RheumNow Podcast Cancer Risk In Sytemic Sclerosis (9.27.19) Save

It's the 09/27/2019. This is the Room Now podcast. I'm Doctor. Jack Cush, executive editor of roomnow.com. This week in the news, actually, this week in Room Now, you'll see reports on Plumbing and Rheumatologists by Sterling West, on Exorcisms in Clinic by Jack Cush, and of course, cover the CBD position paper from the Arthritis Foundation.

Nice. Kind of says nothing. And then what we didn't cover was Kim Kardashian and what she has. We're going to start off with the quote. This is a quote from one of my favorite, leaders, mentors, and that's Seth Godin.

The quote goes, People don't believe what you tell them. They rarely believe what you show them. They often believe what their friends tell them, and they always believe what they tell themselves. Is this not true in clinic? Again, you tell them, you show them, they don't believe you, but yet they believe their friends, the Internet, their hairdressers, and of course, they believe the story that they have in their head.

I think your job maybe is to make you their friend. Then they might believe you. Let's start with a report about ANCA associated vasculitis looking specifically at the association of inflammation in such patients and what happens to lipid levels. This is from John Stone, a bunch of colleagues who studied vasculitis, one hundred and forty two patients with AAV, and they studied their lipid levels. They showed that lipid levels increased when the patient was newly diagnosed with PR3 positive ANCA associated vasculitis and they went into remission.

So they go into remission, but yet the lipids increase. This was not seen in MPO positive patients or those who had relapses of their ANCA associated vasculitis. Overall, there was an association between sed rate levels and lipid levels, actually an inverse association. Now, can we see this in a lot of conditions? What happens is inflammation suppresses lipid levels.

So people who are very inflamed joints, their lupus is active, whatever, before they get treated, their lipid levels may be normal. But then when you treat inflammation, it's very common that you'll see lipid levels rise and they get back what they normally had before if they didn't have inflammation. The question is, do these power plant inflammatory drugs give them higher lipid levels? No, they don't. We see this especially with IL-six inhibitors.

We see this with the JAK inhibitors. We certainly can see this with the TNF inhibitors. A very interesting study was done, using Anakinra, a drug you often don't use in patients with rheumatoid arthritis, and type two diabetes. So not type one diabetes, where Anakinra has been studied and shown, in fact, to work. So forty one patients who had both type two diabetes and RA randomized either received Anakin or TNF inhibitor and patients were studied over six months.

And not surprisingly, they both did very well. Their joints got better. The inflammatory indices got better. Their disease activity measures both got better, and again, equally not different. What was different, however, is what happened to their A1C levels.

Patients who were treated with anakinra were more likely to have significant reduction in A1C levels at three months and six months, whereas those treated with TNF inhibitors did not, suggesting, there might be something there. You might need to use anakinra or IL-one inhibitors more frequently. I think the most comments I've received in a long time about tweets or news I put out came from this next report. It's actually a report about systemic sclerosis and whether or not there's an association with cancer. So this come and I got a of comments from both physicians, major leaders, patients.

It was really surprising. This particular study looked at almost two thousand patients with systemic sclerosis and looked at, their overall risk of cancer compared to a normal age matched population. The SIR, the standardized incidence ratio, was two point one five, meaning a twofold higher risk in systemic sclerosis patients. And that was significant. The confidence interval to 1.84 to 2.5.

Most common cancers seen in systemic sclerosis patients were breast, melanoma, hematologic, and lung cancer. So I don't know that the kind of cancers are any different in patients with systemic sclerosis. It may be that they get more cancer because we don't have a drug to treat them. If we had drugs to treat them, we might normalize their cancer risk by normalizing inflammation. Anyway, I thought this was surprising.

And the other thing that was interesting here was the cancer risk was higher in patients who had antibodies against RNA polymerase III, patients who had calcium channel blockers, and those who had a history of interstitial lung disease. Something to think about. A nice review comes from the renal literature I put up this week talking about whether or not we should be treating asymptomatic hyperuricemia. I think we all have a policy on this. I think it's generally believed you don't treat asymptomatic hyperuricemia.

And this patient, this paper from the renal literature kind of says that, that most nephrologists do not treat asymptomatic hyperuricemia. The point of the paper was they really couldn't find any papers that effectively dealt with this issue. They only found three reports showing that the use of allopurinol or febuxostat in patients with asymptomatic hyperuricemia, anything over seven, two out of the three suggested benefit, long term renal benefit. The other one, not so much. But overall, the numbers here are very low and this is a very common problem.

So I think most people that they referenced in paper said we wouldn't treat it. I think you might change your mind if there are more data on this. I think you might change your mind if we're talking about a certain kind of patient, someone who's really sick. We might talk differently about this. We're talking about very high, asymptomatic hyperuricemia.

So thirteen, fourteen, would you treat it? Absolutely, you would. But would you treat nine? Would you treat 10? My own view is in studying hyperuricemia and gout, I believe uric acid is very toxic.

I think it's very toxic to blood vessels and tissues. And now if I see someone who's asymptomatic hyperuricemia and it's more than nine, I'm treating them. If it's eight, if I don't have a good reason to treat them, I'm probably not going to. But again, we need more research in this area. Speaking of research, Novartis put out a press release this week.

