RheumNow Podcast – Lupus Mortality Declines, But… (6.26.20) Save

It's the 06/26/2020, and this is the RheumNow podcast. Hi. I'm doctor Jack Cush, executive editor of rheumnow.com. This week, autoimmune disease in Wuhan, colchicine with COVID, and WHO VTE, and more acronyms to drive you crazy. We're gonna start with a study about kidney cancer and hyperuricemia, you say.

Well, you know, gout is actually associated with an increased risk of cancer. A few different studies have shown that a lower risk of Parkinson's. We certainly know that hyperuricemia is associated with, you know, more renal disease, risk of hypertension, etcetera. So, in this particular study, which is a very large UK database of almost a half million people, and these people were followed for a mean of six point five years, they showed that just looking at uric acid levels, comparing the lowest quartile to the highest quartile, hyperuricemia, the highest quartile was associated with about a forty five percent increased risk of renal cancer. That's interesting.

More interesting was it was only seen in women. I guess men have enough problems on their own, but, it's nonetheless fine that that's just another thing that we can use in our discussion with our gout patients as to why they need to keep their uric acids under control. There are a lot of consequences to hyperuricemia, which can be flat out dangerous. Just today, J and J had an important announcement. As you know, ustekinumab, the IL-twelve twenty three inhibitor has had some very encouraging preliminary phase two results in lupus, but their phase three program looks like it's on hold.

They had a phase three pro, study called LOTUS. This is a five sixteen patient study that was, stopped because not because of safety concerns or a new safety signal, but an interim analysis showed that it just didn't have efficacy. So it was stopped for lack of efficacy. There was another phase three trial was gonna happen in Japan called the LOTUS C trial that was put on hold. It looks like that could be the end of ustekinumab, although that was not part of their press release.

Tocilizumab as we know has expanding list of utilities, beyond just rheumatoid arthritis and other IL-six mediated diseases, but I found an interesting report, forty seven patients using tocilizumab in Behcet's disease. And this particular report, it was selective, I agree, this is not a really well done study, but I found this to be a useful report because it said tocilizumab may be helpful in those patients with the most severe forms of Behcet's. And specifically, we're talking about refractory cases of ocular Behcet's, neuro Behcet's, and vascular, Behcet's. So in this particular study of forty seven patients, it was effective in twenty four to twenty five patients with refractory ocular Bichette's. Six out of six with, CNS Bichette's, seven out of seven with vascular Bichette's, and two out of two had amyloidosis related to their their Bichette's.

But as much as was great at these really, strange, but, you know, significant, morbid complications of Bichette's, it really wasn't that effective at oral and genital lesions, only eight to twenty one patients who were treated with tocilizumab, skin disease only six of fourteen, or joint disease four out of eleven. So the point being that there are other therapies we might use to manage Behcet's, but when you, you know, the going gets tough, tocilizumab may be a drug that you might wanna look at. Of course, it's not approved, it's off label use, you have to weigh the benefits versus the hazards here. An interesting meta analysis of eight studies of over one hundred and thirty thousand patients with inflammatory bowel disease, both Crohn's and UC shows a significantly higher risk of developing rheumatoid arthritis. Overall, about the relative risk here was two point six.

So a hundred and sixty percent increase risk of developing RA. We don't think of RA particularly happening in IBD patients, but as you know, a significant number of those people will develop arthritis and as we call it enteropathic arthritis or IBD arthritis, often they get called seronegative RA. So, seems reasonable that, one should be considering, RA, inflammatory arthritis, as a complication of inflammatory bowel disease. A new study came out with the NGF inhibitor tanezumab. This is now in phase three and this particular study didn't look at the usual severe osteoarthritis patients hip and knee or hand as other studies with tanezumab have, looked at.

This one was looking at just low back pain, and it was a head to head against placebo and tramadol, and their primary endpoint was at sixteen weeks where you needed a greater than 50% improvement in low back pain. That was seen in thirty seven percent on placebo, forty three percent on tanezumab five milligrams and forty six percent on tanezumab ten milligrams. The odds ratios here was a one point four five odds of a better response to placebo. So a fifty percent roughly, increase over placebo. Again, this will go into their profile as that goes in front of the FDA as a potential drug for treatment of osteoarthritis and then low back pain might be one of the indications based on on this trial.

