ACR20 - Day 3.3 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. I'm doctor Janet Pope here at RheumNow at ACR twenty twenty, the virtual convergence meeting. I'd like to talk to you about something that will change my practice. So I'd like to ask you, do you actually routinely take a vaccination status and have your immune suppressed patients with RA, lupus, other diseases get vaccinated against pneumococcal pneumonia. This is a common pneumonia and there were two sessions or two abstracts that are important in a live session, Abstract four fifty six and four fifty seven.

In Abstract four fifty six what they did was they looked at their patients who got pneumococcal vaccination, albeit it might be a different one than what you use in your country. But in general, they vaccinated the patients who were higher morbidity, more comorbidities, more corticosteroid use, things like that. When they looked and matched the vaccinated patients with the unvaccinated patients, they wanted to look at would pneumococcal pneumonia decrease further pneumonias. And they had five ninety five vaccinated patients with rheumatic diseases and the non vaccinated references were one hundred and three patients who had infections before vaccination, forty eight of the five ninety five that were vaccinated and one hundred three of two thousand three and seventy nine who were not vaccinated that had had infections prior. Then they looked at the event rate after vaccination for up to ten years and they matched on risk factors.

And the bottom line is even though the patients who were vaccinated were higher risk for infection, they had less infection with almost a fifty percent reduction of infection. They had time to first pneumonia being less. And again, when you match for the variables, this still was statistically significant and clinically relevant. So for me that'll change my practice because I really have to go back to my clinic next week and start asking about vaccination status and just getting on with vaccination. The next study was showing us how we could implement this.

So Abstract four fifty seven was a presentation looking at whether or not they could increase pneumococcal vaccination rates in a regular clinical setting. And they did a series of quality improvement implementations. And like anything, if you talk about it, it's more apt to happen with the patient. But if you facilitate it, it's even more likely. So a few things that I do in my practice and will continue to do better is systematically ask annually, ask my high risk but all my patients with rheumatic diseases over a certain age such as 40 and look at putting signs up in my clinic room when I'm seeing them non virtually, also writing a prescription or even better having the pneumococcal vaccination ready and out of hand.

If you need to know more about this CDC has guidelines for pneumococcal vaccination for our immune suppressed patients. Thank you. I hope you're enjoying ACR twenty twenty convergence and follow us at RheumNow and my Twitter is janitburdope. Thanks.

Hello, everyone. My name is Jeff Sparks. I'm a rheumatologist here in Boston, Massachusetts, and I'm coming with you for RheumNow. I'm very pleased that doctor Jack Cush invited me to chat about things. So this is day two of ACR.

Obviously, it's a new experience with the virtual format. And what's on everyone's mind, at least related to rheumatology, is how COVID has impacted both our meeting and our profession. I know we don't like to think about it that much, but I think I'll spend this video sort of summarizing some of the key abstracts that I found related to COVID. I think today is actually, you know, has a lot of really impactful abstracts that potentially practice changing and certainly our patients are asking a lot about a lot of these issues. And the first is whether COVID actually affects rheumatic diseases differently than the general population.

So there's in particular two main abstracts that delved into this question. The first is a plenary today. This is abstract number four thirty. This is presented by Doctor. Kristin D'Silva within a large database that's basically been updated in real time.

And these investigators found rheumatic patients infected with COVID and then matched to comparators without COVID. And they really looked to see about hospital outcomes, hospitalization, ICU, thrombosis, acute kidney injury, CHF, and actually they found that our rheumatic patients were across the board more likely to have those outcomes compared to general population comparators. The only outcome that was not significantly associated was mortality. This is a this is the largest study looking at this and in a way it's counter to some of our information showing that maybe things were similar. And I think we all in the back of our minds always wondered whether it's actually a bit more increased and maybe the previous studies were unpowered to see that.

