ACR2018 Chicago Day2 Save
ACR2018 Chicago Day2 by Dr. Cush
Transcription
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 Cassie Calabrese. I'm here in Chicago at ACR twenty eighteen, and I just left the poster hall where there are many excellent abstracts on gout. One in particular by John Boston and Jeffrey Peterson out of Washington and Alaska looked at the effect of pretreatment with methotrexate on efficacy of pegilodecase. They did a prospective proof of concept study looking at if you give oral methotrexate fifteen milligrams for one month before peglodecase and continue it throughout a treatment, checking uric acid levels every two weeks before peglodecase doses.
Does this increase the efficacy of peglodecase? As we know, this drug is an excellent option for patients with chronic refractory gout, but its efficacy is limited by development of anti drug antibodies. This was a very small study, but they found that they had 100% efficacy, meaning uric acid level for the most part stayed below six, with the methotrexate pretreatment for one month and throughout treatment compared to efficacy of forty two percent that we know from previous studies. This, of course, will need follow-up studies, but I found this to be very interesting. For more, follow us on roomnow.com.
Hi, I'm David Liu from Melbourne Australia reporting again for RheumNow here at ACI twenty eighteen in Chicago. Come from a very interesting abstract about yellow fever vaccination in Sao Paulo, Brazil and I thought it might have some implications for my practice. A lot of my patients want to go to countries which are yellow fever endemic, they might be on immunomodulatory therapy at the time. And the questions are always do we have to, in order to yellow fever, vaccinate these patients because they might need that and to come back, not just to in terms of preventing the disease, but coming back into the country. Should we hold the immunomodulation or should we do something else?
Should we continue it through? Well, we've had some very useful data from colleagues in Sao Paulo where they have a current yellow fever outbreak and they mandate a yellow fever vaccination. It's from Michelle Lopez who is a rheumatologist there. She described the experience with eight hundred and fifty nine rheumatic disease patients who received yellow fever vaccination who were on what they called light immunomodulatory therapy. So that really constitutes conventional synthetic DMRs, no biologics, but methotrexate up to 20, lefunomide up to 20, and that sort of thing, prednisolone up to 20 as well.
Out of all those patients, the long and the short of it is that none of those patients ran into any serious problems. They compared them to some healthy controls, 159 matched healthy controls as well. They had similar rates of cytopenias. The cytopenias were fairly mild and recovered after thirty days. The adverse events were fairly mild as well.
Patients did get some side effects, but really those were short term things. And most importantly, what we were really worried about, the viscerotropic disease, the reactivation like disease that we might see from yellow fever vaccination, we didn't see any occurrences of that as well. So I think we probably do worry too much about our yellow fever vaccine and our rheumatic disease patients. We're naturally cautious people, but at the same time I think we can be reassured by these data that yellow fever vaccine is a safe option for our patients with unconventional sympathomimides. I'm David Liu and go to roomnow.com for any further information.
Thank you.
My name is Ian Bruce. I'm professor of rheumatology at the University of Manchester in England, and I'm here at the ACR twenty eighteen conference in Chicago. There's been a lot of talk this week already about JAK inhibitors. We had a wonderful overview today from John O'Shea, who was really one of the basic discoverers of the JAK pathway. And over the last twenty five years, these drugs have now come into clinical practice and a number of new agents in this class are being trialed and reported to this meeting.
Of note, there were several abstracts yesterday talking about upadacitinib, which is a new JAK kinase inhibitor that's being trialed in rheumatoid arthritis. The notable results from the upadacitinib trial program is that first of all it outperforms methotrexate in early methotrexate naive patients with rheumatoid arthritis. Also in patients, with DMARD failures, it actually outperformed adalimumab as the primary endpoint of, reduction in inflammation and also improve measures of quality of life. So I think there's a lot of exciting work ahead on JAK kinase inhibitors. I think we need to learn a lot more about the doses and the optimal doses in different diseases.
But I think we're hearing really about the rise of the JAK inhibitors and I think we're going to see these becoming increasingly part of the cornerstone treatment of inflammatory rheumatic diseases. If you want to learn anything more, about the ACR please go to roomnow.com. Thank you.
Hi, I'm Jack Cush with RheumNow. We're here in the booth at ACR twenty eighteen in Chicago. I've gathered a group of friends, experts in the field of ankylosing spondylitis and spondyloarthritis to talk about what's happening here at the meeting. I'm joined by Doctor. Jose Cher, Doctor.
John from New York, Doctor. John Rivel from Houston, Doctor. Mohamed Azim Khan from Cleveland, and Doctor. Jorg Erman from Boston to tell us their impressions of the meeting. Why don't we just sort of go down the line and talk about maybe what either what you've seen so far or what you're looking forward to?
Because there are a bunch of presentations this afternoon and a few tomorrow and whatnot. Jose, is there something you're looking forward to?
I am looking forward to seeing the data on Sertolizumab in non radiographic axial SpA. That's a hot topic. It appears that the data is robust. I am looking forward to the 17 class in AS and the ICSI data. And I'm looking forward to a few data sets that look at ways of referring spondyloarthritis earlier, particularly from the German group.
And those are the hot topics that I can think of.
John, you were involved in the abstract selections. You only have about 1,700 that are on your mind.
Right. Although one of the ones that I was most excited by was a plenary session yesterday, which is a presentation from doctor Matthew Brown's group, where they looked at approximately 6,600 European derived Caucasians as well as a similar 6,001 Chinese, approximately 800 Turks, and 600 Iranians, and to generate a panel of snips, single nucleotide polymorphisms, that taken in in a sort of a a a when looked at together, provides very significant predictive value to make a diagnosis of ankylosing spondylitis in the clinical setting. It's a large panel of SNPs and what was ironic so the discovery cohort were of course the 6,000, so European derived whites and the 6,001 East Asians, primarily Chinese. The replication cohorts, of course, the Turks and the Iranians. And it was shocking to to see that this panel of single nucleotide polymorphisms, a panel that costs about $50 performed equally as well as MRI in establishing a diagnosis in an individual patient.
Obviously, applying at a population based level is a bit more problematic, but given the problems we have making a diagnosis in the clinic, when you have a clinical suspicion, this panel may potentially be of important use. Of course, similar movements are being done in other rheumatic diseases and probably is a good sign of where the future is going and how genetics can be applied to diagnosis.
