RheumNow Podcast Periodontitis In RA Relatives (5.10.19) Save

It's the 05/10/2019. I'm Doctor. Jack Cush, Executive Editor of roomnow.com and this is the Room Now podcast. This week we're going to talk about VTE, venous thromboembolic events. The debate continues.

Is it the drug or is it the disease? We're going talk about all in the family, meaning the risk of RA. Is it all in the family or is it just in women? And lastly, we're going talk about gout prevention. A little prescription can go a long way.

We'll start with that story. An interesting study, small study, 75 patients, and looking at predictive factors for gout flares when starting urate lowering therapy. As you know, you start urate lowering therapy and, it's not uncommon to have a flare of gout because you're mobilizing all that uric acid. And in this seventy five patient study, they did exactly that And they observed about half of their patients, seventy eight forty eight percent who actually developed a gout flare within the first three months of starting urate lowering therapy. Predictive factors you ask?

Well, it turns out a high CRP, that's news to me, was a predictive factor in who may flare once you start the uric acid levels. Turns out it was once you start uric lowering therapy, turns out it wasn't the level of uric acid elevation, it was the CRP level, Meaning, the risk was higher if CRP levels were greater than 30 milligrams per liter or greater than three point o milligrams per deciliter. The other predictive factor was not being on prophylaxis. And that makes sense because right now the rules are that when you start on urate lowering therapy ULT, you should start someone on some prophylaxis such as nonsteroidals, steroids or colchicine. Notice my order, I prefer nonsteroidals over steroids and I prefer steroids over colchicine.

Colchicine, it's expensive, it's got side effects, it's not necessary. I stopped using colchicine when it went from 5¢ a pill to $5 a pill and I've been able to manage all gout, pseudo gout, and almost everything else pretty well without it. So you could use colchicine, but the idea is you need to start your rate lowering therapy with a prophylactic drug like nonsteroidals or colchicine or steroids. A nice study looked at, the risk of hospitalizable infection, another better, more concrete measure of a serious infection, when starting biologics. Sion Kim and colleagues looked at this by looking at claims data.

I believe it was Truven and Medicare sort of commercial and Medicare databases, and they looked at over 11,000 matched pairs of RA patients who were starting either abatacept or a TNF inhibitor. Turns out that there were significantly lower, hospitalizations in TNF inhibitors, I'm sorry, in abatacept compared to TNF inhibitors. However, all the comparative differences were really seen between abatacept and infliximab. There was actually no difference when you compared risk of serious infection between abatacep and adalimumab or abatacep and etanercept. And we do know that infliximab seems to always run a slightly higher risk of infection mainly because we up the dose, maybe we maybe because we know they're always getting it.

It's maybe used a little bit more frequently in the elderly. This was not an elderly restricted population however. So pound for pound abetacet may be the safer biologic here, but certainly it's safer than infliximab, it's probably equal to etanercept and adalimumab. Again, there was a lot of other data on other drugs to be otherwise instructive. An interesting study also looked at RA patients and the risk of developing RA from the population.

Specifically, they looked at over fifty five thousand people, they found six hundred-seven hundred patients with RA, mostly women, And it turns out that predictors of developing RA was body fat percentage, waist or circumference and being obese. But this was only seen in women. The same risk factors didn't play out in men and were not significant in men. So this suggests that modifiable lifestyle, things like weight and diet can be important, but probably most important in women. And certainly no women are at a higher risk of developing rheumatoid arthritis.

Another interesting study, and actually in that study they showed you pound for pound what happens. So 5% body fat loss, had 10% higher 5% increase in body fat, had a 10% increase in RA. Five centimeter increase in waist circumference, had a five percent increase in RA. Being obese by BM BMI gave you a fifty increased risk of getting RA. Another population based study looked at first degree relatives of RA patients and compared those who were both ACPA positive and ACPA negative.

So we're looking FDR's first degree relatives and found that in ACPA positive individuals, there was a significantly higher rate of severe periodontal disease compared to those who are ACPA negative. So periodontal disease was seen in ACPA negative people but it tend to be mild to moderate and only in forty percent whereas the ACPA positive patients that was seen over ninety percent and most of those were severe. Suggesting again this tie in between first degree relatives as a risk factor for RA and the ACPA positivity and now one of these other environmental triggers that may work with autoimmunity to further produce a risk of RA. Now there was no risk of RA here, they weren't looking at RA, they were actually just looking at the association of ACPA and periodontal disease in those who may be at risk, the first degree relatives. I think this lends a lot more to the story about, the risk of, RA and identifying those who have preclinical RA and may be at risk.

Our patients probably need to see the dentist more. I mean, I know we recommend it strongly for patients who had Sjogren's Syndrome and significant salivary loss but RA patients, it might make a good bit of guidance to instruct your patients to get frequent dental evaluations, especially if they have a history of periodontal disease. So another study recently looked at claims data, specifically looking at the risk of venous thromboembolic events or VTEs. We know this happens in RA. We know the rate in RA is about point five per 100 patient years, can be as high as point six.