So this does appear that our patients might be a slightly increased for worse outcomes. It's not clear exactly why, and obviously there's some heterogeneity within diseases or medications, but I did think this was a fairly definitive study. Along those same lines, another abstract presented as a late breaker, abstract L01, pretty similar methods, a smaller sample size. I'll mention that I'm actually a co senior author on this study. So this was finding patients at partners here in Boston, which includes Brigham Women's Hospital, Mass General Hospital, finding all of the infected patients with rheumatic diseases, comparing those to general population comparators, looking for outcomes.

The difference for this one is that, we also did find an increased risk particularly for mechanical ventilation. However, that increased risk for, rheumatic diseases actually went away later in the pandemic. So as we've gone on, as we've learned more about the virus, as we've learned how to treat it, it does seem that maybe this increased risk for rheumatic diseases might be the playing field might be leveling, which is, I think, encouraging now that our capacities are better, treatments are better, maybe our patients actually will have pretty similar outcomes when it comes down to it. Some other things that obviously are not on people's minds are what are the factors that predispose patients to poor outcomes. One that's been written about a lot in the general population are race and ethnicity that hasn't really been delved into within the rheumatic disease population until now.

Abstract number six looked to see whether race and ethnicity was associated with poor COVID outcomes within rheumatic disease population. This was a global rheumatology alliance, and it did show that compared to whites, black patients as well as Hispanic patients were at had increased risk for poor outcomes. And then we start thinking about other disease characteristics that might change things, in particular whether targeted therapies might increase risk, either actually have a better hospital course or maybe even a worse hospital course. There's been some previous studies showing that targeted therapies actually have improved outcomes, but those are obviously pretty heterogeneous with different mechanisms of action. And then a abstract number 14 actually looks to try to disentangle some of the mechanisms of actions of biologics to see whether that could affect COVID outcomes.

And that showed that perhaps Rituxan does have a particular increased risk for poor outcomes. So even though that's a targeted medication, obviously, it really turns off an important part of the immune system, particularly related to viruses. So I do think it is something to think about for our patients on Rituxan. And obviously it's got a long half life so even if you wanted to switch it or stop it or patients were worried about it, know the drug is still in their system so that's something else to keep in mind. Speaking of DMARD changes, I think we've all wondered exactly what's happening at home.

Abstract L05, a late breaker, delved into what happened at home as far as DMARD changes. I think it really told us what we already thought, that patients really are changing things, they are, you know, wary to continue medications, if they think that they're in disease control they might be more likely to skip some doses, so this is definitely something that I think is on a lot of people's mind, a lot of patients' minds. And then the other thing are the social distancing behaviors. Does this affect patients with rheumatic disease differently than the general population? And is this why it's hard to find differences?

So late breaker l zero two delved into this, and as expected, certainly patients with particular underlying rheumatic diseases, patients who are particularly frail or vulnerable, patients on potent immunosuppression certainly do seem to be more likely to stay at home, to wear masks, to socially distance. And I think this is really just quantifying really what we have thought all along. But this does give you stuff to talk about to patients and their clinic. So all in all, I think this has been a, you know, really obviously insightful meeting. COVID's changed everything and we're really getting data to understand patient outcomes, understanding the heterogeneity within rheumatic diseases and how that could affect outcomes, and then understanding, you know, whether things like Rituxan put people at particular risk, and how patients are behaving at home.

So I'll be looking forward to more videos and telling you my thoughts about some of the highlights of the meeting. We'll see if some more COVID abstracts come up, but we'll think about some other themes for future videos. So again, thanks for your attention, and thanks to RheumNow for the opportunity.

Hi, ACR twenty twenty. I'm Doctor. Rachel Tate coming to you from my home in West Palm Beach, Florida. Doctor. Vladimir Lajarski discussed 11 pearls for outpatient billing and coding from ACR session 3S017.