So, doctor Khan, you you know, it's not just p twenty seven now. So what's your thinking about this advance?
Well, you can tell me whether how much better it is than just typing for b twenty seven. Significantly better, but but b twenty seven needs to
be put into the mix. If you look at the in individual snips, like 23 and me use, for example, the specificity is only about 53%. But but the specificity for this, is 91 well, 91 in whites, ninety five percent if you look at Asians. And you compare that and the sensitivity of course is eighty three percent. MAP actually performs much better than the current OSCESS criteria.
So in African Americans, fifty percent of the patients lag
Actually forty percent. That's published a couple days ago. We have a paper in Arthritis Animal Jamax Disease.
Hard to keep up with his papers.
So over there, how can any test be helpful? The what? They don't have b twenty seven.
Well, it it obviously has not been validated. When what we found looking in African Americans, what was shocking was that h l a b twenty seven is significantly down in frequency like we saw in the Chinese and like we saw in the whites. Of course B27 is present in sixty percent just like you described in 1978 and we also found similar impact of MAC class two genes such as especially with the HLA DP locus and this was seen in whites and blacks.
Let me rephrase the question. B27 test is helpful but then it doesn't help when somebody has a disease in the absence of B27. Has developed or has Matt you developed some kind of genetic profile that can predict the
Yes, yes.
Can you
rephrase this question again?
He wanted to know about how this applies to making a diagnosis in the B27- -patient. Right. And the answer is it works well. Obviously if you throw in B27, you lose some specificity at that point but the best specificity you see when you include B27 in the process But that said, you know how many false diagnosis of spondyloarthritis you get from B27 positive individuals in the clinical setting.
Jorg, what's your comment on this?
Yeah, actually I have also a question because I think that there's still a lot of work that needs to be done in terms of validating this prospectively. My question is how is this going to perform in patients with the wider diagnosis of axial spondyloarthritis, not the narrow diagnosis of ankylosing
Well, okay. You know there's a publication that came from the same group. This is a study that was commissioned by ASUS. They looked at the top five SNPs, ERAP1, IL-twenty three receptor, the chromosome 2P gene desert, which is seen in every ethnic group. They looked at all those and the answer was they didn't.
They looked at approximately four hundred patients and they did not perform very well. But there were a lot of reasons because there was a lot of heterogeneity between the groups that were referring patients with axial SpA, number one. Some, for example, only referred V27 positives, others looked at other criteria for referral. Secondly, and most importantly, it was vastly underpowered. Most of these SNPs require patient sample sizes of up to a thousand and more because we're dealing with odds ratios of 1.1, 1.2 before you really see the association.
So with a panel with three fifty patients, it's not surprising that you're not going to have the power to really see this. So I think it was a combination of heterogeneity in the axSpA group as well as power that caused it not to perform very well. I think to make this, use this panel, it's going have to be refined a bit more before we can get to the non radiographic axial SpA PEEK.
So I want to get to Jorg, tell us what you're looking forward to at this meeting and same thing Doctor. Khan, just tell us what you're looking forward, what you've seen so far that excites you.
Yeah, so I think something that I would highlight is an effort that was discussed yesterday in the spondyloarthritis study section. And that is a study that's going to start next year called CLASSIC. And that's a combined effort of Spartan and ASUS. This study, the goal of this study is to validate the existing classification criteria for axial spondyloarthritis in a thousand patients worldwide. And this will generate a lot of data.
If the criteria are not good enough, this will also provide a lot of data to improve them in the future, and I think that's very important.
This is like the ideal use of a study group and bring coming together at the ACR. Doctor Khan, is there anything you're looking forward
My main interest is to see how we can prevent syndesmophyte formation and ultimate ankylosing. The data already in 17 inhibitor, executive new map, looked pretty good. Four years, they were eighty percent of the patients did not show progression. And Jose and I are interested in exactly RheumAb also. And so my hope is that now that we can control inflammation pretty well, we hope to prevent bone fusion.
Right. And that flexibility retention will improve functional abilities of the patient. So that's the next hurdle we have to
So two things I want to end with. One is a discussion of IL-seventeen and where we are and two, to go back to the non radiographic axial Spock. But first, IL-seventeen and where we are, we're going to have the three year extension data on the secukinumab study in AS. That's going to be presented today. And we're also going to hear about ixekizumab, another IL-seventeen inhibitor in ankylosing spondylitis, that's going to be presented today.
And an axial spot. And an axial spot. And an axial
non radiographic, yes.
Right. So, where are we with this? This is all very encouraging. Is it changing the paradigm? And what's the hope for IL-seventeen going forward?
Jose?
I'm not so sure it's changing the paradigm. This is what we expected based on prior data. I think what's changing is, just to summarize discussion, is going as early as possible on the treatment of these conditions where we can not only predict who is going to develop, but have actionable therapeutic strategies. The question is who amongst those that are currently classified as non radiographic axial SpA are the ones that will eventually go on to the Osteoproliferative Pathway?
Okay, I'm interested in the fact that prebiotics, probiotics, antibiotics don't yet have any clinical role, but what would be your protection since you are working on gut microbiome? Would there be a way to handle that aspect of trigger or control inflammation at early stage?
Well, there's a very interesting presentation today on trafficking of cells from the gut to the joint.
That's our session. Yes.
So that's gonna be really exciting. Just give a preview of that.
The fundamental question of whether or not modulation of the gut microbes can prevent or delay the appearance of systemic inflammation. I'd say a challenging one, the field is also moving towards something called pharmaco microbiomics. Can we use our gut microbes to predict or modulate our current therapies so we can improve outcomes at the time where we can prevent adverse events. That's fascinating and it's coming this afternoon.
But I think one thing that I think is important to point out that we've learned only recently is that the actual microbes that are associated with disease tends to vary a great deal from center to center, from ethnic group to ethnic group. And probably it's not the issue of the bug, but the pathway that the the what is actually happening.
It is about the enzymatic capabilities of the box that could be the exactly the same with a different name on the box.
Different box. Yeah. Different box. Same Same mechanism.
Same mechanism.
So I wanna end with the story about non radiographic axial accepted nomenclature by all you experts just not necessarily popular in America as it is in Europe and outside of America and it failed as an indication with two companies going in front of the FDA a few years ago, but one company has taken it forward and they have a study today on non radiographic axial SpA. My question is, is America ready to actually start using the term and treating patients as such as opposed to what they've been doing which is probably what we call creative coding, calling it something else.
