ACR2018 Chicago Day3 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 David Borenstein. I'm at the American College of Rheumatology. I was, head of the pain management task force for the American College of Rheumatology, and so I wanted to bring you, news about, pain in general as far as the, meeting this week. I usually report on back pain, but there weren't too many abstracts on back pain this year.

But there were a significant number of abstracts and presentations dealing with pain and how it affects rheumatic diseases, all the various types of rheumatic diseases. And one point I think we really wanna take away from all the various abstracts and presentations is the importance of non pharmacologic therapy as far as pain is concerned. We know about nonsteroidals, opioids, and all those other medicines which can potentially cause side effects. That's one aspect of pain care. But another important pain therapy is in fact non pharmacologic, and that has to deal with the physical therapy aspects, the psychosocial aspects.

So this gets into the bio psychosocial model of pain. So the ARHP, another aspect of the American College of Rheumatology, had a number of presentations talking about support of the patients in regards to these cognitive behavioral therapies and the means by which we try to de stress patients. And in fact, we look at these health care partners with rheumatologists who can help us with these patients with chronic pain, we can in fact take care of a wide range of patients who have really significant difficulties in regards to coping. And when it comes down to it, being able to cope with your pain is actually one of the best means by actually taking care of it. So if you want more information about this topic, please go to roomnow.com.

K. Arthur Lau, reporting here at, room now for RheumNow, from ACR two thousand eighteen Chicago. Wanted to give you guys an update on the, SELECT, COMPARE trial looking at, upadacitinib versus adalimumab versus placebo. So RCT randomized between the three arms, close to six hundred and fifty patients, in upadacitinib and in the, placebo group, three hundred, twenty seven patients in the alemumab group. Overall, upadacitinib had really high ACR, response rates.

So ACR is twenty, fifty, 70 at four at seventy, one, forty five, and twenty five percent. With alememab, it was sixty three, twenty nine, and thirteen percent. And with placebo, it was thirty six, fifteen, and five percent. Overall, higher number of patient of patients, in upadacitinib achieved, DAS, 28 CRP, low disease activity, and remission to both, adalimumab and placebo. And in fact, for, the upadacitinib was superior to adalimumab at achieving ACR fifty at twelve weeks and at at hitting, DAS LDA at twelve weeks as well, which was, quite phenomenal.

Overall, radiographic data at twenty six weeks, similar, in terms of non radiographic responders and, mean total sharp scores, between adalimumab and upadacitinib. Both were much better than, placebo. And overall, in terms of adverse events, no real significant safety signals. There were a higher number of, cases of herpes zoster with upadacitinib as you would expect with a JAK inhibitor, compared to the other two groups. And in terms of, I guess, the hot topic now is, blood clots VTE events, which was very reassuring.

So there were three cases with adalimumab, two with two with upadacitinib, and one in the placebo group. So they did there did not seem to be an increased safety signals for VTEs, with this JAK inhibitor. So overall, you know, this trial is very exciting because the efficacy seems quite good, and there was real no really no safety concerns. So I'm looking forward to seeing where, you know, when we're gonna get access to this in the future and really incorporating into our practice. Signing off, from Chicago for RheumNow, ACR two thousand eighteen.

Hi, my name is Doctor. Brittany Ahmed and I'm a fellow in Dallas, Texas. I'm reporting from ACR twenty eighteen for RheumNow. One of the best parts of this conference is the ability to have an international collaboration. Because our world is becoming increasingly globalized and as well as our patient population is becoming more diverse, I thought I would do a segment on interviewing young rheumatologists from across the world.

So I have the privilege of having with me today Doctor. Etsi Igebu, and she is from the Lagos Teaching Hospital in Lagos, Nigeria. Etsi, welcome. You so much for joining me.

So my name is doctor as she said, my name is doctor Ete Gebu. I'm a resident in training in Lagos University teaching hospital in Lagos, Nigeria and in West Africa. So we are 41 people in training and consultants in a population of 200,000,000 people in Nigeria. So we are training people which we are managing people with rheumatic diseases especially, and it's grown. Over the period of ten years, it's grown tremendously.

We're seeing more patients. We are having more consultants, and we're having more interest in rheumatic diseases. With the medical students being interested and the general practitioners being interested as well.