Now, 11 is great, but I want to take a couple of minutes to highlight just a few of these for your importance. Number one, a new patient is someone you have never seen or with whom you have not had a visit in three years or longer from the actual date of visit, and this includes inpatient visits. So just remember that. Number two, an alternative strategy for your HPI is actually listing the problems and then adding a brief separated history for each of those particular problems that you can do instead of the novel esque storytelling, which I like to do. So consider this for your charting purposes.

Number three, in order to gain points for record review or vaccination records, reviewing labs, imaging or taking history from another person who's in the room post COVID after obviously all of this, but from another person who's in the room, you can also make sure, and you need to do this, you need to make sure that you state the context and the date of all of that information. It's not enough to just state that you did this. Number four, I'm gonna call these easy points. Easy points, social, family, and smoking history. All of these you need to include in your HPIs or pardon me, not in your HPI, but in your actual documentation because you can be penalized if you forget them.

Underbilling to CMS is just the same as overbilling, so don't do it. Overall, remember that good medicine does not imply good billing and vice versa. So these are just a few quick tips that I learned from Doctor. Lajarski, pardon me. For more information and news from ACR Converge, be sure to visit us at roomnow.com and follow me on Twitter UpToTate.

Good evening. I'm Jonathan Kay from the University of Massachusetts Medical School in Worcester. And I have here several colleagues from the rheumatoid arthritis faculty for RheumNow. It is Saturday, November 7. And we've all spent a day, the second day of ACR convergence twenty twenty, sitting in our offices at home watching our computers.

And there have been a number of interesting presentations. So I have here David Liu from Australia, Eric Dine from Baltimore, Sheila Reyes from The Philippines, Jeff Sparks from Boston, Richard Conway from Ireland, and Moral from Cleveland. So we have representation from both blue states and red states and allies of The United States. So we've all been attending the ACR Convergence. David, let's start with you.

What abstracts piqued your interest today?

Well, was one other poster for that I found quite interesting. It was from Leeds and Paul Emery's group and they've done over time a lot of work in the space regarding clinically suspect arthralgias. These patients with musculoskeletal symptoms inflammatory sounding arthralgias who are ACPA positive. And the question has come about, I mean, over a whole series of different things, what should we be doing in these patients? Well, this looked in particular at the value of plain film x rays.

And that might not sound like a big deal, but I guess we shouldn't be doing more investigations than we need to. I think we're thinking more about over investigation. And then also really thinking about, yeah, how does this change our management? So they looked at x rays done in these patients to see whether they predicted clinical synovitis in the future. So essentially, we're able to predict what might look like the progression of inflammatory arthritis in the future.

And what they saw firstly was that only four percent of that overall cohort of clinically ACMA positive clinically suspect arthralgias had erosions. But more importantly, the presence of erosions didn't predict whether a patient would go on to develop an inflammatory arthritis or not. So that's really challenged my thinking about what to do with these patients. I think we often feel a little bit vulnerable. We know that we probably shouldn't treat them.

We're not really sure what to do with them. And perhaps sometimes we order an x-ray out of desperation as not knowing what to do. And I don't think that necessarily adds anything at this point.

There was another, I think it was a poster that came out of Daniel Alataja's group in Vienna that looked at patients who had erosions and joint space narrowing. And they looked at a cohort of patients from Vienna, over 700 patients, and they found that joint space narrowing preceded the development of erosions and that seropositivity and seronegativity had nothing to do with progression. They also found that patients with baseline damage were more likely to progress. That finding in itself, it's not terribly novel, but the fact that joint space narrowing proceeds erosions suggests that cartilage damage might be a process either independent of or possibly related to the bone loss that you see in rheumatoid arthritis. So Eric, how about So

I was just gonna add on to that. I thought that poster was interesting with looking at those patients with bone erosions because, I mean, it was only four percent of the patients. So the numbers was seventeen patients. I mean, one of my takeaways from that was just that if you have arthralgias without synovitis, even if you're CCP positive, there were just so few patients in that group that it's pretty reassuring that they're not likely to have erosion, so you should get the radiographs. Particularly, I think seventy percent of them, sixty five percent of them were in the feet.

