RheumNow Podcast - Top 13 Rheumatology Centers (7-31-20) Save

It's the 07/31/2020. This is the Room Now podcast. Hi, I'm Doctor. Jack Cush, executive editor of roomnow.com. This week on the podcast a bunch of stuff about gout.

COVID results are getting a bit consistent and a top 10 list in rheumatology training programs and hospitals? Tune in for more. We'll start out with a issue that I don't know is an issue, but since there's a publication about it, maybe now it's an issue. What am I talking about? Talking about loading doses when using biologics in RA therapy.

You know, we see them in a lot of drug development trials and then the drugs get developed and FDA approved and it becomes a part of the package insert. And yet, do we often exclude these when we start using the drugs? Sort of started back in the day with infliximab, where we did a zero, two, six and then Q8 sort of regimen, but we've seen this in other drugs over the years with loading doses oral or IV. And again, I don't know that we really adhere to them. Well, one, group of authors looked at this and they only found a small number of studies that really examined, whether or not you gave a loading dose or not and did it have an effect on the outcome.

So the end here is small. It's five clinical trials looking at drugs like abatacept, cerdulizumab, and secukinumab. And overall, when compared to not using a loading dose, there really wasn't much difference. So you've been right all along. Forget the loading dose, let's get on with therapy.

Now loading dose may have certain utility in certain patients and it certainly is approved for such use. So consider that as you go forward. Rituximab has been studied. Actually, something I also posted this week had to do with, a new biosimilar of rituximab versus the reference Rituxan showing basically the exact same results. So maybe we'll see that in the future FDA approval and yet another Rituxan, for rheumatoid arthritis.

But I am now talking about a different Rituxan study where they compared outcomes in older people over the 65 versus younger RA patients 65. And basically they showed really no difference when it came to drug survival or clinical efficacy outcomes as measured by the simplified disease activity index, the SDI. However, when it came to older people, there were more SIEs, 14 six per one hundred patient years, and more pneumonias, ten versus five per one hundred patient years when you compare it to people 65. So we do know that age is a risk factor for serious infectious events. I don't know that there's anything unique here that we can attribute to rituximab, but we could attribute it to the age of the individuals under study.

So that's gonna be a risk factor going forward should you use this efficacious drug in people whom in whom it would benefit. You know, the interesting thing about the elderly with RA is studies consistently show we as rheumatologists tend to under dose and under utilize aggressive therapies in patients who are over the age of 65. And that probably isn't well founded based on any real evidence. I don't know that even this evidence of somewhat higher SIE pneumonia rates would change me from using this kind of therapy in older patients. So exercise, we always talk about exercise more, you know, eat less, treat earlier.

Again, these are part of our dictums. An interesting meta analysis of 10 studies in over five hundred ankylosing spondylitis patients shows that when you look at all the outcome measures for AS, exercise versus a non exercise comparator, exercise wins as far as less pain, improved function, less disease activity, but interestingly, it did not affect CRP and sed rates. So yes, there was an improvement in pain scores, FASDi and FASV, but not the acute phase reactants, meaning that these other measures are basically looking at pain and function, as being the main things that are improved by prescribing exercise in patients with ankylosing spondylitis. We reported in the past about, cannabinoid directed therapy in the form of lenabasum. Lenabasum is actually made by a company called Corbus and they've actually studied this cannabinoid which binds to CB2 receptors and is supposed to give you less inflammation, less fibrosis.

It's been studied in scleroderma, in dermatomyositis and lupus. It's also in phase two trials in cystic fibrosis. The drug is not approved for anything yet, but this is the areas they're going after. Anyway, this particular report looked at a study in a small cohort of systemic sclerosis patients, twenty seven patients versus fifteen patients treated placebo and at week sixteen the patients treated with, lenabasum had less skin activity as measured by a new skin score called CRISP, C R I S S, and at the same time showed reduced gene expression for inflammatory markers and markers of fibrosis. And overall, when you look at skin histology, the lenabasum treated patients did better.

So again, these are all early trials. A lot of these are phase two. We need to see large phase three results, but it's encouraging especially in difficult to treat disorders like scleroderma and dermatomyositis. RA patients with comorbidities, you know, we do know they tend to have more dizzy activity. We do know that they tend not to do as well in treatment.

But when you specifically look at the comorbidities that are psychiatric in origin depression, anxiety, bipolar disease, schizophrenia. You know, a large analysis of twelve thousand, almost thirteen thousand RA patients showed, that when you look at the influence of psychiatric comorbidities, it's not good. They tend to have, basically, more clinic visits. They tend to have more hospitalizations, more hospital days, and they take more drugs. These patients are difficult to treat.

