ACR20 - Day 3.1 Save

This is the RheumNow podcast, and you're listening to highlights from the ACR twenty twenty virtual meeting. Our faculty reporters have been doing videos and recordings so that you could stay up to date. Hope you enjoy these and our panel discussions.

Hi, everyone. I'm Nicola Delbeth from Auckland, New Zealand. And today I'm going to summarize a couple of really interesting abstracts presented at the ACR meeting in 2020, which demonstrate the potential effectiveness of adding immunosuppression to pegylodecase to increase the response to pegylodecase. So when pegylodecase was initially studied in the phase two and phase three studies, it became apparent that a number of people did not have a sustained response to pegylodecase. And overall, in the phase three study, only about forty two percent of patients had a persistent pegylodecase response.

And it was subsequently identified that this was due to anti drug antibodies, particularly anti PEG antibodies. And so there's been quite a lot of interest, particularly in the last couple of years, in whether adding immunosuppressive therapy, therapies that we use often in clinical practice in rheumatology, might reduce the risk of anti drug antibodies and thus increase the number of responders to this therapy. So there's a couple of abstracts at this meeting which address this, and I think will be really useful for us in clinical practice. So the first one is poster number six seventy seven. And this is data from the MIRROR study.

So this was a 12 open label study of methotrexate fifteen milligrams per week in combination with pegylodecase. So the six months data had been previously reported and this poster now reports the twelve month data. So essentially 14 participants in this study at six months, seventy nine percent of patients had a response. So that's certainly higher than what has been seen in previous trials. And in the open label extension or the long term extension, all of those who remained in the study who were responders at six months continued to have a response out to twelve months.

So certainly emerging data that methotrexate may be affected in this situation. We don't have any good clinical trial data yet, as in placebo controlled trial data, but certainly some data to suggest that that's a reasonable or a potential option. The other agent is mycophenolate and the recipe trial was presented at the ACR. This is abstract nine fifty two presented by Doctor. Purjukana today.

So this is a phase two placebo controlled RCT where participants were randomized two to one to receive either mycophenolate or placebo in addition to peglodecase. Patients received mycophenolate one gram daily for one week, and then two grams daily thereafter. And the primary endpoint was the serum urate response at week twelve. Thereafter, from week twelve to week twenty four, participants continued with peglodecase but the investigational product was removed. So that was the peglodecase monotherapy.

So the key findings from this study is that mycophenolate in combination with peglodecase led to a significant increase in response. So in the mycophenolate group, eighty six percent achieved the primary endpoint compared to only forty percent in the placebo arm. And interestingly, even after mycophenolate was withdrawn, there was a sustained response in many of those patients. So at the weeks twenty four time period, there was a sustained benefit in sixty eight percent of the mycophenolate group and only thirty percent of the placebo group. Overall, the AEs were comparable.

There were three infusion reactions in the placebo group and none in the mycophenolate group. So overall, I think this is really exciting. Certainly a potential option for increasing the response to B. Do respond leads to really substantial reductions in serum urate, reduction of TOFI, and suppression of gout flares over time. Thanks.

Hello, I'm Rinalini Day and I'm an academic rheumatology trainee based in Liverpool in The UK and I'm reporting from ACR 2020 for RheumNow. Today, I'm delighted to be joined by doctor James Galloway, who is a senior lecturer and honorary consultant in rheumatology at the Centre for Rheumatic Diseases in King's College London, and he has an interest in infection in rheumatic diseases, it's this that we will be discussing today. So thank you for joining me, Doctor Galloway. Firstly, can you tell us a little bit about how over the last year Covid-nineteen has changed your research and clinical practices?

