousand eighteen meeting. Jack Cush and I just finished our rheumatology roundup session. Couple of the many posters that were very exciting, very interesting and very informative.

There's a poster on the concurrence of ANCA in patients with anti GBM disease, good pastures, and it turns out that this is something we're seeing more in the clinic and that those with ANCA are more likely to relapse. There was a nice basic science poster on the cannabinoids, super hot topic that's getting a lot of play because the patients are using this and with the legalization across different states and countries even, but it may have some medicinal value. As a basic science that looked at an agonist of the CB2 cannabinoid receptor, which has a lot of inflammatory potential and, inhibition of that or some sort of a mixed agonist antagonist including the CB1 may have anti inflammatory features. And then an analysis of NHANES, a large survey of the American population looking at patients with chronic back pain and comparing those to first degree relatives of ankylosing spondylitis patients who have back pain. Bottom line to me is that there's probably a lot of undiagnosed spondyloarthropathy among patients with chronic back pain.

The prevalence of heel pain as a surrogate potentially for enthesitis. The prevalence of psoriasis was harder. So there's a lot of disease out there that we're probably not seeing, and hopefully with new therapies, there's gonna be greater recognition, and those patients will come into the rheumatology offices. So for RheumNow, this is Arti Kavanaugh at ACR two thousand eighteen.

Hi. I'm Jack Cush with RheumNow, and we just finished rheumatology roundup twenty eighteen here at ACR in Chicago. Artie Cavanaugh and I covered about 15 abstracts at the 07:30 hour here on Wednesday morning. Nice session, highly attended. We had fun, we learned a lot.

Here's a few of the highlights of things I presented. First was an interesting abstract about DIP involvement in rheumatoid arthritis patients. This comes from the Ninja Rheumatoid Arthritis Registry in Japan. This includes over 12,000 patients who they looked at their joint exams and specifically looked at DIPs two through five and found that of the twelve thousand patients, two percent had involvement of the DIP joints. Turns out that DIP involvement wasn't related at all to age or HAC or seropositivity, but it was related to disease activity.

Patients who had DIP involvement, two through five, in general, those who had involvement, about 2.6 DIPs per patient were involved. DIP involvement tended to portend more hand joint involvement, DIPs, PIPs, MCPs, and wrist. And that DIP two involvement was associated with higher measures of disease activity, the dash 28, TJC, SJC, and even pain scores much higher in those who have DIP two involvement. So it is part and parcel rheumatoid arthritis, you need to look for Another interesting abstract was, 2220, gout flares. This is a South Australian, patient population based survey where they looked at the incidence of gout and how they're treated and outcomes and whatnot.

What they found was that six point five percent of the population self reported themselves as having gout. Most importantly of those patients, only a third were being treated with urate lowering therapy. When they coned down and looked at those patients who had frequent gout, meaning more than two attacks in the last year, they found that twenty five percent of the population admitted to that and that only fifty percent of those people were taking Allopurinol, suggesting we're not doing a good job. We're not doing a good job identifying these people and treating them. And to that end, there were two other abstracts at the meeting which focused on pharmacist led management of gout.

Very interesting and novel studies, both kind of small and regional, but they basically said the same thing as is currently being reported in Lancet by O'Daugherty, looking at nurse led management of a gout clinic. And what they basically saw there were in your practice, you're only achieving the target of uric acid less than six in less than forty percent of patients. In these clinics, it's either seventy to ninety five percent. You have better adherence, you have less flares. We got to resurrect the gold clinic and bring back the gout clinic, and this time being led by either pharmacists or nurses who can do the job using a protocol that you design.

Turns out rheumatologists, we're just not seeing enough of them. We're too busy to do a good job that we know we can do. We should be outsourcing this really to the improvement of our patients. I'm going to end with a discussion of 08:37, the plenary session on standard dose vaccination versus high dose vaccination in rheumatoid arthritis patients. As you know, the high dose vaccine, usually quadrivalent, is indicated in elderly individuals where it's been shown to work very well.

They have to usually go somewhere to get it. It's usually not in the clinic. They have to go to a pharmacy or wherever. But the question is, would this work well and should we be using it in our RA patients? RA patients have a two to threefold increased risk of getting seasonal flu, and we know that RA patients and other patients in general are not being vaccinated as much as they should be.

So the question was, how should we vaccinate them? And in this study done in Canada by McGill University researchers, looked at I think two seventy patients who were randomized to receive over two different vaccine seasons, either the high dose vaccine versus the standard dose vaccine. And in the end, looking at a serial protection, serial conversion rates, there was a two to three fold increase success with the high dose vaccines suggesting this is a slam dunk. You really should be doing it. And then when they looked at it according to the therapies, most patients were on DMARDs and methotrexate, many of them were on biologics.

Turns out that therapy didn't affect these results at all unless you were on rituximab and maybe a few others, but really it seems like it's rituximab that would impair the response. The reason this is important that there are two drugs that do impair immunogenicity of the vaccine, and that would be methotrexate number one, and in this case, as we just said, rituximab number two. So this data is sort of convincing and may change practice, and I would encourage you to look at it. That's it from ACR twenty eighteen. I'm Jack Cush.

Tune in to room now. Hi. I'm Jack Cush. I wanna remind you to go to RWCS, a fabulous meeting held in Maui every year chaired by C. Cavanaugh and George Martin.

I'm part of the faculty. I'm lucky enough to go. It's a different meeting. It's a different atmosphere. It's a different feel.

It's a consistent faculty within others invited in. Very interactive, great environment to learn. The world's best speakers show up at this meeting. I would strongly urge you to make the effort to go to Maui to attend this meeting. Lord knows, over 200 of your colleagues are going.

Maybe it should be you as well. Hi. I'm Jack Cush with RheumNow. I wanna remind you of RheumNow live occurring in Fort Worth, March 22, Friday afternoon, March 23, all day Saturday. March 24, half day Sunday morning, really exciting meeting called RheumNow Live, cochaired by Artie Cavanagh and I, a program designed by you, the rheumatologist.

It's a very different design. It's a flipped classroom, shorter segments, a lot of discussion, an interactive app, a digital delivery. We want people to accommodate, we're going to cap the attendance at a certain number. The rest of you can watch remotely either live or on the archive content. It's gonna be a fabulous meeting with the great speakers.

And more importantly, we're gonna have these great sessions devoted to RA, PSA, AS, vasculitis, drug safety, orthopedics, and lupus. And then in between, we're going to mix in some TED like talks that we're calling our STEP sessions, sessions devoted by great speakers talking about science, technology, education, and patients. It really is going to be a meeting apart. Go to roomnow.live to see more about this. We'll see you in Fort Worth in March.