TNR - COVID - Rheumatology Registry & COVID In OZ Save

Hi everyone, I'm Jack Cush with RheumNow. Welcome to Tuesday Night Rheumatology. This is our grand round series and tonight we have a real double feature from, down under. Good friends, good colleagues. Work with these gentlemen, every ACR, every UR, they and I work with them because they're so good at information gathering and educating everybody on the latest and greatest in rheumatology.

Philip Robinson from University of Queensland and Peter Nash from Griffith University School of Medicine. Gentlemen, how are you?

Hi Jack. Very well.

All right. So wanna cover a lot of ground tonight. We're gonna have two sort of presentations. One to review the room COVID registry that Philip was instrumental in starting and then getting a perspective from Peter on COVID from down under in the land of Oz. Gentlemen, I wanna start off with a question for you.

The impact of the coronavirus on rheumatology has been quite tangible. Clearly the impact on healthcare has been very tangible. The estimates are that US hospitals are gonna lose $50,000,000,000 a month for the first four months of this crisis. And that a recent Medscape survey says that the loss in income and revenue is substantial in American practice with at least a 55% drop in revenue and a 60% drop in patient traffic, and visits. I think there's so many untold consequences of this, but, how is it affecting, where you guys are practicing and what's your perspective on the impact this has had on rheumatologists?

Peter, do you wanna start?

Well, I think it's had a huge impact. We're doing a lot of telemedicine and many of my colleagues are telling me that they're gonna go bust if that doesn't change over time because it doesn't reimburse them adequately for their time. We're hearing that the patient numbers are down because people are scared. We're hearing they can't get their patients with other important diseases diagnosed and treated because all the public hospitals, the private hospitals have been just about closed to everything except COVID. And what's worse is all the businesses in a small place like where I live on the Sunshine Coast, many of them are gonna go to the wall because they cannot afford this downturn even though the government's trying to help.

So it's got massive repercussions, economy, small business, the dollars dive, the share market's down across all aspects of medicine. And we'll talk a little bit about some of them in the next little while, Phil.

Thanks, Peter. Yeah, the things that have really landed and resonated with me are the things that you just don't think people would stay at home with. So stroke physicians saying that their wards are empty. Stroke is not a thing that you think that you could sit on. Talking to a pathologist saying that monitoring testing has plummeted and not being able to undertake routine things like colonoscopy and endoscopy, this is a time bomb.

We're not treating our current non COVID patients. And we are accumulating a debt that's going to appear down the road with malignancy and complications that I'm frankly slightly scared about. Now in Australia, we've been very lucky that we haven't had a lot of COVID, but we are gonna have exactly the same effect on that non COVID. And I think if you end up dying of stroke or MI or cancer during or shortly after this pandemic because of the impact that the COVID's have on the health system, I think you're just as much a victim of this pandemic or you're affected or you die, just as much a victim of this pandemic as someone who actually is affected directly by COVID.

There's four hundred thousand

patients on the elective surgery waiting list that are sitting there waiting for the hospitals to get going again, which they just have.

Wow, I like the idea of non COVID management. We need to focus on that, you know, And again, the revenues are down, traffic's down, but interestingly in Australia where you have fewer cases, you still have the same impact on this revenue and traffic, as much as what's going, about the same what's going on in New York City where it's obviously a crisis. So it's paralyzed patients. And I think maybe the one thing that we should be doing as a discipline and as practitioners is increasing our engagements, increasing our revenue by reaching out to patients. We're assuming they know what to do.

Right now, they just know they're not supposed to leave the house. And most of them are misguided about their risk so much so they haven't, I have a whole bunch of patients who haven't left the house in over two months. Scary.

It is scary. And,

the last number I saw recently was almost ten percent of US practices have closed, during the crisis, mainly because they didn't know what to do or the docs themselves were fearful about what may happen next.

So, Yeah, and one I of the important things is we work off data and that's what we do, right? So we say, okay, the research shows this, so this shows that it's safe. But of the things that's really hard to do during a pandemic is doing research and collecting good data. So we're trying to collect data in the best way possible, but the pandemic is impairing our ability to collect information about it.

Peter, you wanna say something?

Well, just that the government ramped up for a huge pandemic, which really hasn't eventuated luckily in our country. So everything was shut, everything was closed, borders, hospital wards, fever clinics. They recruited recently retired docs, 5,000 of them re registered them all ready so they could get into the fight against COVID and the pandemic just never came to most parts of the country. Middle Of Sydney, middle of Melbourne, that's different, but the rest of the country, that's the kind of extent they went to get prepared for an eventuality. We've got a billionaire here who bought 32,000,000 doses of hydroxychloroquine to donate.

Is name Trump? Sorry? Is his name Trump?

