RheumNow - RWCS 2018 - Day 2 Save

RheumNow is pleased to present the RWCS Daily podcast from the twenty eighteen meeting here in Maui. These podcasts are a compilation of each day's presentations by our featured faculty and presenters. We hope you enjoy these presentations from RWCS.

Hi, I'm Doctor. Marty Bergman here in Maui, Hawaii at RWCS and I'd like to talk to you about a presentation I gave today on disease activity measures. Specifically, I was focusing on disease activity measures for rheumatoid arthritis and psoriatic arthritis. The rheumatoid arthritis measures all come from the core dataset and are all have been validated, have been shown to be very useful. This can be the ACR twenty fifty seventy, the DOS 28, the CDI, SDI, GAS, Rapid, all are very valuable, all give very useful information, all have different situations where they're better than others.

In particular, I prefer the ones that look at disease activity at the current time rather than something that is a comparator from before. So, I particularly like the DOS, SDI, CDI, and Rapid three as well as the GAS. They're very useful. They have disease activities, they tell you how your patient is doing, they give you ability to treat to target, but they're only useful, one, if you do them, and two, if you look at them. It's simply not enough to look at, to give a disease activity measure so you get your check mark for your MIPS or MACRA, you really have to look at the values and then you should make a determination based on the results.

At the same time, it shouldn't just be based on the results, you still have to be a physician. So you have to interpret the results in the context of the person sitting in front of you, that is the patient, and if the two work, then you should make the changes in medications or whatever therapy you're looking at. When you compare though rheumatoid arthritis to psoriatic arthritis, the measures in psoriatic arthritis are far more complex than they are in rheumatoid arthritis for the simple reason that rheumatoid arthritis is relatively easy. It's the joints. Where psoriatic arthritis is the joints, it's the skin, it's the enthesis, it's the dactylitis.

Do you look at nails? Do you want to look at the site component? What is going to be the best measure to look at it? And the composite measures are all over the scale. In fact, there's a debate going on right now in rheumatology and dermatology.

Should we just look at just the joints? Or should we take a more holistic approach and look at everything develop a composite score that looks at all of

them?

My personal preference? I say rheumatologists do what we do best: we take care of joints and so we should measure joint activity, look at enthesitis and the like, but really direct our therapy at what we can control. If we don't get good results from the skin, that's why we have good associations and good collaborations with our dermatologists. So you have to measure. Measure is important.

Measure makes a difference. There are targets that can be reached when we get our patients to the target, be it rheumatoid arthritis or psoriatic arthritis. They have better work outcomes, they have better life outcomes, they have less hospitalizations. So measure, look at your measures and adjust as per your measures. So thank you.

Hi. I'm Jack Cush with RheumNow, and I'm here at the RWCS meeting two thousand and eighteen in Maui. This morning, I was part of a interesting session wherein doctor Arti Cavanaugh and I discussed some of the highlights in the last year in rheumatoid arthritis. I'll review a few of those from today's presentation. First is the RAM study.

That stands for the rheumatoid arthritis medication study. This is a UK study of five hundred and forty five patients who are prospectively enrolled because they had early arthritis of less than two years duration. And it basically looked at the drugs that were used and the influence of prognostic factors on outcomes. As you know, many of us actually look at prognostic factors like, sed rate, CRP, seropositivity, age, the presence of erosions, etcetera, as, factors that may influence the therapies that we use. May we need to be more aggressive in such patients because those people have a poor prognosis.

Well, in this particular study, they looked at the patients with poor prognostic factors. They called them the PP plus group, which actually was only about fourteen point five percent of the overall population, and compared it to those without the poor prognostic factors group. And while they were perfectly balanced in all respects, as you would imagine, the poor prognostic factor group had more erosions and more seropositivity. But when it came to outcomes after a year of therapy, and the therapies are about the same in both groups, there really was no difference at one year with regard to the HAC score changes and or the changes in disease activity score, suggesting that poor prognostic factors generally do not make that much of a difference when it comes to down the road outcomes. Now it may just be that that this is only one year, and we would need four years or five years to actually see some of the changes between those with and without poor prognostic factors.