So preliminary data on what's called the PREVENT trial. This is a trial of secukinumab, the IL-seventeen inhibitor in patients not with psoriatic disease, not with ankylosing spondylitis, not axial spondyloarthritis. Yes, it's with that condition called non radiographic axial spondyloarthropathy. Recently, the FDA approved cerdulizumab for that condition. A companies lot and drugs would like to be using that condition thinking, it just gets you one more part of the spondyloarthritic spectrum.

There's not a lot of patients who have this. And I think that, some people are uncomfortable with this diagnosis, but they have fairly rigid criteria going into the study. They had to obviously meet spondyloarthritis criteria, not have, New York, criteria for AS, not have clear cut, sacroiliitis, but instead either have, an MRI evidence of that or an elevated CRP that would support the diagnosis. Anyway, their preliminary data, they don't show the numbers, was that there were superior ASAS forty results compared to those on placebo. And the promise is they're going to, present this data in an upcoming meeting, hopefully at ACR in six weeks' time.

Very interesting report appeared yesterday from the CDC and their MMWR report. They actually looked at opioid use in a lupus cohort. The data comes from the MILES study. It's done in Michigan, a lupus cohort from Michigan, where they studied four sixty two patients and compared them to one hundred and ninety something patients who did not have lupus and looked at overall use of opioids. And they found lupus patients threefold more likely to be on opioids than non lupus patients.

Now, the numbers here are kind of small, especially in the comparative group. And there's maybe an issue in Michigan with more opioid use than maybe there is in Connecticut. But nonetheless, they found more in lupus. Specifically, they found that lupus patients who went to the ER were more likely to be the users, if not abusers, of opioids with a twofold higher risk compared to their comparator group. So we don't think of lupus as a condition that needs narcotics, you know, pain.

Certainly it happens with serositis and with, arthritis and with, joint damage, maybe with secondary fibromyalgia. But again, those should be treated with anti inflammatories, simple analgesics, treating secondary fibromyalgia. Why are lupus patients on, narcotics? I don't know. AVN occasionally, but this seems to me like an extreme problem that needs to be paid attention to.

Another really interesting study, appeared in the literature recently, and this is about the use of low dose IL-two subcutaneous injections in patients with lupus. And this is when patients who had pretty active lupus of all kinds, including patients with nephritis. There was some preliminary data a few years back showing that this could be used safely in patients IL-two as an infusion has been given to cancer patients, melanoma patients, high dose therapy was associated with problems. But here they're using low dose therapy. And what they did was they studied a total of sixty patients who had lupus, active lupus, and thirty received low dose IL-two, subcutaneous injections versus placebo injections for twelve weeks.

They then followed patients for another twenty four weeks after the IL-two injections stopped. And guess what? At twelve weeks, significantly better SRI-four, primary endpoint for most lupus trials these days, SRI-four responses in the IL-two group, fifty five percent versus thirty percent in placebo. That's significant. Moreover, when they followed these patients for another twelve weeks after they had stopped the IL-two injections, they continued to maintain efficacy sixty six percent versus thirty seven percent.

Not a lot of difference here as far as adverse events. I think maybe a few more injection site reactions and flu like symptoms and a little bit of fever, but really it was otherwise very well tolerated. Interesting to see if this goes further in clinical trials. Our last report is about persistence of arthritis symptoms in patients who have checkpoint inhibitor related adverse events. As you know, the patients who get these immune checkpoint inhibitors, ICIs, can come down with, immune mediated or immunologic adverse events, myositis, hypothesitis, thyroiditis, myasthenia gravis, PMR, inflammatory arthritis, you name it, they get a lot of autoimmune features.

Not surprising given the biology of this. Well, the Johns Hopkins group, who's done a lot of work on this, a lot of good work on this, did a follow-up of their 60 patients who developed inflammatory arthritis while on an immune checkpoint inhibitor. They were roughly half male, half women. They were followed for a total of about nine months. At presentation, when this group presented, they had a mean of six tender joints, I'm sorry, six swollen joints that had a median C.

Dice score of 17.5. They had very low rates of seropositivity, you know, one percent, two percent rheumatoid factor positivity, five percent CCP, fourteen percent ANA positive. Most of them, if not all of them, had normal sed rates and CRPs. So after the patients had a cessation or a hold on their immune checkpoint inhibitor, active disease remained in up to seventy five or seventy one percent, three months after. And at six months, half of them still had active inflammatory arthritis.

Majority of these patients went on to receive some sort of immunomodulatory therapy, either steroids the most common, DMAR is the next most common, biologics, next most common. And again, most of them seem to respond. The issue here is given this persistence of inflammatory arthritis, how are we going to manage this? We need guidelines for this. When I ask large groups of rheumatologists how often you see this, everybody puts up their hands.

So, you know, at least seventy percent of the audience has seen a case or two of this. So this is something that, as these drugs, if there's five or six of them now in the marketplace and they're being used in a lot of problematic cancers beyond melanoma, as they get wider use, we'll be seeing more of these patients going forward. That's it for this week on the podcast and the Weekend Review. Go to the website to check out the citations links, and you can read up more on this. We'll talk to you next week.