RheumNow Podcast Boiling Hot MAS (7.12.19) Save

This is the RheumNow podcast for the 07/12/2019. I'm doctor Jack Cush, executive editor of roomnow.com. Today, we're gonna talk about risk factors for MAS, that horrible macrophage activation syndrome. Is it safe to get pregnant if you have psoriatic arthritis? There's actually good data on this.

And lastly, is CBD really safe? Is it just a few drops of delight at $70 a drop? Or is it really something you should worry about? Listen more. We're gonna start off with a discussion on PSA and the risk of, what may happen during their pregnancy.

It's actually, a merging of two large registries in Sweden that looked at a total of five forty one psoriatic arthritis patients and compared them to almost forty thousand non PSA pregnancies, in recent time. And what they actually showed was that if you had psoriatic arthritis, you were at higher risk for preterm birth and also for cesarean section deliveries. But other things were not actually at a higher risk, things like preeclampsia, stillbirths, malformations, that sort of thing. So while not entirely dangerous, there's a few concerns and that again being preterm birth and cesarean deliveries. This is pretty much the same story you see with rheumatoid arthritis, suggesting that patients need to be counseled, patients need to be ready, so that they can have the most successful outcome when it comes to pregnancy.

What happens when psoriatic arthritis patients are CCP positive? It does happen. The question is how often? A meta analysis of 14 studies and 3,200, 3,300 patients shows that the risk of CCP positivity was almost ten percent, nine point eight percent to be specific. And that if you had psoriatic arthritis and you were CCP positive, you were more likely to have polyarthritis, a fourfold increased risk of polyarthritis.

Bony erosions, a threefold increased risk of bony erosions, and dactylitis, almost a twofold increased risk. However, CCP was not associated with enthesitis. And this makes perfect sense. We think that enthesitis is certainly mediated by IL-seventeen activity. I would have thought the same for dactylitis.

I was a little bit surprised at that result. I wasn't surprised that CCP brought with a risk of more joint involvement and erosive potential. I think you're going see that in other disorders as well. But it does happen in psoriatic arthritis. And again, if you have psoriatic who are polyarticular, they may well be CCD positive.

My favorite subject adult onset Still's disease analysis of one hundred and eighty two hospitalized patients with adult Still's disease looked at what factors may predict the development of macrophage activation syndrome. As you know, Still's disease is a highly inflammatory disorder, and as sick as they look, as septic as they look, and as much steroids and drugs as they may receive, Still's almost never kills anyone. It's almost impossible. It could happen with pericardial tamponade, but there's very few cases of that amongst the many thousand reported. For a Stills patient to get in trouble, it's going to be a toxicity issue with drugs we may use, including steroids, or it's the development of macrophage activation syndrome, which you know, across all the diseases, MAS is most likely to occur in autoimmune disease and infections and cancer, but the most common one, most common cause is systemic JIA and that carries through to the adults and adult onset Still's disease.

In this particular study, they showed that the factors most likely to, increase the risk would be number one splenomegaly, 5.7 fold increased risk. Number two pericarditis, 6.5 fold increased risk and a ferritin greater than two thousand with almost a five fold increased risk. Now, splenomegaly seen about twenty percent of patients with Still's disease, pericarditis about forty percent if you consider pericarditis and pleuritis together. And ferritin is only seen in about half the patients. So we're looking at patients, a subset of patients with newly diagnosed inflammatory Still's disease, it just happens to be the most inflammatory subset.

I would say that a Still's patient who has rising LFTs, who has rising, ferritin levels, leukocytosis has turned to leukopenia, that's someone who is getting hotter and hotter and hotter like a hot kettle on the stove that's not being turned off and is soon going to melt down and develop MAS. Watch for that. An interesting study looked at the association between how well controlled lupus is and how much money you're going to spend in the care of lupus. They looked at two twelve patients in a single center, analyzed them for, the relationship between, disease activity measures and damage and how much was spent. Turns out that if you had damage at baseline, significant damage, if you were using significant amounts of steroids, were actually increasing the cost of care.

However, if you were someone who spent more than 50% of their time in the lupus low disease activity state LLDAS, they had a 28% reduction in overall cost of care. So certainly these are our goals, right? We want patients to be in low dose activity state, and that's good for the patient, that's good for all the outcomes you're going to look at, but there's a significant cost savings that we often don't talk about in the care of lupus. Lupus patients who are not well controlled can be very, very expensive to society society and and or or institutions, and municipalities. Optimal care is the way to go.

So another study looked at Medicare patients, and this is a very large study, 28 states, over 10,000 Medicaid patients who were on Plaquenil and are supposedly on Plaquenil for their lupus and an analysis of that Medicaid data showed that only fifteen percent were fully adherent to taking Plaquenil. And what they showed was that they matched up who was non compliant to the zip codes that they looked at. Again, is 28 states across The US and showed that those zip codes that had a higher prevalence of African Americans were the ones that had the lowest degree of compliance with hydroxychloroquine use. However, the same sort of findings were not extended to zip codes that were rich in Hispanics and or Whites. And it turns out that those zip codes that extended to those living below the poverty level did not have significant reductions in compliance as you saw in this.