But it sort of, is a detraction from what our current practice is, which is to look at these factors and help that to shape some of our therapy. Next, we looked at long term safety. This is a nice report by Gerd Burmester where he looks at nearly thirty thousand patients treated with adalimumab, and and that's in nine different indications and looked at all the safety events from infections to opportunistic infections to serious infections to the myelin disease, cancer, skin cancer, lymphoma, sarcoidosis, you name it, all the adverse events, common and rare associated with the use of a TNF inhibitor, in this case adalimumab, and they looked at the overall rates reported as events per one hundred patient years. What you need to know from this pretty large study with a lot of numbers is really just two things, that the serious infection rate across the board with nine different indications from uveitis to psoriatic arthritis and rheumatoid arthritis was that the SIE rate for RA was four point six per 100 patient years and as high as six point eight for Crohn's disease and one point eight for some other disease in the group. And all these rates were generally low and stable over time.

And then by comparison, everything else, opportunistic infections, TB, sarcoid, lymphoma, etcetera, all those were basically one in one thousand risk. So that's a big story. That actually tells you when you're talking to patients, you should tell them everything that they're very worried about, that they may read about, really only has a one in one thousand risk across the board in the case of this drug adalimumab. As you know, the new, shingles vaccine was released in September. This is a GSK vaccine called, Shingrix.

It actually is a a subunit adjuvant vaccine against herpes zoster, and, this drug clearly has advantages to the existing vaccine. Compared to the existing vaccine, Zostavax, Shingrix is an inactive virus, Zostavax is live virus. Shingrix actually has better efficacy data where they get ninety percent protection against shingles events. There is no difference in age groups because with Zostafax, you would see that as the older the patient got, the the efficacy waned. That also held true for postherpetic neuralgia events were more common in the elderly.

Whereas, again, with the the inactive virus, the new virus, the new vaccine, there is no, diminution in the protection against postherpetic neuralgia. They're gonna be about the same cost. However, the new vaccine, Shingrix, requires two injections, one done at time point zero and the second one done between two and six months later. And, again, they're about the same cost. The only difference is going to be that there's probably more, toxicity or side effects.

A lot of Neutman side effects, alge myalgias, arthralgias, feeling flu like, etcetera, that are common with the new Shingrix vaccine that are not really seen with the older one. The problem is that both of these have not really been studied in our patients with rheumatoid arthritis or lupus or psoriatic arthritis on biologics. And that's what we need to see. Right now, there's no plans to do those studies. We need to, implore the maker to do those studies in our patients so we know how to best use them.

We certainly have an experience with the rules that we have with the live virus vaccine to, you know, hold the drug, for hold whatever biologic you're using for four, four weeks or so and then vaccinate and wait at least two to four weeks before you restart. We don't need to do any of that with the new vaccine, but then again, don't know how a new vaccine is gonna be tolerated in immunosuppressed patients. So that'll be interesting to see how that's gonna progress over time and how rheumatologists will adopt this into their practice. As you know, there were guidelines that, that came out last year, a lot of new guidelines, and it was an interesting report in JAMA about eight different ACR guidelines over the last decade or so, and and what the evidence was for each of them. In total, there were eight guidelines, 403 recommendations that were looked at.

And the sad unfortunate part of the results that they reported was that almost 60% of these guidelines were based on grade c evidence, meaning expert opinion. And only 23% were based on grade a evidence, that being double blind randomized controlled trials. So given the importance these guidelines have in our daily practice, to have so many of them reliant upon grade c, and it actually would be higher if we looked at a few different diseases as opposed to all of them. It's a little bit disheartening, suggesting that maybe we need new ways of developing guidelines that are aren't so dependent only on, grade a evidence, meaning randomized controlled trials, which, by the way, are all pharma sponsored and tear intend to serve the interest of the drug understudy by the the pharmaceutical sponsor. Real world drugs like myositis treatment with azathioprine or combinations of different conventional DMARDs in rheumatoid arthritis, those the kind of trials, that would tell us about their efficacy and safety really aren't done because there's no funding to do them.

