RheumNow Podcast Tricked Up Lupus Criteria (8.9.19) Save

It's the 08/09/2019. This is the RheumNow podcast. I'm doctor Jack Cush, executive editor of rheumnow.com. This week, we're gonna talk about a number of interesting articles. You know, if you give a vaccine, you expect good things to happen.

Did you know that you may cause a gout flare? How do you keep infection rates low? Well, vaccinate. And, also, why not use a biologic? What?

And lastly, if you're gonna start a biologic, which is the best one to start? A TNF inhibitor or a non TNF inhibitor? We have the answers. Let's start with that report about gout and vaccination. It's an Internet based study that comes from Hai Yun Choi who enrolled patients via the Internet, collected data via the Internet via surveys about their gout, confirmed their diagnoses, and then looked at the association between receiving a vaccination or not.

The issue here was whether or not, these adjuvant vaccines could cause activation of the immune system and maybe the inflammasome, and maybe that would make more, gout attacks possible. So when they surveyed these patients, these five hundred and seventeen patients, they showed that those who received a vaccination had a twofold higher risk of having a gout flare, a significantly higher odds ratio of one point nine nine. So I don't know what to do with this data. I think I probably have to tell my patients that if we do the vaccine, your gout could get a little bit worse, but I still think people people need to be vaccinated. I came across a very interesting patient this week, someone I've been following who's had myalgias and fatigue and pain and fatigue and myalgias and pain.

And, of course, he had a sleep disorder, and I diagnosed fibromyalgia. He actually went to the, fabulous Johns Hopkins myositis clinic and, had a consultation there. And they noted as I did, he did have occasional elevations of CPK and aldolase. And the question was, what was this about? He had had a negative biopsy previously, an EMG that was nonrevealing.

They suggested a repeat biopsy. And so we did a repeat biopsy of the deltoid, and the biopsy came back as, guess what, not fibromyalgia, macrophagic myofasciitis. This is like the third patient I've had of this in my career. It's a very rare myopathy. It can present as myalgias, weakness, fatigue, even fever, and they can have muscle tenderness.

They can have muscle enzyme elevations. It's not gonna be 40,000, but it might be a thousand or so, which this gentleman did at one point. The question is, what do you do about it? Well, first, you have to make the diagnosis. The diagnosis is based on a muscle biopsy showing PAS positive and Mornstein positive, containing macrophages that are meant to be representative of aluminum deposits.

So the idea is that this is maybe an aluminum induced myopathy. Obviously, you tend to get it where they've got the the the vaccine like in the deltoid as this gentleman did, and then how do you treat them? No one seems to know. If they're bad enough, you might give them a course of steroids. Turns out that many of them do have basically what is called a soft myopathy and tend to have a lot of fibromyalgia symptoms.

So treat what you're certain about. Don't get too wrapped up in the diagnosis, which is strange, a strange name, myophagic myofasciitis. Sounds like it's very inflammatory. There's very, very little inflammation associated here, and that's what we found in this gentleman's biopsy. I thought you'd wanna know about this rare presentation.

Another unusual, investigation came about this week, looking at IL sixteen in patients with systemic sclerosis. IL sixteen is basically a chemoattractant. It can be found, in lymphocytes and, I guess, blood vessels. And in this particular study, they studied scleroderma patients and found that scleroderma patients had a lot of IL sixteen positive lymphocyte staining, especially in a perivascular distribution and and and more so in people who had diffuse systemic sclerosis than those who had limited, disease. So forty four percent versus twenty nine percent, and that was significant.

Moreover, serum IL 16 levels tend to be higher in systemic sclerosis patients compared to normal controls, and IL 16 levels tended to correlate with having diffuse cutaneous disease, the modified Rodnan Skin score, and, pigmentation changes in erythema. So is it gonna be involved? Is this, causal or casual? Is this epiphenomenal? I don't think it's really known, but I think it's interesting, and I think any new information about scleroderma should be welcome.

An interesting study of 83 patients, with gout, they looked at them prospectively to see what would happen if they're on urate lowering therapy, and they looked at the three different urate lowering drugs, including the ones that you're familiar with, and seventy seven of the eighty three patients were on urate lowering therapy, six were not. And specifically, looked at not just what happened to them clinically and what happened to them, as far as their serum urate levels, but also they all had deck scans, dual energy CT scans to quantify the amount of uric acid deposition. So what they they had a way of quantifying the, MSU deposits and they showed that in the patients who were not on urate lowering therapy, there was basically no change in their serum uric acid levels and no change in their size and volume of MSU deposits. However, the urate lowering therapy group had a significant reduction not only in their serum urate from 7.2 down to 5.8, but they also had a significant p equals zero zero zero seven point zero zero seven reduction in the volume of monosodium urate crystals, suggesting that when you do lower uric acid, you are lowering total body deposition.

