RheumNow Podcast - Bad Disease & Bad Outcomes (10.9.20) Save

10/09/2020. This is the RheumNow podcast. Hi. I'm doctor Jack Cush, executive editor of rheumnow.com. This week, the consequences of COVID, bad disease and bad outcomes, bad news.

And what do you call that punched out gaudy x-ray change? I've got a name. Actually, I've got several names. We're gonna start out with COVID news. An interesting study came out this week that compares COVID to influenza.

And it actually uses large population based data, six month of COVID data versus one year of influenza data from Korea, Spain, and The United States. So they compared thirty four thousand COVID patients to eighty four thousand influenza patients. They basically showed that COVID-nineteen patients were more likely to be younger, male, and have fewer comorbidities and basically take less medications than do patients with the flu. Again, we know the death rates are high. We know that the consequences of COVID compared to flu, it's either seven times more prevalent or 14 times more prevalent depending on who you look at, and certainly the death rates are more disastrous.

But this shows you sort of the clinical profile, and it fits with what we said last week in that, yes, early on in COVID there were a lot of elderly people, and those were the ones who were dying. Now, that we're six months into it, the ones who are being hospitalized are in the twenty to twenty nine age group. That kind of fits with this data. Another study came out this week on the heels of the president getting dexamethasone and being miraculously cured in the infectious wing of the White House, steroids can help mortality rates in COVID nineteen. Seven is meta analysis, seven randomized trials, 1,700 patients who either received dexamethasone, chitrocortisone, or methylprednisolone, about seven hundred patients who were compared to about one thousand patients who received usual care or placebo.

They basically showed about one in three patients treated with dexamethasone died, two twenty two out of six seventy eight, versus four out of ten who died when they got usual care, suggesting about a ten percent reduction in overall mortality, and that was significant. In fact, the odds ratio showed about a one third reduction in overall mortality, that was very significant. An interesting UK survey study came out, and I have this idea, I have some data I'm accumulating on the consequences of COVID, you know, the aftermath, if you will, that, of the bad things that have happened while we were shutting down, while we were changing our lifestyle, while patients were being cared for or not being cared for. In this large cohort from The UK, almost 700 patients, they actually had survey data, soon after COVID. And, they took their survey data about six weeks after COVID started and showed that, fifty three percent had self reported worsening of disease, One third had, access problems with their hospital or their clinic.

Yet eighty eight percent were able to get their meds and their refills and all that seemed well. But still, of those, about half of them still required help, meaning that they were older people or they seemed to need help with a change in technology in getting their meds to them. So this is one of several examples. You know about patients who are probably not getting their cancer care, their bone density treatments or screenings. There are a number of things that are happening during COVID that we're going to find out.

It's not quite as simple as the lost income and the disruption of our lives. There's a lot of things that are going to happen as a result of COVID that we're going to find out in the next few months. That's what happens with lockdown. I found this interesting study, reported it yesterday as a tweet. It's a study of almost two hundred patients with axial spondyloarthritis who undergo switching of TNF inhibitors.

You know, we tend to love to switch TNF inhibitors. If one doesn't work, let's try a second. If that doesn't work, we can try a third. I'm not a big advocate for that. I would say that after you've failed one TNF inhibitor, you show up and go to another MOA in RA.

And the data is pretty clear that in RA when you start going from first to second to third, you lose efficacy, meaning ACR20, which should be sixtyfortytwenty with the first one becomes fiftythirtyfifteen with the second or maybe even worse. And this is a study showing the same thing in patients with, ankylosing spondylitis, actually axial spondyloarthritis. So using the most stringent criteria for outcomes, the ASDAS ID, I can't keep up with the ASDAS people, the ASAS people who are coming up with new measures all the time, but nonetheless, the most stringent measure of outcome shows that you're going to do okay if you stay within the TNF class, you switch from first to second, if you're switching for the purposes of a secondary non response, meaning they once responded, you lost response. You actually don't lose much in the way of response, or if you're switching for adverse events. But when you compare those two reasons for switching to primary non response, they're way better, seven to nine times better than those who have a primary TNF refailure, meaning as soon as you got your first TNF number, you never got better.

That's your clue to switch. This works and applies to, in this case, spondyloarthritis. It also applies to RA. I'm sure it applies the same way with psoriatic arthritis. In fact, there is data to suggest that.

A new biologic hit the markets, a new study with an anti GM CSF monoclonal antibody studied in twenty two patients twenty two. Let's try two twenty two patients with rheumatoid arthritis. The drug is called Otilimab. Otilimab, O T I L I M A B. This is in an early phase two trial where they're trying five different doses versus placebo.

The drug is given weekly for five weeks and then every other week thereafter. It was a one year study. The primary endpoint was six months. And guess what? At six months, it didn't look good.

The five doses were twenty two, forty five, ninety, one hundred and thirty five or one hundred eighty or placebo. Again, the dose the CRP remission rates, the CRP less than 2.6 was like five percent, sixteen percent, nineteen percent, fourteen percent. Got no better than fourteen to nineteen percent. Again, you sort of like to see an RA somewhere in the range of thirty percent or higher. So, this did not meet its primary endpoint.

They talked about it with some degree of encouragement, but I look at this data and say, this is a crash and burn. The placebo response rate was three percent. So yes, it was better than placebo. That was the lowest dose. The other doses were better, but I'm not certain what's going to happen with this anti GM CSF monoclonal antibody.