In fact, my lecture is on and I wrote an article on RheumNow on the difficult RA patient speaks to just this. It is, you know, certain comorbidities, especially psychiatric comorbidities that make such patients much more difficult. They're gonna take more of your time. They're gonna take more effort on your part to engage other consultants to optimize the treatment of that psychiatric comorbidity and to ascribe the responsibility of that to the primary care doctor is a gigantic mistake in my opinion. So again, this is a tough bunch and this data bears that out.

Good news for the JAK front, another JAK inhibitor, is poised for approval. In this case, in the European Union where the EMA and its CHMP division, has recommended for approval filgotinib for patients with moderate to severe rheumatoid arthritis not responding, or having inadequate response to DMARDs. There looks like they're gonna be Put up for a hundred milligrams and two hundred milligrams once a day. It's a once a day JAK1 inhibitor. It has a new trade name.

It's not filgotinib as its generic name Oh, no. It's not. It's a JAK inhibitor coming from, the folks at Gilead. So this is also slated for, a regulatory consideration, by the FDA sometime this year as well. So maybe we'll be seeing yet a fourth JAK inhibitor hit the market this year.

I found an interesting report on, and I think it's in a pediatric journal, JAMA Pediatrics on Down syndrome associated arthritis, which, you know, when I was working at the Texas Scottish Rite Hospital here in Dallas with Chester Finklin Panero, some great pediatric rheumatologists, I would see these Down syndrome kids, and there were a number of them in their clinic. They had inflammatory arthritis and they were often called seronegatives and whatnot. Well, review was a review of many centers and pediatric rheumatologists that basically says this is a real syndrome. It is a serum negative polyarticular erosive inflammatory arthritis that unfortunately has a very long delay in diagnosis in their experience a nineteen month delay. And yet these patients are basically treated as seronegative RAs and the bad news here is that many of the treatments that we would normally use to treat JIA and methotrexate biologics etc.

Are poorly tolerated in general less effective in Down syndrome associated arthritis. So this is sort of sobering data. We need more cohorts, more studies in this unique population that can get a really severe inflammatory arthritis. A retrospective study actually examined anakinra in patients with COVID and showed very favorable responses. So this retrospective study, there were twenty two, patients who were treated with, let's see, it was ten who treated with standard of care and twelve who were treated with standard of care plus IV anakinra receiving three hundred milligrams of anakinra on day one, and, and actually day one, through day five and then tapered over the next three days.

And the bottom line is in this study, all of the anakinra patients had rapid improvement, no deaths, less oxygen demands, and no need for mechanical ventilation. And this was significantly better than the standard care of patients where there were deaths and were needs for mechanical ventilation suggesting this is like the second or third study now all open label not head to head trials saying IL-one inhibition really works well in patients with severe COVID. Another interesting, and consistent report comes with the recent report of colchicine. This comes from JAMA just this week where colchicine used in COVID patients gave really positive results. So this is a single center study of a 140 patients in Northern Italy who were treated with a standard of care.

And the standard of care there was a combination of things including hydroxychloroquine and or dexamethasone and or antiviral therapy. And then they had another cohort of a hundred twenty two patients who were, treated with the same plus the addition of colchicine one milligram per day. And in the end, the colchicine treated patients basically had better survival eighty four percent versus sixty four percent in the standard of care, group only. So this is similar to the results of the Greco study that we reported a few weeks ago, suggesting that maybe early use, of colchicine would be a powerful and simple addition to therapy. So we have a bunch of reports about gout this week that are kind of interesting.

What I didn't report on this week, but maybe next week, there a number write ins, by numerous authors complaining of or offering a different perspective to the most recent ACR guidelines on the management of gout. Maybe we'll review that another time. But there was a report from one of the nephrology journals basically talking about a rising amount of evidence suggesting a potential link between hyperuricemia and hypertension. It's not a done deal. There is unfortunately not enough strong evidence and really well controlled evidence.

