RheumNow Podcast – More Than A Spot Of Tea (8.2.19) Save

Welcome to the RheumNow podcast. It's the 08/02/2019, and I'm Doctor. Jack Cush, executive editor of roomnow.com. This week, the TOFA black box story, how to keep gout patients out of trouble. For something totally different, how about a spot of tea?

My apologies to all of The UK for a very bad English accent. I guess I should have done it in Brooklyn. Yo, you want some tea or what? Tea could be the answer to osteoporosis and fracture risk. What?

This and more in this week's edition of the RheumNow podcast. We'll start with my favorite subject again, Still's disease. An interesting study looked at the association between serum IL-eighteen levels, and the association with Still's disease and risk of MAS. As you know, IL-eighteen is very much produced in the same manner as is IL-one. It is sort of caspase dependent.

It is, made by the inflammasome. When IL-one is made, usually IL-eighteen is made and they have reversed down regulators to regulate their production. IL-eighteen has been associated with activity and disease in Still's disease. A small study of forty patients with systemic JIA showed that IL-eighteen levels were elevated even in inactive patients, but were very high in patients with active disease and even higher in those with MAS and a history of MAS, MAS being the macrophage activation syndrome. It was strongly correlated, correlation coefficient of 0.74 with ferritin less so with CXCL nine, the chemokine 0.56 and s 100 proteins again 0.47 suggesting this is, in play in patients with Still's disease and may be useful in diagnosing those possibly at risk for MAS.

Very high levels could be associated with a greater risk of MAS. Again, that's a hard thing here. The hard thing is making the diagnosis. The harder thing is identifying early those who are turning into macrophage activation. And I think the clues there are pretty obvious.

A high white count becomes a dropping white count. Thrombocytosis becomes thrombocytopenia. Ferritin levels are astronomical and very, very high. These are people who are developing a cytokine storm and will need to be treated differently. Interesting study looks at the association of, metalloproteinases specifically MMP7 and patients who have, myositis, specifically the antisynthetase patients, who have myositis and also those who have the MDA-five antibody.

This particular association looked at the risk of having PMDM polymyositis dermatomyositis associated interstitial lung disease and these, in these two cohorts and what the risk would be if you looked at MMP seven levels. They found a fairly strong correlation, not only with having ILD but also with a worse prognosis and worse survival, an odds ratio of eighteen point zero if you have elevated MMP seven levels. Again, a biomarker in, patients with myositis beyond CPK and aldolase, it would be welcome. I don't know it's totally necessary. And I think that these patients in general have a fairly high morbidity, if not mortality, if they go unrecognized, but it's nice to look into a biomarker that could be predictive and is not currently being used in practice.

I found an interesting study of a thousand patients followed for ten years and looked at what the associations might be with abdominal aortic calcifications. You see it all the time on KUBs and other imaging films and it's there and you wonder, is that just age? Is that someone has extensive atherosclerosis or could that mean more? In this particular study, they showed that having moderate to severe AAC, abdominal aortic calcification scores was associated with an increased fracture risk, not a small one, but about a fifty percent increase and that was highly significant. This was not otherwise predicted by other markers of bone strength and so this finding is either a really interesting, you know, factoid or it's, something that you may want to pay attention to.

I have a few nice reports on gout this week. One study I found really interesting was that if you're treating a gout cohort, in this case they were treating a hundred and twenty four patients with gout who also had high cholesterol, high hyperlipidemia and high triglycerides that when they looked at the subset who were on urate lowering therapy either with febuxostat, allopurinol or the one that's not available in United States but is in the EU benbromarone, ben some someone's gonna have to explain that one to me. They did show that urate lowering therapy not only lowered uric acid levels and helped to manage gout, but was also associated with significant reduction in lipid levels. And I think that's important because we know that patients with gout, the uric acid tends to run with a lot of other bad players. Runs with glucose, creatinine, lipid levels, obesity.

Again, it's part of the, I think it's part of the metabolic syndrome. I think that treating hyperuricemia has many downstream effects and this could be one of them. So it'll be interesting to watch your patients who have hyperlipidemia treated or otherwise and see that when they go on effective urate lowering therapy what happens to their lipid levels. Check it out, let us know. Another study looked at the association between gout and surgical flares.