As you know, these nerve growth factor inhibitors, are unique in how they work. The downside has been, they hit a bump in the road when many of their trials showed an accelerated amount of, DJD leading to joint replacement in both hip and knee. The FDA put those studies on hold, analyzed the data, and basically said that by giving a nerve growth factor a nerve growth factor inhibitor, you are almost causing a Charcot joint in the most severe patients and that that led to continued damage, repetitive damage due to use that ended up in replacement. Now replacement is not such a bad thing in people with advanced disease, but people were worried about would this give you a Charcot joint? And it's not really a Charcot joint, but nonetheless, that is a downside to, using the nerve growth factor inhibitors, but there's a real upside here in that it does something that other drugs don't do.

We don't have enough options in patients with advanced moderate to severe osteoarthritis. I think it's going to, move forward. I hope it moves forward. Another interesting study came out, recently about MRI imaging of the SI joints and where you may be led astray. As we reported before, this has been seen in other non spondylotic conditions where you could have abnormal MRI, especially with bone marrow edema, the SI joint, questioning its utility in diagnosis.

In this particular study of thirty five pregnant women, they did MRI, SI, imaging at baseline prior to pregnancy and then, postpartum. And they found that seventy seven percent had some evidence of SI bone marrow edema postpartum, and that sixty percent of these would have met the ASAS MRI definition of, a spondyloarthritis. Turns out that that bone marrow edema persisted, even out, not just at, what was it, six weeks, but at six months and at twelve months, it was still there at forty six percent and twelve percent of the individuals suggesting that there's a limitation to bone marrow edema. I saw a patient I saw a patient this week who has an undiagnosed condition with fevers and GI and lung manifestations, but this individual, who's never had joint pain, never had back pain, did develop iritis, did have an MRI and showed bone marrow edema. And the question is, could he have a spondylarthropathy underlying these things?

Again, this gentleman needs more workup, but bone marrow edema is not diagnostic of a spondylarthropathy based on this study and ones that have gone on recently. So where are we? Next study. WHO has actually undergone they have a large global safety database which draws from multiple countries, multiple sources on the safety of drugs. This particular analysis looked at the risk of venous thromboembolic events or VTE, specifically DVT, deep vein thrombosis, and PE, pulmonary embolism, in patients receiving either tofacitinib or baricitinib.

They found out that the patients who are likely to get VTE were more likely to be older, and that's not surprising. They found some interesting differences between the EU, the European dataset, and the American dataset. In the EU, TOFA had an increased risk of VTEs and odds ratio of two point three, and that was significantly higher higher. Barry had an increased risk of VTE at three point four, also significantly increased. However, when I looked at Barrie in The United States, there was no increased risk.

Would that be because it's only approved at two milligrams in The United States? Hard to say. But TOFA had a slightly increased risk at two point o. The point is that this is a worldwide phenomenon that these events are part and parcel of inflammatory diseases like RA and that these drugs may add to the risk especially in people who may be at higher risk such as the elderly or people who have prothrombotic tendency. People who had a prior VTE are likely to get another VTE especially if on a JAK inhibitor, keep that in mind.

The big report this week I think was the mortality risk in lupus. There's a lot of data out there, but none of it really is recent. None of it really looks at overall risk over time. And so this particular analysis looked at a large data set, three forty million hospitalizations that included almost 2,000,000 who are hospitalized for lupus. During this period of analysis from 2006 to 2017, they showed that the odds of a lupus hospitalization actually rose slightly in this ten year period from zero point five percent of hospitalizations in 2006 to zero point six percent of hospitalizations in 2016.

However, during that same period amongst the lupus patients only, death rates went down, they went down from two point two to one point five percent and that's very encouraging. However, all that benefit was seen between 2006 and 2008. We got we were brilliant in 2006 and 2008. Those were my best years. It's like saying, you know, third grade, two of my favorite best years.

You know, I don't know why it was just those two years and why after 2008 it plateaued and didn't have a significant increase. It could be that there's been no major advances, since that time. It could be a reporting bias. It's really hard to say. It can't be a reporting bias.