That's fantastic. Etzi, one of the questions that I wanted to ask you was with regards to Nigeria, what are some of the manifestations of lupus and how do you feel like that is relevant for our communities in America, particularly with our African American population?

Lupus was previously thought to be uncommon in Nigeria because there was paucity of data. But in recent times, we're finding that lupus is very common. And we are seeing similarities in the clinical manifestations with people in African American people as with Nigerians as well. Because most of the African American people are descendants from West Africa in particular, and that's where Nigeria is. So they have similar manifestations.

Typically, a worry for us is a lupus nephritis, which is so common in Nigerians and sometimes it's the first manifestations we see. Like the Caucasians, they have the malarash. We typically don't see patients with malarash. We see with lupus nephritis, neuropsychotic manifestations, and the hematological manifestation. However, the most popular clinical manifestations are the polyarthritis and polyatralgia, but worrisome for us is the lupus nephritis because it has a very quick progression to end stage renal diseases.

So knowing that and combing it early is very important for us in our management. So now we have a policy that most young people with elevated ESR that come on with end with chronic kidney disease, we tend to screen them for systemic lupus erythromatosis. And we have seen increasing number of patients presenting with lupus nephritis.

Very interesting. Can you discuss a clinical trial that's going

on at Lagos Teaching Hospital? Presently, we have this trial going on. It's called the APO-one gene trial, where we are assessing patients with lupus nephritis and seeing if there's a genetic predisposition to it. We've started in Lagos and we intend for it to spread throughout the whole country. So what we do for the patients basically is when we see them, patients that have been diagnosed with lupus with lupus, using the ACL criteria or the SLEEK criteria, we assess them, we do, the gene study, the APO one gene study, we look for cytokines and we follow them up for a period of one year.

We do the SLEC to assess the damage the SLEC to diagnose them. We do the SLEC to assess their disease activity as well as the the to as well as to assess damage. So we've just started the study, and we were recruiting patients now. We intend for it to last for a period of one year. Okay.

Can you give us any updates from the AFLAR meeting earlier this morning?

Okay. For the first time, AFLAR meeting started last year, and we had another one. Initially, we had a one hour AFLAR meeting last year, but this year, we progressed to one hour thirty minutes. So our strong point in the meeting was to tell people that rheumatic diseases and rheumatological manifestations are not as uncommon as previously taught. So we had presentations saying the burden of rheumatic diseases in Africa as opposed to the previously thought that most of the burdens were infectious disease.

And we had to also say that pediatrics and juvenile rheumatoid arthritis common and we're seeing a lot. Pediatric rheumatic diseases as well as common and we're seeing a lot too. And also that there needs to be advocacy. We need to advocate for the patients. The medical students are supposed to be taught these diseases in medical school so it can spread over them because most times, in Africa, they are the first point of contact, the medical students and the medical officers, and so they can do early referrals and patients can be treated on time.

Also, we need to collaborate with the international community in the sense that, we should have people come over. Nigeria, we're lucky as I said. We have 41 people in 20. But some places in East Africa, they are no special rheumatologists. So patients are being seen by the general practitioners.

So by the time we have people coming, exchange programs being done, people send to those places and people are also sent to the to the Western world and then people are they now know that are trained both ways and it can help in management of these patients.

You actually mentioned an exchange program which was my next question. The ACR does have an exchange program between PANLAR and the ACR where a fellow from both governing bodies will actually go spend four weeks and vice versa. Do you feel like there would be a benefit from an exchange between Aflar and ACR or even a potential collaboration, for example, physicians going to Africa and helping to train and, you know, foster interest in rheumatic diseases.

Yeah. I think it will be very helpful because as I said earlier on that, we don't have so much challenge in West Africa now because we have, a training. We are being trained by professor Adelo Owa. He's the only one certified to train in West Africa, and he's trained a lot of people. So he's gone from being the father of rheumatology there to the grandfather of rheumatology because people he's trained are now training people.

When East Africa, there's paucity of rheumatology. So it will be very helpful for them if rheumatologists are sent there. Likewise, people are trained with interest and and and are sponsored to do the training in the Western world to improve their knowledge and to better, in the long run, better the patient's outcome.

