RheumNow Podcast Take It Back Jack! (4.26.19) Save

It's the 04/26/2019. This is the RheumNow podcast. Hi. I'm doctor Jack Cush, executive editor of roomnow.com. This week, the deeper checklist, things that you may not have thought of come from the literature like, are you checking your lupus patients and their adherence by checking drug levels?

Should you be checking for PJP risk in RA patients? And what about your rheumatoid arthritis siblings? Are they at future risk? What's your role in that? Could this be a cardiovascular thing?

A deeper checklist. But first we'll start with a report on drug safety. There's actually a few new items and one is a recurring item. This is the DEA take back program, drug take back program, which happens twice a year, every April, every October, it's well publicized. Website has a link that you can go and put in your zip code and find out if you have a program and you have lots of these programs.

This is a DEA run program to rid you and your patients of unwanted medicines. A drug trust, a drug a drawer full of medicines that are dangerous, out of date, don't know what to do with them, don't throw them down the toilet, that's a bad idea, but you worry about throwing them in the garbage and don't worry, nobody's going through your garbage, but doesn't seem all that safe. Well, especially when it comes to narcotics, there's a big concern again about the safety of keeping these around and how to dispose of them. So this big DEA sponsored drug take back program is run by police and public health safety people in your town. There's a cooperation of a number of different big pharmaceuticals and the website, again plug in your zip code and you'll find 10 different sites right around the corner where you can pile, take piles of drugs and just drop them off.

Every six months they take in about 470 tons worth of unwanted, unused, possibly dangerous medicines. Along the same vein, the FDA has a new program called Remove the Risk where you can and they have a number of sort of modules that you can go through where you can remove the risk of having medicines within the home. And again, that link is on one of our tweets that came out just yesterday, this week. So this is an important program. It's something you should let your patients know about.

It does happen again every April and every October. We'll try to give you that update. Seminars in arthritis and rheumatism had a nice report about what happens in RA patients when it comes to pregnancy. So what happened here was a very large database, the National Inpatient Sample Database covered about eight years, looked at over forty two million obstetrical hospitalizations and amongst that data set there was thirty one thousand RA pregnancies. And generally some of the things that we're seeing from that are important, important for you to know.

One of which is that our patients tend to have pregnancies at a later age, 31 years versus about twenty six years for the rest of the population. Our patients are at significantly higher risk for a number of different things, and this is why you need to be involved in the management of patients once they get pregnant. This is often not the case. Often all medicines are stopped, you turn them over to OB, but again, you need to be involved. The things that they're at greater risk for include hypertension, premature rupture of membranes, antepartum hemorrhage, premature delivery, intra uterine growth retardation or meaning small gestational, growth, and weight, higher rate of c sections.

These are all sort of coded things that are in the hospital record. What's not coded in there is what happens to their RA, what happens to their arthritis and often it's not quite as good as everyone thinks because again no one's really watching it other than you and you're not involved. So again be aware this is a big problem, thirty one thousand patients a year at least and those are the hospitalized ones. There might be an population of un hospitalized RA patients with similar complications. An interesting data comes from Nature Communications which looks at the potential role of neutrophils and NET ptosis in driving anti phospholipid mediated thrombotic events in patients with autoimmune disease or the anti phospholipid syndrome.

And using an animal model, they showed that if they use an agonist of adenosine, they could actually mitigate some of the thrombotic tendencies and what they would do is they turn to have more adenosine on hand, and that actually reduces cyclic AMP and supposedly actually reduces the amount of neptosis and has been shown with not just the, the agonist that they use experimentally but also with dipyridamole which tends to do the same thing. It's a different way of looking at how we might manage, thrombotic tendencies in patients who are at risk. Again, this is not yet primetime. This is sort of research, and those of you who are interested in antiphospholipid research might want to look at this report. A Swedish study looked at the general population and RA patients and looked at cardiovascular risk.

You know that RA patients were at higher risk for cardiovascular events in their study. Again, eight thousand RA versus the general population and they threw in their eleven thousand first degree or direct full siblings of the RA patients. They showed that the coronary syndrome, acute coronary syndrome was increasing RA patients by as much as fifty percent. But the interesting thing here was that the siblings of RA patients also had an increased rate of acute coronary syndrome by about twenty two percent. Turns out that all this risk was seen mainly in seropositive RAs and also seropositive siblings.

