RheumNow Podcast – Gout Guidelines (7.3.20) Save

It's the 07/03/2020. This is the RheumNow podcast, and hi. I'm doctor Jack Cush, executive editor of rheumnow.com. This week, good news for gout, some scary news for rituximab. Things are looking up for cytokine therapy and COVID, and it's Independence Day.

We should all be independent. It's the only way to live. Let's start with a Twitter poll I did this week. I was involved in an, discussion with a number of learned colleagues about lupus nephritis and how we treat it, how we manage it. Do we do biopsies was the question?

I said I don't think a lot of practicing rheumatologists do, right, routine, kidney biopsies and people getting, treatment for lupus nephritis, my academic, friends, that includes me now, I changed back to UT Southwestern where I'm an academic now, and, but most of them said, yes, we all get biopsies. I did a Twitter poll. And, over three days, a 194 responses, presumably from learned rheumatology colleagues on Twitter. And here's the vote. The question was, if you treat SLE patients, do you get a renal biopsy before starting lupus nephritis therapy?

10% said yes. 53% I'm sorry. 10% said no. 53% said yes. Looks like I was wrong.

And 33 or 35% said it depends. It's kind of a bailout answer, don't you think? I think what this really means and, the question is what are the thirty five percent depends mean? That depends. Yes.

I do it. Depends. No. I don't do it. I think it means that 10% say definitively no, unless something else comes up.

Half or more say definitively yes, unless something else sways me otherwise. And then the other 35% are saying, it depends. I don't wanna make a decision now. I'm kind of slow. Not like the other guys.

I need time and data. Well, what you know, who needs time and data besides the government? You know, sometimes we have to make decisions here. So, I think this is gonna be a big issue because if you look at the drug development in lupus right now, it seems like the best trials that are going to maybe succeed and maybe get a drug to market new drugs to market for lupus are the ones that are targeting lupus nephritis as opposed to treating lupus globally with an SRI four outcome, looking at lupus nephritis outcomes. And then if that's the indication, will you need a biopsy to do, to use those therapies?

These lupus nephritis studies actually have all relied on, a biopsy. There's, some data about influenza vaccination that you should probably know about. This is a a rare rare risk of subdeltoid bursitis after you take an influenza vaccination. Never heard of it. Never seen it.

But you know what? It's statistically significant, but it's clinically meaningless. But it's still important. I guess three million people getting the influenza vaccine, the attributable risk attributable risk was almost eight additional bursitis cases per one million people vaccinated really, really low. But, you know, this is the kind of stuff that leads to reluctance to receive vaccines.

There's another study that came out from a British clinical practice research database registry looking at vaccination for the pneumonia vaccines, and they found that overall in their dataset of twenty one thousand plus RA patients, thirty eight percent had received the pneumonia vaccine. It was more likely, forty four percent if you were elderly, a little more likely in women. And, really, you know, only a third of people starting a new conventional DMARD would actually get a pneumonia vaccine, maybe a little more if it's you're older. These vaccine issues are kind of important in the time of COVID when right now everyone's waiting for a vaccine, but the whole issue here is one, is it going to work? How successful is it gonna be?

Is it gonna be likely influenza or even better vaccines? Are it gonna be like pneumonia, pneumonia vaxx, which is actually not quite as good as influenza? And will people use it? And what's going to be your role as a rheumatologist in making sure people get this? This is all gonna be important.

We're gonna talk about this in the months to come. This week, a federal appeals court upheld a ruling that was a patent dispute between Amgen over Enbrel and the Enbrel's biosimilar made by Novartis or Sandoz called Arelzi. There was a patent dispute here, and it upheld Amgen's patent issues where the drug is protected until, like, 2024 or something like that, which is going to delay the availability of Aralzi, the biosimilar for etanercept, until that time. Again, a federal appeals court upheld this. As soon as I published this, I got, like, three emails from people who are in the business of making sure this happens or doesn't happen.

I'm getting kinda tired of legal issues with biosimilars, delaying the availability of biosimilars. You know, it's kind of a a bit of nonsense. I thought we developed these to save money. I don't think we're using them, and I don't think we're saving much money, and we're waiting until patent issues expire. Shame on the people that are doing this.

So what else? Here's a study about, the most serious infections that you might see in systemic sclerosis. Now there's so much to worry about with systemic sclerosis. It's hard to think of, you know, serious systemic infections being a big issue. Well, this is a a very large, study of sixty five sixty one thousand systemic sclerosis patients hospitalized between 1993 and 2016 to look at how many of them had serious infections.

The most common of these was, was what? Sepsis and pneumonia. Pneumonia is forty five percent, sepsis thirty two percent. No. Actually, it's not quite that.