Well yes, I mean the impact has been phenomenal I think for all of us. I recall doing a journal club I think in January where we talked about things that were going to be on our horizon this year and came up with vaping vaping associated lung disease and this new virus that was emerging in China, and I think we spent most of the time talking about EVALI, the vaping associated lung disease, and obviously we're then within a matter of weeks after that overwhelmed by the pandemic. My research team has almost entirely got redeployed from doing our usual rheumatic disease research to doing Covid-nineteen research, although there's a lot of synergy there because of course we've set up one of The UK national platform trials called the TACTIC trial where we are looking at immune modulation in COVID and so there's sort of an expertise from the rheumatic disease field that has come to that. And of course from an academic perspective my research interest is epidemiology and so there's a synergy there that we've been able to adapt and been doing epidemiology work around Covid-nineteen.

Fine, great and something which you alluded to just now is the interplay between rheumatology and infectious diseases. Could you just expand a little bit on that further, and maybe if you could tell us about any abstracts that particularly caught your attention with regards to that at ACR?

Yeah, I think there's a long standing interest between the overlap between rheumatic disease and infection because so many of our treatments alter the body's immune system and potentially alter people's susceptibility to infection. Also I think that just the nature of having an autoimmune disease changes our immunological response to infectious insults. Actually there is an ACR abstract committee group that looks at infection and autoimmune disease, Cassie Calabresi and I oversee, and there have been some, I mean normally it's a relatively niche area in terms of submitted abstracts, and obviously this year there's been a huge wealth of some really great research come through. Can I flag there's a few that I think are really interesting? The first one, and it's easy to remember, it's abstract number one Jas Singh, who has presented the data from the Veteran Affairs database, just looking at describing the impact of the pandemic on care.

One thing, and it's great abstract they put together, one thing that struck out to me was the fact about medication shortage. They highlighted that a third of respondents to the work they've done highlighted medication shortage as being an issue during the pandemic because of course we saw this massive interest in drugs like hydroxychloroquine for being repurposed for treatment of Covid or prevention of Covid, rightly or wrongly. The second I wanted to flag and this is a slightly self promotion but there was on Friday afternoon an oral presentation which I moderated on infection and rheumatic disease, and there were some really great abstracts in there and I don't want to say that any one was better than the other. Abstract was by Rachel Flood from Dublin looking at a cohort of people who had been admitted with Covid, who'd had Covid. They had community data on Covid and hospital data, and they looked at whether or not being on biologics or being on immune modulation altered the chance of getting a severe outcome or dying from Covid.

Like we're seeing across the board, there appears to be some protective effect of being on immune modulators if you develop Covid in the community. They start to sound quite novel though that I hadn't seen reported by anyone else, which was nosocomial Covid appeared different. So people with autoimmune rheumatic disease who acquired nosocomial Covid acquired Covid-nineteen diagnosis whilst an inpatient had worse outcomes and that was an interesting, a very interesting observation. I'd encourage people to look at that abstract. And then the final one, so that abstract number was four fifty four, and the final abstract is one of the late breakers, so it's easy to find under the name Mark Yates, and that was a very nice piece of so not in that session.

It was looking at shielding behaviour and whether people with autoimmune rheumatic diseases shield. And what's really interesting, think, you look at the data, multiple data sets, the registries under the data sets that have suggested people with autoimmune rheumatic disease on biologics who are on target of therapy may be less likely to develop a severe course of Covid. However, one of the great confounders in this is being exposed to how many of them were actually exposed to Covid, and what Mark Yates's work does is it's a large international it's a global survey looking at shielding behaviour, showing that people on biologics compared to other people with autoimmune rheumatic diseases were much more likely to adopt this behaviour where they were in The UK we use the term shielding, it's not used globally but they were basically taking extra caution around their exposure to Covid. So it's possible that some of the potential protector effect of the drugs may be behaviour related. Really interesting abstracts.

Great, thank you. Actually, the infection related rheumatic disease oral session yesterday was really interesting. I'd encourage people to go back and watch that on demand if they can. And it's interesting what you say about the availability of drugs globally as well. I think I saw a poster in the infection session on drug availability from the Aflar group.