So making sure you are imaging the feet if you're gonna do images, but it's pretty reassuring that so few of them had erosions. I don't the finding that you can't really predict with it just because the number was so small. I think it's harder to interpret moving forward how to treat those patients.

Sure, the point that you make about looking at the feet is very important. There are patients that have no erosion change in the hands and wrists, but have erosions in the feet. So always get those foot films when you're working up your patient with rheumatoid arthritis. Sheila, how about you?

Yeah, well, basically it's we've all been interested in the same abstracts on biomarkers. Yeah, well aside from that, aside from the joint space narrowing and the x rays, there are also interesting abstracts on rheumatoid factor using the RF titers and one particularly that piqued my interest was that about the anti peptidyl arginine deaminase antibodies, the anti PAD antibodies where they saw a third of patients that were at risk for RA and a third of patients with clinically suspect urologists were reported to have these antibodies. And so you see here possible implications as a predictive tool of these antibodies. So I'm excited to hear more about that. And again, we see here how there's an increasing trend toward focusing on the identifications of patients at risk for disease progression and who would benefit from early intervention.

I'd also like to add that there was the session on difficult RA, difficult to treat RA which was equally engaging which mentioned or talked about ILD, refractory disease and liver disease.

So now that that three letter term ILD came up, let's turn

to If Jeff

you'll forgive me, I'm going to not talk about ILD and I'm actually going to talk about an abstract from yesterday. I was moderating yesterday. And so this morning, the beauty of a virtual meeting, could basically attend as if I was there. I wanted to talk about what I thought was one of the highlights, which was, DMARDs and incident dementia risk within RA patients. I mean, I think this panel would all agree that RA is particularly interesting to study given how inflammation is important in every organ system and how it can tell us about how the pathogenesis of types of diseases.

It's also very interesting to repurpose our drugs for different reasons, even though we're prescribing them to treat joint pain. We all know that there's probably systemic inflammation, there's inflammation in other organ systems. So this was led by Doctor. Sebastian Satoui and colleagues. It was a Medicare database.

So really obviously big numbers and they really looked at drug classes, biologics versus conventional synthetic DMARDs and pretty remarkable reduced hazard ratio for incident dementia risk. Obviously it's a claims database study, so it's not causal. There's obviously more work that needs to be done, but I think this is a really novel path both for our patients as well as the general population about how our drugs might affect neuroinflammation.

Since it was a claims database, they weren't able to assess the effect of these drugs on inflammation in individual patients or even across the population. It's interesting to speculate that perhaps chronic inflammation drives amyloid formation. We know that amyloid deposits in the brain in Alzheimer's disease, and I wonder if there might be some increased amyloid formation SAA in these patients that's being suppressed better by TNF inhibitors than by conventional synthetic DMARDs. It'll be very interesting for someone in neuro and immunology to pursue the topic of trying to work out mechanism. Perhaps some animal models will be relevant.

So I'm already leads the way.

Absolutely. Richard, how about you?

Yeah, I found a couple of interesting posters in the real world data session. And the first of those was by Doctor. Movahadhi and colleagues from Toronto. And they were looking at time to discontinuation of patients on either tofacitinib or TNF inhibitors, either as monotherapy or co prescribed methotrexate. And so coming back to what was talked about in the great debate and what should be our first line biologic in some ways.

And what they found was this tofacitinib, it didn't seem to matter in time to discontinuation, whether you were on methotrexate or not, whereas with TNF inhibitors, time to discontinuation was longer if patients were co prescribed methotrexate. And the second very interesting poster I saw was from Doctor. Dalal from Brown University. And they were looking at patients with rheumatoid arthritis, elderly patients, so over 85. And they found that eighty five percent of those patients in the first year after they were diagnosed with rheumatoid arthritis did not start on a DMARC.