Thank you so much Doctor. Egebu for being with us today. Thank you for joining us. You can find us at ACR18 and also at RheumNow on Twitter and also rheumnow.com. Thank you.

Thank you.

Hi, I'm Jack Cush with RheumNow. We're here in the RheumNow booth at ACR twenty eighteen in Chicago. Exciting meeting. More exciting is I've been able to gather up the Gout Mavens and bring them together to have a discussion about what's happening in Gout here at ACR twenty eighteen. Thankfully, I'm joined by Naomi from New Jersey, Ken Sagg from Alabama, and Nicola Dalves from New Zealand.

And we'll start off by saying thank you and welcome. And I'd like to know from each of you what is the one thing at this meeting that you seen or are looking forward to seeing that you want to bring up so that we can maybe have a little discussion. Let's start with Naomi.

Well, so there are too many to name. I'm going to actually start with the new treatments from the different uricases, the oral uricase, pyelodecase and the new immunogenicity abstracts and the select actually posters, one that's gonna be presented today showing, inflammation reduction when using uricase.

Let me add to Naomi what you're saying because I think this is really an important area. You know, for those of us, particularly in academic centers, we see very severe gout. See people that come in with topaceous deposits and the use of uricase has really been a salvage therapy that we look forward to having available. The major problem is immunogenicity. You can't take it forever.

People develop immunogenicity and it loses its effectiveness. So the idea about administering either co therapy with methotrexate, which is the poster that I think you were referencing and other approaches, Very exciting, more data is needed. It's certainly one of the things that we look forward to understanding I've more

seen a series of posters and actually one of the really interesting things is that it seems that this preparation with Rapamycin and apigylated uricase may well have anti inflammatory effects through the effects of the rapamycin actually. So there's co administration and then inhibition of IL-one release reduction of flares. That's really, that is very exciting,

I I think the real question for me is what is the right immunomodulatory therapy to use? I'm not sure we really know, and it may turn out that one size fits none. And we may need other options. We may be rapamycin, methotrexate, we're looking at mycophenolate in a small study we're doing. So you know, we've got to understand this better and figure out for the patient depending on their comorbidities what what's the optimal thing to give with peglodecase and how safe is it to do that ultimately?

So for the audience, again the issue here is that peglodecase may be limited by its immunogenicity against PEG, even your case in different forms may have immunogenic responses as well and how do you limit that to get the most out of the drug. The combination of uricase with rapamycin is interesting because you eliminate immunogenicity as you mentioned and also do better but then if you're using peglodecase then what's the drug that you use? Why don't we start off by talking about Jeff Peterson's abstract about methotrexate? Anybody want to give us some of that result?

Sure, basically nine patients given methotrexate, as I mentioned before, peglodecase infusions and throughout their time on peglodecase, somewhere between six to nine weeks. And this is showing that none, surprisingly, these patients actually had infusion or any other problems with using pyglodecase. This is actually very promising here. Methotrexate, the rheumatologist who are very comfortable using. Right.

Fifty milligrams. For in these very severe patients with gout.

Let me add two caveats that I think are important. One is that methotrexate, appealing because rheumatologists have a lot of experience and knowledge with it, may not be optimal in our gout patients because a lot of them also unfortunately drink. And so that's a concern. Moreover, there may be some potential for drug interactions with other things they're doing and the need to titrate up. We don't really know for sure whether that's going to work.

Mean, is all predicated on a series of transplant patients who have had protracted efficacy of uricase therapies in combination with their use of immunosuppressive therapies and in some cases actually have had an increase in urate levels when they stop their drugs transiently such as using Imurane, azathioprine. So that's my next question.

This experiment is with nine patients, pretty interesting and it all responses, no untoward effects, but as you say, that may not be the right drug. What are the other options? You have a trial that's going to be starting. What are the other options that are out there?

We're looking at Mycophenolate in part because there's less interaction with other drugs. One of the concerns is that if you're treating people with gout, sometimes there's other doctors involved and they may for example decide to start Allopurinol even and a it's conceivable that if you were to say use Imuran there might be a problem with drug drug interactions there. So that was one of the reasons when we polled doctors that they were enthusiastic about but it's not to say that it's the only reasonable therapeutic option. I think rapamycin is interesting, I think methotrexate is interesting and obviously azathioprine is the other one that has gained some traction here.

