The Best Goes On (5.8.20) Save

It's the 05/08/2020. This is the RheumNow podcast, and I am doctor Jack Cush, executive editor of rheumnow.com. Peter Nash loves it when I say that. This week, the title of the show is the beat goes on. Of course, I'm talking about the COVID crisis, that strange new reality that is unfamiliar, if not unnerving, and just doesn't seem to wanna stop.

But yet, we have lots of new news and general reports that's probably worth talking about. I'll start off with some general rheumatology. We've talked about Anakinra and its use in pseudo gout before. EULAR and ACR had reports on that. Well, I think they materialized in a meta analysis recently where they looked at seventy four patients who were treated with anakinra for refractory CPPD or a few, and that was about eighty five percent, maybe about twenty percent who had other contraindications to other therapies.

And in this cohort, anakinra was effective in eighty one percent of those with acute CPPD or gout and in forty three percent of those with chronic disease. That's sort of new data. The good news is very well tolerated adverse events in only four point one percent, something to consider beyond steroids or colchicine in people with acute CPPD or pseudo gout. There's only one drug on the market that's approved for non radiographic axial spondyloarthritis and that is right, sertilizumab or Cimzia. Well, there are other drugs that have been studying this and looking at this, and that includes Cosentyx or secukinumab.

And this past week, the EMA has approved Cosentyx for, its use in active non radiographic axial spondyloarthritis, based on the results of their phase three trial, the PREVENT trial. It is not yet approved for non radiographic axial SpA in The US. I would expect it to be so in the months to come. There's a an article that we missed, but I think it was reported in JAMA a few weeks ago about cigarette smoking in ANCA positive associated vasculitis. Really interesting study.

John Stone and coworkers looked at four seventy three ANCA associated vasculitis patients compared them to about fourteen hundred controls, and did basically smoking questionnaires. They showed that the ANCA associated vasculitis patients were more likely to be former smokers or current smokers with basically having a one point six or two point seven fold increased risk of developing ANCA associated vasculitis. However, it was only seen for MPO associated ANCA associated vasculitis and not with PR three AAVs. Kinda interesting. So vasculitis being, a major issue, let's talk about vasculitis and a COVID patient, specifically about the use of rituximab.

I found this as an interesting case report. You remember two weeks ago, three weeks ago, we said, you know, B cells could play a role in COVID infections and talked about Italian case series of two patients with A gamma globulinemia that did better than the five or six patients who had what was the other one? They had a common variable immunodeficiency. The common variable immunodeficiency patients did poorly. The agammaglottulinemic patients looked like they did really, really well.

Well, here's a report of a stable GPA patient who's been on rituximab for over a year, received their last dose of rituximab on the March 5, and the next day developed symptoms of active COVID infection. Within four or five days, the patient had progressed, was hospitalized, had high fever, developed respiratory failure, went on mechanical ventilation, was then treated with the usual, you know, onslaught of many drugs including antiviral therapy, ten days of BID hydroxychloroquine, and guess what? The patient continued to do well. On day 20, the patient was extubated. At that point, the patient was negative for nasal, PCR swabs for active infection was discharged nine days later on day 29 and went home.

The point of the paper was one, you can get COVID infection taking rituximab. Two, this wasn't a death. So I don't think that's a negative story. It might be a positive story in this end of one experiment. Again, I think B cell therapy, you can't really stop it.

You might want to avoid it in people who are well controlled if they develop the infection. But again, this patient did fairly well. The World Scleroderma Foundation came out with recommendations for the management of COVID in that population with scleroderma and its variants. That was a long paper with a lot of recommendations, including the usual ones on social distancing and hygiene and whatnot. And I I tweeted five points that I thought were were worth repeating, especially to a scleroderma audience.

Number one, patients with systemic sclerosis could be at risk largely because of their lung disease, and only if they have lung disease, that being interstitial lung disease. So, again, there I might be saying, extra precautions would be in order for someone with systemic sclerosis and lung disease. Number two, it's best to continue scleroderma therapies mainly because you don't want to avoid the therapy and develop a lapse in disease control which could increase risk. Number three, scleroderma patients don't need to be tested unless they have evidence of symptoms suggested of this infection. Number four, ACE and ARB should be continued in these patients.

That's been the general guideline for many agencies while they're studying the role of, you know, ACE two receptors and what they mean in doing well or not doing well with COVID. And lastly, number five, there is no good reason to start or use hydroxychloroquine as a preventative agent in patients with scleroderma. It doesn't work with scleroderma, I'm not sure why you would even be using it there. Maybe to manage arthritis, that might be possible. You know, bad news is coming down the line about, the financial consequences of this disorder.

The American Hospital Association has projected that in The US, there'll be a loss of $202,600,000,000 between March 1 and July 1 in The United States. That's roughly a loss of about $50,000,000,000 a month while we're under siege and under lockdown. When this will change? Hard to tell, but that's the projection for right now. An interesting study came out this week from GUT.

