The RheumNow Podcast - Merry Lupus Christmas (12 - 20 - 19) Save

Ho ho ho. It's a merry lupus Christmas. That means, yes, this is the Room Now podcast for 12/20/2019. I'm doctor Jack Cush, executive editor of roomnow.com. Today, we're gonna talk about a lot of lupus stuff.

But before that, did you know that domestic violence could be responsible for rheumatology's number one problem? When do you start to worry about CCP consults? We don't see many of them. We see a ton of ANA consults. Blow those off all the time, almost never amount to much.

But what about other autoantibodies? Should you worry about them? Will we ever get good news in lupus? I think it's here, just in time for Christmas. So an issue came up.

I got a lot of issues in clinic. I'm always thinking of, if only I knew the answer. And I saw a young man who has had ankylosing spondylitis for, oh, ten years. And he's kind of fused, low back, a little bit in his neck. And the question is, you know, I ask the usual questions like, you know, psoriatic disease, bowel disease, eye disease.

When do I worry about his aortic bowels? Know, AS patients certainly get aortic insufficiency and whatnot, and the question is, should we routinely be doing echocardiograms on our patients who have established ankylosing spondylitis or spondyloarthritis? And I think the answer is yes. So I looked at the literature, a very large Swedish study. They call it Bectarev syndrome, they got a lot of patients in this particular study, almost six thousand five hundred ankylosing spondylitis patients who were studied by Echo.

And guess what? They showed that in their population, eighteen percent of patients had an aortic insufficiency murmur. It was more likely with long standing disease. It was more likely with increasing age, especially over the age of 50. The question is how many of those, you know, sort of, you know, bottomed out and needed aortic valve replacement?

They didn't address that. But just having an AI murmur puts you in the category of, let's watch this. Another study also looked at this, one hundred and eighty seven patients also showing a higher rate of eighteen percent. The previous study didn't show an eighteen percent, showed a twofold increased risk if you had AS compared to non AS. This is eighteen percent.

I think the data really kind of suggests that you should be doing echos in your patients who have, especially long standing disease. I wouldn't do it at baseline. I wouldn't do it when you're in your 20s or 30s. But after that, you might want to do it. A retrospective study looked at individuals who had a positive CCP antibody, but no evidence of rheumatoid arthritis.

Are these people preclinical RA? Well, they had a positive family history and maybe some joint pain without synovitis, they could be preclinical RA. First degree relatives of CCP, you know, the literature looks like you've to worry about those people. There is a significantly high rate of conversion to RA. In this particular study, they looked at what was the influence of CCP on conversion to RA, and it was in those individuals who had the highest titers of CCP.

Compared to low titers of CCP, there was almost a fivefold increased risk and conversion was seen as much as forty six percent of patients. So, it's a different can of worms, if you will, compared to all those ANA consoles that you get in these people. If they have a first degree relative, if they have joint pains, if they have very high titers of CCP, I wouldn't say, know, you have no arthritis, don't come back. I would say, good news is you don't have arthritis today, but let's, you know, follow you every six months or every year and see what changes, because it's possible it could change. It's possible it couldn't change.

You don't know until you just sort of follow them and discover what will happen. I saw an interesting, journal report. It's not from one of our journals, comes from like the touchy feely journal about domestic violence or bad relationships or psychology. I can't remember the name of the journal. It's in the link.

But I thought it was an interesting observation. It was a population based study based on a survey called the Health Improvement Network done between 1995 and 2017. And they looked at a large number of women, like eighteen thousand women, who were exposed to intimate partner violence, also known as IPV or domestic violence, and compared them to four times as many who did not have exposure to violence in a relationship. And when they looked at the outcomes, they found that there was a twofold increased risk for fibromyalgia and for chronic fatigue syndrome. Odds ratio for fibromyalgia was one point seven three.

And you know, this abuse has been linked to the onset of fibromyalgia in children. And it's not surprising this would be seen also in adults. You know, of course, they went a little haywire and cockamamie crazy when they started talking about stress causing inflammatory and immune reactions. You know, I don't think you can make those connections quite yet. But it's not surprising that, domestic partner violence could set someone up for whatever the major life event that leads to a central pain processing problem.

And this is something we should be asking our patients about because this might be an area of intervention in people who need intervention. The Journal of Rheumatology has a nice report about how early you get damaged in lupus. In the early lupus study of two thirty patients followed longitudinally, they showed that the damage index was abnormal and high by one year and twenty two percent, and went up to like thirty six percent by three years. The risk factors were dyslipidemia, older age, number of organ systems involved, cardiovascular or respiratory involvement as predictors for further damage. It's not surprising since those themselves are damaged.

But I think what I found interesting about this was it was seen early in disease. In the first twenty four months, let me correct what I said, it's twenty two percent, suggesting that lupus is, as we know, a very aggressive disorder in some, and early intervention, early treatment, effective treatment is going to be important. Which leads me to several of the, two more or three more abstracts that I think are important this week. One from Alzheimer's disease, that if you have lupus patients and you treat them with low dose steroids, that they may not flare in the future. Was that a duh kind of observation?