And to me, that's quite a scary thing. If eighty five percent of this population, not an appropriate treatment for the rheumatoid arthritis, it'd be interesting to explore further why that might be.

Absolutely, and try to come up with interventions to hasten the referral of patients for the appropriate DMARC therapy. Morell, you're muted.

All right, can you hear me now?

Absolutely.

Okay. Well, I was really excited about abstract nine fifty two, which was recently actually just presented at the 05:00 hour 05:20PM by Doctor. Pooja Khanna of the University of Michigan. It's titled reducing immunogenicity of peglodecase or the recipe study with concomitant use of mycophenolate mofetil in patients with refractory gout. It was a phase two double blind randomized control trial and its primary objectives were to assess the feasibility and efficacy of MMF to achieve a serum urate level of less than six at week twelve.

It also had another primary outcome of assessing the instance and type of adverse events potentially associated with MF. And the results were actually really intriguing in that it did show at week twelve, a reduction in serum urate in nineteen of twenty two of the patients in the MMF peglodecase arm. So eighty six percent in the MMF arm achieved the primary outcome at week twelve, comparatively to the placebo arm where only forty percent met that outcome. Even more so, they stopped treatment with MMF at week twelve and thereafter they saw still a sustained benefit maintained at twenty four weeks in the MMF arm. So then the question becomes, were there any changes in terms of the adverse event profile?

And actually the estimated rates of adverse events were comparable between the two groups. And even more so interestingly, they saw reduction in the number of gout flares every month in the MMF arm. So I think this is potentially practice changing. It's a small sample size, so the status should be validated in a larger study, but it's really exciting stuff.

Absolutely. That's a big problem with use of that drug. Peggoticase in treating gout, the potential immunogenicity and loss of efficacy. So that's an interesting study. So no one has mentioned scene.

I think the plenary abstract today, we don't have to go into it because I think Richard filmed an individual discussion of that presentation and I did as well. And perhaps we have a third. So if you go to RheumNow, you'll be able to see several discussions of that plenary abstract. So we can probably avoid discussing it now. But I'd like to bring up a post oral presentation that was given by Elizabeth Siakta from Cos Petalis Group at the William Harvey Research Institute in London.

As almost everyone knows, Pitcellus's group has divided rheumatoid arthritis into several groups based on synovial biopsy. And what Elizabeth did was she looked at network analysis to work out networks of protein interactions in each of the different subtypes. She then subtracted from those networks, the common features so that she had differential networks for each of the three different pathotypes. And then she was able to come up with a way of associating response to treatment with conventional synthetic DMARDs with these various biomarkers. This is very similar to the commercially available tool that's been developed by Cypher, which is a genetic profile that predicts non response to TNF inhibitors, and potentially might save money by choosing which patients should not be treated with a TNF inhibitor so that you can pick patients who will respond.

It'll be very interesting if this work from Petsalis group could identify patients who might respond inadequately to methotrexate early on before waiting for a six month trial, or a four month trial. And you could start biologic therapy or other agents, either in addition to methotrexate or instead in that group. So using this kind of non biased machine learning to understand networks in different pathologic subtypes of rheumatoid arthritis might lead to a clinically useful tool.

Absolutely. I mean, I think the exciting bit about this is that we're getting to the point where we previously, I guess we thought about it phenotypically and we've got a whole bunch of diseases which we label as rheumatoid arthritis. Then we start getting to this deep phenotyping and then something which is actually potentially meaningful by the bedside to be able to have a have a tool where we can try and unravel that a little bit more. At the moment, I still feel like we're, a lot of the time, guessing in terms of what the response is going to be. So to be able to have another further step, I mean, those diagrams are beautiful today.