So I'd like to pause back a bit and talk about what I found interesting, which is really kind of not this group of people, small group of people with very severe disease, but actually the bigger gout population. And for me, some of the really interesting data has been, has been presented by in this meeting is a is a abstract from who in the oral concurrent session presented a a very large survey of people with gout and asked them about, you know, in the community, asked them about actually the number of flares that they had reported to their doctor versus the number of flares that they had actually experienced over that period. And what was really striking to me was that the number of patients that were or the number of flares that patients were experiencing was in the order of what? Six per year? Something like that.

And reporting, you know, two or fewer. And so I think this really speaks to the sort of broader issue around gout management where we see and we've seen, again, seen lots of posters today of, you know, very and we've seen this for the last decade, maybe even longer, probably longer, is, you know, these these these reports of very low use of allopurinol as kind of, you know, this philosophical issue with different groups of medical professionals saying actually, you know, who should be getting allopuramol, know, out the patients that are treated by the rheumatologists are different to the patients treated in primary care. And actually, think we're releasing some data to say actually we're substantially underestimating the flare burden and burden of disease if we're only looking at what the patient tells us in our office.

It underscores the under management of gout. Have a Twitter poll out right now that says what is your max dose on allopurinol. It's overwhelmingly eight hundred milligrams. Who uses it even though even rheumatology? And it's shocking.

There are two reports, one just in Lancet about a nurse run gout clinic and one here about pharmacist run What gout do you think of that?

Well actually my colleague Jeff Curtis and a collaborator Ted Michaels were involved with the pharmacist led approach within the Kaiser system. I think this is a strategy we've got to move towards. We've got to figure out how to unburden the busy clinician and to bring in arthritis health professionals that can help be it nurses, pharmacists, health system approaches to improve quality in this area. I want to come back to the flare thing because I think it's really interesting. You've talked about the clinical ramifications.

The other problem with flares is in our clinical trials. We're not doing a good job of capturing flares. We've got to come up with better ways to be able to assess disease activity in an episode that is occurring mostly at home and is subject to a lot of recall. That's probably a big part of the problem with detecting this in studies of new therapeutics. Got a lot of noise in the There's got to be new approaches.

I'd like to add another point that here we see inflammation being common, inflammation being a major problem in gout patients, inflammation contributing to cardiovascular disease and kidney disease, and yet we're not treating it because we don't know about it. And I think this is where education is important both for patients and for physicians. We need to treat that better.

Absolutely. And so there's a report here and it's kind of out there right now in the literature and at the regulatory agencies about xanthine oxidase inhibitors and cardiovascular events. And there's a report here about allopurinol versus febuxostat and we're seeing more with febuxostat. Where is

this going in your Yeah, well I can comment on that. I was part of that study and regrettably, think the bottom line is it raises more questions than it provides answers. There was a very high dropout rate. The primary endpoint, which was non inferiority of a combined cardiovascular safety signal, was non inferior, yet we saw this increase in all cause mortality and cardiovascular mortality. And we're just frankly not quite sure what to make of it.

There's another study that's being done in Europe that will read out and that'll be very important. There's a recent one done presented at a European Cardiology meeting this year called the FREED study, where in patients with hyperuricemia but not with gout, febuxostat actually looked cardio protective. So I don't know that we really know. In an active comparator study where you're looking at two xanthine oxidase inhibitors, it just makes it very difficult to disentangle whether we're actually seeing a safety signal or we're just seeing a difference possibly due to chance or possibly due to one drug being a little more protective than the other.

Yeah, I agree, but I also think actually we can take some things out of it and actually there's been this huge fear about allopurinol dosing and if you look at the protocol in the Cares trial, people with CKD had allopurinol dose escalation up to four hundred. Those who had normal kidney function, allopurinol up to six hundred. And at least as good outcomes as with leboxistat. So I think this is actually reassuring, at least, dose escalation of allopurinol is safe and effective. And that's really what

we should And that's really been a great contribution of you and Lisa to the field of showing us that the old handy criteria really are not very evidence based and that we probably if we go start low and go slow we can get away with a better dose of our xanthine oxidase inhibitors even with CKD.

