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Hi. I'm Jack Cush with RheumNow. I'm here at RWCS two thousand nineteen in Wailea in Maui. Great meeting. Great faculty.

We're just had our first morning. We led off the meeting, Artie Cavanaugh, myself, with an update in RA, what we thought was exciting or interesting from, recent meetings and what was published in the last year. I'm gonna cover three things, that being prednisone, seropositivity, and cardiovascular issues. The first, prednisone. The SEMIRA study, authored by Gert Burmester and Frank Bucharek looked at the value of being on continuous low dose prednisone.

These are RA patients who are on conventional or biologic DMARDs, and they're either on five milligrams of prednisone and they're in remission. And they continue half the group on the five milligrams of prednisone, and the other half, they have a tapered withdrawal of steroid. And they look at the outcomes after twenty four weeks. Well, there's positives and negatives to this. Clearly, patients who stayed on the five milligrams of prednisone did better.

And and significantly better, you look at the graphs, it's like this and this, and, and it looks like, well, I should probably continue the five milligrams of prednisone. And the side effects and toxicities were a little bit more when you were on the prednisone versus off the prednisone, but it wasn't very significant. But remember, there's only twenty four weeks. What would have happened if that was taken out for two years or three years? What was seen, however, was that two thirds of patients who they tried to withdraw the steroids on actually did very well and were able to withdraw and stay off the steroid.

When you look at, again, the continuous group, they had, 14 flares. When they look at the steroid withdrawal group, they had 34 flares. So there's a price to pay in getting off steroids, but the benefit is that two thirds of patients can get off, and then there's a long term consequences. So, again, maybe the story really has to do with the activity of the patient. The patient has really severe disease, low dose prednisone might have to be part of your long term regimen.

On the other hand, if you're doing very well with therapy, why not try to get to no steroids in two thirds of the patients, even risking the chance of flares in some? A really interesting paper could spurn a lot of discussion. The second issue is seropositivity, We presented a few different things about seropositivity. One was clearly the benefit the the hazards of the titer of CCP. The authors on this particular paper looked at low titers of CCP versus medium versus high, and these are in patients who are just CCP positive but did not yet have rheumatoid arthritis.

Clearly, medium and high levels of CCP was associated with significantly increased risk of developing RA in, I think it was one year or two years. And the high titer ones were were a fifth more than fifty percent developed rheumatoid arthritis. I think that tells you a lot, especially when considering what the seropositivity means in someone with preclinical RA not yet diagnosed. Another interesting abstract looked at the, whether you go positive or negative on rheumatoid factor or CCP. This is a large study, the improved study that looked a lot of different, therapies, a lot of different patients, and basically showed that with therapy, patients' rheumatoid factor and CCP will usually decline so that the seropositivity is a function of how much inflammation you have.

However, even though it does come down, it does not correlate with clinical measures of activity. You are good responses, other types of responses, etcetera. So you really can't use as an outcome or biomarker and whatnot. And likewise, they showed that when people flared, their rheumatoid factor CCP usually rose. So again, there's a real limitation to this seropositive issue as far as either choosing therapy or monitoring therapy, but it is an expectation of therapy.

And lastly, cardiovascular issues. We showed a lot of different slides showing what you all know. Methotrexate clearly reduces cardiovascular risk, cardiovascular death. TNF inhibitors and other biologics further add to that reduction, and that's all well and good. The question is, with those great therapies, especially methotrexate or biologics, can that be applied to patients who don't have rheumatoid arthritis?

Patients at high risk for cardiovascular endpoints like MI and stroke and whatnot. So these are patients who cardiac patients, no arthritis, and two main major studies we reviewed. One was the CANTOS study, and the second was the CERT study. CANTOS was a study of canakinumab, the I one inhibitor, where patients who are cardiovascular high risk were enrolled, and they had to have a high CRP going in. The CANTA study was great.

It showed that there was a significant reduction in cardiovascular events and cardiovascular deaths, but there was these additional things that were really astounding. There was less gout attacks in people that were on chronic IL one. There was, less need for orthopedic and, and and hip and knee surgery and joint replacement. And lastly, there was less cancer, especially lung cancer in the patients who were taking the IL one inhibitor. However, the real study everybody was waiting for was the search study.