No, different billionaire.

He actually paid for them. So there's 32,000,000 doses sitting in a warehouse. I wonder what's gonna happen with that lot.

It was unregistered. It's not registered with our FDA equivalent. Well,

we say in medicine, when you treat yourself, you got a fool for a patient. What can we say about Doctor. Trump? So let's get on with talking about data. You know, I think that the, what we need is data, what we need is certainty, and numbers are our best way in moving forward.

So, Philip was one of the principal leaders and instigators behind the Global Rheumatology Alliance and we asked him to come on and give us an overview of what they have accomplished in a very short time. And I think it's really quite amazing. I wanna remind the audience that to please use the Q and A button throughout the talks to register your questions that we will get into in the last twenty minutes of our session today. So, Philip, you could take over.

Thank you. So that's gonna work out ahead and move forward. All right. Okay. So those are my conflicts.

So look, I think we've talked about why a registry, but I suppose it's of value to think about the different ways that it might be important or we might be able to think about this. And everyone's focusing on drugs a lot, but we also have to remember that rheumatic disease potentially presents a risk in and of itself. Now there's not much we can probably do about that risk, but our patients have immune dysfunction as a baseline. And then we further complicate the matter by introducing immune suppressing or modulating drugs on top of that. And then really, it's been rheumatology front and center with therapies really.

It's not the time or the I don't have the energy to go into hydroxy chloroquine too much today. Hydroxychloroquine, tocilizumab, they've really been front and center of people discussing and we're seeing data about anakinra. So our drugs have been, are they maybe of value as well? So that's another reason to think about collecting data. And really because of the characteristics of the virus, SARS CoV-one and MERS infections really didn't have the impact.

And so we didn't really have any data from these things. So this is a new space really. And even if we did have data, it's a different coronavirus and the scientists who know much more about this than me say, even based on comparisons, we need to be very careful because of the differences in these viruses. So all of that really led to the need or the want to collect data on our patients who get infected. But I want to put front and centre the really important thoughts about the fact that this is really just a grand case registry, a case series that we're thinking about.

Now we can do, we can try and limit the ability to bias but really where patients are reported into the registry And so we need to think about things like selection bias. So what happened and how did this come about? Really, it started with a tweet by Lynne Calabresi to say, Look, other people are doing this, is this a value? And then it sort of snowballed from there. You can see that's My apologies, it's actually incorrect.

That is March. So it took really less than two weeks to come on stream to get this registry up and going. And again, I'm getting my months wrong, sorry. As of yesterday, we have 1,500 cases. And we're probably pretty soon because we are going to be at around the 1,800 mark because we're connecting with a whole lot of country specific registries who are able to give us huge data dumps.

So I think very soon we're going to have north of 2,000 patients and even more as time goes on. So the registry is really building significantly. So we're doing a number of different things at the registry. We're looking at a few different aspects, but I'm just going to talk about the registry data today. But we've got other teams of people thinking about other aspects, looking at the literature.

So we've got a massive team that's really contributed to by many, many countries all around the world. 40 countries in the data that I'm going to talk about and it will be further expanded. So I think this is really a credit to global rheumatology that they've got behind this and recognise the importance of this. So this is a representation of the countries that have contributed data. And you can see there's a key on the right there.

Again, is slightly dated but there's significant contributions from Europe and North America and then a number of other countries. I see 40 other countries. So the data that I'm going to present really represents global patients. So what information are we collecting? We're collecting de identified demographics, diagnoses, so that's physician allocated diagnoses, rheumatic drugs that the patients are on up to their infection, comorbidities that they have, the diagnosis and how it was made, including what laboratory test or imaging that was done, labs and then outcomes.

And then we're also collecting reporting details because often patients will get reported when their infection isn't totally resolved. And so it's good to be able to try and go back and totally resolve all the patients because outcomes are what we're interested in. Data, collecting data quickly is important, but also knowing what the eventual outcomes are. So this is the first report that we published on the April 16. This was our first one hundred and ten patients.

And these are seventy percent female, eighteen percent over the age of 65 with very typical rheumatic disease cohort with lots of rheumatoid psoriatic and lupus with axial SpA and the other rarer diseases also represented. And we saw a good broad range of conventional synthetic DMARDs, JAK inhibitors, biologics. But you can see that forty five percent of patients in this cohort are on biologics. So this is probably a more severe cohort depending on local practice trends. And that's probably reflective of the fact that this is a physician reported registry and patients who maybe have mild disease, they got a swab maybe in the community and went home and self isolated and haven't got unwell, are staying at home and they're not getting in front of physicians and being reported.