She wants to make America great again.
In 1985, I described this entity, I called it Spondylitic Disease Without Radiographic Evidence of Sacral Reaction. So the word spondylitic disease is actually better than spondylitis or spondyloarthritis. Just like rheumatoid arthritis, we call it rheumatoid disease. The disease has wider spectrum, not just musculoskeletal, but extra skeletal as well. So that particular entity is now called, we call it non radiographic axial spondylosis, but it is a very wide spectrum.
Maybe most of the people with non radiographic may not develop sacroiliac. Right. And just like lupus, many have ANA positivity, they may get thrombocytopenia, but they may never develop. So the whole field of non radiographic excess, There's so much heterogeneity that it is a big problem for FDA to really readily approve that indication.
But we'll see. But I think it's it's important about, you know, the studies that are done. That's important. You come from Germany where obviously it's very well accepted. What's your impressions of how we consider non radioactive spot here?
My personal opinion is I think that axial spondyloarthritis is something, it's a valuable category. I'm not so sure about the category of non radiographic because this is a very difficult term that is also very confusing because the difference between non radiographic disease and radiographic disease is very blurry. And so I think that still needs some discussion whether we should use that qualifier non radiographic just say,
exercise Gentlemen, final comments on that.
Yes. The fact of the matter is that if you look at insurance databases, only fourteen percent of people with chronic back pain in The United States ever see a rheumatologist. You look at those with onset between the age of 20 and 29 years, it's nine percent. So the problem here is that low back pain affects nineteen point four percent according to NHANES of The US population in the ages of 20 and 70. These people, if you look at the concept of axial spondyloarthritis, it is virtually unknown outside of the rheumatology community, and these people aren't getting the rheumatologist.
So this is probably represents one of the big challenges and unmet needs that we face in this country is dealing with the issue of chronic back pain, inflammatory back pain which occurs in seven percent of the population and axial spondyloarthritis.
The point being also that if we did this right, we'd be diagnosed with people earlier and we as experts, wouldn't be seeing people at the supermarket or in the airport who have spondylitis who have never been diagnosed. Jose?
The counterargument to that is the pharmacoeconomics. How many people that will never develop true inflammatory, osteoporosis, axial spondyloarthritis will see biologic therapies that are only skyrocket.
And how many of the indirect costs given the back pain is the leading cause of disability in US. Would we be saving by diagnosing those people earlier?
Obviously, challenges ahead. Thanks for tuning into this panel on spondylitis. I want to thank my panel for their expert opinions. Enjoy the meeting.
Thank you.
Hi. I'm Jack Cush with RheumNow. We're here in the RheumNow with ACR eighteen, and I'm talking with AJ Narula, doctor AJ Narula from Eli Lilly and Company. I asked AJ to come by today to talk about, basically, the issue of drug development. This is sort of an issue that we're seeing more and more need drugs and the drugs themselves start out with an indication, and then they go on to have their own life.
So, would you tell us your approach at Eli Lilly on drug development, just in general the start? Know Phase one, Phase two, Phase three, but what's behind the scenes that maybe the world that college doesn't know about?
Yeah. Well, I think when we start thinking about future drugs for development, you know, one of the first things that comes to mind is what are the unmet needs for the patients? So what diseases do we still need to develop drugs for where there are no good therapies? And for existing diseases, where can we improve the standard of care? So that's the first step as we start to go through the drug development and selection process.
The next I think is trying to have a really deep understanding of the biological pathways that drive the disease so that helps drive us towards which pathways we want to target with specific drugs. And one good thing now is that we have developed some therapies already in rheumatology and autoimmune diseases. We can now go back to some of our biological samples from previous trials and we can probe which pathways are amplified in disease that helps us pick some new targets. And also look at which pathways serve as a marker for non response. We can try and understand therefore which pathways we should go after to help those patients who aren't responding to existing therapies.
So at the company level, when you were making decisions, really, I like the idea of unmet need and understanding the pathogenesis and having biomarkers. That applies to common diseases and rare diseases as well. Lilly has been a leader in diabetes, osteoporosis, now rheumatoid arthritis, psoriatic disease, and that's a makes sense to go down that path. Yeah. How does a company consider rare diseases, open diseases?
Because same things exist there. There's really unmet need.
You
often do understand the type of thing. That something companies are thinking more about?
We are. Mean, you know, even though diseases may be rare, you know, for those patients it's an important, you know, be really, some of these diseases can be really catastrophic. So, we are looking very closely at those diseases, again trying to understand the biological drivers. We look at a number of things, biomarkers, genetic markers of disease. Sometimes we'll come up with a target that might fit well for a very rare disease and we will actually, especially in the future, really consider studying those diseases as a proof of biological principle.
It's an important unmet need to meet even though the disease may be rare. It's something important rheumatologists would
We are all very good at the common disorders, but we have to be good at the uncommon ones. So we like it when we see breakthrough status for chronic conditions. So once you take a product to market, like you recently now have, it's a it's an exciting time. There's a lot of opportunity for education and whatnot. The growth of a product I've seen over the years is often depends on the first indication, but also then subsequent indication.
Absolutely. Yeah.
So how is there a strategy involved in basically finding your audience, finding the best indication? Maybe your primary indication for a new drug, let's say, is rheumatoid arthritis. Yeah. You know, finding what's the subset of rheumatoid arthritis? I mean, are there other diseases?
So, what's the strategy of the thinking there?
Yeah, I mean, obviously as we develop a drug, it tends to be a lead indication, but after you've got a proof of principle, a proof of concept with that lead indication, even before a drug comes to market, start thinking about where else it could go and where else it could help patients. So that process starts early and we now like to actually already be evaluating it in other diseases even by the time the first drug is out there for the first disease. Again, I think it fundamentally comes down to the biology. We look at overlapping biology between these diseases and we try and understand where the drug could fit other diseases. So I think it's largely driven by the biology and where we think we can make a big difference.
Also to me seems like it's often driven by anecdotalism. One that, know, ending or even without more plants in the hands. You know, people are trying another condition and you And then, obviously, there's probably investigator initiated grants.
Absolutely. Yes. Yes.
So in the end, you know, the other the backside of all this is the safety side.
Yeah.
