RheumNow Podcast – Drive Them Crazy (4.17.20) Save

It's the 04/17/2020. This is the RheumNow podcast, and I'm doctor Jack Cush, executive editor of roomnow.com. You wanna drive a surgeon crazy? Tell them you can continue the biologic throughout surgery. You wanna drive a patient crazy?

Tell them you're going to do physical therapy instead of a joint injection. You want to drive me Cush crazy? Give me guidelines and tell me I have to adhere to them. We're going to avoid the craziness and talk about the news this week on the podcast. We're going to start with a report about Allopurinol and mortality in gout.

We have published before that there are papers out there that Allopurinol will lower mortality rates in patients with gout. We've also published that colchicine has also sometimes been associated with this. Turns out that there isn't a uniform agreement of this. A recent meta analysis looked at the risk of mortality in gout when Allopurinol was used. Turns out there was only four studies that qualified, two were positive, two were negative, and you know what, It just missed being significant by this much.

The hazard ratio was 0.8 and the confidence intervals were 0.6 to 1.05, saying that allopurinol doesn't increase mortality, it might could decrease mortality, but the data so far not so good. Well, one of those studies was like 6,500, the other three studies were like three hundred and two hundred patients. I think it's a little bit underpowered. I still think there's good evidence that good control of uric acid levels in patients with gout will lead to an overall reduction in mortality. It's been shown high uric acid levels, higher mortality.

Those with lower uric acid levels, lower mortality. Turns out that our use of valapurinol isn't all that good as you know. Turns out that all of amongst all gout patients, maybe a third of patients are on a urate lowering therapy. Amongst all people on a urate lowering therapy, how many achieve or treat the target goal? Not so good, like maybe only forty percent.

So there are many other reasons why this study is not quite as positive as we like it to be. Now, I don't know about you, but I've actually seen a case of chikungunya arthritis recently. It happens. As you know, there's been a flurry of mosquito borne, arthritities in the last few years from Zika to chikungunya, and, chikungunya presents, often in confusion with dengue fever. But dengue fever doesn't usually give you arthritis.

Chikungunya and Zika could. Acute fever, high fever, polyarthralgias, polyarthritis, headache, rashes, a lot of GI symptoms at the outset. The thing is about sixty percent of these patients are going to settle into a chronic arthropathy that can look just like rheumatoid, large small joint symmetric polyarthritis. Well, the people at Johns Hopkins, actually Bing Bingham was one of the authors and they had a lot of other authors from down in the Tropics. Can't say I know them as well as I know Bing.

And they reported on a retrospective series of forty eight patients treated with methotrexate. And while there's a lot of descriptive stuff in the paper and kind of short on actual data, it did look like methotrexate in fairly modest doses, a mean of nine point two milligrams per week of methotrexate. They had significantly lower functional scores and pain scores in swollen joints. Now, they only gave you single variable outcomes like what happened to the pain score, what happened to the number of swollen joints, but they were significantly less and that's kind of good news. That's what we did with our patient who presented to us many months after their initial infection in India, and now they're being treated with methotrexate for their rheumatoid looking, seronegative rheumatoid looking chikungunya arthritis.

There's a New England Journal report this last week that talked about the value of physical therapy versus intra articular steroids. It's a military study, one hundred and fifty six patients. It was a protocol. Patients were randomized to either receive one or the other, and the outcomes clearly favored the physical therapy. So they looked at a one year outcome and they showed that people were more likely to get better when they were given physical therapy.

Another study looking at knee OA looked at the impact of chondrocalcinosis on whether or not you're at higher risk to need, total knee replacement in the future. This is a study of six fifty six knee OA patients showed that chondrocalcinosis in fourteen percent and a similar number fourteen percent went on to total knee replacement or TKR. Turns out they're not the same fourteen percent. So having chondrocalcinosis did not significantly increase the odds of needing future knee replacement. The hazard ratio is one point two six, but it overlapped, one, so it was non significant.

Slightly higher risk, but not significant. We do know that chondrocalcinosis comes with age. Osteoarthritis comes with age. Knee replacements mostly done in people over the age of 60, but it is not a certainty that the presence of chondrocalcinosis will lead to future knee replacement. We've talked in the past about opportunistic infection, especially as it relates to the use of biologics in RA.

You know, operatively affection also occur in kids with arthritis, the systemic not systemic, I'm sorry, polyarticular, usually polyarticular JIA, Juvenile Idiopathic Arthritis. A large registry analysis by Pharmachild and Printo looked at eight thousand two hundred and seventy four JIA cases identified over seven hundred adjudicated infections and seventeen percent of those were classified as opportunistic infections. My goodness, that seems like a lot. What were the most common you think? Well, strangely enough, was herpes zoster, sixty six cases amongst the eight thousand.

The next most common was TB, eleven cases. And then you're now looking at the, at the long tail, the very infrequent events that included candida, HPV, pneumocystis, and CMV, a few cases. So, does occur in other forms of inflammatory arthritis. Now, when we don't know what to do in our patients who have rheumatoid arthritis, like what are the big problems there? Like, nodulosis and extra articular manifestations and ILD.