It's something yeah. Yeah. Forty five percent pneumonia, sepsis thirty two percent, skin and soft tissue infection almost twenty percent. And, again, it's sort of scary. The interesting thing here is that, again, sepsis and pneumonia are at the top of the lips list, and that's something to worry about.

While their hospital stays and their more infectious mortality rate has gone down over time, death from infection was that went for ten percent down to eight percent. Hospital charges went up during this period. So this is sort of a serious minor issue that's in the background of managing systemic sclerosis, and it's really not minor. It's big time. A very interesting study appeared this week.

I think this was a science and translational report, something like that, about, the use of a genetic probability tool to predict, diagnosis and basically patients with early rheumatoid disease or inflammatory arthritis. They looked at three different large cohorts, 1,200 patients from the EMERGE cohort, this is sort of an online available cohort of patients, two forty five patients from the partners cohort in Boston, and another two forty three patients with an early undifferentiated inflammatory arthritis. It turns out when they use this genetic probability tool, using what we know about the genetics of RA, and applying that to people, who may be at risk, that genetic profiling could increase the odds of developing a right diagnosis. So the area then under the curve was significantly high, seventy to eighty five percent, in in those three cohorts. They were a likely diagnosis was going to be made in sixty four percent of cases and an unlikely or rule out diagnosis was correctly made in forty five percent of the patients.

Again, this is sort of big data meets genetic profiling, and the question is, could this be used in the future to more accurately diagnose people in clinical practice? I think it's a long ways off at this point. I think it's encouraging that we're going this route. Yes. You know, the bean counters and the geeks are working against you clinicians gonna put you right out of business by doing it all on the computer.

And I'm being facetious, of course, and I I think there's always gonna be a role for the clinician and clinical acumen in making these diagnosis, but sometimes it's not so easy. And having a genetic likelihood, a probability score, if you will, might make for more accurate diagnosis, earlier diagnosis, make you a little more confident in the therapies you use. I saw an interesting report in JRheum this week that I really wasn't aware of, and don't know if you're aware of this as well, but it's rituximab associated autoimmune disease flares. I give a lot of rituximab for vasculitis, and, I haven't really seen flares from using rituximab. In this particular cohort of a hundred and eighty five patients, there were seven cases of what was called a rituximab flare.

And interestingly, all seven of them seven of these cases occurred when rituximab was used for type two mixed cryoglobulinemic vasculitis. So these flares occurred a median of eight days after their last rituximab dose. They manifest as acute renal insufficiency, purpure, myocarditis, and GI involvement. Again, these people were really quite sick. So who was more likely to get this were people who did have renal disease, obviously the type two mixed cryoglobulinemic vasculitis.

People who had evidence of B cell proliferation, higher cryoglobulin levels, the highest levels were more likely to be associated with this, and low c four levels. The bad news was, again, this rare event, half of them died, and that's kind of shocking and may may be worth noting. Biopsies of kidneys in these patients showed that there was a immune complex deposition and basically glomerular obstruction by the cryoglobulins that led to this renal demise in this in this cohort, Sort of a scary story. Another scary story I think comes from, my buddy Henrik Schulz Koops, who reported and his colleagues reported on two patients with rheumatoid arthritis who had received rituximab and died of COVID pneumonia. Now, certainly know that our patients are not immune to COVID, although we're seeing less COVID in them, and we're not we've seen patients admitted to the hospital and even deaths on all the drugs that are ours and supposedly even being used for the management of COVID.

I had a report out, a month or more ago that theoretically B cell inhibition might be a good thing in COVID. Well, story of two cases says not. In these two cases, what happened was one who had multiple comorbidities, COPD, hypertension, osteoporosis, had received rituximab two weeks before developing COVID and then died. And then another patient, had received it six months before, also had a comorbidity or two, and both of them had normal IgG levels but died as a result of COVID. So, something to take take note of.

The another report about COVID was that there is another report about multiple antiphospholipid antibodies being associated with COVID, and this looked at sixty six critically ill COVID patients and compared them to thirteen non critically ill. The whole thing about these COVID reports is low numbers and suspect comparator groups. But nonetheless, that the antiphospholipid antibodies were more likely in those who were critically ill, half of them, and they may only be present for about a month or or six weeks and then go away. The problem is that their presence was associated with a higher risk of thrombotic events or the antiphospholipid syndrome. And again, it is these sort of hematologic, microthrombi manifestations which can complicate COVID.

Another report from COVID comes from hospital for special surgery where they reported on eleven patients treated with anakinra, and timing was everything in this particular report. Seven of the 11 received their anakinra really within the first thirty six hours of presentation to the hospital. None of them required ventilation, and, and were discharged. The other four, got their anakinra after four days, and were more likely to have, progressive respiratory symptoms and require mechanical ventilation. Of those four, one died.