There's an interesting study that came out from the Greek registry, Hellenic registry. This includes three eighty five patients and it showed, it looked at patients who were in remission or low disease activity state and compare them to those who had moderate disease activity and higher. So patients with worse disease, what happens to them? Well, it turns out they actually had fifty to eighty percent more serious adverse events. That's something we've seen over and over again.

Patients who have the best response, you know what, they tend to have the least amount of adverse events, especially even serious adverse events. Patients with the worst response, that's where all the serious adverse events, SIEs, cancer death, malignancy, whatever, those occur in people who don't respond well. There's something about efficacy and safety that in fact does go hand in hand. Bad disease, expect bad outcomes. That unfortunately applies, to many situations.

So lupus and lupus cerebritis can present as psychosis. We don't see much psychosis, but it can sort of appear. There was an interesting study that came from one of the psych journals about April mental health patients who were admitted to the hospital for psychosis. Could they possibly have lupus? Could they have autoimmune disease?

Could they have neuropsychiatric lupus? Well, of the cohort that was tested, it wasn't all four thousand seven hundred, I think it was, I don't know, three hundred, 400. Actually nineteen percent were tested and one hundred and thirty five had a positive ANA with titer of one to 160 or higher, meaning that fifteen percent of those tested were ANA positive. I can tell you as someone who screened a lot of autoantibody positive results looking for early disease, you find a lot of positive autoantibodies without necessarily having the disease in the psych population. So fifteen percent are ANA positive.

To me, I kind of expected that. But of those one hundred and thirty five, only four met criteria for lupus. And only two of those four actually had criteria for neuropsychiatric lupus. So de novo, incident, psychosis, could that be the presenting feature of neuropsychiatric lupus? Not a chance.

Not a chance. When it is, there'll be other many manifestations of lupus, they'll meet criteria real easy. And yes, neuropsychiatric lupus could be the presentation, but again, psychosis masquerading as lupus is really not likely. So I asked you earlier, you know that scooped out lesion that you see in gout? It's different than RA lesions, we've got a little bit of a rat bite on the corner at the articular synovial junction.

These are a little bit lower and they're lucid lesions that have a scooped out appearance. It's got a name. Actually, was first described by the famous radiologist from University of Michigan, Doctor. William Martell. So it's called the Martell sign.

It also is called the G sign. Think about it, G or rat bite erosion. I just said the rat bite erosion is what you saw in RA. That's the wrong name. But a G sign I like, the scooped out erosion I like, but now I'm going call it the Martell sign after Doctor.

William Martell. Again, it is a lesion that is a scooped out lesion with a sclerotic margin and an overhanging edge. Those are the classic features of the gout radiographic change. So what about risk of future damage in spondyloarthritis? What better population to look at than an early spondyloarthritis population as found in the DeSear cohort?

Four zero six patients with axial spondyloarthritis, and they were followed over five years. They showed that smoking was a risk factor for developing five years later MR evidence of sacroiliitis and MR evidence of lumbar disease as well. Turns out that actually this was even higher in blue collar job individuals and those who had low education levels, which is a little bit like what you see with psoriatic arthritis and psoriasis where trauma is a major inciting factor or risk factor for future arthritis. They're suggesting that blue collar jobs or mechanical stress may be a risk factor for developing sacroiliitis and spondylitis in these early spondyloarthritis patients. An interesting concept.

Our last report comes from that CANTOS study. We talked about it a lot in the past. Remember the CANTOS study was the canakinumab, study looking at its effect as an IL-one inhibitor in patients who are high risk cardiac patients who go into the study with an elevated CRP. And it showed that, yes, an IL-one inhibitor is capable of reducing cardiovascular events and cardiovascular death. Other spin offs from that study, it was a 10,000 patient trial.

Again, none of them had to have arthritis getting in. They found that patients who were on panikizumab compared to those who weren't were less likely to have new incident gout. They found they were less likely to have death. They were less likely to have lung cancer. And again, these are all surprising findings.

This particular report looks at the risk of future arthroplasty. So a small subset of these people going into the study did have osteoarthritis, but most did not. And they were looking at the risk of a future total hip replacement or total knee replacement. And again, it was comparing placebo treated patients to those who received one of the five different doses of canakinumab, fifty, one hundred fifty, or three hundred every eight weeks. Altogether, those who received canakinumab had a forty two percent lower risk of developing the need for joint arthroplasty.

This does suggest that IL-one inhibition could be effective therapy, but there have been studies looking at IL-one inhibition in treating osteoarthritis of the hand. Again, it might be a cohort, an entry cohort, criteria that may give you different results, maybe very early for people who are at high risk but don't yet have, you know, grade three or higher, osteoarthritis of the knee. Is an interesting finding. Anyway, that's it for this week on RheumNow and our podcast. Go to the website to find citations for these reports and more.

Again, I want to encourage you to click on back talk and present your case or ask me your question. Will feature those in future, editions of the podcast. And lastly, I want you to be on the lookout for all that we're going to be doing for ACR twenty twenty, the virtual meeting. RheumNow has got a wild and crazy plan, and what we want you to do is give us two hours, and we'll deliver the meeting to you. It's gonna it's our promise, and we're working hard to make sure that happens.

Thanks for tuning in. See you next week.