When it's above that number, that means that it might well be due to other factors more than the disease of rheumatoid arthritis or inflammation, it may be due to drugs or cancer or other other risk factors. So in this particular study, again claims data, they looked specifically at tofacitinib related VTEs versus TNF inhibitor related VTEs. And again, using a large number of patients, they found that there was a non significant difference between the rate of VTEs and TOFA versus TNF inhibitors. However, it was numerically higher for those that were on tofacitinib, zero point six per 100 patient years versus zero point three per 100 patient years in one data set, that's the commercial data set, and another, older patient Medicare data set, it was one point one two per 100 patient eight years versus zero point nine two. Again, tofacitinib 1.012 and tienfenib was 0.92 per 100 patient years.

But remember I said that's Medicare elderly patients, increased risk of developing VTEs. So the overall hazard ratio might be increased with, with tofacitinib, but it's not significant. It's has a ratio 1.33, but it straddles one with confidence intervals ranging from point seven eight to 2.24. So again, it seems like this is mostly an RA related risk. It seems like it's, it may not be related to the JAK inhibitors, but there's always a little bit of evidence to suggest it might could be as we say here in Texas.

So I think we need to watch this and maybe avoid JAK inhibition in those who have a history of venous thromboembolic events, and then follow those who don't have a history for such events. Lupus patients are at risk for a lot of different comorbidities. One interesting one that we used to see a fair amount of, at the County Hospital here in Dallas, the Parkland Hospital, is pancreatitis associated lupus. It can be associated with the disease, the drugs, azathioprine, steroids have all been really, you know, linked as possible causes. In a fairly large cohort study of 400 patients with four twenty patients with lupus, they found a total of six cases over a number of years, a rate of one point four percent for pancreatitis due to steroids, meaning they had criteria as to, you know, starting steroids then getting pancreatitis soon thereafter.

The sad thing about this data set was out of the six cases, very low number, half of them died and that's shocking and bad news. They did a literature review and they found another four fifty lupus pancreatitis patients and also showed a very high mortality rate of almost fifty percent. Arti Kavanaugh studied these patients a long time ago at Parkland and showed kind of the same data, although there were two kinds of pancreatitis. There was those who just had mild amylase and lipase elevations without a lot of symptoms, and those who are really sick and in the hospital. It's the ones who get really sick in the hospital, very high amylase and lipase elevations who are the ones who are really significant risk for morbid if not mortal outcomes.

I found a very strange study in PLOS-one. This is about the relationship between insulin resistance and fibromyalgia. If you asked me, is there a relationship? I'd say, hell no. Well, in their studies of 23 patients, they looked at the hemoglobin A1c levels as a measure of insulin resistance and found that the fibromyalgia patients tend to be a little bit on the high side, although only a few of them actually were in the abnormal range at six or above.

But when they compared the cohort of fibromyalgia patients to non diabetic patients in the Framingham study or the NHANES data set, they found fibromyalgia patients had significantly higher hemoglobin A1C levels. And then more importantly, of the twenty three patients, there were sixteen who were treated with metformin and, of course their cholesterol and whatnot came, I'm sorry, their hemoglobin a one c came down, but they also noticed of the sixteen, fifty percent had their pain scores go from whatever it was four, five, six, seven to zero. I mean, all of them go into zero. So I find this strange, I find this bizarre, I find it interesting, and since I don't know what causes fibromyalgia, I'd like to see more research on something like this. Our last report is about calcium neuron inhibitors in, patients with the antisynthetase syndrome in dermatomyositis who also happen to have interstitial lung disease as part of that syndrome.

This is a Japanese study of 32 patients who were studied prospectively and they were randomized to receive either prednisone plus a calcium or inhibitor or just prednisone alone. And they followed them and their outcome here was flare free survival or they didn't, no flares, no getting worse, no dying. They didn't really look at things like CPK and other organ involvement. They did show that the use of the calcineurin inhibitor did give better outcomes compared to steroids alone and that was significant. I bring it up because I think those these patients are very difficult to treat, dermatomyositis, especially the ones who are anti synthetase positive, who have lung disease.

And I think that, you know, we're always looking for a good alternative to patients who need a steroid sparing agent to manage their dermatomyositis. And you may use methotrexate, she may use azathioprine, I tend to use, a lot of, leflunomide often in combination with methotrexate. And now there's good data on the use of, of calcineurin inhibitors that means cyclosporine, tacrolimus, sirolimus, these drugs work fairly well. They use them a lot in Japan for very difficult cases of RA, and lupus and in this case dermatomyositis with great success. Again, these are good drugs, they need to be watched closely, they can be toxic and especially nephrotoxic, but this is a worthwhile alternative for those patients who are hard to manage.

That's it for this week on RheumNow. Go to the website, check out these citations. If you want to find out more information, go to roomnow.live and register to view the content from our meeting from last month. Over 30 lectures, some fifteen minutes, some twenty five minutes, panel discussions, a great set of content all for free. Just register and you can look at it and tell your friends about it.

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