So that's one thing, certainly one thing to remember when we're looking at this data. So one thing that we, you know, that I certainly worry about when I think about immunosuppression is whether patients present in a typical way, whether they present with the typical features that we think about or whether they present with atypical features. This really, I think, demonstrates that they present with fever and cough and shortness of breath just as we would expect a non rheumatic disease patient to present. So this is certainly reassuring from that point of view. Thirty five percent admitted to hospital, which is higher than the general cohorts, but again we need to think about how this data was collected.

And five percent died in the first one hundred and ten patients. And they had pretty typical comorbidities. And this was really our first shot to get some data out there that people could have a look at. And then the other thing that we've been collecting is patient data. So patient reported data.

So clearly patients who get infected are important, but there are a whole lot of patients out there who are at risk. And so we wanted to know how they were going how they were feeling about this and what issues they had. The other thing to remember is that this is a mechanism to collect milder cases. Because if you got your swab at your local lab, you went home, you self isolated, you've got rheumatoid and you're on methotrexate, you can sit here and complete the physician survey. And so we can get a slightly different cohort of patients.

Now clearly there are limitations in directly asking patients, but there are certainly strengths as well. And so this is the data that that so we've had a huge uptake in this and this is data on nine thousand five but we're well north of twelve thousand now, and we're getting further data sets, brought in. So again, typical rheumatic disease group, rheumatoid, lupus, axial SpA. And around five percent have been infected and that sort of stayed up. So we've got about seven fifty or so in twelve thousand.

This data was very informative to be able to publish that in fact patients with lupus on hydroxychloroquine do get COVID. So that's certainly information that we've got from the survey that's been helpful to dissuade comments that have been made by officials and information that's been going around. So this is our second report which currently is in press and will be out very shortly. So this is data from the physician registry on our first 600 patients. This again is a typical rheumatic disease cohort with seventy percent females, median age 56.

Again, the majority collected from North America and Europe, but with a fantastic showing from the other global countries. And we're now starting to see some other diseases which things like gout and inflammatory myopathy. And if you think now that we're at sort of triple list cohort, you can think that if the numbers hold, then we're starting to develop decent numbers of the subgroups as well that we can look at obviously in detail. So how they're diagnosed? So the majority with PCR testing, which will be your standard swab that everyone's talking about, that feels like it's going into your brain as I'm sure everyone who's had one will appreciate.

Some people have been diagnosed with typical symptoms on things like a CT scan, which in the context of presentation and access to testing in the middle of a pandemic is clearly an appropriate thing that the Chinese took on board. Now looking at outcomes, again forty six percent were hospitalised. So again this is we're probably seeing a more severe cohort and that's just the mechanism of how we're collecting this data And then nine percent died in this cohort. So now what we're interested in is what are the things that influence hospitalisation? We didn't feel that we had power to look at harder endpoints like death and ventilation and they are currently being worked on in the larger data set and then we have more power.

But you can see in this data set when we do regression controlling for factors that we think are important, there was no difference statistically significant difference in odds ratio between the different diseases. Now, can speculate about what we may or may not see when we increase power, but certainly when we look at the first six hundred patients, there is no statistical difference. And the reason that we're not presenting the finer print diseases is because we just don't have the power. That's why we lump them together into other and we'll be being more fine scale when we're able to. So here are comorbidities and I don't think it will be a surprise to anyone based on other data that we've seen from general cohorts that if you've got a comorbidity, hypertension, lung disease, then you're more likely to be hospitalised because you're at risk of that.

There's been some interesting data about smoking, but certainly in our cohort, we didn't see a difference in ever smokers in hospitalisation. When we look at medications, you can see here that CSD MADS, so you can see down the bottom those here methotrexate, leflunomide, hydroxychloroquine and then a list of super fine print drugs like azathioprine didn't impact. We did not see an impact on hospitalisation with hydroxychloroquine combining your standard oral daemas like methotrexate and leflunomide with your targeted therapies and biologics. There was no difference on hospitalization. And again, we specifically looked at NSAIDs because of the comments very early on in the pandemic that the French made that they felt like this was a risk.

Certainly, with this power in this cohort, we did not see a significant difference. If we look purely at BTS DMARDs, there was a reduction in the odds of hospitalisation and then TNFs alone. So again, it's important to remember that this is a selected cohort of potentially severe patients. We don't know what the denominator is, but it certainly doesn't look like these things increase your risk of hospitalisation. So this is reassuring for the patients out there.

I don't think it would come as a surprise to anyone that prednisone is a risk in this population. Now one of the things that our reviewers really wanted us to drill down on is often people are on this because of bad disease. So when we put in disease severity as assessed by physicians, we did not see differences in the results that we saw. So we see this in other cohorts as well. And I don't think this is a huge surprise that being on greater than ten milligrams of prednisone increases your odds of hospitalization.