So it could be an educational issue here. And I think that obviously compliance is a gigantic educational challenge to all of us. An interesting study comes from Korea that also looks at lupus compares one hundred and twenty lupus patients to I think it was two forty match controls and looked at the risk of developing serious infections. And not surprisingly, the risk factors for developing a serious infection include serositis, hematologic involvement, or daily steroids above seven point five milligrams per day. Serositis and hematologic, they're also gonna get steroids.

Now these are supposedly adjusted for things like steroids and sex and other things. So I guess independently those disease activity markers, psericitis and hemosologic disease identify a population that's a greater risk because they're more severe. Again, it's really wasn't well worked out. This is a number study, but I think interesting nonetheless. Cannabis is obviously all the rage, I think is like 30 plus states that have it approved or going to be approved.

It probably will be approved at some point in most states. The problem is the drug would never be approved by the FDA if it went in front of the FDA. They don't have the studies and it's likely they ever get the studies to prove its efficacy and safety. There are a lot of safety concerns with this, but it is getting more and more popular. Analysis of a thousand patients from two adult dispensaries in Colorado showed that the majority of cannabis use was for primarily pain in sixty five percent and seventy four percent to promote sleep.

Obviously, it's being used for everything from lumbago to itchy teeth, but, that's the predominant use, and I think that that makes some degree of sense. Where this is gonna go in the future is unknown. I think that the leading edge of this, however, is the big movement of CBD oil and also the management of pain and sleep and God knows what. The FDA had a large, hearing on this recently, a public hearing to find out, you know, what the issues were, who the stakeholders were. There was both negative reports and positive reports and pleased for, you know, approving this drug, but it's not going to be approved.

It's going be regulated by the FDA as a food product. But a Forbes report recently, that's the Forbes Magazine, laid out some of the evidence showing that CBD is not entirely safe, that there is a significant, small but significant risk of liver issues. So there is actually one drug on the market, it's called Epidolex. It's a CBD containing compound that is marketed for seizures. It's modestly effective, but it is FDA approved.

But in their clinical trial development program, five to twenty percent of patients had some degree of liver toxicity. The FDA, also warned during their hearing and put out the information about it's not just liver toxicity, it's also issues of suicidal ideation, actual suicides, agitation, depression, aggression and panic attacks in people who are taking CBD. Now, of course, that could be the people who are taking CBD who are prone to those things regardless of the CBD. But the question is, does CBD add to that? And again, it's not gonna be an approved drug, an FDA approved drug.

We're not gonna see good trials about safety for this product. So while all the rage, we in rheumatology are left to give advice on something for which there is no data. And this is a problem. But nonetheless, I think you have to listen to your patients, talk to your patients, and develop a scheme which may help them, one that they can afford, and one that will help them to avoid risk. Two more reports, an interesting one that was also presented at EULAR and that is Tanezumab, which is an NGF or neuro growth factor inhibitor.

I think this is being developed by Lilly and someone else who is it maybe, I don't know, some other company who will write me a nasty letter at the conclusion of this, report. But, it went into its clinical trial with six ninety eight patients, a randomized double blind placebo controlled trial where patients with moderate to severe OA of the hip and knee, who had failed, standardized therapy with analgesic drugs went and received either placebo or one of two dosing regimens with the NGF inhibitor tanezumab. And while the data look modestly effective, comparing the three regimens, There was a slight edge, a statistically significant edge, but it didn't look much different than placebo. So for instance, the main outcome, one of the three main outcomes was the Womack pain score zero to 10 scale. The mean change was something like 7.4 to 3.6 for the two, Tanezumab regimens and it was like 7.3 to four with the placebo.

So it was different, but not that much different. And the real kicker here is that it's not entirely safe. Obviously, there are some reports of neuropathy and neuropathic kind of findings when you use these drugs, but what they saw was that the risk of rapidly progressive OA, only occurred in Tanezumab treated patients. The two point five milligram group had five cases or two point two percent, the two point five five milligram group had an incidence of one case of zero point four percent but none of the placebo. The incidence of progression of total joint replacement in this cohort was higher on tanezumab three point five and six point nine on tanezumab percent versus one point seven on placebo.

As you know, by taking away, the pain perception with this drug, you may promote a Charcot like joint rapid progression of the joint that would lead to the destruction and or joint replacement. This is why the drug was initially held by the FDA. And then with this being worked out and understood, it's now back in clinical trials. The problem with this drug is while it's a novel new approach, does it really change the game sufficiently to, incur a small but significant risk for progressive, rapidly progressive joint damage maybe so rapid as to lead to joint replacement. The last report comes for improved pregnancy outcomes in lupus.

This is an analyst of internal medicine article from last week, a very nice study of 93,820 lupus patients who were pregnant compared to seventy eight million pregnancies, seventy eight million, imagine doing the calculations on this, patients without lupus who are hospitalized in The United States between 2013 and 2015 and then earlier from 1998 to 2000. So they compared these two timeframes, 1998 to 2000 and then 2013 to 2015. During that timeframe, the, outcomes in lupus improved significantly, that's over eighteen years. So maternal mortality significantly improved. The rates went from four forty two in lupus and one hundred and thirteen in non lupus patients.

That's thirteen per one hundred thousand population in 1998 to down to less than fifty and ten in 2013 and fifteen. That's a 35 fold reduction in maternal mortality. Fetal mortality rates also declined but it was not significant. We're doing a much better job in managing our lupus patients and I think that's a great report. That's it for this week.

At RheumNow, go to the website, you can read more about these links. We'll talk again next week. Thanks for tuning in. Take care.