So we have to rely on real world. So, anyway, there's a there's a detriment to, and a limitation to the current use of guidelines by the ACR. And lastly, there's an interesting report that appeared, I think, in New England Journal and in The Lancet at the same time called the CANTOS study, that's c a n t o s. It is a study that's not not done in arthritis patients, but instead in patients with cardiovascular risk. So these are patients who previously had a cardiovascular event, who have higher a high number of risk factors, who have an elevated CRP, and they put them on either placebo or one of three different doses of, canakinumab, the IL one inhibitor canakinumab.

And what they showed was that the two highest doses actually showed protection against cardiovascular events. So the placebo group had a rate of 4.5 cardiovascular events per 100 patient years, and it was decreased to 3.9 if you were on the IL one inhibitor canakinumab. Also in this trial, what they showed was that patients who are on canakinumab had a lower rate of cancer, especially lung cancer, leading the manufacturers of this to study canakinumab in patients with lung cancer going forward as adjunctive therapy. This is one of three trials that are out there out there that are looking at the use of anti inflammatory therapy in heart failure and high risk cardiovascular patients to see if control of inflammation may yield better cardiovascular outcomes in those at high risk. Anyway, that's it from RheumNow.

Great meeting. Tune in for more videos on RheumNow and at rwcs.com. Hi. I'm Jack Cush, RheumNow. I'm here at RWCS two thousand eighteen in Maui.

Fabulous meeting. I wanna tell you about a session that I ran yesterday called Hot Seat. Hot Seat's a session I've been doing for the last four years where I'm the moderator, and I present real world vignettes to an expert panel of faculty who get to weigh in in a sort of stump the chump manner on what the diagnosis, what the approach is, how you would manage some real world patients that I've seen in the past year. I'm gonna give you three examples of what we covered yesterday. First is a case of a 32 year old white male who presents with, three tender joints, two swollen joints, and he's had a three month history.

And he's not done well on nonsteroidals over the counter. He comes in and sees me, and the question is, what do you do? Obviously, he was tested. All of his tests were negative. He's seronegative for ANA rheumatoid factor, CCP fourteen three three eight, a parvovirus, hep b, hep c.

Everything's negative in him, and he gets treated with a short course of steroids. Ten milligrams a day for two weeks, five milligrams a day for two weeks. He returns a month later. He says the steroids didn't help him very much, but he no longer has any swollen joints, but he still has two tender joints. And the question is, what do you do with these patients?

This was discussed by the panel. Most felt that you basically manage such a patient symptomatically, unless, of course, he's a person who needs his hands for his job, in which case you may want to be more aggressive in managing inflammatory arthritis from the outset because he clearly did have inflammation when he first presented. This is best termed undifferentiated polyarthritis or oligoarthritis or undifferentiated arthritis. Turns out that such patients are more common than rheumatoid arthritis and their outcomes are different. Undifferentiated arthritis patients have a greater than fifty percent chance of going into remission whereas RA seldom goes into remission, less than ten percent of cases.

Undifferentiated arthritis often responds very well to steroids and symptomatic management and may not need, but they sometimes will need short courses of DMARDs such as methotrexate or hydroxychloroquine. This patient is still being followed up. His course seems fairly benign at this point. He's being managed with nonsteroidals rather than methotrexate. The second case is a, young girl, 14 years old, who presents with polyarthritis and is found to have an elevated aldolase.

She's 14 years old. She presents with arthralgias and aches and pains and not being herself. And she's athletic and she's still doing her sports, but she feels that, you know, the pain is is bothersome to her. On exam, she actually has seven tender joints, six swollen joints. She has erythema and Gottren's like lesions over her knuckles, and she has periangular erythema.

Labs are fairly normal, although she does have an elevated sed rate and CRP, and her aldolase is 14, but her CPK is normal. On further testing, hepatitis serologies are all normal. This patient was considered as having possibly minocycline being used for her acne. Minocycline induced, lupus or arthritis turns out that even when minocycline was withdrawn, her symptoms persisted. So what does she have?