Both of these were authored by Paul Rittger out of Harvard. The SEARCH study looked at methotrexate as the intervention. The studies were roughly the the same in their design, who got in, what the endpoints were, but the SEARCH study, the methotrexate study did not require a high CRP going in. And as such, that study failed. It was actually prematurely, halted.

They had, equal number of cardiovascular endpoints, with either those are on placebo or those are on methotrexate. And that study has basically killed the idea of control of inflammation in cardiovascular patients at high risk outside the arthritis clinic. We will continue to use these therapies in our rheumatology clinics, but amongst cardiologists, the talk is that didn't really work. And oh, by the way, the CANTO study, which was so successful, went in front of the FDA and was re denied by the FDA to have cardiovascular risk as an indication for the use of the IL-one inhibitor. Now they're negotiating and maybe that'll come out differently in the future, but it doesn't look good for treating inflammation to manage the inflammatory component that goes along with cardiovascular disease.

We certainly know in RA, there's an inflammatory component. We're managing it in a sort of bystander way and using it as a way to push therapy. So, anyway, these are this was just a small sampling. Audio will give you the rest. Check out the videos for RWCS on RheumNow and rwcs.com.

Hi, I'm George Martin. I'm here at Rheumatology Winnowhere Clinical Symposia on the beautiful island of Maui where I practice dermatology. And for today's session, I covered what's new in dermatology for the rheumatologist. I started off with talking about atopic dermatitis and dupilumab monoclonal antibody directed against the IL-four alpha receptor really knocks out two cytokines, IL-four and IL-thirteen, which are the primary drivers for atopic dermatitis. And the data is very strong, and it's been out in practice, and a total game changer, in an arena where moderate to severe atopic dermatitis has historically been treated with cyclosporine, methotrexate, azathioprine, and the like.

And so we're very excited to have dupilumab on board, but given the science behind dupilumab and its efficacy, there is a whole host of monoclonal antibodies now entering the atopic dermatitis treatment spectrum. They are the IL-thirty monoclonal antibodies, trilacicizumab and lebrikizumab, and both of them have demonstrated significant improvement in moderate to severe atopic dermatitis. The anti IL-thirty one monoclonal antibody that's directed against itch also appears to be very effective in treating atopic dermatitis. There's a whole host of monoclonal antibodies coming forth, that includes IL-five and IL-thirty three monoclonal antibodies. Also of interest is the impact of JAK inhibitors for the treatment of atopic dermatitis.

It turns out that the JAK1 inhibitors are performing almost as well as the monoclonal antibodies for the treatment of atopic dermatitis. Baricitinib is certainly an effective agent for the treatment of atopic dermatitis That along with other JAK1s will make its way to market. Topically, Tepinerof, aryl carbon hydrolase receptor agonist, has shown very nice efficacy and is an alternative to topical steroids and it's making its way into phase three. On the psoriasis front, we're about ready to receive risankizumab, a very potent anti IL-twenty three inhibitor where PASI 90 scores are up in the seventy five percent range and nearly half the patients get complete clearance. This is the new anti IL-twenty three monoclonal antibody that's set to make its way to market in April.

In addition, we have another IL-twenty three blocker that is in market, just recently approved, and that's Tildracizumab, also called ILLUMIA. It's dosed at one hundred milligrams at week zero and four and then every twelve with very nice, efficacy and long term maintenance. Cimzia, cerdulizumab just was approved, in May for the treatment of psoriasis. The effective dose is a four hundred milligram every two week dose And, because of its unique structure, and its lack of penetration, through the, placenta and into breast milk make it a really nice choice for women of childbearing years. Those are women between the ages of 15 and 35, and that's an age group that psoriasis oftentimes presents.

So that's my summary on the atopic dermatitis and psoriasis medley of what we covered at RWCS this year. Hope you'll join us next year in 2020.

Hey, I'm Jack Cush. I'm here at RWCS in Maui 2019. Great meeting. I want to tell you about my debate with Doctor. Roy Fleishman.