In this particular study, they looked at 70 patients prospectively and found, and these were patients who actually were going into surgery, found that nearly half of them, forty four percent of them had a post surgical flare of their gout after surgery. In their analysis, they showed that the risk factors for this post surgical flare were patients who had elevated levels of, uric acid above nine before surgery. So pre surgical urate levels gave you as much as a fourfold higher risk if it was above nine for developing a future gouty attack after surgery. Also, again, the changes of SUA before and after surgery was somewhat predictive, and, allopurinol itself reduced the risk, and being on allopurinol also reduced the risk by almost eighty five percent. For those who did have a post surgical flare of gout, the mean time to flare was three point seven days.

So it's not common in day one, but it is common thereafter and could be common a number of different days. What was interesting a little tidbit from this particular study was that, of the gout flares that occurred they were more likely to occur in the knee than an MTP1. So we think of podagra as being the leading, manifestation of gout. Well, in surgery, in gout patients who may flare, it could be the knee. Now, course, surgery, flare in the knee, is it septic arthritis or is it gout?

Again, only a rheumatologist will know. Thank God you're a rheumatologist. The NHANES study also showed, an association between, higher uric acid levels and an increased risk of coronary artery disease and stroke and mortality from stroke. This was mainly seen in women, over the age of 50s. There was no link between serum uric acid and overall, cause of death, overall, mortality rates or cancer mortality rates.

But again, and NHANES analysis, showed that again, the uric acid level in patients with gout was associated with a higher, rate of coronary artery disease and stroke mortality. Again, that's not in gout, it's actually overall serum uric acid levels. Correction there. So spotless tea, what's that all about? Well, an odd study and I don't know if this is a factoid or something that's worth really considering but a fairly large meta analysis of 16 studies and 700,000 participants looked at the association between tea consumption and the risk of fractures.

And when you compare those who had a high tea consumption and those who had a low tea consumption, they showed that higher tea intake was associated with a fourteen percent reduced risk of fractures and that was significant. So why would that be? Are you is it really the tea or are we profiling some other unrelated aspect like smoking? Well, tea drinkers are often smokers, but smokers are often associated with a higher risk of fracture, not a lower risk of factor. So is it something else?

Is it body habit? Is this other factors? Couldn't tell from this, abstract whether what the factor there was, but tea is a good thing also if you happen to have osteoporosis. What's a good thing? Well, maybe not testosterone therapy.

You know, I have a number of patients as I'm sure you do who are taking testosterone replacement therapy for a lot of different reasons. Obviously, of them are male, most of them are doing it for overall well-being, for, sexual enhancement or performance or interest. And the question is, does it really work? I'm not necessarily of the belief that this is really an effective hormonal manipulation. The vast majority are taking it.

And the question is, is there a downside to it? Well, this case, there was a fairly large study of 15,000, participants who were over the age of 45 who had low testosterone, no, history of testicular or hypogonadotropism, and you know, over a twenty plus year period it was shown that testosterone replacement therapy was associated with twenty one percent increased risk of cardiovascular events either MI, strokes or TIAs when, and again the risk here when they looked at it was highest in the first two years of, the hormonal therapy. So if your patients are asking for guidance, consider that kind of data. A few more interesting reports. I've always been interested in the patients who are on TNF inhibitors inhibitors and who develop psoriasis when they have rheumatoid arthritis and no history of psoriasis.

So in my clinics, you know, I think I have about 500 or so RA patients and I probably have two or three who've developed psoriasis from taking a TNF inhibitor. So not all five hundred are on TNF inhibitors, maybe it's only three hundred on TNF inhibitors and two or three that's a one in one hundred risk. Well, the population risk based on some well done studies says that it's only about one in a thousand patients on TNF inhibitors will develop, the complication of new onset incident psoriasis. Now there are also reports of patients who have psoriasis or RA patients who have psoriasis and going on a TNF inhibitor where they may have a flare and it's supposed to be pretty rare. Well, this particular analysis comes from the German biologics registry called rabbit and they analyzed almost fifteen thousand patients with RA who did not have psoriasis and another three seventy five RA patients who did have psoriasis and looked at the influence of being on a biologic compared to being on other conventional DMARDs and they compared biologic uses either TNF inhibitor or the non TNF inhibitors, specifically abetacept, rituximab, tocilizumab.