Well, you know, again, many of us were taught to get our patients off of steroids. Steroids are bad. But, you know, I learned from many years of treating a lot of bad lupus in Dallas at the Park Memorial Hospital And a little bit of lupus, a little bit of steroids, it was a long way in keeping lupus under control, keeping pretty active and severe lupus patients out of the hospital. That's been my observation. Well, we have two studies recently that support that one from ACR, which I talked about during ACR, and this one in ARD, which said they compared sixty one patients who were maintained on low dose prednisone, five milligrams, and sixty three who were weaned off of prednisone.

And guess what? Eighty percent fewer flares in the group that was maintained on steroids. Also, time to flare was better in patients who were maintained on steroids. Again, I would assert that if you have real lupus, I mean, not just like a little aching pain positive ANA, but patients who have, you know, three, four, five, six or more criteria, I think about three, but more like five, six, seven, whatever criteria and major organism involvement, the goal is to have them effectively managed and maybe a little bit of prednisone. Maybe the big splash at ACR were the TULIP one and TULIP two studies.

Tulips were two studies done in systemic lupus erythematosus using the drug anofrolimab, a monoclonal antibody against type one alpha interferon. And Rishfuri presented the first during a plenary session, showing that TULIP one failed. Meaning that, you know, three hundred-four hundred patients enrolled with active disease on background therapies failed at its primary endpoint of an SRI-four response. I think the number was like forty percent placebo and anifrolimab thirty six percent met the primary endpoint. This is in stark contrast to the report that Fiori gave two years earlier at ACR and UR, where anifrolumab looked great.

It almost had double the response compared to placebo, which had a seventeen percent response and a thirty four percent on anifrolumab. That was phase two. It looked really good. This was all the rage. Finally a great drug with a mechanistic reason to treat lupus.

So then comes TULIP one, it fails. Well, guess what? Then there's a TULIP two that made New England Journal article this week, and is a positive study. A very well done, similarly done trial, almost the same patients, another phase three trial. This one, a three sixty two patients.

The only difference was that they changed primary endpoints, in this case, to another outcome measure called Biclo, and it was significant. Forty eight percent on anifrolumab, three hundred mg IV, versus thirty one point five percent on placebo. A really good response. By the way, the SRI-four, which failed in the TULIP-one study, also was a positive response in this TULIP two study, and also a positive result was seen with CLASI that's the outcome measure for chronic skin disease in lupus. So the question is, is this drug going get approved for lupus or not?

Great phase two, split decision on phase three, or are they going to have to do a deciding trial? Again, that's kind of the great enthusiasm for this phase three in the New England Journal is sort of tempered by the failure of TULIP1. The other disappointment here is that this drug is a type one alpha interferon inhibitor, but if you look at people in the trial who have that signature, who are high expressers of the alpha interferon one genes, are no more likely to respond than those who don't have it. So, again, it's got some grayness to it. I bet that the FDA actually will go ahead and approve this.

In fact, I would recommend they approve it. By the way, have no say in any of this. I'd recommend they approve it and put stipulations on what they want to see in a post marketing study to further prove the efficacy and the safety of this particular approach in lupus, where we really would like to see some newer, better drugs. Which leads me to my last study, belimumab. Many of you have heard me talk about belimumab in the past.

I'm not too wildly enthusiastic about belimumab. It works. It didn't work in phase two. It worked in two phase threes. It worked by this much, meaning not very much.

But you know, when you don't have many new therapies for lupus, it was a welcomed addition. And my gripe with a lot of lupus trials is that they're trying to get the drug approved with sort of global response measures like Bicla and SRI-four and Salinaslidein, as opposed to going after specific manifestations of lupus like nephritis, hematologic disease, the arthritis disease, the skin disease of lupus, where you have much clearer and maybe better defined outcome measures as compared to all those others, which none of you do in practice, Classy, Bicola, again, they're all kind of confusing and really don't have much practicality in real world management of lupus patients. Well, GSK reported the top line results of their trial called the BLIS LN trial, standing for a lupus nephritis trial. This was reported just two days ago. Four forty eight patients were studying this trial of belimumab versus placebo in active lupus nephritis patients who are maintained on background therapy, which could have been a number of different therapies and different induction regimens.

And the bottom line is in this two year study, forty eight week study, belimumab was superior to placebo in meeting a renal response definition of forty three percent versus thirty two percent. That was significant at zero point zero three. There were a few other measures that were significant. Complete renal response and time to either death or first renal event were also significantly better on belimumab compared to placebo. Not much, in that trial as far as new safety signals compared to what we already know about belimumab.

Again, this is a welcome addition. This is the kind of trial I think we should be doing. Belimumab is not currently, belimumab being listed, is not currently approved for use in lupus nephritis, but this is the kind of trial they need to do to possibly get this indication going forward. Again, we should encourage, the companies to do more organ specific trials in lupus as opposed to trying to hit a home run with, their next new miracle drug, which is, as you know, difficult to do for many drugs. Good news for lupus, just in time for Christmas.

Make sure you check out rheumnow.live. That's our upcoming meeting in March 2020 in Fort Worth. I want to wish all of you a Merry Christmas, a great holiday. Hope you have a lot of time off with family and friends, and that your patients will be there and waiting for you when you come back from the holiday. Take care.

Merry holidays. Oh, check out the links on the website. Bye now.