So, all these people are relatively sick. They were SARS CoV two positive. They had fever. Ferritin is greater than a thousand, and they had evidence of resp impending respiratory failure. And that's one of the reasons why anakinra was used in these particular patients.

So, again, I think a lot of the the big issue with, use of anti cytokine therapy and many of the drugs that are ours being used in COVID is timing. Timing is everything. And this, I think, speaks to maybe the right way to use Anakinra at least. Speaking of the anticytokine therapy, another interesting report appears about tocilizumab, benefiting people with COVID nineteen pneumonia. This is a study of, like, five hundred and forty five patients or so who who were sick, and one hundred seventy nine of them received tocilizumab, three sixty five did not.

The ones who received tocilizumab were less likely to require mechanical ventilation, and they were going to have less death, seven percent versus twenty percent. Interestingly, although they seem to do better, the ones on tocilizumab had more infections, thirteen percent versus fourteen thirteen percent versus four percent on TOCI versus not on TOCI. And the infections weren't mild infections. There were cases of sepsis, pneumonia. There were some UTIs, PJP pneumonia, hep B reactivation, and and and herpes simplex.

So that may be the downside of using anticytokine therapy. New England Journal this past week, again, featured this new syndrome of multisystem inflammatory syndrome in children, MIS C. I think I previously called this PMIC and other reports that we've done. Eric Topol had a nice sort of simple tweet on Twitter, basically giving you the highlights of this. It's a nice read if you wanna understand the the syndrome.

But unlike Kawasaki's, the kids affected by this tend to be older, 10 years of age and up. They have fever like Kawasaki's that more likely to affect African Americans, Asian populations, and Hispanics. And the cardiac manifestations, including aneurysms, appear in twenty to forty per sorry sorry, ten to twenty percent of patients. And the interesting thing is it's not an initial manifestation of COVID. It's a late manifestation of COVID occurring two to four weeks into their initial diagnosis and management.

So is this a late stage hyperinflammatory state not that, different from the cytokine storm syndrome? These people have high LDHs, very high ferritins, high BNPs, and D dimers. They can be sick. Thankfully, only two to four percent have died in the thousands of patients that have been thus far reported. Also unclear is how they should be treated, although they're being treated aggressively with cytokine therapy.

We're gonna wrap up with two reports about gout, a simple one about coexisting gout and rheumatoid arthritis. The VA RA registry, Vara, 2,000 patients being followed amongst their patients. They had seventeen percent who have elevated, uric acid levels, hyperuricemia. And in that two thousand population of RA patients, six point one percent were also diagnosed as having gout. Turns out these patients with hyperuricemia and gout had a higher rate of cardiovascular events, and that's worth noting.

I think it's important because I've always taught you can't have gout and can't have RA. These are like you can't have them together because it's a great teaching point. If you're not sure it's gout or RA clinically, get a rheumatoid factor and uric acid, and that takes care of the vast majority. But we know managing so many people with gout and RA that there are some crossover patients, and this gives you a nice good number to to hang on to. Lastly, we missed it in May because we were so busy covering COVID in May.

The ACR 2020 gout management guidelines came out. It's probably worth taking a look at. We give you the highlights in our report today on the website. First and foremost, in these guidelines, there's 42 of them by the way, 16 have strong evidence, and then they're strong recommendations as but then the vast majority of them are not strong. There's a lot of expert opinion in here.

But they make a big thing about allopurinol being first line therapy for people who need urate lowering therapy. They make a big thing about the evidence favoring treat to target in the management of gout. They expand the use of allopurinol, and you no longer have to be people who have repeated attacks. Now it could be people during their first attack or maybe after one or two attacks or two two attacks if you should you start allopurinol if they have a severe chronic kidney disease stage two, three, or higher. Stage three or higher is what they said.

Market hyperuricemia, urate levels greater than nine, or a prior evidence of, kidney stones would be reason to, use allopurinol really automatically and early. And lastly, there was, well, they make a big case for, prophylaxis, when you're starting your RET living therapy, not just for three months, but really for up to six months and then continuing to monitor them thereafter. And then they, make a big thing about the genetic testing that you would normally do for Han Chinese populations, Korean Thai, but they also include African Americans in that group. And I think that that was a surprising new thing. That's a conditional recommendation, by the way.

Anyway, that's it for this week on the podcast. Go to the website, check out these citations and others. Hope you're going to have a good holiday next week. RheumNow will be giving you the best of as we're gonna be on vacation, but we'll put up good content to watch, and we'll return the week following, on the network. Bye.