That's not a good or right answer. But what the authors did note that nonetheless, there was a still a still a high, disproportionate representation amongst those deaths by, blacks, Hispanics, Asians, and Pacific Islanders, suggesting that those still are high risk groups for death and hospitalization, and we need to keep that in mind in developing plans to manage lupus on a population level. There was a nice report about, I often asked amongst this coronavirus pandemic, where's the data from China, you know, about their experience with their arthritis patients? So it was really very little seen, over the years, over the months that this has happened. So now we have a report of the, like, an early cohort from Wuhan, China, twelve hundred and fifty five patients who developed, the COVID disease.

They were, you know, mostly male, 64 years of age, two thirds had comorbidities, but amongst this population, they did find seventeen patients who had autoimmune conditions like RA and lupus and whatnot. The age was about the same, autoimmune disease being, more likely to affect females, eighty three percent of their seventeen patients were female. And they went on to describe a lot of nothing. There was one admission to the ICU, there was one death. Amongst those seventeen patients, ten had stopped their DMARDs and five of those or half of them had noted worsening.

So how do I read this? Well, it's another small selective report about the coronavirus, but it does seem to suggest a pattern that I think I'm seeing, which is amazingly, our patients with autoimmune disease have not been affected, to any significant degree. They're getting there's their reports, their reports of lupus and lupus patients on hydroxychloroquine, you know, who've been hospitalized and even died, but the numbers are low, and the numbers of severe disease are also low. And I think that's a credit to you, those of you who are managing lupus and RA and autoimmune disease, rheumatic disease patients, effectively keeping them stable, encouraging them to stay on their medicines, and, following the guidelines on, you know, isolation, distancing, masks, etcetera. There was an important study that came out a few weeks ago, but we missed and just reported this week about hydroxychloroquine failing as prophylaxis, for the treatment of COVID nineteen.

This particular study, they enrolled eight twenty one individuals who had a documented exposure to someone with known COVID nineteen infection, and then within four days were treated with either, nothing or hydroxychloroquine. The dose hydroxychloroquine was an initial dose of, I wanna say, eight hundred milligrams, and followed six or eight hours later by six hundred milligrams, and then they were given six hundred milligrams for the next four days after that. The endpoint was, at weeks along the way, but finally at week twelve, how many of them had developed, the coronavirus infection. And in all, the COVID illness was only seen in twelve percent of the hydroxychloroquine treated patients and fourteen percent of placebo, no significant difference suggesting there was no protective prophylactic benefit to hydroxychloroquine administration. They did have more GI and other nuisance side effects with hydroxychloroquine, no serious side effects, no cardiac side effects compared to those on placebo.

So, again, another hit for hydroxychloroquine. Thank god they won't be using it for COVID management. We can continue to use it in our lupus and rheumatoid and other patients. Lastly, an interesting report in JAMA open network reports. Thanks, Artie Cavanaugh, for show sending this my way.

This is a report about colchicine, being used in about a hundred and five, hundred and ten patients with the COVID infection. This is a randomized controlled trial called the GRECO trial, it was done in 16 centers in, Greece. And in this study, patients with who are hospitalized with COVID were given either, colchicine, three doses the first day, and then basically BID for a few days, five days, something like that afterwards. And when you compare the outcomes, there was a significant benefit to those treated with colchicine as far as the time to worsening, and basically not necessarily survival, they didn't look at that, but, basically worsening statistics were lower in the colchicine group. They had hoped that you would actually have seen improvement in biomarkers like CRP or cardiac troponin, but there really was no difference in biomarkers.

So, this is an important early result for colchicine, being used in patients with early infection, in this case hospitalized patients. There is a large study out there that we reported before that's that's coming from Mike Pillinger's group at NYU and the Montreal Heart Institute. It's a nationwide study. I think UCSF is in on that study looking at, again, the potential protective effect of colchicine in COVID patients. That result probably will not be available until September, probably October, November.

I think it ends in September. So that's it for this week on the website. Go to there to find these citations and more. Continue to tune in to RheumNow. We appreciate your patronage.