One of the points in the study that there's no placebo arm could be that actually allopurin is protective and fungicide is not so bad. Had you had the placebo? Placebo or maybe And I think that's

what the

free to use. Actually. So so I think the word is not is not out yet. I think this is not the final end for febuxostat. I think we still need to see further studies comparing

Well, it's still around in full flair. Yes. I wanna thank the panel for an interesting discussion. Well, thanks for your interest

in gout. We're glad

we got some pretty good news. AR this year. Eight point three million people in our country, so we got a bit more attention to it.

And many

more over the world. Yes.

Right. It's growing, unfortunately. Yeah.

As we are growing.

Yes. Thank you. Alright.

Bye. Thank you.

Hello. Welcome to RheumNow. I'm doctor Janet Pope. I'm at the ACR in lovely Chicago again, and I wanted to report on a really interesting study. So doctor Nicole Ward, one of the trainees, did a study looking at the British Columbia database, and the question was, what are the pregnancy outcomes like in the moms with before they ever have lupus?

And they it was a large population billing database, and they found a couple 100 patients with lupus, some of whom had had their pregnancies before their lupus and some after. What I think is really interesting about this abstract is that adverse pregnancy outcome occurred way before the diagnosis was ever made. Smaller for dates babies, so growth restricted, earlier, births, pregnancy induced hypertension and some infections as well. And I think it leads to saying that the autoantibodies predate the lupus or some of the features and we really have to, think about making an appropriate diagnosis but realizing that before their disease is diagnosed they can have adverse pregnancy outcome. Something to think about.

Thank you.

I'm Jonathan Kaye coming to you from ACR twenty eighteen in Chicago for roomnow.com. At the ACR meeting, we always see data about existing agents, more data long term follow-up, data about novel agents, phase one trials, phase two trials, phase three trials, long term extension, and there's lots of data about biosimilars. But infrequently do we see a complete paradigm shift with a new mechanism of action, a new approach to treating rheumatoid arthritis. Today, we saw two posters about neuroimmunomodulation. There is a small implantable vagus nerve stimulator, which was implanted into patients with active rheumatoid arthritis refractory to multiple therapies.

This pacemaker or vagus nerve stimulator was activated transcutaneously, and in these patients suppressed disease activity. When it was shut off, disease activity recurred, and again, when it was turned back on, suppressed disease activity. This is a new approach whereby stimulating the vagus nerve suppresses TNF production and decreases disease activity, leading to effects similar to those with pharmacologic intervention, but without the, adverse effects observed, with exogenous TNF inhibition. This pacemaker or vagus nerve stimulator is now in clinical trials, and I look forward to seeing more data about this. And for more information, go to roomnow.com.

I'm Jonathan Kaye. I'm Jonathan Kaye coming to you from ACR twenty eighteen in Chicago for roomnow.com. At the ACR meeting, we always see data about existing agents, more data long term follow-up, data about novel agents, phase one trials, phase two trials, phase three trials, long term extension, and there's lots of data about biosimilars. But infrequently do we see a complete paradigm shift with a new mechanism of action, a new approach to treating rheumatoid arthritis. Today, saw two posters about neuroimmunomodulation.

There is a small implantable vagus nerve stimulator, which was implanted into patients with active rheumatoid arthritis refractory to multiple therapies. This pacemaker or vagus nerve stimulator was activated transcutaneously, and in these patients suppressed disease activity. And when it was shut off, disease activity recurred. And again, when it was turned back on, suppressed disease activity. This is a new approach whereby stimulating the vagus nerve suppresses TNF production and decreases disease activity, leading to effects similar to those with pharmacologic intervention, but without the adverse effects observed with exogenous TNF inhibition.

This pacemaker or vagus nerve stimulator is now in clinical trials, and I look forward to seeing more data about this. And for more information, go to roomnow.com. I'm Jonathan Kaye.

This is doctor Julio Gonzalez reporting live for roomnow.com from ACR twenty eighteen in Chicago. And today I want to talk about a couple studies that have been presented, novel treatments in the field of spondyloarthropathy, specifically in psoriatic arthritis first, and then some non radiographic axial spondyloarthropathy. So first I'm going to talk about two small molecules phase two studies. The first one is a study on a TYK2 inhibitor. So it's a selected TYK2 inhibitor in psoriasis actually, not psoriatic arthritis.