But you know, this stems from the study in a pediatric population of kids with hypertension, and who had a hyperuricemia and who were given Urate lowering therapy and their blood pressure improved. And I know Hypertension is part of the metabolic syndrome and and gout should be part of that metabolic syndrome as well. So I'm a strong advocate for aggressively treating hyperuricemia, especially in gout patients obviously, but even in patients maybe who have asymptomatic hyperuricemia, it can't be a good thing, especially with levels above nine milligrams per deciliter. So there's this nice review that we have a link for you in the website. The idea is that, know, uric acid leads activation of the renin angiotensin system and the authors make the claim that maybe therapeutic intervention in with the renin angiotensin system would be akin to initiating urate lowering therapy in patients who don't have gout.

A nice case report series came across that mirrors what we talked about previously about the use of methotrexate in patients receiving peglodecase. As you know, peglodecase has, it's a very effective drug, but, unfortunately only about forty two percent of patients have a great response to the drug based on two clinical trials that have been out there, and it's limited by the development of anti peglodecase antibodies, which can ultimately lead to, not only toxicity but a limited, therapeutic benefit. So one way of dealing with that propensity to develop anti peg antibodies is to use immunosuppressive therapies. You wouldn't wanna use leflinamide because leflinamide lowers uric acid levels. It is a a basically uricosuric kind of agent, and that would obscure your one biomarker that you watch when you're looking at patients on peglodecase, which is serum uric acid levels.

Instead, people have used three drugs that I know about. One is azathioprine. Mike Pillinger wrote about that. That's been my experience to work with azathioprine works really well. Second drug in clinical trials, Ken Sag's group is running a large peglodecase, a mycophenolate trial looking at its ability to inhibit anti drug antibodies.

And then this particular study is similar to that seen in, Seattle where 10 patients were given methotrexate when they were also given peglodecase. So in this study, these are patients with really severe refractory gout, erosive disease, tophi, recurrent flares, you know, it failed either febuxostat or allopurinol, and they were all initiated with, peglodecase. Nine out of the ten received IV prior to starting the peglodecase, one received oral after starting it. The bottom line is that eighty percent of the patients responded overall 15 infusions, given over about 32 different thirty two weeks with significant lowering of serum uric acid levels. And again about an eighty percent response rate that is double the historic published, clinical trial data.

Really can't compare the clinical trial data to this real world data, but it is still this is encouraging and we would need to look at the study that Ken Stag's doing with microphenolate. We should see more trials of these kinds of agents and use and we should be using more picolodecase. It works really, really well. And then lastly, there's an interesting editorial in arthritis and rheumatology by Danby and Nioji looking at the burden of gout in our society. So commentary on an article in the same edition by SAFRI where they report the results of the global burden of disease study from 2017 that showed that between 1990 and 2017 is a doubling of the worldwide burden of gout going from twenty million to forty one million in 2017.

As part of this overview, they talked about the many things that have accompanied this rise in gout including the fact that even that very few people are started on urate lowering therapy despite the onset and diagnosis of gout less than twenty seven percent. Yet a majority patients continue to have flares in the ensuing months. It's compounded by a lot of comorbidities including hypertension, chronic kidney disease and seventy percent obesity in half the patients cardiovascular disease and ten to fourteen percent hypertension and seven seventy five percent going back to what we just talked about and its relationship to hyperuricemia. And you know, it looks like the rise in obesity in society has led to this also rise in the rates of gouts that we've seen over time. And then lastly, gout is associated with one point three million years of living with disability in 2017.

Yet there's little gout education, yet there's disagreement on guidelines for managing gout. Gout remains a gigantic public health problem that we as rheumatologists need to take the lead on. Lastly, I'll end up with a top 10. Actually, no, it's a top 13 list of the best rheumatology hospitals according to US News and World Report. Of course, they would know.

This is what it's like a whole marketing. But number one on the list for like the at least third year in row that I know of is Johns Hopkins. Number two, Cleveland Clinic. Three, Mayo Clinic in Rochester. Four, New York City's Hospital for Special Surgery.

Five, the Brigham and Women's Hospital, six, Mass General, I wonder if that's a fight in Boston, seven, UCSF, eight, NYU Langone Medical School Medical, University, nine UCLA Medical Center, 10 the University of Alabama at Birmingham, 11 University Colorado and its hospitals, 12 University of Pittsburgh making the list, and 13 Duke University Medical Center. This is where you want to go if you got a rheumatologic problem or at least they can boast about it. Yes, we're still working on, calls and, questions from you the viewers. We don't yet have it on the website. Look for that in the weeks to come.

That's it for this edition of the RheumNow podcast. Go to the website, check out these links. Be sure to tune in. Be sure to tell your friends. Be sure to give us a good ranking.

That couldn't hurt either. We'll talk to you soon. Bye bye.