Absolutely. I sat in on the animal model session, the oral presentations at the very end of the day after Tony Fauci's lecture on COVID-nineteen. And Jenny Stabra, who's a junior faculty member in our department at UMass, gave a presentation about the effect of Shneuri3, which is a gene in mice that seems to suppress osteoblast function in an animal model of rheumatoid arthritis. And what she found was that by using small inhibitory RNA to suppress shnuri three, she was able to restore osteoblast function, and through linkage with osteoclast development, suppress osteoclast function. So interestingly, there's a humans have a story three gene, that's about 80% homologous to that in mice.

So there might be an opportunity to try using an adenovirus vector to introduce an inhibitory RNA to downregulate story three, and perhaps increase bone formation through coupling decreased bone destruction in rheumatoid arthritis still not ready for prime time, but a very interesting concept introduced in the animal model session. So any other abstracts that piqued anyone's interest today? There was an abstract that Bill Robinson presented about fine specificity of auto antibody, which predicted response to abatacept and methotrexate as I recall. Eric, did you review that abstract?

Yeah, so that was a it was interesting. They looked at exactly that find specificity ACPA showing that you can use them to help predict therapy that those patients had a better response on dual therapy with abatacid and methotrexate compared to methotrexate monotherapy alone in all patients were seropositive RA in that group. Specifically, if we're looking at these specificity, don't recall exactly what they specified which ACPA they were looking at, and you can see that you can use this to help predict outcomes as to how patients are going to do. So it's just incredible to think about that we might get to the point, you think about in myositis, we're so specific with which antibodies and the phenotype based on that and what drugs we use as a result of that. This is just an indication that patients with this phenotype or with this marker, maybe they're the ones that should be on the dual therapy or they should be on certain therapy.

So we're really getting to personalized medicine now, even more so this year. I listened to the Hinch lecture this year, Kurt Burmester from Charite in Berlin gave a very nice historical overview, a tour through the development of treatment for rheumatoid arthritis. And I would recommend that session highly to those of you listening to this podcast or this video on RheumNow. Jared really showed the development from the early days when Hedge and Kendall first pioneered the use of compound E to treat rheumatoid arthritis in 1948, up through the development of oral biologic equivalent drugs that targeted synthetic DMARDs, and talked about all of the people in rheumatology who've contributed to these developments. So a very nice historical overview.

So as we're nearing the end of the time for this panel discussion, I thank each and every one of you for participating and the panelists. And please go to room now for more information to see individual faculty discussions of presentations. And please come back tomorrow when we will reassemble to review tomorrow's day at ACR Convergence twenty twenty. Stay safe and well. I'm Jonathan Kaye for David Liu, Eric Dine, Sheila Reyes, Jeffrey Sparks, Richard Conway, and Morales.

Good night.

Hello, everyone. I'm Richard Conway reporting from ACR twenty twenty for RheumNow. And I'm joined today for an interview by Doctor. Sinead Maguire to talk about her study, Pregnancy in Axial A Systematic Review and Meta Analysis, which was presented on Sunday in the poster session, it's abstract number thirteen twenty three. Thank you for joining us, Doctor.

Maguire. Can you tell us first why you do this study?

Sure. So I think it's an important area to cover because typically at the time of diagnosis, most women with axial spondyloarthropathy will be in their childbearing years. And pregnancy is a major life event for any woman, but for women with axSpA, it comes with a lot of extra questions and concerns. And when you look at the research that's already been done in this area, unfortunately, there's not a clear consensus in terms of our pregnancy outcomes and asthma associated with more pregnancy complications or fetal complications and what actually happens to disease activity during pregnancy. So because this is an area that I think is very impactful for our patients going through pregnancy, I put together this systematic review just to pool all the research that's been done in this area to try and see if we could pick up true prevalence trends to inform our patients going into pregnancy.

Fantastic. And that's probably going to become even more important, which hopefully the improvements in the diagnostic delay and diagnosing people earlier when they're even at a younger age, and particularly in women. And can you tell us what your results showed?