Roy and I have been calling it the great debate, trying to drum up some interest. It wasn't actually billed as such. We had a good crowd. The topic of the debate was should pre RA, should preclinical rheumatoid arthritis patients, should they

be

treated? Meaning that if you identify them, should you put them on a DMARC? As you know, this is a growing area of research interest that we know for many years that long before the diagnosis of RA is achieved, that patients can have autoantibodies going back ten years earlier that would antecede the onset of disease, And, this has led to a whole new area of investigation, preclinical RA. You start out with someone who's at risk, genetically at risk, having a shared epitope or being homozygous for the shared epitope, that along the way they develop autoimmunity, usually as a result of environmental triggers like smoking, obesity, etcetera. And then the autoimmunity they get is manifest as autoantibodies, CCP, rheumatoid factor, CAR P antibodies.

These are all present as far as ten, fifteen years before the onset of disease. The interesting thing is that as they get closer to their diagnosis date or the onset of synovitis, bilateral symmetric synovitis, they get more and more of these autoantibodies. So you know that early RA patients, patients who are diagnosed often only are going to be rheumatoid factor positive in forty to sixty percent of the time, but that is over time that will go up even further. It is a continuum of auto antibody, expansion, epitope spreading that will lead to more auto antibodies. So the idea here is that, is it a defined point that you need to be worried about or you need to be worried about them beforehand?

I made the case in favor of, in fact I was forced to take this position, that you should treat patients at the preclinical RA stage. So I wanted to start out with what's the definition of preclinical RA? There's two that were reviewed in this session. One is a first degree relative of someone who has a diagnosis of rheumatoid arthritis who is CCP positive and has arthralgias. That would be one definition.

Second one that Roy also reminded the audience was someone who has one of these rheumatoid factor, rheumatoid like autoantibodies along with symptoms. Now, either definition cannot actually achieve old 87 criteria for rheumatoid arthritis or the newer twenty ten ACRULAR criteria for the diagnosis of rheumatoid arthritis. So, the idea is that, again, they're sort of set up. Well, the data I showed showed that if you're just seropositive, the risk of developing future inflammatory arthritis and rheumatoid arthritis ranges from roughly twenty to as high as seventy percent. So there is some risk there.

The numbers go up when you start adding in other risk factors being double positive for CCP and rheumatoid factor or being found in a secondary clinic like a rheumatologist clinic as opposed to a general health fair screen. You know, obviously there are other things including the environmental and lifestyle triggers that can further add to that risk. Being first degree relative adds to that risk, but just based on the autoantibodies alone, it ranges and probably it's around maybe a thirty percent, but might be the average risk. I think that's something very important and worth knowing. But is that enough to make you treat?

The whole issue here is it's an opportunity for prevention. That was my tact, get people to think if we treat during this window, this true window of opportunity, that in fact, that you may be able to affect the outcomes. The evidence of that, however, isn't so good because the trials aren't so good. There's a number of trials done in steroids, in dexamethasone, high dose steroids, where it didn't work. Short term improvement, no one got any long term protection or no deterrent from getting rheumatoid arthritis.

There's the prompt trial where they used methotrexate in undifferentiated arthritis, which is not the same. Those patients are a little further along the continuum. Again, continuum starts with genetics over here, then environmental triggers and autoimmunity, then early undifferentiated disease, over here you get rheumatoid arthritis. Undifferentiated So, patients not meeting rheumatoid arthritis criteria, they were given methotrexate, and early results looked good, later results, long term results didn't look good at all. But there were people in that subgroup who did benefit from getting methotrexate even at the pre diagnostic stage.

In the end, Roy showed data that wasn't too impressive, the steroid data, the prompt data, the prairie study, a few others. Again, the studies weren't very good, but the studies are limited by short duration of exposure. Prairie study was a study of rituximab being given one infusion, one thousand milligrams, and following people out for thirty months. It actually did forestall the development of rheumatoid It took sixteen point five months versus eleven point five in those who got placebo. There was fewer cases of rheumatoid arthritis, you know, thirty four versus forty.