What do you do? Well, everybody always brings up rituximab because it seems like it might be the drug that you can use in patients with those seropositive associated manifestations. Turns out there is no good treatment or effective treatment for the extra articular manifestations of RA. I like this report because it looked at rituximab being used in patients with rheumatoid vasculitis. I don't know about you, I haven't seen rheumatoid vasculitis since my fellowship, which was like two or three years ago.

And, they found seventeen patients in this analysis who had also received rituximab. Seventeen patients, they had an active disease score with a BVAS, Birmingham Vasculitis Activity Score of greater than four or greater. And these seventeen patients, when given standard doses of rituximab at six months, forty percent of them achieved complete remission. At the same time, six months, fifty three percent had a partial remission suggesting, yes, it may in fact work. Uncontrolled single center report, a handful of cases, but this may be as good as it gets when trying to study, what to use in people with problematic rheumatoid vasculitis.

An interesting study came across looking at the influence of immunosuppression, meaning biologic therapy, in individuals undergoing surgery. As you know, it's been looked at in the past, especially in the context of those undergoing hip and knee replacement, and whether or not being on biologics around the time of those surgeries changes infection rates or death rates. And there's some positive results suggesting that it doesn't, but there's also some mixed results suggesting it doesn't. So it that it does cause some of those complications. So in this particular study, published in Alzheimer's Rheumatic Disease, they looked at ten thousand patients undergoing non arthroplasty surgeries for either, a heart or, I can't remember what the other ones were.

But nonetheless, they were non arthroplasty surgeries and they did not show any increase in either ninety day mortality or thirty day readmission rates when people were taking either a TNF inhibitor or a non TNF biologic, within eight weeks of their surgery. They compared these numbers to patients who were on methotrexate within eight weeks of surgery, and they didn't show an increased risk, suggesting that having recently received the biologic would not be a contraindication to having, hopefully, important surgery that was needed. In this study, they did show what you're supposed to show, which was if they weren't on steroids, there was a clear cut dose related increase in the risk of these poor outcomes, either being mortality or readmission rates where mortality rates were either forty to sixty percent higher at five and ten milligrams, and readmission rates were either twenty six to sixty percent higher at five and ten milligrams of prednisone. Don't be on prednisone or recognize the risk associated with surgery if the patient is on surgery. We had a few interesting COVID reports this week.

I did a report on other systemic involvement in patients with the COVID-nineteen infection. Obviously, patients present with respiratory symptoms, fever, myalgias, sore throat, loss of smell and whatnot. But other things can happen at presentation or during the course of illness. You might want to look at this report. Does detail that some patients can present with rashes, maculopapular rashes, vesicular rashes, even urticarial rashes that are usually not pruritic or with GI involvement.

Now, actual vomiting is uncommon, diarrhea four to twenty five percent, LFT's and up to a third of patients, nausea up to twenty or so percent of patients, GI involvement not uncommon, CNS involvement, there's a lot of talk for those of you who are working in hospitals and hearing about corona patients in the ICU and things that are going wrong. There's a lot of talk of encephalopathy associated with the coronavirus, but yet there's very little in the literature. Well, there are some new reports showing that patients with encephalopathy often have abnormal MRIs or CT scans with evidence of infarcts that are either within the hemispheres or cerebellum, often around the thalamus, and that these are often hemorrhagic. There was a report that we put out last week about the association of these CNS events and CNS bleeds and infarcts in COVID patients who had bad disease in the ICU on a respirator, developed these CNS manifestations, and they were found to have, what was it, IgA, anticardiolipin antibodies and IgG beta beta two beta two glycoprotein one antibodies. Again, not known if it's causal or casual and epiphenomenal, but it is an interesting thing.

And and I also end with a description of the cytokine storm syndrome, which is often a terminal event in those hospitalized ICU patients. Look at all that data. It looks just like, MAS, macrophage activation syndrome, and hence the treatments are IL-six inhibitors and there are studies of IL-one inhibitors. And why aren't they using the gamma interferon monoclonal antibody and mepalumab, Gamifant, or our other therapies we use for MAS like Calcineurin inhibitors or Etopacide. And then you should lastly look at what we put on the website this week, which was the ACR COVID-nineteen guidance for patients with rheumatic disease.

This was a North American task force who quickly got together and came up with a tremendous document with I think about 30 different guidelines for patients, our patients in general, our patients who are being tested, our patients who may have a positive test or you're waiting to test, and then those who we know to be positive. I think you should look at that. I think the take homes from that, from me, were in overall for our patients, don't stop your biologic therapy, don't stop the steroids, don't lower anything. Again, continue to use what works and recognize we make the same recommendations for patients who are suspected of having cancer or do have cancer. We make the same recommendations for people who are undergoing surgery.