And what they showed was that there was an increased risk of, TNF inhibitor induced psoriasis. The rate was three per one thousand patient years, not that different than what's been in the literature, suggesting that this is a really uncommon event. Again, that fifteen thousand patients was only one hundred and seventeen new incident cases of psoriasis. At this rate was significantly higher than that seen in, when compared to conventional DMARDs. And that conventional DMARDs were not that different when compared to, the other non TNF biologics.

So non TNF biologics did not have a higher rate of new onset or flare of psoriasis. Again, interesting numbers if you're advising patients about what's happening with them and their risk of psoriasis. There's a study that came out last week about the efficacy or lack thereof of abetacept in patients who have systemic sclerosis. Now you know that there's a lot about this right now with TNF inhibitors and systemic sclerosis. This particular study looked at only eighty eight and it gets hard to do these studies but eighty eight patients who have the widespread form.

This is the diffuse cutaneous form of systemic sclerosis. These patients going in had fairly significant, scleroderma skin disease and that was a primary outcome change in modified Rodman skin scores, MRSS scores. Going in there modified Rodman scores was over twenty two. That's a lot of skin disease. And at the end of twelve months, getting placebo or getting abatacept, the changes were not significantly different.

Yes, there was more reduction in MRSS, it was minus 6.24 units in the Abbotassa group versus minus 4.49 in the placebo group but that was not significant. Also not significant were changes in lung function as measured by forced vital capacity. I don't think there's another disappointment for the management of scleroderma and I wouldn't advocate using it in the future. We're studying it in the future. Lastly, tofacitinib last Friday, just as we went to press on our last podcast, there was a press release from Pfizer and from the FDA about a new black box, or sorry, boxed warning.

They don't do black box anymore. It's scarier than it really needs to be. But it's a boxed warning for tofacitinib, with a higher risk of venous thromboembolic events, blood clots, and death when using the ten milligram BID dose. Now ten milligram BID is not the dose of tofacitinib for anything but ulcerative colitis. We're not treating ulcerative colitis and there's numerous reminders in this, press release that this should not be a dose that's being used in rheumatoid arthritis and hence it shouldn't really pertain to us.

But then again does it, you know, tofacitinib hit the market with really no reports of VTEs, and they had a post marketing requirement to do a safety study and in this safety study, high risk individuals, they were looking at the risk of cardiovascular outcomes and infection and cancer outcomes and compare those on tofacitinib different doses to and this is an RA population to those, receiving adalimumab. Well, in the end what they found was, only the ten milligram BID dose posed a risk, in almost three thousand eight hundred patient years of exposure with tofacitinib. There were nineteen cases of pulmonary embolism on the tofacitinib group but there was only three cases in the three thousand nine hundred patient years of adalimumab exposure. That's why that's a part of the box warning. And similarly there were more deaths in patients on tofacitinib ten milligrams BID only compared to those on adalimumab forty five versus twenty five deaths and that's why that's in there.

So again, this I think tells us more about the risk of VTE. We know it's increased in rheumatoid arthritis. It appears now that it may be increased further by the use of, JAK inhibitors. We've seen that with baricitinib. We have other Jackson development.

I believe this is going to be a class effect. Hence, you're going on a JAK inhibitor, my advice, is one, treat them for a shingles risk by giving them the Shingrix vaccine ahead of time. And two, if they're at risk or have a history of VTEs, pulmonary embolism, DVTs, they're probably not a candidate and should seek other therapy. And obviously, you shouldn't be using high dose JAK inhibitor therapy. Lastly, check out my piece on the war on RA.

It's the second installment. This one is all about you, the rheumatologist, and why rheumatologists are the ones who have to make the big changes to fight the war on RA. Gonna do two more of these. Want your input, want you to join in, become one of the soldiers in the war against RA. We'll talk to you next week.

Oh, one more thing. If you are a member of RheumNow Live, you know, you can go, you're gonna get an invitation today or, on Tuesday to go in and do the post test. I need you to do the post test. We need some data. It's what we do in education.

Please do the post test. You can actually get free registration for next year's meeting if you do that, but you had to have been a participant and signed on and either been at the meeting or viewed it remotely by streaming video. We'll talk to you next week. Take care. Bye.