So what is our latest data? This is just from the global registry. We combined, that was combined data. This is from global registry. So this is now the 800.

So this is about the half that are sitting in the global registry and you can see that numbers have really risen. We're still getting good numbers on synthetic DMARDs. Our bio DMARDs has come down slightly from the earlier reports, but we're still getting good representation. Then this is certainly these numbers will grow. And we're not seeing a huge change in the rates of hospitalisation and death as our numbers grow.

And certainly, so I think the take home messages would potentially be that this is reassuring data for our patients. If you want to get more information or you want to keep up to date, then I would suggest that you go and have a look at the website. Certainly there's data tabs there that you can keep up to date with and you can subscribe and you can have a look at our Twitter feed as well. And final thing I want to say is I really want to thank everyone that's contributed to this registry and everyone that supported this registry, because we would not have this data if we did not have the global buy in of everyone. Thank you.

Peter, that was great. I'm sorry, Philip, that was great. Peter's gonna take over now and show us his slides. Again, for the audience, if you have questions, use the Q and A button, not the chat button, and we're gonna get to questions in the next ten-fifteen minutes. Doctor.

Nash?

Okay, thank you for the opportunity Jack, I just wanted to show you where Philip and I live, you can see we're over here between the sharks and the cyclones, where we've got big spiders and lots of cane toads, but Australia is a very big place and the real interest is how that impacts particularly on telemedicine. We'll talk about that a little bit. If I can make this slide advanced, that would be handy. There we go. So we've become like the plague doctors at the moment.

And if only those wet markets wouldn't be eating all those strange animals. Now we've been very lucky in this pandemic, it has not been a major issue to Australia. Australia has free testing and we've tested one in twenty of our population. And we've ended up with seven thousand cases but only a hundred deaths and over six and a half thousand recoveries. And that's the split, how many are still in hospital at the moment, New South Wales twenty two, hardly any inpatients at the moment.

So the country's desperately waiting to reopen. Lots of tests done. We've got 22,000,000 people and they've done over a million tests of which zero point seven percent have been positive. And you can see how the curve has flattened off and that's the distribution of different States of the country. So to the infection, state nearly all came from overseas.

We had direct flights from Wuhan to Brisbane that they canceled very quickly. The borders were closed, everyone was tested and isolation happened very quickly. The real question is why we got such a light dose. We don't have extended families living together under one roof, our population density except in the middle of the big cities is small. And I was interested in this paper that looked at phylogenetically that there were already three variants of this virus and Australia had the A variant and France, Italy, Sweden, England, where they've had lots of deaths had the C variant of this virus.

And I just wonder if the natural mutations change virulence significantly and that's something perhaps we could talk about. There's a B virus that affected Hong Kong. So we had lots of advice, the Australian Rheumatology Association, the ACR, the BSR, we had lots of advice for our hospitals, how you cope with intensive care, who to ventilate, who not to ventilate, etcetera, etcetera. More advice than we actually had patients infected. They tell me if you live in Florida, physical distancing is one alligator length.

So what we did was we did a lot of screening, anyone with symptoms couldn't come to the clinic, we did a lot of telemedicine, only seeing the very urgent acute patients face to face and we did the usual stuff with masks and gloves, we didn't really have an issue getting our hands on those things. They deferred a lots of cases that should be 400,000, disinfected the room, people waited in their cars till they were called in, the issue of hospital discharges and what to do with our therapies and when to go back on therapies again is something that we can talk about. But they're always the common questions that our patients had. Will my medications make me more likely to get COVID? Will it be more severe if I get it?

Should I stop all my drugs? Philips Registry is helping us answer some of those questions. What about if I'm on these drugs and I work in a high risk situation like in the hospital, should I go to work or should I not? Who should have swabs and bloods, and when is it safe to restart my medications when I come out of hospital? There are many, many questions and we could think about all of them.

But let's talk very briefly about telemedicine because we've been doing telemedicine and I listened to Alvin's beautiful presentation. We've had reimbursed telemedicine since 2013 because the government was paying for patients to come down to specialists from out in the bush and that was costing them money, so they thought they would save money by reimbursing telehealth. And there was a long list of things that you had to do, you had to get consent, contact details, everything had to be private, secure, the consultation had to be of a certain type and then you have to send patient information securely and they have to live a certain distance away, etcetera, etcetera. So telemedicine is not new to us, but I make a plea, we are the only physician to examine the patients anymore. And I know in the middle of a pandemic, you can't be seeing patients face to face but please, are we gonna be rheumatoid arthrologists or are we gonna be physicians of rheumatic disease?