So this is a big story about what? About first degree relatives and their potential risk. We know that if you're a first degree relative and you have CCP, much more so than rheumatoid factor, you have a substantial risk and that once you start having arthralgia's, other lab abnormalities, the risk goes up and up and up. But now we're looking at patients who are just seropositive, and who are first degree relatives obviously of an RA patient, and they too have an increased risk of cardiovascular events, suggesting that subclinical inflammation may be going on in patients who are first degree relatives. I've always said to my patients who were first degree relatives or offspring, no, don't worry, don't worry, it's just not that big a deal.

I think it could be a bigger deal than what, we've been thinking and I think watching this story, will be important. So, I don't know you need to alarm your patients and their siblings right away, but I do think you need to take more seriously this issue of first degree relatives, especially when they're seropositive and how they're going to be managed and their complete management, including sending them to other doctors like primary care and or cardiologists. I don't know about you, but what about these reports from the orthopedists that worry about nonsteroidal use and how nonsteroidals are going to screw up the outcomes of their surgery, never understood these reports and why they have this in their brain. Well, I found a meta analysis and it shows, it's actually a systematic review, I'm not sure about the rigidity of this, but it looked at a number of different reports and it showed significant reductions in union and significant increases in non union for patients who are taking nonsteroidals. This is looking at patients with fractures, osteotomies, spinal surgery, fusions, etc.

This was seen in adults, not seen in kids. This was not seen in people who had short term exposure, a low dose exposure to nonsteroidals, and it's sort of an alarming report. But you know what? It's from the ortho journals and it's not really, they don't really describe the rigidity by which the analyses were done. Again, if you I tried to look up the rest of the literature on this, found 12 papers all from ortho journals.

What I'd like to see is sort of a Cochrane analysis of this issue, or some other more rigid analysis or better yet claims data that would look at whether these complications occur at a higher rate. I want you to know about this report. I'm still not convinced this is a big issue on our patients. Yeah, it would be great for all our patients having surgery to be on no medicine but that's impractical and improbable and also hurts our patients. So we need more research in this area.

United Kingdom National Health Service study looked at almost, what was our number, thirteen thousand nine hundred and sixty one RA patients, follow them, over, a number of years and show that overall RA patients have a one in five or nearly a twenty percent lifetime risk of having, joint replacement surgery. Twenty two percent for knee replacement, seventeen percent for hip replacement, and this was for people who were the average RA patients, meaning that if you were 64 female non smoker, normal BMI, then those were the rates and those are sort of high. The rates go higher when you have worse disease and when you have younger patients. So it's an interesting number and one that you can, I think, reliably quote to your patients? Of course, we know that surgeries have gone down with more aggressive therapy, the advent of biologics and combinations, but still one in five is nothing to, shun as being, inconsequential.

An interesting report comes from Japan about PJP, PJP prophylaxis, Pneumocystis urovecis pneumonia, what used to be called PCP is now PJP. They studied, twenty six hundred RA patients and found only nineteen cases of PJP in their population. The risk factors, then they actually assigned a risk score to these risk factors methotrexate in a high dose. In Japan that's greater than six milligrams per week. What's the equivalent here?

Maybe it's greater than fifteen milligrams per week in The United States or in other developed countries outside of Japan. Elderly, threefold higher risk. By the way, the high methotrexate, four and a half full higher risk. Use of multiple immunosuppressants, two or more, 3.7 fold risk. Prednisone greater than five, a 12.4 fold higher risk.

And what they show is that a combination of two or three of these that gives you a score or risk score of greater than five gives you, either a two point three to five point eight percent risk of PJP. That's interesting. I don't see much PJP even in my very bad patients, but it might make me rethink and look for it again. In our analysis and others who have looked at PJP amongst RA patients, one of the unifying factors right now amongst our patients is actually rituximab use. So I think you should think about this.

I don't routinely prophylax our patients that are on that have active or bad rheumatoid arthritis. I think I need more data. I would consider prophylaxing if I'm going to use chronic, rituximab, especially if they have very active disease, steroids, high methotrexate, all these things I already mentioned. Should you check hydroxychloroquine levels? You know, we had a nice report from Michelle Petrie and her group that looked at this showing that it doesn't have much utility, in the management other than number one telling you about how adherent the patient is.

So this was a discussion that came up in a recent report. I tweeted it because I think I want you to think about this. We do know that RA patients on hydroxychloroquine is about fifty percent non adherence to hydroxychloroquine. It's sort of shocking and surprising. And again you can routinely assay for hydroxychloroquine levels.