And has the FDA changed much of what what it's done? Have REMS programs become important to every company, every product or only some companies and some products? REMS being risk mitigation Absolutely.
Think one of the key things when we develop a therapy is we want to deliver meaningful efficacy for the patient, but it has to also safety is tantamount and we want drugs to have a good benefit risk profile. So I think our approach at Lilly is we want to work closely with the regulatory agencies to do the right things for patients and if a REMS approach is appropriate, we work closely with the agency to put that in place and really to continue to understand the safety as we take a drug into market. It's a collaborative thing I think.
And lastly I want to ask about the challenge of educating docs.
Yeah.
Know, docs, sometimes their education is by experience and by, you know, happenstance as opposed to being something that's better thought out. How do you best educate the docs about new products that are new indications? They'll hear it.
Yeah.
Often, you know, they're very comfortable in what they're already doing. Yeah. Know, they might not have few other drugs they can use. How do they get knowledgeable about a new product when it comes to market?
Yeah, well you know what, when a drug comes to market and it's early in its life cycle, you know what we try and do is some, you know there's a lot of data that comes out of a phase three program for example and so what we try and do at meetings like ACR is really present some of our sub analyses of the data to really you know make some clear points about what we do understand about a drug. We do understand that you know when you finish a Phase three program you know there's still a lot to learn as a drug comes into market. Need thousands of patients of years of experience to really fully understand drug but we try you know on a regular basis to share what we have learned about specific aspects of drug from its efficacy to its safety profile. It's an iterative process I think where we continue to try and share what we're learning about a drug as it moves through its life cycle and make sure that clinicians have the most up to date information.
Yeah,
that reintroducing the trial in maybe a different way Yeah. I think it's really valuable.
Yeah. Most
people have additional knowledge that can get supported, and ultimately, they they're tipping point, and they get a comfort level. So that's kind of Mhmm. Good news. Yeah. Thank you.
Thanks for coming by.
Good to see you, Jack. Take care. Bye. Thank you.
Hi. I'm Jack Cush with RheumNow. And I wanna tell you about the best thing I saw today. It's abstract sixteen fifty seven by Philip Hellowell, and it's entitled guselkumab and the treatment of enthesitis. This is a phase two trial of guselkumab, against placebo in patients with active psoriatic arthritis.
To get into the study, they had to have greater than three tender and swollen joints. And it turns out that seventy two percent of the one hundred and forty nine patients had enthesitis at entry. Using enthesitis as an endpoint, looking at at the leads enthesitis index, they basically saw significant reductions in enthesitis by week eight in those treated with guselkumab, the IL twenty three inhibitor. Overall, there was a fifty percent of the patients who actually resolved their enthesitis while on therapy, obviously much better than those on placebo, and it turns out that enthesitis seems to parallel a lot of the other activity measures seen with psoriatic arthritis. So enthesitis responses tended to be better in patients who were ACR 20 responders.
Enthesitis scores tended to correlate with other activity and and inflammatory indices in patients with psoriatic arthritis. Enthesitis is a significant challenge for the rheumatologist and having drugs that will work very well, in this arena, they're very important. So this is important, and I think it's one of the important things I've seen today. That's it. Tune in for more RheumNow.
Hi. I'm doctor Janet Pope. I'm a room reporter here at ACR twenty eighteen in Chicago at the RheumNow booth. I wanted to tell you about an abstract that was presented as a poster, number twelve fifty two by doctor Karim Ladakh. He trained, in Canada and in hospital for special surgery.
He did a study looking at how good we are or possibly are not at doing TB testing prior to initiation of a TNF inhibitor. He found that less than sixty percent of patients, fifty some percent, had TB testing done prior to TNF initiation. And of course Rheumatologist better did it better than the gastroenterologist who are using the TNF inhibitors for inflammatory bowel disease. So there's a couple things that strike me. In general, my practice is not to do a TB skin test prior to every single drug.
So if I've done it a year before and I have a low risk patient, I'm not gonna retest it. So he might have looked in too short a window. But I think the bottom line is we have to remember TB reactivation can occur, we have to follow the guidelines. Thanks, and thanks for listening.
I'm Jonathan Kaye coming to you from ACR twenty eighteen in Chicago for rheumnow.com. I just heard a terrific talk by Kat Liao from the Brigham Women's Hospital in Boston speaking on behalf of the RISE Registry looking at the prescription of biosimilars in The United States over the past year. She looked at data from the RISE Registry and compared prescriptions of reference infliximab, Remicade, to that of the biosimilar infliximab, Inflectra. They found no incidences of the biosimilar infliximab, Renflexis, having been entered into the registry, and they found that about two percent of infliximab prescriptions were for the biosimilar. The vast majority of prescriptions were patients who had previously been treated with the reference product, Remicade, who had been transitioned to the biosimilar.
The data came from community practices, not solo practices and not academic centers, which is quite reasonable given that academic centers have not had available biosimilar infliximab because of pricing issues. The practices in Georgia and Nevada were the greatest prescribers of biosimilar infliximab, although there are very few practices in Nevada that were participating in the RISE registry. In the rest of the country, the prescriptions for the most part were less than 1%, biosimilar prescription, But these data are the first data to look at biosimilar infliximab prescription in The United States and certainly parallel the estimate of about 2% market penetration that has been in the public domain for biosimilar infliximab DYYB or Inflectra. More to come from these data in MRI's registry in the next year or so looking at future trends in biosimilar prescription. For more information, go to rheumnow.com.
I'm Jonathan Kaye, look forward to seeing you again tomorrow.
Hi. This is Naomi Schlesinger reporting from the ACR twenty eighteen regarding gout. An abstract I really liked today was the peglodecase trial using methotrexate to prevent antibodies and flares. In previous studies of peglodecase, we've seen infusion reactions in up to twenty six percent of patients. The triple trials haven't quite shown that, and only one out of three fifteen actually had an infusion reaction.
But here we have two rheumatologists, both actually interestingly presidents of their state associations. We did this trial looking at methotrexate a month before, they used fifteen milligrams a day for a month before starting pygodecase and then six to nine months later. And basically showed in the nine patients that they conveyed in this abstract that there were no infusion reactions in these patients. Thus here we have a new modality, an immunosuppressant that should be maybe used with peglodecase to decrease infusion reactions. Other medications are also being tried and used for pegglodecase now in trials.