Because our patients always tell us, Doc, you are the only one who's laid hands on me in ten years and it's what we pick up outside of the joints. It's the thyroid lump, the heart movement, the enlarged spleen, the funny lymph nodes, what you hear in lungs. We need to not give up examination because we're getting reimbursed and it's easy to do telemedicine. I might sound like a dinosaur but I think it's important. And what we've always done for the first visit pandemic aside, you come down and get seen and examined.

Once you're started on therapy, well, fair enough, we can follow you up over Skype, we can follow you up over WebEx, GoToMeeting, Zoom, and we can look at your joints and etcetera, etcetera. We've got all your blood results. The patients can be taught to do a joint count, they can even be taught to do DAS28s and things. Now all the software has got all that stuff, we've got the results and you can follow people along, but please don't give up examining our patients. And when you look at some studies on telemedicine and this is just one of them, would you like to be seen again?

One in three said no, they weren't satisfied. Only a half were very satisfied. They do find it convenient but there's significant dissatisfaction element and what they basically boils down to, the people who are best for telemedicine are those that have been assessed and are stable, well established disease or those who have well established disease having an acute flare that you can handle over the phone or over telemedicine. So we've not seen these beautiful toe things because we don't have enough patients. We've not seen this severe Kawasaki, there's not one case of the Kawasaki like disease in Australia as far as my paediatric rheumatologists are telling me.

But vaccination is something that Australia is very good at. That's my old boss when I was immunology registrar in nineteen eighty seven-eighty eight and he invented Gardasil. So they've got very strong vaccine background and the Queensland University just got a big grant from the Gates Foundation because they've got a molecular clamp system. You take the spike protein off the coronavirus and you make antibodies do it for your vaccine, but that spike protein is unstable, it deteriorates and changes quaternary shape. But this molecular clamp system, which I don't understand the details of, maintains the spike protein, maintains these surface proteins and you can really make a much more effective vaccine.

And University of Queensland is working very hard on that and we're into clinical trials. I know Oxford got big ones, all pharma are trying to make them, but they've got quite a deal of promise with the UQ vaccine. We still need to know if this vaccine is gonna be immunogenic in our patients. One of the questions about Shingrix for example, that it's immunogenicity and the same issue will come up as far as the COVID vaccine is concerned and Phil's registry will have to help us with that. There's another big Australian trial looking at BCG vaccination in some of the European studies that has not turned out to be protective, but there's a big study going on around Australia.

And our Commonwealth Serum Laboratory is also working very hard on convalescent serum to develop a treatment for those patients who are hospitalized and very sick and they're very good at making those kinds of things. Now the serology will come, what it really means is very difficult to know unless somebody does some decent groundwork, seroconversion, false negatives, false positives, cross reactivity, how durable it is. You can see these people coming along with the idea of you're immune because you've got antibodies, but does it really mean that or not, somebody needs to work those details out and I'm hoping the registry will help us. So possible treatment choices, we can't get remdesivir in this country, has made it available to one hospital in Sydney and one hospital Melbourne in a clinical trial situation. Lots of these other things are being looked at.

We've been telling our patients like the ACR recommends, do not stop your therapy unless you become proven infected because when you flare, you'll go up on steroid doses and that might be even worse. But what about teaching our students, doing examinations this year on our students, teaching our registrars, how do you accredit this year's advanced training? And Philip alluded to clinical trials, well for three or four months these patients couldn't come in and get assessed in the middle of a clinical trial, we're doing a large number of trials. What do we make with the four to six month gap of data in the middle of that clinical trial? How do you analyse data moving forward?

The trials are just starting to recommence now. So registrar training, accreditation of advanced training, examinations have all been cancelled, student teaching has all been cancelled. What do they do with this year of training? So clearly very challenging, can be alarming, but in our country manageable, the collaboration is important and we're adapting what we're doing and there is hope out there Jack. So I pass that back over to you.

That's just fabulous, both presentations really, really insightful. I wanna start with, again, the low numbers in Australia, is there any concern that while you may have forestalled the peak or helped it go away, do you think that your numbers might be, might foreshadow a return to higher numbers at a later date when you open up and whatnot? Since you had, you sort of missed the first wave, but you're not immune to the second wave, what's the thinking locally?

The politicians are very concerned about a second wave but as long as international borders are shut, they can't come in, they can't get into the place. And even those affected have recovered And Kevin Winthrop tells me because I've pinned him down, when can I restart my therapy in someone who's been infected? And he feels that after two negatives and a fortnight, the PCR might be positive but the virus is no longer viable. It doesn't last. So the cases in the country I think will die out.

And then if we don't let international customers in, then I don't think we'll get a second wave for that very reason. Nearly all our cases came in on flights and on cruise ships, the Ruby Princess infected half the country and had thirty five deaths. So I've got a feeling that they'll be very concerned but I've got a feeling as long as the borders are shut we'll be okay.