So certainly there seems to be a lot of regional variation in that it's quite interesting to see. But I guess that's the beauty of ACR where you get all of this culmination of global information so you can compare local practices with what's going on worldwide. So thank you very much Doctor Galloway for joining us today. And don't forget, if you want to be kept updated during ACR twenty twenty, you can follow me at Doctor Mini Day on Twitter, or you can follow the RheumNow Twitter feed. And thank you very much for watching.

This is Doctor. Catherine Dow reporting for RheumNow. I'm at the ACR twenty twenty convergence virtual meeting. And I want to share a study with you, that was conducted by Jeff Curtis, and he's looking at male osteoporosis. Now this is a topic we don't talk about, but it's one of the things that we have to, be aware of and we have to make an impact because this is a study looking at older male adults, right?

So it's a Medicare population group and they identified men who had osteoporotic or fragility fractures. And they found there were nine thousand eight hundred and seventy six men who suffered from fragility fractures. About sixty one percent of them were over the age of 75 years old. Ninety percent of them were white. There were more instances of spine fractures compared to hip or ankle fractures.

And this is the shocking part. Less than six percent of patients actually had testing with a bone density, DEXA or other means to assess bone density within two years of their fractures, less than six percent. So male osteoporosis is often underdiagnosed. We really need to be vigilant because the same risk factors apply to men as they do for women. And that risk includes age, the use of glucocorticoids.

I mean, think about how many patients you prescribe glucocorticoids, you know, for rheumatoid arthritis, polymyalgia rheumatica, giant cell arteritis, vasculitis, sarcoidosis, and also other risk factors, traditional ones like smoking, alcohol consumption of three or more drinks a day, the presence of a family history of fractures. So think about these patients. Men also have osteoporotic fractures. And then if you're in doubt whether or not you should be treating them, use a FRACS calculator. This is Doctor.

Catherine Dao for RheumNow. Follow me on Twitter kdao2011.

Good evening. This is Leanne Gensler from San Francisco reporting for RheumNow on spondyloarthritis at the ACR twenty twenty convergence meeting. Today's meeting, this is the second day of the meeting, and for spondyloarthritis there were no scientific oral abstract sessions today. However, there were a couple of abstracts that caught my eye in the poster session that I thought I would discuss, and then I'd also like to discuss the study group that was in a session today. So in the posters today, there were the two abstracts that caught my mind.

The first one is eight seventy six, and this was presented by Marina McGray from Case Western Reserve University on behalf of all of the coast investigators. So this was a study that integrated the results of all patients enrolled in the ixekizumab trials for axial spondyloarthritis, including those with ankylosing spondylitis and those with non radiographic axial spondyloarthritis. And in this study, one of the things they noted was that there were not unexpectedly more men that enrolled in the AS trials compared to women, but actually in the non radiographic trials, it was relatively equigender. Not surprisingly, women tended to have a later onset of disease compared to men, and that's something that has been reported before, and women tended to be less frequently HLA B27 positive and non radiographic patients were less frequently B27 positive compared to the AS patients. Now that is not entirely surprising either because remember that this is not daily practice and the way we see patients in clinic, this is a clinical trial recruiting patients with active disease.

And so in particular, the non radiographic patients really required an objective sign of inflammation, and that was either an MRI that was positive or a CRP that was elevated. And so we know that women tend to have lower serologic burden of inflammation or CRPs, and you might imagine that they might be more likely to have an MRI that's positive to get into a trial like this. The other interesting point was that uveitis was more common in the male patients with AS, and that is also not surprising in that, again, B27 associates with uveitis in patients. So I think this was an interesting study in looking at the phenotype of patients with axial spondyloarthritis, but recognizing as well that this is a clinical trial and may not represent daily clinical practice. The second abstract that caught my eye was the follow-up of the C VUE trial.