If you want more information, look at RheumNow. Thank you.
Hi. I'm Cassie Calabrese. I'm here in Chicago at ACR twenty eighteen, and I just left the poster hall where there are many excellent abstracts on gout. One in particular by John Boston and Jeffrey Peterson out of Washington and Alaska looked at the effect of pretreatment with methotrexate on efficacy of pegilodecase. They did a prospective proof of concept study looking at if you give oral methotrexate fifteen milligrams for one month before peglodecase and continue it throughout a treatment, checking uric acid levels every two weeks before peglodecase doses.
Does this increase the efficacy of peglodecase? As we know, this drug is an excellent option for patients with chronic refractory gout, but its efficacy is limited by development of anti drug antibodies. This was a very small study, but they found that they had 100% efficacy, meaning uric acid level for the most part stayed below six, with the methotrexate pretreatment for one month and throughout treatment compared to efficacy of forty two percent that we know from previous studies. This, of course, will need follow-up studies, but I found this to be very interesting. For more, follow us on roomnow.com.
Hi, I'm David Liu from Melbourne Australia reporting again for RheumNow here at ACI twenty eighteen in Chicago. Come from a very interesting abstract about yellow fever vaccination in Sao Paulo, Brazil and I thought it might have some implications for my practice. A lot of my patients want to go to countries which are yellow fever endemic, they might be on immunomodulatory therapy at the time. And the questions are always do we have to, in order to yellow fever, vaccinate these patients because they might need that and to come back, not just to in terms of preventing the disease, but coming back into the country. Should we hold the immunomodulation or should we do something else?
Should we continue it through? Well, we've had some very useful data from colleagues in Sao Paulo where they have a current yellow fever outbreak and they mandate a yellow fever vaccination. It's from Michelle Lopez who is a rheumatologist there. She described the experience with eight hundred and fifty nine rheumatic disease patients who received yellow fever vaccination who were on what they called light immunomodulatory therapy. So that really constitutes conventional synthetic DMRs, no biologics, but methotrexate up to 20, lefunomide up to 20, and that sort of thing, prednisolone up to 20 as well.
Out of all those patients, the long and the short of it is that none of those patients ran into any serious problems. They compared them to some healthy controls, 159 matched healthy controls as well. They had similar rates of cytopenias. The cytopenias were fairly mild and recovered after thirty days. The adverse events were fairly mild as well.
Patients did get some side effects, but really those were short term things. And most importantly, what we were really worried about, the viscerotropic disease, the reactivation like disease that we might see from yellow fever vaccination, we didn't see any occurrences of that as well. So I think we probably do worry too much about our yellow fever vaccine and our rheumatic disease patients. We're naturally cautious people, but at the same time I think we can be reassured by these data that yellow fever vaccine is a safe option for our patients with unconventional sympathomimides. I'm David Liu and go to roomnow.com for any further information.
Thank you.
My name is Ian Bruce. I'm professor of rheumatology at the University of Manchester in England, and I'm here at the ACR twenty eighteen conference in Chicago. There's been a lot of talk this week already about JAK inhibitors. We had a wonderful overview today from John O'Shea, who was really one of the basic discoverers of the JAK pathway. And over the last twenty five years, these drugs have now come into clinical practice and a number of new agents in this class are being trialed and reported to this meeting.
Of note, there were several abstracts yesterday talking about upadacitinib, which is a new JAK kinase inhibitor that's being trialed in rheumatoid arthritis. The notable results from the upadacitinib trial program is that first of all it outperforms methotrexate in early methotrexate naive patients with rheumatoid arthritis. Also in patients, with DMARD failures, it actually outperformed adalimumab as the primary endpoint of, reduction in inflammation and also improve measures of quality of life. So I think there's a lot of exciting work ahead on JAK kinase inhibitors. I think we need to learn a lot more about the doses and the optimal doses in different diseases.
But I think we're hearing really about the rise of the JAK inhibitors and I think we're going to see these becoming increasingly part of the cornerstone treatment of inflammatory rheumatic diseases. If you want to learn anything more, about the ACR please go to roomnow.com. Thank you.
Hi, I'm Jack Cush with RheumNow. We're here in the booth at ACR twenty eighteen in Chicago. I've gathered a group of friends, experts in the field of ankylosing spondylitis and spondyloarthritis to talk about what's happening here at the meeting. I'm joined by Doctor. Jose Cher, Doctor.
John from New York, Doctor. John Rivel from Houston, Doctor. Mohamed Azim Khan from Cleveland, and Doctor. Jorg Erman from Boston to tell us their impressions of the meeting. Why don't we just sort of go down the line and talk about maybe what either what you've seen so far or what you're looking forward to?
Because there are a bunch of presentations this afternoon and a few tomorrow and whatnot. Jose, is there something you're looking forward to?
I am looking forward to seeing the data on Sertolizumab in non radiographic axial SpA. That's a hot topic. It appears that the data is robust. I am looking forward to the 17 class in AS and the ICSI data. And I'm looking forward to a few data sets that look at ways of referring spondyloarthritis earlier, particularly from the German group.
And those are the hot topics that I can think of.
John, you were involved in the abstract selections. You only have about 1,700 that are on your mind.
Right. Although one of the ones that I was most excited by was a plenary session yesterday, which is a presentation from doctor Matthew Brown's group, where they looked at approximately 6,600 European derived Caucasians as well as a similar 6,001 Chinese, approximately 800 Turks, and 600 Iranians, and to generate a panel of snips, single nucleotide polymorphisms, that taken in in a sort of a a a when looked at together, provides very significant predictive value to make a diagnosis of ankylosing spondylitis in the clinical setting. It's a large panel of SNPs and what was ironic so the discovery cohort were of course the 6,000, so European derived whites and the 6,001 East Asians, primarily Chinese. The replication cohorts, of course, the Turks and the Iranians. And it was shocking to to see that this panel of single nucleotide polymorphisms, a panel that costs about $50 performed equally as well as MRI in establishing a diagnosis in an individual patient.
Obviously, applying at a population based level is a bit more problematic, but given the problems we have making a diagnosis in the clinic, when you have a clinical suspicion, this panel may potentially be of important use. Of course, similar movements are being done in other rheumatic diseases and probably is a good sign of where the future is going and how genetics can be applied to diagnosis.