So, Philip, any, one, your registry doesn't include anybody from China and Southeast Asia and, is that a weakness? And also, you know, it's also really hard to find any Southeast Asian, you know, experience with COVID and rheumatologic patients. You'd think with all the cases they had in Korea, in China and Japan, even that you might've seen some reports and I've not really been able to find anything. What's your thinking on their omission or what might have been gleaned from those populations?

So there are certainly different attitudes to reporting data around the world. And there are also cultural and language barriers. At the moment, we are a grassroots organisation that up until very recently had $0 to help us. And so creating multilingual surveys was beyond our capacity. I certainly am aware of data coming from China that is not public yet.

So I think they have had obviously a huge amount of this and they're just trying to catch up and their priorities was clearly patient care to start with. So I think that you'll probably see data from China coming out.

Phil, it's almost like our patients are protected. They're getting lesser infection than we would have thought. Is that an impression with any data behind it? And is a five percent death rate higher than the kind of one to two percent that everybody claims is the death rate or is that just selection in your registry?

Look, I'd love to be able to give you definite answers about that. Look, I get the impression and it's really nice to get confirmatory data. And one thing that I have looked at and everyone is very open to look at is to go and look at the secure IBD data and they're on their website. And they certainly seem pretty similar trends to us. If their paper isn't out yet, it's gonna be out very soon.

And they're a different type of patient clearly because having an entirely swollen large bowel is different from having synovitis your NTP joints. But I think their data helps to confirm that this is not an aberration that our data is. I definitely think that we're getting more severe cases. And if that's the case, we're getting more severe cases and our outcomes are slightly worse, it's very hard to be sure about what's going on. Now I had seen and I'm aware of a non public data that is coming out that uses a denominator and that's what we want.

We want, hey, I look after ten thousand rheumatoid patients or ten thousand rheumatic disease patients and these are the patients who've got infected. There is preprint out. I know it's out on MedRx that's out already. And now I know there's other non public data out. So those are the sort of studies that are gonna help answer that question that is really hard to answer from this registry data.

So Philip, your data shows kind of what the New York City report that Jose Sher showed that the patients who were on the more aggressive therapies, biologics and targeted synthetics, were the ones that looked like they were doing better. They were more ambulatory and had seemed to have better outcomes, whereas the ones who were on traditional DMARDs seemed to have a higher number of hospitalizations. That may go to Peter's point that maybe our patients are doing better, especially if they're well controlled and doing better. Do you have another view of that?

Yeah, so certainly that's what we seem to see in the IBD patients and that's what we seem to see in our patients. So are we seeing the fact that our therapies are not impairing viral responses, but our therapies are impairing the aggressive immune response that tends to really affect people in cytokine storm situation. Clearly this is speculation, what fits with biological plausibility, because that's when people are using anechidna and tocilizumab. They're using it when people get into this horrendous over immune stimulation. And if you think that being on tocilizumab or a JAK or a TNF can prevent that happening, then you can prevent the damage that your own immune system is doing to yourself.

So certainly it makes total biological sense. But as I say, that's to be determined if that's actually what's going on. But yes, that's certainly a one theory that you could take from the data, yes.

So this registry, one of your numbers said it was seventy one percent female, whereas most cohort studies, especially the ones who are hospitalized like many of your patients are, were predominantly male, sometimes even as much as like eightytwenty in favor of males. Is that just one reflective of our patient population with autoimmune disease or do you think there's something unique about the number of females that you have?

Look, no, I think that probably just reflects the cohorts of rheumatic disease patients. So I don't think that's anything separate or different. And I would be slightly worried if we had equal numbers of male and females because that's not what we really see in the clinic. Look, I can see that there's lots of, there's totally lots of interest in the different, the finer dissection about this data. We're all super interested in that as well.

And that's something that we can do when we get bigger numbers.

So there's a recent paper that we put out that shows that men might be more effective. I think it might be more effective because men are the imbeciles of healthcare. That might be number one. We like to delay therapy more than anybody else. But also this recent paper saying that men have higher, more circulating soluble ACE2 receptors than do women.

Anybody else have a theory as to why men are having the worst forms of disease and the worst outcomes?

Smoking, comorbidities, hard to know. Yeah, there really is.

There's just so many, you know, if you look across the world, there is just so many non medical factors that you can think of. Sociocultural factors, access to healthcare, all of these other things that it's just so hard to sort of try and fit a theory that captures them all, right? So as I said before, is such an important area but the pandemic makes it so hard to collect great information about it.