Although it's on a small scale and it's very gradual, it is important. I found this to be an interesting study looking at ANCA associated vasculitis and its responsiveness to IVIG. I don't use much in the way of IV immunoglobulin to treat lupus, myositis, or certainly vasculitis, But a meta analysis of, initially 22 studies whittled down to nine showed that in people who people who were treated with IVIG had significant and rapid reductions in their Birmingham vasculitis score, the BVAS, significant reductions in ANCA titers and in CRP levels, it happened as quick as two weeks. Some took as long as twenty four weeks. Again, not generally in my arsenal of drugs I'll use in ANCA associated vasculitis, but it may be worth consideration where other therapies may not be possible.

And a claims analysis looked at the, risk of cardiovascular events in patients on tocilizumab. This has been done before, you know, there was the INTRAC study that compared, I think it was a three year study comparing cardiovascular events in patients on either etanercept, which would be the normal control, and tocilizumab, which would be the test drug because, you know, the tocilizumab, other IL-six inhibitors, and JAK inhibitors all have the potential to raise all your lipids. It's not just LDL, it's also triglycerides, VLDL, and HDL. And the question is whether there's an, a a coexistent, cardiovascular risk to such a side effect seen in twenty percent of patients. Well, the INTRACT study did not show a risk, and there was basically the same rate between those on Enbrel and those on, Actemra.

Well, in this study, that was that was a claim study basically. I think it was actually eighty fourth eighty eight thousand, so between 2006 and 2015, and show that the cardiovascular event rate was about twelve per one thousand patient years with tocilizumab and fifteen with the TNF inhibitors. And they also looked at tocilizumab showing no difference between the three of them. So there really is no increased risk when you're using, a drug that may cause hyperlipidemia such as tocilizumab. Another claim study looked at the, risk of having a serious infection if you're either on triple DMARN therapy, almost fourteen hundred patients, compared to those starting TNF inhibitor plus methotrexate.

And you would think, well, the data is pretty clear. TNF inhibitors tend to have a higher rate of, serious infection events compared to background therapy with DMARDs. Well, in the real world studies, and this is a real world study, there was no significant difference in the rate of SIEs, and they were both low in this real world population, very large population, two and a half, events per 100 patient years, versus two on triple DMARR therapy. That was not significant between the two. And the question is why?

The hazard ratio is 1.23, but it crossed over one. The hazard the the 95% confidence intervals are point eight seven to 1.74. The question is, is this higher or not higher? Again, statistically not so. Clinically meaningful?

No. It turns out that as time has gone on, I think that our risk of getting serious infections has gone down as patients have been less sick, less inflamed, and you're gonna get basically the same rates when you use triple DMR therapy with methotrexate, sulfasalazine, hydroxychloroquine as you will if you're using a TNF inhibitor plus methotrexate. Again, the risk of a biologic causing infection only becomes substantial when the patient's really sick, elderly, on high dose steroids, lots of comorbidities, prior serious infectious events, that's when a TNF inhibitor can add to the risk. Otherwise, there is not a significant bump in infectious risk for serious infections when using a TNF inhibitor or really any of the biologics. That's the data, and that's my interpretation of the data.

An interesting report showed that oral candidiasis might be a marker for those who might be at higher risk of infection. The point being that maybe if you can't handle fungal infections, you have a defect in T cell mediated immunity that you might be at greater risk. Well, they actually looked at ANCA associated vasculitis patients, 71 specifically, and looked at their risk of getting a serious infectious event. Now these people are all on background immunosuppressive therapy. They all had active disease.

And when they show looked at the predictors of severe infection, it was number one, low albumin, very inflamed, very sick. Number two, pulse methylprednisolone, steroids are always a bad player with a hazard ratio greater than five, and a history of oral candidiasis, and that was not related to steroid use, in what I saw from the the the report. The adjusted hazard ratio also 5.3. So that may be an interesting clinical finding that may tell you this patient's at a higher risk should you proceed in managing that patient. You might wanna limit steroid use.

You might wanna get more, rapid control of their infection. Three more reports, periodontal disease and P. Gingivalis. This is a a forty eight patient study of individuals at risk for RA. They did not have RA.