Does she, does she have arthritis? Is it drug induced? Whatever my diagnosis was, and and we had had a few that reluctantly went along with this, was that she has JDM, juvenile dermatomyositis. And it turns out that half of such patients will have arthritis and polyarthritis that can be quite aggressive and needs need to be treated. When I saw her with her first presentation waiting for labs, I put her on methotrexate, twelve and a half milligrams a week, along with some low dose prednisone that we withdrew.

And then in, several months of follow-up, she's done great. Her skin lesions have faded. Her alkalase is normalized, and her, joint counts have gone way down. So that's JDM with an arthritis presentation. Again, when you're seeing kids, if you see kids, the early diagnosis of JDM can be challenging, and you need to look for the heliotrope rash, which we seldom see in adults, and be aware that they can get arthritis.

They can get a high amount of calcinosis in children also with JDM. Last case was a fibromyalgia patient who all of a sudden started having FUOs. She presents with a several month history. A 30 year old woman presents with several month history of fevers almost daily of a 102 to a 104, highest being a 104.7. Labs looked fairly crazy in her, but not much in the way of clinical findings other than non painful, non itchy urticarial lesions that tend to come and go with the fevers.

On exam, she had a lot of tender joints due to her fibromyalgia, but no swollen joints, no lymphadenopathy, no hepatosplenomegaly. The lab showed very high sed rate, very high CRP, a ferritin of 1,280, and negative tests for hepatitis and other infectious etiologies, including, TB and mycobacterial infections. She did, however, have a very abnormal S PEP with a, a big increase in the gamma fraction. And on immunohlex immunofixation, she actually had, biclonal gumopathy. So the question is, here's a person who has what appears to be an auto auto inflammatory syndrome, and what is it?

The panel thought it was adult Still's disease, but she didn't really fit the quotidian fever of Still's disease. She didn't have any swollen joints, she didn't have the rash of Still's disease. She actually was very characteristic of someone who has adult onset Schnitzler syndrome. Schnitzler syndrome is an adult onset disease. It's an adult onset febrile syndrome that's classified amongst the auto inflammatory disorders.

And like systemic JIA and like adult onset Still's disease, it presents with daily fevers. It is distinctive in that it often has non painful urticaria associated with it and in that it also has a monoclonal or polyclonal gamopathy associated with it. Such patients are at high risk for, lymphoplasmacytic malignancies and Waldenstrom's macroglobulinemia developing in up to fifteen percent of individuals. So they do need to be followed by the hematologist as well as rheumatologist. As this is an inflammatory syndrome, have a unique and special, a great response to IL-one inhibition.

This patient went on anakinra. Her symptoms went away just like that. She's being followed out now prospectively. She's doing incredibly well on daily shots, but she needs to be watched for hematologic malignancy. Anyway, some interesting cases.

The panel and the audience loved it. A lot of discussion. We'll see you next year here at RWCS. Thanks very much.

Hi. I'm doctor Marty Bergman, and I'm here in Maui at the RWCS meeting. Yesterday, I gave a lecture on meta analysis and how to interpret it. I think it's important for us when we look at meta analysis to go beyond simply looking at the title and conclusion because what goes into the meta analysis is just as important as what comes out. Meta analysis at its best can be the pinnacle, can be the best of all studies, but if done improperly, it can truly be garbage in garbage out.

The best way to do to look at it is to really look at the components. You have to see what was done, how they pick how they pick the different articles, the different journals, did they look for biases, how did they combine the studies, and then how did they finally interpret the studies. And if you don't look at each of those components or if each of the components aren't present, then you're wasting your time looking at them. These are really complex studies that have a lot of potential of being beneficial, but a lot of problems with being fraught with biases and problems. You start by looking at how they picked those journals, how they did it.

There should be a systemic review, and they should tell you how they did it and what their biases were. Were their biases? You have to look at whether or not the journals and the articles that they picked, were those studies, should they have been combined? And there's something called heterogeneity, which is a measure of how different they are. If the heterogeneity is way too high, either they shouldn't be combined or you could separate out.