So do you foresee that the registry data can be used to show that lupus by itself may not be a risk factor, but lupus plus two comorbidities now puts you into another category. I think that's what people are kind of worried about amongst their patients who they have to advise.

Yeah, look, and I think one of the important things to think about is that when you have a rheumatic disease patient, everyone focuses on the rheumatic disease the drug that they're on. And I think our data is potentially is able to say, well, look from the rheumatic disease point of view, I don't think that there are significant asymmetrical risks based on the data, based on the limitations. But clearly all the things we know from the large cohorts are important as well. So age and comorbidity and other things as well. So you can get really hooked up on what you think might be important, but it's so really valuable to think about, look, you're elderly, you've got comorbidities that may be having a much greater impact on your risk of a poor outcome than being on methotrexate or your TNF inhibitor.

So, again, your registry does sort of coincide with some other cohort data that's out there showing that there's that people that are being enrolled have, there's just a few that are on JAKs. Can you make much out of that? Does that mean maybe the patients on JAKs are protected or just that it's an under representation due to a low amount of use of JAK inhibitors in general?

Yeah, look, the JAK question is really interesting because clearly there's been discussion about whether JAK inhibitors might in fact be protective. And the fact we haven't teased out the JAK data is purely a numbers data, as numbers thing. Because we as a group of academics and clinicians, number one, do not want to do harm. And if you start analysing super small data sets and start drawing conclusions off that, we are worried that we are going to send people down the wrong track. And I think that the pandemic has well demonstrated that people take academic papers straight into the clinic during this pandemic or straight into the ward.

And so we need to be careful about that. So that's something front of mind for us. And that's something that we'll clearly be looking at with this paper that's being worked on right now of around 1,800, potentially 2,000 patients. Because we're gonna have a three or four times as many patients to look at.

Peter, do you think that the IL-seventeen inhibitors poses a different risk or is apparently or possibly as beneficial as the IL-six and the TNF inhibitors in our patients?

Well, was approached by both of the big IL-seventeen companies to do trials because they're so convinced that seventeen is part of the cytokine storm that they wanted to look hard to see if suppression was helpful rather than detrimental. So I think that in our hands, we've been using them for six, seven years, we've not seen much in the way of the usual bacterial infection that you see with the TNFs. A little bit of fungal okay but I think it'll be a safe drug to choose in this situation as far as other things and complications are concerned, just a question whether suppressing seventeen is worthwhile or not. My gut feeling is it will be.

A number of the audience including Catherine Dow wants to know about, can you be more granular on the people who died? What was it about them that made or stood out from those who didn't die that are in the registry? Do you have an analysis of that at this point?

No, not at this point. We didn't feel that we had the power to look at death, but that is being worked on right now. So rest assured that is something that is important to us. We felt that we were able to power for hospitalization in this analysis and we are looking at death and ventilation in the next one.

But do you know death is cardiac or respiratory or renal? You got a feel for that?

Yeah, look, one of the real decisions that we made early on was we could give people We wanted to collect data and we wanted to collect data fast and asking for too much detail we felt would mean that we wouldn't get any data. So essentially we had to make some calls. We had to decide, well, we're not going to ask about this. We are going to ask about this. And that just meant that we got the data set that we've got.

I think we'd all love to have much more detail but I think that we would have a fraction of the cases. We don't have that data.

Peter, Frank Welborn in Houston says, thanks for your comments on telemedicine. He agrees when your rooms are the best clinicians in the world and our ability to touch has obviously distinguished us. What is your experience, either of you, on telemedicine and the virtual joint exam? What can you say other than when it's really good, it's fine, and when it's really bad, it's good. Where is the virtual joint exam really helpful and where does it fail you?

Peter?

Well I think, with a bit of help with your biologics nurse or your nurse educator, they can examine their joints reasonably well. They're not so good at swelling because they can't distinguish, this has been studied in PSA, they can't distinguish a Heberden's node is swollen from a synovitis in the joints. So they're not so great on swelling, they're very good at pain and tenderness. And really it's just one of those measures that you take into account with the ESR and the CRP and bloods and everything. So I don't think we have an issue that the joint count will make or break our management decisions.

I'm really kind of interested that we shouldn't miss other serious disease because we don't examine these patients.

Again, another question about when to resume meds, especially biologics. But now before we get into that, let me ask you point blank, what are you telling your patients if they get infected? If that patient gets infected, positive test, doesn't matter, to me it doesn't matter if you're in the hospital or not, are you telling them to stop their biologic or not?

At the moment, I'm telling them do not change your current prednisone dose, that's like thirty, forty percent of patients. I'm telling them to stop and to stay in touch and if they flare, then we have to pick up the pieces. I'm hoping that with evidence we can say continue your TNF because if anything in Philips data, it looks protective to be on the TNF. I'm hoping same with IL-six inhibition, a Plaquenil you can stay on. So at the moment we're saying to stop and stay in touch and if you flare then we have to decide what to restart.