I don't do it but I probably would do it if I had lupus patients not doing well or getting worse especially when I had issues about what dose I was using high versus low and the new guidelines and should they be on two hundred or four hundred should always do the calculation on everybody on hydroxychloroquine especially in women to make sure you're within the current guidelines of being five milligrams per kilogram or less, and that's if you believe the new guidelines. So what's your best therapy for calcinosis cutis? So last week I tweeted out that NXP two antibody is associated with dermatomyositis may be also associated with a higher risk of calcinosis cutis. So I put out a tweet and we had a lot of response, two sixty responses on the Twitter community. This is what everybody came back with.

15% basically said thiosulfate. Some people actually said they would use topical thiosulfate. 16% calcium channel blockers, 15% bisphosphonates, and really the majority, 56% saying, I don't know. I have no idea. Nothing works.

I've not seen any literature that works. And really that's true. The literature is not good here. There are no good studies. I saw some cockamamie things on the Internet like people digging out the calcium deposits from their skin.

Don't do that. You should have them surgically removed by an experienced plastic, surgeon or dermatologist who does that kind of surgery. But really we are in dire need of therapy for patients who have calcinosis, whatever the cause, whether it's from calycephalaxis or associated with MCTD, dermatomyositis scleroderma, etc. Corona took a good look at their patients who had, solid cancers who were on biologics, and there's some interesting data here. As you know, the new ACR guidelines, old ACR guidelines at this point said that you can use whatever you want in a patient with RA who has a solid tumor, lung cancer, skin cancer, pancreatic cancer, etcetera.

What they, you know, again, there's a little bit discussion about what to do with hematological malignancies, but solid tumors go right ahead. But in the corona experience, this is very interesting, at the time that they had their cancer, forty two percent were on the biologic and or, a, an oral small molecule like one of the JAK inhibitors, and that's in the twelve months prior to the cancer. Post cancer, thirty one percent stayed on the same therapy. And then after the cancer was diagnosed, five percent switched to a biologic and ten percent started a new biologic. The point being that, I'm very proud of many of you who are not afraid to treat or continue aggressive therapy in the face of cancer.

I've always said, let cancer be managed by the hematologist, oncologist, you manage the arthritis. Really, really, your drugs are not impairing or impeding the management of cancer. And I think it's an important thing to consider. A few new reports. One is SKYRIZI.

This is rizenkizumab, recently approved by the FDA for psoriasis. These are, this is a new drug. It's an IL-twenty three inhibitor. It's now the third IL-twenty three inhibitor, approved by the FDA, approved by the FDA in the last twelve months. SKYRIZI, great name, sort of sounds like an Internet game or a ride at Euro Disney, but SKYRIZI SKYRIZI SKYRIZI again, it's risankizumab.

There are trials going on in psoriatic arthritis and other conditions. We might see that in rheumatology in the months to come. Two more reports. Ustikizumab effective in Behcet's disease. This was a surprise.

As you know, Behcet's is not much. Is, data about aprimilast, well designed studies. This is a 30 patient study, open label study, where what they showed was at week twelve, the mean number of oral ulcerations decreased from a median of two down to zero. There was definition of complete response which was achieved by sixty and eighty nine percent at week 12 and week twenty four respectively, and that, you know, twelve months later eighty five percent of patients are still taking the ustekinumab which is given every three months. This needs to be further studied.

This sort of encouraging. I don't know if I'm gonna jump in and use this in my patients. I think I'm more likely to use Behcet's and hope that that's gonna get FDA approved in the next year or so. I had a report last Friday on, hidradenitis suppurativa and a high comorbidity rate. And the takeaway on that is that patients with hidradenitis actually more likely to have, comorbidities than our psoriatic patients.

We know psoriasis patients have a lot of comorbidities. It's even higher in, hidradenitis patients. The most common comorbidities are COPD, diabetes, with or without complications, liver disease, and then when they have higher rates of complications and multiple comorbidities, actually the mortality rate goes up significantly. If you have a, Charleston comorbidity index of five or more, you have a fivefold higher rate of mortality compared to patients who had no comorbidities. So something to think about in the few patients you have who have hidradenitis, I know they're difficult to manage, you know, etalimumab is probably the only drug right now that's approved for this, but there are multiple things that rheumatologists do to manage these people, but comorbidity management is probably going to be a big thing.

We'll end with a reminder to go to roomnow.live to register and start looking at some of our videos from roomnow.live. Sixteen hours of fabulous lectures by the world world's leading, lecturers. Look at some of the TED talks. We call them step talks by myself, Lenny Calabrese, Philip Conahan, a whole bunch of people gave some really great, step talks that I think are worth looking at. They're just fifteen minutes, real quick looks.

That's it for this week. Go to the website, check out these links and more. We'll talk to you next week on rheumnow.com.