That's a GI journal where they talked about limited cohort study of IBD patients, seventy nine patients. And these seventy nine patients were reported because they developed the COVID nineteen infection. In that population, forty six percent had pneumonia, twenty six percent were hospitalized, and eight percent died. Six percent were admitted to the hospital, and what they basically found that were at the outcomes were more likely to be related to active IBD and disease activity and not related to IBD treatment. So again, it was the IBD and or the comorbidities that we would associate with bad outcomes with COVID infection, but it wasn't the therapies that were being used for treatment of inflammatory bowel disease.

An interesting report comes from the Journal of Allergy and Clinical Immunology, where they, a group of French investigators reported on their studies in 26 patients specifically looking at type one interferon immunoprofiling in COVID patients. Type one interferons, as you know, are important in innate immune responses and have antiviral properties. They can run amok during adaptive immunity when an excess of, type one alpha interferons can lead to a worsening of autoimmune disease and maybe even infections. As we heard from during grand rounds on Tuesday night, there seems to be in many patients a deficit of interferon and that during the later phases when they're doing poorly, there's an over overabundance of it. Well, in this particular study of twenty six patients who were critically ill, hospitalized in the ICU, and being treated with standards of care including antiviral therapies or immunotherapies.

These patients did not do well, fourteen out of twenty six were on mechanical ventilation. When they looked at alpha interferon 2A, they showed that there was a rising peak in levels by eight day eight to day 10, they peaked. And this sort of coincided with the increase in viral replication. And what they did show was that 20 of their population failed to make a rise in type one interferon. Turns out that those were the people who tended to do the worst, have longer ICU stays, worse outcomes, etcetera.

An interesting report from Italy about type one interferons playing a role in COVID. So we on the website this week, we talked about a number of things related to outcomes in COVID-nineteen. Thursday's report looked at thrombotic complications really based on a number of reports that have shown up in the literature, in New England Journal, in the British Journal of Hematology, and in a pathology journal looking at basically vascular outcomes in COVID. And what was reported and what you can piece together, what I pieced together was, number one, there's a lot of vascular pathology in the poor outcomes and the late phases of COVID infection where is where people die. So in the late phase of COVID infection, people that get to that phase are ones that have usually handled or gone by the viral phase of the illness and then have gone into a disease magnifying phase driven by an abundance of inflammation.

If they're unlucky, they get the cytokine storm syndrome. There are other patients who are having complications related to thrombosis. So in the pathology series, the autopsy series that I quoted, know, yes half of them had bronchopneumonia related to viral infection, but there were a lot of patients with pulmonary embolism, pulmonary vasculitis, thrombotic microangiopathy, basically pointing to the role of vascular disease in these poor outcomes. Researchers at Johns Hopkins are starting to look at the mechanisms underlying the thrombotic microangiopathy seen in COVID patients, and they postulate that it looks like a complement mediated process or what Michelle Petrie has called a complementopathy where there's activation of c five and downstream effects leading to a lot of complement mediated damage, including all the things that you see in that terminal phase, and the cytokine storm. They have lymphopenia, high LDH, anemia, sometimes microangiopathic, anemia.

They have organ damage. Again, this is what is commonly seen in HUS and in the, catastrophic antiphospholipid syndrome. And anyway, these in this British, Journal of Hematology report, postulate that this is a complement mediated thrombotic microangiopathy and make a case for complement inhibitors being studied in patients with COVID infection, severe COVID infection. In fact, trials are going on right now. Also, New England Journal yesterday talked about the presence of patients with the lupus anticoagulant with active COVID infection.

Thirty four patients studied, thirty one had evidence of a lupus anticoagulant. This sort of seems to dovetail well with an earlier report in New England Journal looking at the presence of anti phospholipid antibodies, IgA anti phospholipid antibodies along with glycoprotein-one antibodies as well in patients who had thrombotic complications and CNS disease. So, seeming to come together. I think that this is what has led to a lot of centers treating hospitalized COVID patients with anticoagulation and then there are these trials of complement inhibitors. We need to see more of this going into the future.

I had a report about hydroxychloroquine and QT prolongation that comes from JAMA cardiology. It's a study of ninety hospitalized patients with severe disease. These ninety patients were treated with hydroxychloroquine. There was they were fifty three of them, about half of them were also on azithromycin. Overall, there was a twenty percent risk of QTc prolongation in those treated with hydroxychloroquine defined as a greater than 500 QT interval.

This was a little bit more frequent in those who are also taking the azithromycin or those who are taking loop diuretics. I bring this up because there seems to be a lot of concern about cardiovascular outcomes in the antimalarial treated patients. Recognize number one, these are sick patients with COVID who are hospitalized and have other cardiovascular comorbidities. These are patients who are getting high doses of chloroquine and or hydroxychloroquine, and maybe it is under this circumstance that patients may be at higher risk for arrhythmias or cardiac complications or cardiac death, etcetera. Turns out a lot of these deaths and a lot of these severe cardiac complications seem to be more linked to the comorbidities and the age of the patient rather than to QTc prolongation.