They did not have arthritis or synovitis. They just had a CCP positivity and some musculoskeletal complaints. On ultrasound, they had no joint inflammation. But it turns out when you looked at this cohort and you compared them to early RA patients or controls, seventy three percent of the CCV positive individuals had clinical periodontal disease, periodontitis. But this was higher than that seen in healthy individuals, thirty eight percent, or early RA, fifty four percent, suggesting that, at risk individuals if they have periodontal disease may be at higher risk to go on to RA and it's not surprising that you'll see you're seeing this.

We know periodontal disease is a risk factor for RA. Your first degree relative and your CCV positive, the data seems pretty clear. The risk of developing RA could be as high as thirty five percent, could be as low as ten percent, but I'm thinking it's closer to twenty to thirty five percent. You wanna get some dental screening on those individuals to make sure they're they're not gonna be at risk for developing RA, or you can do what you can to minimize that risk. An interesting study comes from Sweden and the Swedish registry of RA that they have there.

This is a fairly large registry that looked at what is the most effective and safest regimen to use. This is a study conducted between 2,010 and 2016 and looked at individuals who are starting their first biologic DMARD. Again, patients are on background, regular DMARDs, conventional DMARDs, and patients either started either a TNF inhibitor, rituximab, abatacid, or tocilizumab, they had over 9,000 new biologic starts. They also looked at people switched from their initial TNF inhibitor to, another biologic, and they had almost 4,000 of those people. And you know what they showed?

At one year in new biologic initiators, the TNF inhibitors were not the best performing. When looking at a EULAR good response, 24.9 with a TNF inhibitor, twenty eight point six with rituximab, thirty one point nine with abatacep, and fifty point nine percent with tocilizumab, you are good responses at one year. When you looked at the people switching, from a TNF inhibitor to another drug, switching to another TNF inhibitor about eleven percent, switching to abatacip wasn't much more, it was like thirteen percent. Switching to either, tocilizumab or rituximab gave you almost thirty percent responses suggesting that it's the non TNF biologics, that may be as good if not better than TNF inhibitors, and again, that sort of smashes the convention that we are currently, living under and certainly forced to practice under, especially with regard to managed care. The last report is about the new EULAR ACR classification criteria for systemic lupus erythematosus.

You should look at this report in, on RheumNow. I'll read you my first paragraph, which I thought was brilliant because I wrote it. Again, these new criteria developed jointly between ACR and EULAR prompted by the fact that old criteria are either too sensitive or too specific and they wanted something that was just right, a la gold Goldilocks. The net result was these new criteria which one, require the presence of a positive ANA and two, a long list of weighted criteria that you must use to calculate a score of 10 to be included in the study or to be said to have, lupus. The idea here is that maybe you could treat, quiescent lupus, maybe you could study quiescent lupus or study early lupus with these criteria.

Again, a long process, many thousands of patients over 25 centers worldwide. The point was that the old original Ang 10 criteria of '82 modified by a Hochberg in '97 had sensitivity of only eighty five percent, but a specificity of ninety five percent. And that was again the four out of 11 criteria. The new the slick criteria from 2012, they gave me a headache, I never used them, but they had much better sensitivity at 97%, but a lower specificity at 90%. Well, the new criteria are the best of both worlds.

98% sensitivity, and 96% specificity in the derivation co cohort when it was validated in another cohort over a thousand patients, 96 sensitivity, 93 specificity. The problem is that it's a long list. Like, these these are gonna be great for clinical trials, gonna be confusing as heck for practice, and I don't know how I'd use it in practice, but again, they if you look at the the algorithm, one, you must have an ANA, and then you get points. You get two points for fever, two points for delirium, you get two points for a lupus anticoagulant, you get high points for class three or four lupus nephritis on biopsy. You get only four point, and that's 10 points.

You have the diagnosis. You get four points for proteinuria. You get four points for SCLE. You get six points for acute LE. Like, all in all, it looks like there's about 15 criteria here with point scores of two to mainly two to four or six points with only a 10 score for biopsy proven class three and four.

Again, great tool for clinical research. Remains to be seen how it'll be used in practice or if it will advance practice at all. That's it for this week on RheumNow and our weekly podcast. For those of you who went to RheumNow live, I think we sent you an invitation to do the post test. I need your help.

Please go and do it. We need some data for outcomes. Tune in next week for more good news on rheumatology from RheumNow. Bye.