Yeah, so our primary outcome was looking at pregnancy complications in And the most significant outcome that we had was actually looking at was in cesarean sections. And so asthma pregnancies had a much higher prevalence of cesarean sections compared to control pregnancies. And this was significant even after we broke it down into emergency and elective cesarean sections. And you might say, well, the prevalence of AFSPA of cesarean sections is rising globally and that's for lots of different reasons but what we did show is that despite that there still is much higher prevalence of cesarean sections in ASBA compared to controlled pregnancies. And then on top of that there also is a trend towards a higher prevalence of a number of other complications, including intrauterine growth restriction, preeclampsia, and then also preterm birth on sensitivity analysis.

We also captured prevalence of fetal complications, and all the complications that we actually captured in our analysis had a trend towards a higher prevalence in pregnancies compared to controls. Seize activity was a little bit harder to capture, but we did find that a very high portion of axSpA women experienced active disease during their pregnancy. So these results certainly are a cause for concern and very much a call for research, further research in this area so we can understand why is this happening, what can we do to address this a little better And how do we inform our patients about this?

That's fantastic. It's really, really interesting results. As you say, very important to bring that all together. What do you think the next steps are in this area?

I think first and foremost, it's going to be getting more research in this area. And I think one of the best potential resources for this is going to be looking at large registries because they are a way to get information, a large volume of information very quickly. And I'm actually doing work with the ankylosing spondylitis registry of Ireland, and we have developed now a section on pregnancy as part of our registry. So for all women being entered into the registry we're now capturing information on pregnancy in terms of pregnancy and fetal outcomes, breastfeeding, just to get more information on this topic for our patients. So when we sit down and we have conversations with our patients, we can say this is data from our own population.

But using registry data also means that we have a large volume of clean data so it makes it easier to compare between different registries. So hopefully that will help us to better understand this area and hopefully help our patients in this area much more.

That's fantastic. Thank you very much, Doctor. McGuire, and thank you everyone for listening in. Please remember to log into RheumNow for more coverage and updates from ACR twenty twenty.

Hello, my name is Jeff Sparks at Boston, Massachusetts, an ACR ambassador, I'm happy to get the opportunity to report for a room now as well. I'm here with my good friend, Doctor. Janet Pope, and we're gonna talk about rheumatoid arthritis risk factors and early RA, two of our favorite topics.

Yeah, hi Jeff.

Hi. So I think most, we want to mostly focus this on two of our, you know, data sets that we do a lot of our studies in. Some of mine are the nursing health studies and yours are in CATCH. So I wonder if you could just tell people about CATCH first.

Absolutely. So the CATCH cohort is an incident cohort of suspected or proven early rheumatoid arthritis. So symptom onset a year or less with proper suspicion of RA and we have about 4,000 patients and sometimes we have less because we migrated the database and asked different questions but it's multi site throughout many provinces in Canada and it's a rich data set that we collect data and the patients do as well. We do freeze serum at some sites as well.

Great. And I'll fill you in on the Nurses Health studies again. So this is nationwide studies that started actually in 1976. So over forty years of prospective follow-up, and there's actually two cohorts, Nurses one and Nurses two, which was started in 1989. Each of them have about 120,000 women.

So we got over a quarter million women who have had prospective follow-up for over forty years. And we've been identifying incident rheumatic diseases, particularly rheumatoid arthritis and lupus within those cohorts. And one of the strengths is that there's really, really high follow-up. Patients, people, they're not patients yet necessarily. Nurses are really follow-up with all their questionnaires.

So we're able to answer what things happened prospectively prior to disease onset. So it's been a real wealth of information.

And I think that's a real strength that you actually have factors that truly predate symptom onset, because I know you've looked at depression, you've looked at, and others in your team and group have looked at healthy living. Can you tell me about some of those things?

Sure. So we have some abstracts this ACR20 to talk about. Some of these, I'm a co author on all of these, I'll say. The first one that we were excited about is related to passive smoking. As you probably know, inhalants are thought to be really important in RA pathogenesis.