When you look at it, check to see the weighting. Look to see whether or not one study drove the entire result or was it truly a meta analysis of multiple results. And when you finally look at it, check the confidence intervals. Make sure your confidence intervals for the final result doesn't cross the one or the unitary or the midline. If it touches or goes over that midline, you've shown no difference between the therapies that you've been trying to look at.

So again, meta analysis, beautiful work. It's wonderful studies. It can be the absolute pinnacle of studies. It can give us information and ability to combine different studies together that ordinarily wouldn't have had given us the results, but at the same time, when done poorly, it truly is garbage in, garbage out.

Hi, I'm Doctor. Rachel Tate coming to you from Rheumatology Winter Clinical Symposium in Maui, Hawaii. And I am here today interviewing Doctor. Philip Alekshiauk from USC about his poster. Phil, tell us about what's going on.

Hi, everyone. So I'm Phil. I'm, from USC. I'm one of the second year fellows, and I'm here to present my poster on drug induced ANCA vasculitis. So essentially, I had a elderly gentleman in his seventies, with multiple comorbidities, including heart failure with reduced DF, CKD, CAD status post multiple CABG's, actually.

He presented with a couple months of inflammatory arthritis within his elbows and his knees, alterations within his mouth and his buttock, and he also had these vasculitic lesions over his fingertips. Of note, he was on high dose hydralazine for many years, and he also had a recent, cardiac catheterization, performed prior to admission. So essentially, when he was admitted, we did find that he was leukopenic. He was anemic. He had high inflammatory markers.

His UA and his chest X-ray were completely normal, but what was interesting was that his serologies, were very remarkable. He had a high titer ANA, high titer double stranded DNA, high histone antibody, P ANCA, high titer MPO and p r three, anticardiolipin IgM, and DRRVVT. So it was quite interesting. Aside from that, we did an infectious workup, of course, and, his TEE did show that he had a four millimeter vegetation on his aortic valve. And the one part that we actually couldn't figure out to this point was why his HIV screening was positive.

So he had an HIV screen that was positive with HIV one RNA that was detected, but, the quantitative analysis was still pending at that point. So I, you know, I I came across this pretty large differential diagnosis for him. I wasn't sure if it was related to endocarditis, drug induced lupus, drug induced ANCA vasculitis, HIV associated vasculitis, APLS, cholesterol emboli syndrome because he did have a recent cardiac catheterization, and malignancy, of course. So what kind of differentiated this towards a drug induced ANCA vasculitis for me was when I did my literature search, I had come across these similar serological profiles from another study, essentially. And the study included four patients here, up in the top right, where they all had high titer ANA, double stranded DNA.

They had low complement, high titer ANCA, and high titer NPO. And then they also had positive, anticardiolipin IgM IgG, beta two IgM, and IgG. And essentially what kind of differentiated between drug induced ANCA vasculitis and drug induced lupus was that the double stranded DNA is more typically elevated in drug induced ANCA vasculitis as opposed to drug induced lupus. And also, those patients with drug induced ANCA vasculitis, typically present with more severe presentation, most severe vasculitic lesions, and also they may have placentic glomerulonephritis, that type of thing. So, yeah.

There you go.

Phil, you did a fantastic Thank you so much for presenting your poster. And it goes to show that research is still important in what we do every day in clinical practice as well. So taking note of everything that we've learned today, it's really important to be able to determine between drug induced lupus and drug induced ANCA vasculitis. So again, I'm Rachel Tate. I'm presenting from Rheumatology Winter Clinical Symposium in Maui, 2018.

And for this and more information, check us out on roomnow.com.

Thank you very much. Hi, I'm Orin Traum. I'm a practicing rheumatologist in Santa Monica. I'm the clinical faculty at the University of Southern California in Los Angeles. We're here at the RWCS twenty eighteen meeting in Maui, and Alvin and I just went over some things that we're gonna talk about in just a second.

Alvin?

Yes. I'm Alvin Wells. I'm a rheumatologist in private practice in Franklin, Wisconsin. Arne and I just did a 2017 review talking about gout, osteoarthritis, and scleroderma. Arne, you show some data about new intra articular injections.