So this is abstract number eight eighty one, and this was a phase four open label clinical trial of patients with active axial spondyloarthritis that were being started on socilizumab pegol, but they required to have a history of recurrent anterior uveitis in their past, and in fact, at least one of the uveitis attacks had to be in the year preceding enrollment. And they then followed patients for ninety six weeks, and the question was, did they have less flares, sort of the flare rate or event rate in the follow-up period compared to the period before starting therapy? And they met their primary endpoint, but keeping in mind that every patient had to have flared in the year preceding the enrollment to the trial, it isn't surprising that patients had less flares after follow-up because that is just the natural history of uveitis being a remitting process. And so the question is, does cetilizumab pegol truly decrease the rate of flares in patients with axial spondyloarthritis and a history of flares? Now interestingly, they looked at patients sort of stratified by whether they had one flare or two flares in the prior year, and of the thirty six patients or forty percent of patients that had one flare, then nine percent of them had a flare in the follow-up period, and interestingly, sort of similarly, of the sixty patients that had at least two flares, eleven percent had a flare in the follow-up period.

So that is certainly a lower number than the eighty percent that had a flare in the prior period, but I'm not sure that this truly is evidence that it prevents flares as opposed to regression to the mean still, and I would recognize that this is not controlled data, and I would love to see some controlled data against this. I do think this follows the guidelines, though. Guidelines do recommend a monoclonal antibody for those patients with active axial spondyloarthritis and recurrent uveitis. So this is in keeping with what we currently recommend, but I think we do need more stronger evidence to truly say that this is as good as the other monoclonal antibodies that have strong evidence for anterior uveitis treatment. The final session that I wanted to highlight today is the session on the study group for spondyloarthritis, which really dealt with nomenclature and what are the terms we should use to define the disease of axial spondyloarthritis, and the question of whether to use non radiographic axial spondyloarthritis and ankylosing spondylitis instead of, or rather the newer term radiographic axial spondyloarthritis.

What wasn't discussed, but which I think is incredibly important, is that seronegative is a term that should never be used for this disease state where there is not an antibody to test for. That is an archaic term really relevant for rheumatoid arthritis, and spondyloarthropathy, which really has gone by the wayside, though you still see people use that term in the setting of talking about spondyloarthritis. So the gist of it is that ICD-eleven, which is coming, really is going to help reshape the terminology a little bit, where now we'll see axial spondyloarthritis as the leading term, and then you'll be able to define it potentially by whether patients have damage or not, and I think that's similar to the way we think about other disease states, where the disease is defining the term axial spondyloarthritis. This is one disease state, and then you can qualify it with prognostic features like radiographic damage or not. So that's it from Ami for spondyloarthritis at the meeting today.

For more information, please go to RheumNow. Thank you very much.

Hi, I'm Doctor. Janet Pope at RheumNow, and I'm joined by an ACR ambassador, Doctor. Jeff Sparks, and we're going to talk about ACR twenty twenty. So thanks for coming on board, Jeff. I'd like you to tell me about where the field's going with interstitial lung disease and rheumatoid arthritis, because you and others have some pretty exciting abstracts at ACR twenty twenty.

Sure, and thanks for the opportunity, Janet. Think interstitial lung disease has obviously been known about a long time in rheumatoid arthritis, and it seems to be a bigger deal now. And I think it's because it's probably one of the few things that's not getting better with rheumatoid arthritis despite all of our armamentarium. And what we've also found is that there seems to be a large spectrum of, lung abnormalities in rheumatoid arthritis. And it doesn't just seem to be parenchymal abnormalities, it also seems to be related to airways.

And this is particularly intriguing since, lung inflammation, in particular mucosal inflammation in the airways may actually be part of a RA pathogenesis where autoantibodies are made years prior to clinical onset. So our group has really been trying to understand this quote respiratory burden of RA, and also try to dissect sort of what part of the lung is affected and why is that? I think the first thing people think about is maybe it's all due to smoking. Smoking is a known risk factor for rheumatoid arthritis and obviously it's bad for the lungs. So that was really the first question that we wanted to figure out is, are these manifestations really just explained by smoking?