But again, I don't think this is going to change what we do in rheumatology. We're using low doses, we're monitoring, we don't see this. I don't think an EKG is in the near future for any of my patients who are gonna be started on hydroxychloroquine. That would be a different story if one of my patients was being treated instead for active COVID infection with current protocols. Yes, monitoring EKGs and QTc, intervals seems to be prudent.

But in our regular care, I don't think we're gonna be changing, the cardiac risk profile, of what we're doing. Again, this tends to be a relatively rare phenomenon in RA and lupus patients taking hydroxychloroquine. I had an interesting report I thought, because I wrote it, on hydroxychloroquine and a lot of the confusion that abounds, you know, I basically said that there seems to be reason for it as to why it might work hypothetically, but in reality it hasn't worked in other infections, and in reality it hasn't yet proven itself to work. There's actually a New England Journal report from yesterday showing it didn't harm and it didn't help, and there are several reports showing worse outcomes in early reports. But you can read that if you want to get the lay of the land on hydroxychloroquine in COVID.

But I'll end with the report part of the report that looked at basically supply issues of hydroxychloroquine. So what we do know is that there was a real concern that this was going to go into short supply and our patients with RA and lupus wouldn't be able to get the drug. And there have been some reports of some constraints on finding drug, but it turns out that in the last month that hasn't seemed to be the case. Well, if you look at the FDA website on drug supply issues, there's only one report of a short supply and that comes from some farm Sun Pharmaceuticals where they say they have limited availability. If you look at the other source of short supply and shortages, that comes from the AHP site.

That would be the I don't know what that stands for. American hosp Society of Hospital Pharmacists, something like that. Number one, they list that there are many suppliers of hydroxychloroquine, including Amneal, Doctor. Reddy, Major, Concordia, Mylan, Prasco, Rising, Sandoz, Sun, Teva, and Zydis. Of these, less than half of them have a listing of having a short supply that would include Major, rising sun, tiva, and zydis, and that they say for most of them that they expect to replenish their supply within the next few months.

There are a number of reports about stockpiling of hydroxychloroquine. There's a report that 22 states and local governments have reported to stockpile thirty million doses of hydroxychloroquine. In addition to that, FEMA has shipped and stockpiled over 19,000,000 hydroxychloroquine tablets that were distributed to major cities around The United States into VA centers. So, again, I think it looks good. Number one, because the negative reports about hydroxychloroquine and chloroquine may lessen the fervor to hoard this drug or to take it as prophylaxis, which really nobody should be doing these days.

And I think that again there are there is enough supply out there right now to get us through I think the bulk of this into the summer. So here are my recommendations about hydroxychloroquine. Number one, don't use hydroxychloroquine or chloroquine to prophylax against the COVID infection. There's no evidence that would work. Don't stop hydroxychloroquine in your patients who are on it chronically.

There's no sense in stopping good therapies, safe therapies that are working well in patients just because we're in an environment of hydroxychloroquine craziness. It is okay to start hydroxychloroquine during this era as you normally would. Think that if it's the preferred drug for the condition you're treating, go ahead and use it. I think it makes sense. There's no read to stop and I don't think there's any reason to stop hydroxychloroquine in patients at the doses you use, in patients who are actively infected with COVID nineteen.

Recognize that, these drugs are being studied in many centers around The United States. And if the patient is hospitalized and already taking hydroxychloroquine, they'll be excluded from those clinical trials, but they'll should likely continue the drug. Overall, there is an exceedingly low low risk of cardiotoxicity or cardiovascular death in the doses and the manner in which we use hydroxychloroquine in our patients with rheumatoid arthritis and lupus and other indications in your clinic. I I think it's okay to refill hydroxychloroquine as you normally would. My patient wants a one month supply, they get a one month supply.

If they've been getting three months supplies, I give them a three month supply. I let the local pharmacy be a bit of a gatekeeper, and we've seen some of that where I write for a three month and only one month is filled, but there's plenty of refills there. No one so far in my clinic has gone without hydroxychloroquine. And lastly, you have a patient with suspected one of your patients in your clinic with RA, lupus, SPA, psoriatic arthritis, whatever, and you suspect them as having COVID-nineteen or they have confirmed COVID-nineteen, please register that patient with the Global Rheumatology Alliance. The website is roomcovid.org.

They're collecting amazing data. They have over a thousand patients accrued thus far. In two weeks, you'll hear from the guy who started that, doctor Philip Robinson, and he's gonna tell you the update from that registry and what's going on. A lot of interesting videos this week. I have a video, coming up, very soon with Barry Gruber talking about denosumab and whether you should be stopping that during the COVID era.

I have an interesting conversation with two practitioners, Danny Ricciardi and Herb Barraff in Marilyn about how they're getting through the current era. And lastly, sure to tune in every Tuesday night for Tuesday night rheumatology, the grand round series next week. Joan Merrill from the University of Oklahoma is gonna talk about what's the difference or what the similarities are between COVID and lupus. Should be an interesting session. Thanks for tuning in.

Watch the website for more news. Take care of yourselves.