So the effects were not great here, they got suboptimal therapy. The same was seen with six months of therapy with Abitacin, where again, the long term benefits were little, but they only got six months of Abitacin. There are more studies that are in progress right now and maybe we'll know more. In the end, we had a vote. Roy taking the position, showing the the the negative view by the crappy data that that we both were using, seemed to sway the audience into thinking this is not, something you should be doing.

I tried to make the case that that I was right and people just had a hard time understanding my my masterful presentation. But in the end, I think it was a good discussion. We had a lot of questions from the audience. I would tell you that the takeaway from this should be the following: The people you need to worry about who are not yet diagnosed with rheumatoid arthritis are the following: Those who are double positive for RF and CCP, a high, high percentage of those people are going to get rheumatoid arthritis. I'm saying greater than two fifty CCP, many hundreds, hundreds or thousands as far as international units of rheumatoid factor.

People who have seropositivity and who are first degree relatives, that's also a group that you need to worry about. Of course, people who have one joint becomes two becomes three becomes four, you're already on the way to making a diagnosis of rheumatoid arthritis and how you intercede is going be up to you. That's it from RWCS. Tune in for more interesting videos from this great conference.

Hi. I'm doctor Marty Bergman. I'm here in Maui at the RWCS meeting. I just finished talking about burnout and, what you can or can't do about it. Burnout's a serious problem.

It's been estimated that fifty four percent of physicians are experiencing burnout, and this is having a significant impact on health care. There's a high rate of of depression, high rate of drug and alcohol abuse, and there's a three to five time increased rate of suicide among physicians, mostly attributable to burnout. There are many causes of burnout. It goes from the personality of who we are, who we the the people that go into medicine. We have a certain personality.

We tend to be individualistic. We tend to be very, altruistic, and we tend to try to do our best at all times, but that's not always the best way for us to be. There are also institutional issues, too much burden on the patient, on the physician, too much documentation with EMR and the like, loss of autonomy with pre certifications, not having to choose. We have increased risk or what's called asymmetrical risk where we when we succeed, there's very little reward. When we fail, there's major repercussions.

So what can we do about it to make a to to end this problem? Well, there's no one solution, but I think it starts with us, ourselves. You should spend a lot of time in the beginning of your career. You should start telling yourself, what is it that I want out of my career? Do I want advancement?

Do I want family? Do I want free time? Do I want no free time? And come up with something that is satisfying to you. Recognize that you don't have to spend a lot of time on yourself.

Studies have shown that if you spend at at least 20% of your time while working doing something that you find clinically meaningful, that's all it takes to significantly reduce burnout. But I think we also have to involve our institutions. Our patients are suffering, but our institutions are suffering. So the same people who are asking us to do more and more with less and less, we have to make it clear to them that they're suffering. There's less productivity.

There's less income. There's less patient satisfaction. They're losing services. So it's not only us. It's not only the physicians that are suffering.

It's not only the patients who are suffering because of increased medical errors, lack of satisfaction, depersonalization being treated like meat rather than a real person. It's also an institution. So I think any solution that comes is not going to come from one group. It's going to come from all of us, and I think some of that may also be a role for organized medicine. So it's a major problem.

I think we have to face it. You can't pick up a journal today or pick up anything today and not see it, but I really think this is something that we have to face. So thank you for your attention. If you have any more interest in this, please go to RheumNow, and thank you for listening. And once again, greetings from sunny Maui.

Have a good day.

Hello, I'm Paul Emery. I've just given a lecture at RWCS which is about the optimal use of imaging. The take home message from that is that because joint counts, joint examinations are less accurate at the most critical time points which are the presentation of disease and at remission, we tend to use imaging a lot in those points and they are the time points when the most critical decisions these days are being made. I also try to make the point that you shouldn't image everybody but you should consider that if imaging is going to change your management or the findings of imaging are going to change your management then you should undertake it but if they are not it's an unnecessary examination. I also made the point that MR can do things that ultrasound can't particularly in variegated disease identifying the sites of lesions and of course imaging can be very helpful in SpA.

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