And what we found is certainly there's some explanation due to smoking, but there's really still a large part of rheumatoid arthritis lung disease that seems to be not related to that. And it's not just a parenchymal lung disease, it's also obstructive lung disease. So there's really a spectrum where patients might clinically act like they have COPD or asthma, and it could actually be a manifestation of RA. Certainly there's some patients with that might have mild interstitial changes that aren't symptomatic. And we have to really work on trying to figure out who are the ones that progress those things that are clinically significant.

So there's really a lot of work to do and it's an exciting field.

So one thing it seems at this meeting that when you did a large study, you found, I think it was a few three to six percent, depending on how you cut the data of interstitial lung disease, UIP.

Can you

tell me more about that study and what the take home message might be?

Sure. Well, we've been finding interstitial lung disease within our BRAF cohort here at Brigham Women's Hospital. And then we've also been using other data sets. So within our BRAF cohort, we really do a lot of work to try to find, you know, really granular detail about trying to find when our ILD develops and what the severity is. For this meeting, we've also branched out to looking at administrative claims databases, which obviously have advantages in numbers.

And we recently validated an algorithm where we're able to look at the incidence and prevalence of RA ILD throughout all of Medicare. Obviously, that's really The entire US over the age of 65. And what we found is that nearly five percent of patients with RA had what was validated as a clinically significant ILD. So this is not a rare issue.

And that would be certainly up to my experience that I think ILD is more common than that, but clinically relevant, probably five percent. And I think of it in, I realize you're going to prove me wrong in a second, but I always used to think of it in longstanding, strongly seropositive, RF, ACPA or both, a bit more common in men than women. And that in some people it's a long, long time, but certainly does lead to decompensation and death. So am I thinking about it the right way or is it incident far earlier than what I'm suspecting?

Well, I think that's what our group is trying to understand and shed some light on novel risk factors for rheumatoid arthritis. Certainly longstanding RA and older age and smoking were really the risk factors that have been known for several years. And maybe the epidemiology is changing. Again, it does seem like the prevalence of ILD is getting worse actually with calendar time. So I think this is really a good time to try to identify new risk factors.

Some other abstracts have actually shown that this can happen pretty often within early RA, about half of ILD seems to occur within two years of clinical RA diagnosis. And then our group here at this meeting looked at other risk factors. We found that high disease activity, high CRP, high MDHAC, obesity. And we also found that a threshold of smoking above 30 really seemed to increase the risk of RA ILD. So if you have an RA patient who's smoking, but but they haven't hit that thirty pack year threshold, that's really the time to try to get them to quit smoking.

Right, never too late to quit and never too early is better of course. And then I think it leads to treatment. I know at EULAR and in some recent publications, it looks like I think we can say that methotrexate does not cause or exacerbate ILD other than that acute bilateral pneumonitis, which is a different problem. However, when someone's on methotrexate and they have ILD and breakthrough, I realized we're not sure what to do. So there was an abstract, someone had that abatacept looked like a reasonable treatment.

Historically, thought of using rituximab and less so we kind of think that the TNFs might be a problem. So shifting gears, I certainly can say that the ILD and RA is different looking than in systemic sclerosis. In systemic sclerosis, it's usually about fifteen percent of patients where it's clinically relevant, about double that who really actually have it And we tend to think of it starting early and losing lung function early and then it might level and then maybe you aspirate or have pneumonia or something happens or have a bad cold and then you lose ground again almost stepwise. And certainly, there are treatments that we think of such as MMF, so immune suppression, the way we think in RA and cyclophosphamide like an RA and then entendonib has data both in, significant ILD in systemic sclerosis and then they did that other study in RA. So I think we're unraveling it and I think your group and other groups are also saving serum where possible in the brass cohort for genes like that MUC gene and other things.

So hopefully we will have a chance of unraveling more and treating our patients more effectively.