So, doctor Khan, you you know, it's not just p twenty seven now. So what's your thinking about this advance?
Well, you can tell me whether how much better it is than just typing for b twenty seven. Significantly better, but but b twenty seven needs to
be put into the mix. If you look at the in individual snips, like 23 and me use, for example, the specificity is only about 53%. But but the specificity for this, is 91 well, 91 in whites, ninety five percent if you look at Asians. And you compare that and the sensitivity of course is eighty three percent. MAP actually performs much better than the current OSCESS criteria.
So in African Americans, fifty percent of the patients lag
Actually forty percent. That's published a couple days ago. We have a paper in Arthritis Animal Jamax Disease.
Hard to keep up with his papers.
So over there, how can any test be helpful? The what? They don't have b twenty seven.
Well, it it obviously has not been validated. When what we found looking in African Americans, what was shocking was that h l a b twenty seven is significantly down in frequency like we saw in the Chinese and like we saw in the whites. Of course B27 is present in sixty percent just like you described in 1978 and we also found similar impact of MAC class two genes such as especially with the HLA DP locus and this was seen in whites and blacks.
Let me rephrase the question. B27 test is helpful but then it doesn't help when somebody has a disease in the absence of B27. Has developed or has Matt you developed some kind of genetic profile that can predict the
Yes, yes.
Can you
rephrase this question again?
He wanted to know about how this applies to making a diagnosis in the B27- -patient. Right. And the answer is it works well. Obviously if you throw in B27, you lose some specificity at that point but the best specificity you see when you include B27 in the process But that said, you know how many false diagnosis of spondyloarthritis you get from B27 positive individuals in the clinical setting.
Jorg, what's your comment on this?
Yeah, actually I have also a question because I think that there's still a lot of work that needs to be done in terms of validating this prospectively. My question is how is this going to perform in patients with the wider diagnosis of axial spondyloarthritis, not the narrow diagnosis of ankylosing
Well, okay. You know there's a publication that came from the same group. This is a study that was commissioned by ASUS. They looked at the top five SNPs, ERAP1, IL-twenty three receptor, the chromosome 2P gene desert, which is seen in every ethnic group. They looked at all those and the answer was they didn't.
They looked at approximately four hundred patients and they did not perform very well. But there were a lot of reasons because there was a lot of heterogeneity between the groups that were referring patients with axial SpA, number one. Some, for example, only referred V27 positives, others looked at other criteria for referral. Secondly, and most importantly, it was vastly underpowered. Most of these SNPs require patient sample sizes of up to a thousand and more because we're dealing with odds ratios of 1.1, 1.2 before you really see the association.
So with a panel with three fifty patients, it's not surprising that you're not going to have the power to really see this. So I think it was a combination of heterogeneity in the axSpA group as well as power that caused it not to perform very well. I think to make this, use this panel, it's going have to be refined a bit more before we can get to the non radiographic axial SpA PEEK.
So I want to get to Jorg, tell us what you're looking forward to at this meeting and same thing Doctor. Khan, just tell us what you're looking forward, what you've seen so far that excites you.
Yeah, so I think something that I would highlight is an effort that was discussed yesterday in the spondyloarthritis study section. And that is a study that's going to start next year called CLASSIC. And that's a combined effort of Spartan and ASUS. This study, the goal of this study is to validate the existing classification criteria for axial spondyloarthritis in a thousand patients worldwide. And this will generate a lot of data.
If the criteria are not good enough, this will also provide a lot of data to improve them in the future, and I think that's very important.
This is like the ideal use of a study group and bring coming together at the ACR. Doctor Khan, is there anything you're looking forward
My main interest is to see how we can prevent syndesmophyte formation and ultimate ankylosing. The data already in 17 inhibitor, executive new map, looked pretty good. Four years, they were eighty percent of the patients did not show progression. And Jose and I are interested in exactly RheumAb also. And so my hope is that now that we can control inflammation pretty well, we hope to prevent bone fusion.
Right. And that flexibility retention will improve functional abilities of the patient. So that's the next hurdle we have to
So two things I want to end with. One is a discussion of IL-seventeen and where we are and two, to go back to the non radiographic axial Spock. But first, IL-seventeen and where we are, we're going to have the three year extension data on the secukinumab study in AS. That's going to be presented today. And we're also going to hear about ixekizumab, another IL-seventeen inhibitor in ankylosing spondylitis, that's going to be presented today.
And an axial spot. And an axial spot. And an axial
non radiographic, yes.
Right. So, where are we with this? This is all very encouraging. Is it changing the paradigm? And what's the hope for IL-seventeen going forward?
Jose?
I'm not so sure it's changing the paradigm. This is what we expected based on prior data. I think what's changing is, just to summarize discussion, is going as early as possible on the treatment of these conditions where we can not only predict who is going to develop, but have actionable therapeutic strategies. The question is who amongst those that are currently classified as non radiographic axial SpA are the ones that will eventually go on to the Osteoproliferative Pathway?
Okay, I'm interested in the fact that prebiotics, probiotics, antibiotics don't yet have any clinical role, but what would be your protection since you are working on gut microbiome? Would there be a way to handle that aspect of trigger or control inflammation at early stage?
Well, there's a very interesting presentation today on trafficking of cells from the gut to the joint.
That's our session. Yes.
So that's gonna be really exciting. Just give a preview of that.
The fundamental question of whether or not modulation of the gut microbes can prevent or delay the appearance of systemic inflammation. I'd say a challenging one, the field is also moving towards something called pharmaco microbiomics. Can we use our gut microbes to predict or modulate our current therapies so we can improve outcomes at the time where we can prevent adverse events. That's fascinating and it's coming this afternoon.
But I think one thing that I think is important to point out that we've learned only recently is that the actual microbes that are associated with disease tends to vary a great deal from center to center, from ethnic group to ethnic group. And probably it's not the issue of the bug, but the pathway that the the what is actually happening.
It is about the enzymatic capabilities of the box that could be the exactly the same with a different name on the box.
Different box. Yeah. Different box. Same Same mechanism.
Same mechanism.
So I wanna end with the story about non radiographic axial accepted nomenclature by all you experts just not necessarily popular in America as it is in Europe and outside of America and it failed as an indication with two companies going in front of the FDA a few years ago, but one company has taken it forward and they have a study today on non radiographic axial SpA. My question is, is America ready to actually start using the term and treating patients as such as opposed to what they've been doing which is probably what we call creative coding, calling it something else.