What do you think is gonna be one of the things that our rheumatology colleagues to look out for?

There are there was presented at both EULAR and ACR some new data about potential demodes, disease modifying anti osteoarthritic drugs that are really exciting. The potential here is to not only increase cartilage growth, but to decrease pain. And some of those look very promising, although there are still phase one and two studies.

I think it's really exciting because now with osteoarthritis, just like with rheumatoid arthritis and psoriatic arthritis, we're looking for structural changes. No longer is it just good to help their pain and their function, but we're looking for cartilage growth. That's why some of these new small molecules you talked about as well. I, from my perspective, I think is good news and bad news. We talked about maybe some of these intra articular injections might not work as well as we think.

But we also talked a little about opiates. I know, Oren, this is something you talked about in the past. What do you take on opiate medications for treating OA?

So there was a very nice study that was done that really looked at the use and really overuse of opioids, and there was a particular section of the population, younger women, less than 65 years old, that were getting spinal osteoarthritis surgeries that were most likely to overuse opioids. So we really have to be careful about the use of opioids and potential for overusing them and for overprescribing them.

And We shared some of this too with the link also on the website as well. Some other things we kind of feature looking at what's new for exercise recommendations and also as we get into scleroderma. It's a challenging part. We don't have any great disease modifying medication, but some phase two data looking at subcutaneous tocilizumab might be the first hint that this is something that's going to help for our patients with lung disease and also skin involvement for scleroderma. So I think it's kind of exciting.

So I think overall, Oren, your take home message. So osteoarthritis, gout and scleroderma, what are some things that really our colleagues can use to use really tomorrow in the clinic?

The other aspect of our discussion was really about gout and the fact that there is such an increase in comorbidities associated with an increasing rate of gout in The United States. And so to target those patients and to really make sure that we are reducing their weight and having them exercise not only for osteoarthritis but also for gout and some of the newer therapies for for gout that are really outstanding in in in particular in reducing the tophaceous deposits like the Glodecase and other newer therapies that are on the horizon.

I think this is exciting time for rheumatology and exciting to be here for RWCS two thousand eighteen.

Thank you very much. Thank you.

Hi. I'm doctor Rachel Tate coming to you live from Rheumatology Winter Clinical Symposium two thousand eighteen in beautiful Maui, Hawaii. We wish you were here, but since you're not, presenting for roomnow.com, I wanted to take to tell you a little bit about the fellows posters this year. So I have the pleasure to interview doctor Shuba Colombare who's here to discuss her poster. Shuba, thanks for coming.

What brought you to Maui?

I was chosen by my chief of rheumatology to, you know, I was given an opportunity to attend this conference and that's how I am here.

Well, that's great. Tell us about your poster.

So in a nutshell, this is a case of eosinophilic granulomatosis with polyangiitis. 72 year old woman with no significant past medical history, with the recent onset of asthma, and this history of this new onset altered mental status, was transferred transferred to our facility for further management. And upon examination, she was found to have this mononeuritis multiplex and also this, you know, non blanching, vilecious rash that was very vasculitic in nature. And then upon biopsy, it was noted to have leukocytoplasmic vasculitis thereby ruling out hypereosinophilic syndrome. And she also was found to have eosinophilic or eosinophilia in her blood, 39%.

Yeah. And also a p anchor that was positive with a high titer of actually 80. And then with all this in mind, we had ruled out hypereosinophilic syndrome and it was, you know, highly likely that this was eosinophilic granulomatosis with polyangiitis. So we basically pulsed her with methylprednisolone one gram for three days. She didn't really improve much.

And with that altered mental status that is progressing, we wanted to give her intravenous cyclophosphamide. And we've been doing we did that. We used her for monthly for every six months. I mean, monthly for a total of six months, followed by maintenance with azathioprine, she's doing really well at this point in time. She does have the mononeuritis multiplex that's persisting, but, with everything else, she's doing well.

That is a great case. So when you think about eosinophilia and you think about potential for mononeuritis multiplex as well as for altered mental status, I think we need to be thinking about EGPA. Thanks, Shuba. Shuba. Thank you very much.

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