So this study presented strong data on PASI scores, PASI 75 PASI 90 data, and also significance in pain reduction, vast pain reduction scores. This novel mechanism of action that seemed to have a significant promise in the field of psoriatic arthritis. Most impressive was that there were really no safety signals seen in terms of serious infections, DVTs, so a lot parameters were also within normal range. It sounds like it's going to be kind of a pretty safe alternative down the road for patients that are suffering from complications such as serious infection. The data needs to be seen in psoriatic arthritis but it's looking pretty well at what was seen in psoriasis.

The other study I want to talk about is another phase two study. This one is on psoriatic arthritis actually on filgotinib. This is JAK1 selective inhibitor and this was a study on PSA. Patients were able to fill around twenty percent of the patients, fifteen to twenty percent had failed a TNF. This is very, some of them early PSA patients.

The study was done mostly outside of The United States. And the study showed pretty impressive ACR20 responses of around eighty percent respond at week twelve, if I'm correct. So again, pretty promising data right there. In terms of safety, there were no cases of DVTs or thrombosis reported and safety was more or less on par with what is to be expected of a JAK inhibitor. Third study I want to talk about is a study on bimekizumab on psoriatic arthritis.

This is a IL-17A and F inhibitor. So basically we're blocking both A and F or neutralizing both A and F, IL-seventeen A and F. So this study, again, this was a Phase 2B study that showed significant benefit of Rimekizumab as compared to placebo in terms of ACR scores. Their primary outcome actually was an 50 this time and had pretty strong ACR fifties in the forties at week 12 with continued improvement at week 24. In terms of safety signals, there was, no cases of IBD reported, so pretty much on, consistent with what is to expect and again no cases of IBD.

And lastly, the one last study I want to talk about is a study on non radiographic axial Spout which is presented as a late breaker today. This study is going presented be by Doctor. Diola, if I'm correct. And what they did is they looked at ASUS 40 in this population with non radiographic axial spondyloarthropathy, meaning no evidence of sarcolytes on their plain films or x rays. So they didn't meet New York criteria.

They just meet criteria for non radiographic axial fat. These patients had significant benefit at week twelve and at week fifty two as compared to placebo with what we see in ASAS 40 scores in the 40s in the treatment arm with certilizumab, which actually was a medication that was being used, Cimzia, versus seven percent in the placebo arm. And this carried on to week 52. There was also pretty neat data that they presented on absenteeism from work and you can see the number of absenteeism reduction over the time of the study. So, Sertilizumab sounds like it's going to be a new target in patients with non radiographic, it's an old drug with new indication in patients with non radiographic autosomal arthropathy.

This is great, need more therapies in this area and I think this is new data, guidelines are going to be presented later on or actually were presented these non radiographic and radiographic spondyloarthropathy. So impressive data on early treatment, early compounds in the development of psoriatic arthritis phase two and some data on the non radiographic axial spasm. So that's all for me for this ACR Congress and thank you so much for tuning in.

Hi, I'm Philip Gardner. I'm a rheumatologist from Ireland. I'm reporting from ACR Chicago twenty eighteen and today I'm going to talk to you about vasculitis. As a clinician, I was interested to go to the posters and to find out a little bit more about PET CT imaging and I found two interesting posters that I'm going to tell you about. One study from Barcelona, Doctor.

Estrada, told me about how using a bolus of steroids actually meant that the PET CT scan result was showing up as negative. But on one of the other posters, it was clear that if you treat patients with a few days of oral steroids that the PET scan was still positive. So I've been learning from these tests that they're using a score called the PETVAS to assess how severe the vasculitis is and that some units are also repeating the PETVAS scan after about six months and they're able to show significant reduction in activity. One of the other groups, Doctor. Schonen from Erlangen, looked at the difference in activity before and after methotrexate and before and after tocilizumab and in the eight patients who received tocilizumab, all eight patients had complete remission of their PET CT scans.

Whereas in the group treated with methotrexate, there were about thirty one percent of patients who still had activity on their scans. So for me the take home message was that I need to be doing more PET CT scans and I need to be getting more access to Tocilizumab to treat these patients. Now if you want more detail on research on vasculitis, please visit rheumnow.com. Thank you.