And in the Nurses Health Study two, they really asked about passive smoking throughout the entire life course. So this was analysis that was led by me and an instructor in medicine, Doctor. Kazuki Yoshida. And we really looked to see whether there was an important time in life when passive smoking might impact rheumatoid arthritis. So we looked at, maternal smoking.

So when the nurse is actually in the womb, we looked at, passive smoking at the childhood, looking at whether, they lived with a parent. And then we also looked at passive smoking throughout adulthood living with other smokers. And what we found is that there was a pretty specific association of passive smoking in childhood to predispose to later adult onset zero positive rheumatoid arthritis. And our speculation is that this could sort of be the first trigger, you know, put epigenetic changes perhaps that might set up patients to have developed rheumatoid arthritis in the future. So some other abstracts that we're pretty excited about are related to lifestyle.

So we're also interested to see whether lifestyle factors affect RA risk. And again, these factors have been collected for many years prior to the clinical onset. So, there are two sets of analyses that are presented at this meeting. The first is related to RA, which is being led by, Doctor. Jill Han.

And really what we're looking at is, five particular health behaviors, obesity, diet, smoking, physical activity, alcohol consumption, and whether this is related to incident RA risk. And what we found is that those who are really healthy, do seem to have a much lower risk of rheumatoid arthritis. And in a similar analysis that was led by Doctor. Mei Choi, she looked to see whether these factors were related to systemic lupus onset. And this one actually was particularly associated where these factors could really explain up to fifty percent of lupus risk, which is really quite impressive.

So I think it really emphasizes that healthy lifestyle could have some alterations in the immune system, systemic inflammation and really it's quite important from a public health standpoint.

Yes, and it seemed like it was explaining maybe one third of the risk of RA too. I think the take home is we can drink alcohol if that suits you and you're not against that for other reasons, that we need to exercise regularly, that the Mediterranean diet's good, not smoking, and then things that weren't really looked at, I guess avoiding stress and all that would be helpful and probably not living with a smoker and choosing your parents wisely so that they don't smoke and maybe choosing them because genetic risk is still there.

Yeah, it's all nature and nurture but anything we can modify to improve does

seem That's to be right and it just links in with all the comorbidities or multi morbidities that our patients might have too. If you have some of these lifestyle features that are for the better, again probably never too late because certainly some studies show that a Mediterranean diet, exercise and weight loss can help things like psoriasis and psoriatic arthritis and a little bit of data emerging in RA as well. So there's a lot of linkages with we are what we eat and what the environment is.

I know a lot of catches related to, you know, early RA, particularly remission. I wonder how you think about how these factors relate to some patient reported outcomes that might affect patients' chances to get into remission.

Right, so we have found indeed that remission is less if you're overweight and the least amount if you're obese. Time to remission, it takes longer. The proportion in remission or less and sustained remission is less as well. The other thing is we're presenting that even people in remission irrespective of lifestyle, sustained remission is very difficult to achieve and over the next two years a large proportion of those who are in remission at one point in time aren't still there a couple years later which I think talks about the evolution of RA and drug resistance and possibly adherence and lifestyle factors too. We have to really disentangle why each individual might be losing their remission.

What's really fascinating when you think about what all your patient has gone through once they come to see you in clinic. And it's not necessarily just about the drug you pick and there's really a lot that goes into, you know, what, how they're gonna do and how they're gonna perceive things. So really a lot more disentangle if you will.

That's right. I think for research and I think some of the clinical take homes are that it's so important that patients feel that you're listening to them. There's some care gap pathway issues that are going on that if a patient is more apt to be adherent, if they buy in, if they tolerate the meds, and if they think that you're actually listening and have their best interests at heart. So you're right, there's so many things that go into our art or our practice of medicine, and someday practice will make perfect.

All right, Jenna, I think we could talk forever about this, so we'll spare the viewers any more. Thanks again to the RheumNow viewers, and I hope everyone's having a great meeting. Thanks again.

Thank you.