Well, absolutely. We're certainly learning a lot from systemic sclerosis related ILD. You guys are leading the field, but obviously they're different diseases. So you can't necessarily think that everything that works in systemic sclerosis will work in RA. I think it really is exciting that it seems like beyond MMF and Rituxan that Avatacep certainly seems promising, but obviously you really need trials to really understand how to best treat these patients.

It's a tough disease to diagnose as well, and how these medications might affect risk for ILD is also up in the air. There are trials ongoing about anti fibrotic in RA, but certainly it would be interesting to look at, you know, some of the other medications that rheumatologists often use to see whether they could help with the ILD disease course.

Absolutely, and we think it's quite serious, a serious complication in both RA, which can be lethal for sure over time and in systemic sclerosis we have an abstract looking at incident population based from a claims database and in over three thousand patients with systemic sclerosis in Ontario over about the last ten years. You have ILD then really your survival is only fifty percent as high so you double your mortality over the next five to ten years. So very serious complication of both our diseases.

Yes, and our abstract in Medicare also showed around a twofold risk of total mortality, even in older patients who already have a high risk for mortality. And then we also found the expected increased risk for respiratory mortality, but we found a novel risk for cancer mortality. So I think that's actually gonna be a new angle about how to treat and manage our patients about whether these patients are at risk for cancer.

And it wasn't just lung cancer, think, in your study, it was all cancer mortality?

It It was total cancer mortality correct.

Yeah and then when you adjust for smoking who knows what will happen but I think it still exists.

It still was present so I think it's important these patients you know really have a serious disease and we got a lot to do to uncover it.

Well, let's hope that our fields move forward and I think they're continuing to do so. And thanks everyone. Please go to RheumNow and thanks for attending the ACR twenty twenty Convergence meeting. Thank you.

Hi, I'm Doctor. Sheila Reyes from The Philippines reporting for RheumNow from ACR twenty twenty. I'd like to discuss the skip pain trial by doctor Dennis Vademi and colleagues with abstract number zero eight nine nine presented during the poster b sessions. Spinal pain in axial spondyloarthritis is a common complaint and can affect the quality of life in these patients. This study evaluated the efficacy and safety of secukinumab in reducing spinal pain and disease activity following a step up dosing approach.

SCIPPain is a randomized double blind multicenter study that enrolled patients with axial spondyloarthritis with active disease defined by a best eye score of more than or equal to four with an average NRS more than four and inadequate response to two or more NSAIDs more than four weeks apart. Patients were randomized to receive subcutaneous secukinumab one hundred and fifty milligrams or placebo weekly, then every four weeks at week four. At week eight, placebo patients were re randomized to either secukinumab one hundred and fifty milligrams or three hundred milligrams up to week twenty four. On the other hand, patients who were originally randomized to secukinumab one hundred and fifty milligrams were further classified into responders or non responders based on their spinal pain NRS course. Responders were then reassigned to continue treatment with one hundred and fifty milligrams every four weeks up to week twenty four, while non responders were re randomized to receive treatment with one hundred fifty milligrams or a step up dose of three hundred milligrams up to week twenty four.

Now for the results. The primary endpoint was met with the proportion of NRS corresponders favoring secukinumab over placebo. At week twenty four, further reductions in spinal pain was noted across treatment groups, especially those who were switched to the active drug at week eight. There were also pronounced improvement in SDAS CRP scores. No new or unexpected safety signals were reported.

In conclusion, secukinumab provided rapid significant improvement in spinal pain and low disease activity in patients with axial spondyloarthritis. I think this trial is worthy of our attention for two things. One, compared to other clinical studies in axial SpA, this used spinal pain as their primary endpoint. And two, results are interesting to take note of because it provides clinicians an option for dose escalation of secukinumab in patients not initially responding to the drug. Follow me on Twitter at RheumOrampa and tune in to RheumNow for more videos and reports.

Thank you.