She wants to make America great again.
In 1985, I described this entity, I called it Spondylitic Disease Without Radiographic Evidence of Sacral Reaction. So the word spondylitic disease is actually better than spondylitis or spondyloarthritis. Just like rheumatoid arthritis, we call it rheumatoid disease. The disease has wider spectrum, not just musculoskeletal, but extra skeletal as well. So that particular entity is now called, we call it non radiographic axial spondylosis, but it is a very wide spectrum.
Maybe most of the people with non radiographic may not develop sacroiliac. Right. And just like lupus, many have ANA positivity, they may get thrombocytopenia, but they may never develop. So the whole field of non radiographic excess, There's so much heterogeneity that it is a big problem for FDA to really readily approve that indication.
But we'll see. But I think it's it's important about, you know, the studies that are done. That's important. You come from Germany where obviously it's very well accepted. What's your impressions of how we consider non radioactive spot here?
My personal opinion is I think that axial spondyloarthritis is something, it's a valuable category. I'm not so sure about the category of non radiographic because this is a very difficult term that is also very confusing because the difference between non radiographic disease and radiographic disease is very blurry. And so I think that still needs some discussion whether we should use that qualifier non radiographic just say,
exercise Gentlemen, final comments on that.
Yes. The fact of the matter is that if you look at insurance databases, only fourteen percent of people with chronic back pain in The United States ever see a rheumatologist. You look at those with onset between the age of 20 and 29 years, it's nine percent. So the problem here is that low back pain affects nineteen point four percent according to NHANES of The US population in the ages of 20 and 70. These people, if you look at the concept of axial spondyloarthritis, it is virtually unknown outside of the rheumatology community, and these people aren't getting the rheumatologist.
So this is probably represents one of the big challenges and unmet needs that we face in this country is dealing with the issue of chronic back pain, inflammatory back pain which occurs in seven percent of the population and axial spondyloarthritis.
The point being also that if we did this right, we'd be diagnosed with people earlier and we as experts, wouldn't be seeing people at the supermarket or in the airport who have spondylitis who have never been diagnosed. Jose?
The counterargument to that is the pharmacoeconomics. How many people that will never develop true inflammatory, osteoporosis, axial spondyloarthritis will see biologic therapies that are only skyrocket.
And how many of the indirect costs given the back pain is the leading cause of disability in US. Would we be saving by diagnosing those people earlier?
Obviously, challenges ahead. Thanks for tuning into this panel on spondylitis. I want to thank my panel for their expert opinions. Enjoy the meeting.
Thank you.
Hi. I'm Jack Cush with RheumNow. We're here in the RheumNow with ACR eighteen, and I'm talking with AJ Narula, doctor AJ Narula from Eli Lilly and Company. I asked AJ to come by today to talk about, basically, the issue of drug development. This is sort of an issue that we're seeing more and more need drugs and the drugs themselves start out with an indication, and then they go on to have their own life.
So, would you tell us your approach at Eli Lilly on drug development, just in general the start? Know Phase one, Phase two, Phase three, but what's behind the scenes that maybe the world that college doesn't know about?
Yeah. Well, I think when we start thinking about future drugs for development, you know, one of the first things that comes to mind is what are the unmet needs for the patients? So what diseases do we still need to develop drugs for where there are no good therapies? And for existing diseases, where can we improve the standard of care? So that's the first step as we start to go through the drug development and selection process.
The next I think is trying to have a really deep understanding of the biological pathways that drive the disease so that helps drive us towards which pathways we want to target with specific drugs. And one good thing now is that we have developed some therapies already in rheumatology and autoimmune diseases. We can now go back to some of our biological samples from previous trials and we can probe which pathways are amplified in disease that helps us pick some new targets. And also look at which pathways serve as a marker for non response. We can try and understand therefore which pathways we should go after to help those patients who aren't responding to existing therapies.
So at the company level, when you were making decisions, really, I like the idea of unmet need and understanding the pathogenesis and having biomarkers. That applies to common diseases and rare diseases as well. Lilly has been a leader in diabetes, osteoporosis, now rheumatoid arthritis, psoriatic disease, and that's a makes sense to go down that path. Yeah. How does a company consider rare diseases, open diseases?
Because same things exist there. There's really unmet need.
You
often do understand the type of thing. That something companies are thinking more about?
We are. Mean, you know, even though diseases may be rare, you know, for those patients it's an important, you know, be really, some of these diseases can be really catastrophic. So, we are looking very closely at those diseases, again trying to understand the biological drivers. We look at a number of things, biomarkers, genetic markers of disease. Sometimes we'll come up with a target that might fit well for a very rare disease and we will actually, especially in the future, really consider studying those diseases as a proof of biological principle.
It's an important unmet need to meet even though the disease may be rare. It's something important rheumatologists would
We are all very good at the common disorders, but we have to be good at the uncommon ones. So we like it when we see breakthrough status for chronic conditions. So once you take a product to market, like you recently now have, it's a it's an exciting time. There's a lot of opportunity for education and whatnot. The growth of a product I've seen over the years is often depends on the first indication, but also then subsequent indication.
Absolutely. Yeah.
So how is there a strategy involved in basically finding your audience, finding the best indication? Maybe your primary indication for a new drug, let's say, is rheumatoid arthritis. Yeah. You know, finding what's the subset of rheumatoid arthritis? I mean, are there other diseases?
So, what's the strategy of the thinking there?
Yeah, I mean, obviously as we develop a drug, it tends to be a lead indication, but after you've got a proof of principle, a proof of concept with that lead indication, even before a drug comes to market, start thinking about where else it could go and where else it could help patients. So that process starts early and we now like to actually already be evaluating it in other diseases even by the time the first drug is out there for the first disease. Again, I think it fundamentally comes down to the biology. We look at overlapping biology between these diseases and we try and understand where the drug could fit other diseases. So I think it's largely driven by the biology and where we think we can make a big difference.
Also to me seems like it's often driven by anecdotalism. One that, know, ending or even without more plants in the hands. You know, people are trying another condition and you And then, obviously, there's probably investigator initiated grants.
Absolutely. Yes. Yes.
So in the end, you know, the other the backside of all this is the safety side.
Yeah.