And again, there's not a lot of evidence discontinuing those drugs makes much sense. I think it's very clear that the thing that is going to hurt our patients most if they are diagnosed with a COVID infection is if they have uncontrolled disease, and if they have other comorbidities known to increase risk, such as age, diabetes, chronic lung disease, and chronic heart disease. For instance, in the previous paper talking about chronic, or heart disease associated with the COVID-nineteen infection, it turns out that patients who have pre existing cardiovascular disease often do worse. They tend to have worse overall outcomes, presumably because their hearts are involved with inflammatory disease and it just gets worse in the state of inflammation. There are cases of acute myocardial damage in the form of myocarditis or cardiomyopathy associated with, a corona, infection.

But it turns out that again, I think our patients who are going to get in trouble are likely to have heart disease and lung disease more so than our disease. What seems to be odd to me is that we're not seeing more of our supposedly immunosuppressed patients taking supposedly immunosuppressive drugs in the ICU or being hospitalized or being severely affected by this pandemic. I think we should use our drugs as we always have used them. I think the guidelines were smart in addressing the issue that if we develop a shortage of medicines, there are other medicines to choose. So, if we don't have a shortage of hydroxychloroquine, you can switch to chloroquine, or you can switch to azathioprine if it's for skin lupus, or you can switch to another DMARD if it's for the management of rheumatoid arthritis.

Same thing for the IL-six inhibitors. If they go into short supply, you can either switch to the subcutaneous version of those drugs or switch biologics, for the time being. You should also reevaluate whether the patient in fact needs those drugs during the period of shortage. Now, the last two things on these guidelines that I found a little bit debatable was that when treating stable patients following a SARS CoV exposure and they don't have symptoms, meaning we know they've been exposed, they could either been actually directly exposed or we know them to be positive, but they have no symptoms. The ACR, task force said you should continue treatment with hydroxychloroquine, sulfasalazine, and nonsteroidals, but they say you should stop all others, even though the patient's asymptomatic and has stable disease.

I'm not sure what that's about. I'm not sure I agree with that. And and then they take it one step further. Now they give them the infection. It's a known infection.

I mean, why would you stop let's let's before we get to known infection, the patient's asymptomatic with a known exposure, I'm not sure why you would stop. How is that different than, an asymptomatic patient who could well be positive and shedding virus, but you don't know because the patient hasn't been tested. We're not recommending routine testing of all our patients at this point. They go on in their last, address, the last, point, what about treatment of, patients who have a documented or presumed positive COVID nineteen infection? They say you should continue hydroxychloroquine.

Wait, but stop sulfasalazine? Why? They say you can continue the IL-six inhibitor if it seems to be appropriate. Otherwise, if you have a documented infection, they say stop everything. That looks good on paper, but recognize many of the drugs that you're talking about stopping here are drugs that have very long half lives.

It's gonna take three to twelve weeks to get that drug out of their system. By then, they'll are going to be over this problem or not doing all that well. Again, the detrimental effect of continuing a DMARD, an immunosuppressant like azathioprine or mycophenolate, a biologic like a TNF inhibitor or an IL-six inhibitor, or even a JAK inhibitor is really not known in these situations. We do know those drugs work. If they are really helping patients who are otherwise a mess, I would be in favor of continuing it, but it's obviously going be a case by case consideration.

Again, methotrexate is not an immunosuppressive drug, not in the doses we use. It's a powerful anti inflammatory. You can say that about most of the drugs that we use. I mean, do you really want to get your patients all worked up that they're on immunosuppressives and they have the sword of Damocles hanging over their head? It's not true.

It's not going to be true. But yet, as much as I might be permissive in my thoughts about methotrexate, methotrexate, rituximab, clearly blunts, humoral responses when giving vaccines. And maybe that's a reason to hold methotrexate. It's reasonable to hold those drugs, the biologics, the immunosuppressants, maybe methotrexate in patients who are just admitted to the hospital and therapy is being begun or they're observing the patient. You could be off these drugs for two, three, four weeks and probably not suffer much in the way of a decline in their health or worsening of their inflammation, which will add to their COVID problem.

So again, I think this is a difficult scenario. I think we're going to learn more as time goes on. I could have put in here more information this week about two new reports about hydroxychloroquine, one showing it doesn't work, one suggesting it might could work. But these are preliminary pre releases. The I I need to see the full paper before we start to review those.

Look for that in upcoming reports here on RheumNow. Go to the website. Check out these citations and more. We'll talk to you next week on rheumnow.com. Take care of yourselves.

Make sure everybody is wearing the mask. Where's the mask? I had a mask around here. Here it is. Make sure everybody wears the mask.

Yell at people who don't wear a mask. The death rates are just going, like, doubling every five days. 04/10, it was nine thousand deaths in The United States. 04/14 no. It was four five nine thousand deaths.

04/10, it was nineteen thousand deaths. Today, the seventeenth, it's over twenty eight thousand deaths. It's gigantic, and yet people are walking around without a mask. You need to lead. Take care.