What about you, Phil?

Look, I'm in the good position that I haven't had any of my personal patients in either setting I work have this. But I'm telling all my patients currently to stay on their current therapies because the risk is low. If they get infected, look, this data is very reassuring. But the thing is that this data cannot tell us is what, and this is one of the decisions we've made, what actually happens at the coalface? Have these patients, I know they've been on their biologics up to a time that they've been infected, but have they actually stopped them or have they continued them?

I've certainly seen non public data to say that there's a number of patients that have continued on their medications during this time. And based on this data, I think that's reassuring. Would also look, that probably changes based on the therapy they have. Look, it would be based on underlying disease and probably severity of their infection. But I think the reality is that unless you're using a short term agent, something like etanercept, then lots of these drugs are still sitting around.

You're on golimab or adalimumab or infliximab. These drugs are still sitting around whether you stop them or not. So that is partly the question is taken out of our hands.

What do you think about Plaquenil? Let's say you get COVID, would you take Plaquenil?

So, if people are interested in the thoughts that I have on plaquenil and on the people who are thinking about this at the registry, we've just published a paper in a correspondence in animals with rheumatic diseases. The take home from my understanding and my thoughts and discussions with clinical pharmacologists is you probably need to be on much higher doses than what we use in rheumatology to really make any difference. And the risk benefit of that changes substantially. So to answer your question, I don't think I would go on hydroxychloroquine if I got infected because I'm totally unconvinced by the data. Would I go on it for prophylaxis?

No. Would I go on it for treatment? Probably not. Certainly the thing is that if you have to go on twelve hundred or sixteen hundred milligrams, everything changes. Your risk benefit changes.

And we don't have the data to say that's effective or even safe. And based on the people, the way that people have been using it, it's not a home run regardless of what certain people have said. So I think in uncharted waters.

So we get a lot of Ross River virus, a lot of arboviruses and we're working with QIMR years ago for a vaccine. And they were saying that if they put chloroquine into the test tube they kill Ross River virus which is an RNA virus. But it's pharmacological dosing which is exactly what Phil's saying and I wouldn't take it because the dose you need is very high and you know sixteen hundred milligrams again it might be arbitrary but that's what they're using and not showing major effect. So at this stage, I would say no.

So everyone's looking forward to a return to some degree of work as we once knew it. And the question is, how are you each going to approach the return to work? What are the rules that you're looking to employ to encourage patients to come back to face to face meetings?

Well, in our country you need to catch up with people reasonably frequently to continue reimbursed therapy. So in a way we've got to control over that large group of people. Still gonna do a lot of telehealth. I've got patients in Singapore, Fiji, Darwin, Bali scattered everywhere and you you still manage those by telemedicine. People who live eight twelve hours drive away you manage by telemedicine anyway but it's the acute, it's the urgents, we'll keep the distancing going, we'll keep some gloves and some masks going for a while but I really think that that'll slowly stop and will gradually go back to work and the patients get more and more confident that they're not going to be at risk.

The waiting room's all spread out and social distanced. So I think once you can go back to a restaurant now, 10 people, you can get back into a club and a bar and a cafe. All of that will slowly turn around and change.

Yeah, I think having talked to family in The United States that we have, they find it hard to conceptualize the environment that we have here. So I can go to the shops, I can go to a restaurant here recently and open, but I can go to a restaurant here. I can go to the park, I can put my children on the playground. And so to Peter's point, I am now seeing more and more patients face to face because trying to see patients over the telehealth, essentially I gave up because I can't do my job if I can't, you might sound like you've got fibromyalgia, maybe you've in fact got disseminated cancer. And so I just felt that I was helping nobody by seeing especially new patients, stable patients who I knew and understood that's different.

But new patients, I actually gave up because I said, I'm helping nobody here. So I'm seeing more and more, I now see new patients face to face because the chance of them having COVID and our hospital screens people at the door essentially like a metal detector, but temperature and I make sure that people aren't unwell before they come and see me. I'm seeing patients face to face and more and more, and I need to see those ones that I need to procedures on as well. So it's going to return to normal and that's going be an individual situation based on your population prevalence and community transmission.

Well, of our audience has said great lectures, great session, they learned a lot. Thank you both for being on this Tuesday night rheumatology. Tell your friends everyone that we're gonna post this on the website tomorrow for all to see. Gentlemen, we'll see you soon. I guess it's time for you to go for your morning run as we go to bed.

Get back to work. Thank you very much, Jack.

Yeah. Thank you very much, Jack.

Alright. Bye bye.