And has the FDA changed much of what what it's done? Have REMS programs become important to every company, every product or only some companies and some products? REMS being risk mitigation Absolutely.
Think one of the key things when we develop a therapy is we want to deliver meaningful efficacy for the patient, but it has to also safety is tantamount and we want drugs to have a good benefit risk profile. So I think our approach at Lilly is we want to work closely with the regulatory agencies to do the right things for patients and if a REMS approach is appropriate, we work closely with the agency to put that in place and really to continue to understand the safety as we take a drug into market. It's a collaborative thing I think.
And lastly I want to ask about the challenge of educating docs.
Yeah.
Know, docs, sometimes their education is by experience and by, you know, happenstance as opposed to being something that's better thought out. How do you best educate the docs about new products that are new indications? They'll hear it.
Yeah.
Often, you know, they're very comfortable in what they're already doing. Yeah. Know, they might not have few other drugs they can use. How do they get knowledgeable about a new product when it comes to market?
Yeah, well you know what, when a drug comes to market and it's early in its life cycle, you know what we try and do is some, you know there's a lot of data that comes out of a phase three program for example and so what we try and do at meetings like ACR is really present some of our sub analyses of the data to really you know make some clear points about what we do understand about a drug. We do understand that you know when you finish a Phase three program you know there's still a lot to learn as a drug comes into market. Need thousands of patients of years of experience to really fully understand drug but we try you know on a regular basis to share what we have learned about specific aspects of drug from its efficacy to its safety profile. It's an iterative process I think where we continue to try and share what we're learning about a drug as it moves through its life cycle and make sure that clinicians have the most up to date information.
Yeah,
that reintroducing the trial in maybe a different way Yeah. I think it's really valuable.
Yeah. Most
people have additional knowledge that can get supported, and ultimately, they they're tipping point, and they get a comfort level. So that's kind of Mhmm. Good news. Yeah. Thank you.
Thanks for coming by.
Good to see you, Jack. Take care. Bye. Thank you.
Hi. I'm Jack Cush with RheumNow. And I wanna tell you about the best thing I saw today. It's abstract sixteen fifty seven by Philip Hellowell, and it's entitled guselkumab and the treatment of enthesitis. This is a phase two trial of guselkumab, against placebo in patients with active psoriatic arthritis.
To get into the study, they had to have greater than three tender and swollen joints. And it turns out that seventy two percent of the one hundred and forty nine patients had enthesitis at entry. Using enthesitis as an endpoint, looking at at the leads enthesitis index, they basically saw significant reductions in enthesitis by week eight in those treated with guselkumab, the IL twenty three inhibitor. Overall, there was a fifty percent of the patients who actually resolved their enthesitis while on therapy, obviously much better than those on placebo, and it turns out that enthesitis seems to parallel a lot of the other activity measures seen with psoriatic arthritis. So enthesitis responses tended to be better in patients who were ACR 20 responders.
Enthesitis scores tended to correlate with other activity and and inflammatory indices in patients with psoriatic arthritis. Enthesitis is a significant challenge for the rheumatologist and having drugs that will work very well, in this arena, they're very important. So this is important, and I think it's one of the important things I've seen today. That's it. Tune in for more RheumNow.
Hi. I'm doctor Janet Pope. I'm a room reporter here at ACR twenty eighteen in Chicago at the RheumNow booth. I wanted to tell you about an abstract that was presented as a poster, number twelve fifty two by doctor Karim Ladakh. He trained, in Canada and in hospital for special surgery.
He did a study looking at how good we are or possibly are not at doing TB testing prior to initiation of a TNF inhibitor. He found that less than sixty percent of patients, fifty some percent, had TB testing done prior to TNF initiation. And of course Rheumatologist better did it better than the gastroenterologist who are using the TNF inhibitors for inflammatory bowel disease. So there's a couple things that strike me. In general, my practice is not to do a TB skin test prior to every single drug.
So if I've done it a year before and I have a low risk patient, I'm not gonna retest it. So he might have looked in too short a window. But I think the bottom line is we have to remember TB reactivation can occur, we have to follow the guidelines. Thanks, and thanks for listening.
I'm Jonathan Kaye coming to you from ACR twenty eighteen in Chicago for rheumnow.com. I just heard a terrific talk by Kat Liao from the Brigham Women's Hospital in Boston speaking on behalf of the RISE Registry looking at the prescription of biosimilars in The United States over the past year. She looked at data from the RISE Registry and compared prescriptions of reference infliximab, Remicade, to that of the biosimilar infliximab, Inflectra. They found no incidences of the biosimilar infliximab, Renflexis, having been entered into the registry, and they found that about two percent of infliximab prescriptions were for the biosimilar. The vast majority of prescriptions were patients who had previously been treated with the reference product, Remicade, who had been transitioned to the biosimilar.
The data came from community practices, not solo practices and not academic centers, which is quite reasonable given that academic centers have not had available biosimilar infliximab because of pricing issues. The practices in Georgia and Nevada were the greatest prescribers of biosimilar infliximab, although there are very few practices in Nevada that were participating in the RISE registry. In the rest of the country, the prescriptions for the most part were less than 1%, biosimilar prescription, But these data are the first data to look at biosimilar infliximab prescription in The United States and certainly parallel the estimate of about 2% market penetration that has been in the public domain for biosimilar infliximab DYYB or Inflectra. More to come from these data in MRI's registry in the next year or so looking at future trends in biosimilar prescription. For more information, go to rheumnow.com.
I'm Jonathan Kaye, look forward to seeing you again tomorrow.
Hi. This is Naomi Schlesinger reporting from the ACR twenty eighteen regarding gout. An abstract I really liked today was the peglodecase trial using methotrexate to prevent antibodies and flares. In previous studies of peglodecase, we've seen infusion reactions in up to twenty six percent of patients. The triple trials haven't quite shown that, and only one out of three fifteen actually had an infusion reaction.
But here we have two rheumatologists, both actually interestingly presidents of their state associations. We did this trial looking at methotrexate a month before, they used fifteen milligrams a day for a month before starting pygodecase and then six to nine months later. And basically showed in the nine patients that they conveyed in this abstract that there were no infusion reactions in these patients. Thus here we have a new modality, an immunosuppressant that should be maybe used with peglodecase to decrease infusion reactions. Other medications are also being tried and used for pegglodecase now in trials.
If you want more information, look at RheumNow. Thank you.
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