RheumNow Podcast- - The Elusive Hand OA Problem (12.13.19) Save

It's the 12/13/2019. This is the RheumNow podcast, and I'm doctor Jack Cush, executive editor of rheumnow.com. In the future, you will be what you wear. I don't know if you've been keeping count on biosimilars, but there's quite a few of them out there. Do you know how many?

And lastly, in those patients of yours who are weaning off their medicines or spacing it out or you're experimenting with how low can you go. Do you know how to predict who's going to get worse? Because you know, there is a subset that will get worse. There is a cost to be paid for trying to be on less medicine. Let's start with data from Caltech.

Researchers there are developing a wearable sensor that will actually detect uric acid levels. I find this fascinating. I know that, you know, high-tech is going to be all the rage in the future. You know, if you're a diabetic right now and you want to monitor your blood sugars, you wear a patch, you put your cell phone up to it, it tells you at that moment what your blood sugar is, it monitors it either periodically or 20 fourseven. You can again send that to your doctor.

Imagine how that will be for your patients with other diseases like gout or lupus or rheumatoid. I think wearable technology is going to have a long future and I think that we should be aware of what's going to happen there. This is this Caltech tool sensor is not yet available, but believe me, it will be soon. So lupus and smoking, do you think there's an association or not? Well, J.

Rheum has an article out that shows a meta analysis of 12 studies and almost three thousand lupus patients compared 10 to one to normal control showing that smoking is associated with a risk of lupus. However, it is the only those who are active smokers, former smokers, never smokers don't seem to have a higher risk of developing lupus. Whereas those who are active smokers seem to. Not surprising because, you know, bad stuff going into your lungs, there's all those accessory cells in those alveoli that are just waiting to do something right or do something wrong, and smoke induces a lot of the wrong things, as we'll talk about in a few more reports. An interesting report comes from South America that compares the outcomes and behavior of lupus in, five different cohorts that they have down there.

And they look at, those who are, patients who are of Latin American descent versus those who are European Caucasian and see if that influences how the disease is expressed. Well, it actually had no difference when it came to overall damage, mortality rates, comorbidities, but other features, it was different. So, Latin American lupus patients tended to have more myositis, hemolytic anemia, nephritis, the bad autoantibodies of SM, Rho, RNP, and overall had more disease activity. Not surprising, other studies have shown similar types of behavior. I think this does speak to the fact that lupus probably is more than one disease.

I don't know if that's a surprise to any of you, but the question is, is it two, three, five, nine? It remains to be seen. And maybe it is this factor that makes lupus hard to study in clinical trials. In RA, we tend to unify and homogenize our clinical trials by having patients who are generally CCP or rheumatoid factor positive. The same cannot be said by doing a serologic, grouping, if you will, of patients with lupus.

I think it's much more complex. Speaking of complex, the biosimilar story, it continues to grow. The FDA has granted another approval this time for Amgen's infliximab biosimilar. It's called Avsola. It's infliximab dash a x x q.

You know you need that suffix here in The United States. The rest of the world is laughing at us about that. They just go by the name of the biosimilar Avsola. It's got the same indications as does Remicade and all the other, three other infliximab biosimilars. This makes it the fourth infliximab biosimilar joining Inflectra, Renflexis, and Effixi.

The question is, how many biosimilars are there? Well, I got the number. The number is there's 11 TNF biosimilars, 11 of them. Oh my God. And then how many for each one?

There's five for adalimumab, there's four for infliximab, and there's two etanercept biosimilars. The overall number of biosimilars in the rheumatologic market is actually 13 if you consider the two rituximab biosimilars that are out there. Only one of them actually is approved for rheumatologic indications and none for rheumatoid arthritis. Only one, I think, Ruxemma, not Truxima, but it's actually Ruxience is approved for use in GPA. Overall, the numbers on new drugs and RA is astounding.

There's 21 biologics that includes the biosimilars, and there's three new JAK inhibitors, maybe a fourth by next year. You've got 24 drugs to choose from in treating rheumatoid arthritis that were made after or approved after 1999. Oy vey. So, let's move on and talk a little bit about, what happens in osteoarthritis of the knee and revision knee arthroplasties. You know, some patients do consider the use of these unicompartmental or hemi arthroplasties.

They're done via the arthroscope. They're less invasive. They're not as widely done, but they are novel and you can be walking tomorrow on a brand new knee. They're usually like a medial compartment or a medial unit compartmental procedure. The question is, what's the long term success?

I actually looked into this when I had my knee replacements. I was not a candidate because I already had, Genuverum and you need to have perfectly good alignment and also a perfectly talented orthopedist who actually does this kind of surgery. So it's really not for a lot of people. But what it is, it might seem work. It does seem to work.

People I know who've had it, it doesn't seem to work any more than five to ten years. And then you need a total knee. The question is, if you had a unit compartmental and you go on to knee arthroplasty, are the outcomes the same? Well, an orthopedic journal looked at this and showed that those people have a medial unit compartmental procedure followed by a total knee that actually have a three fold higher rate of further revision knee arthroplasties in that group, suggesting that there may be long term a downside to using the, hemi arthroplasty, the mini procedure, if you will. So, I don't generally recommend them, and then again, neither does my orthopedist, and the mavens who do orthopedic, arthroplasties here in Dallas.

An interesting report comes on predicting who will relapse in those patients who are undergoing a drug withdrawal, trying to limit the amount of use, go from two drugs to one drug or spacing it out. Well, there are two studies that actually looked at this, the improved study and the retro study that were designed withdrawal studies to look at what happens. As you would expect, the more you withdraw, the worse they do. If you can just withdraw one drug, patients tend to do better. Again, the ACR guideline on this particular issue is if you are in low disease activity state, you don't withdraw anything.

But if you're in remission, you can withdraw one of the drugs, but not all the drugs, because again, patients will flare, there's a radiographic downside, etc. Anyway, in these two studies, they looked at predictors and they showed that serum calprotectin, an acute phase reactant, it's an S100 protein driven by inflammasome and other things. Anyway, was actually predictive of those who are going to relapse. And it might be a useful tool. We're not doing calprotectins in our clinics.

It's being used a lot to predict who's having an infection. It's being used in GI on calprotectin on stool, stool samples to look at inflammation in the gut. It might be something we should expand our use to. Some interesting data comes out of South Africa about TB rates. Now, the TB rate in South Africa is crazy high.

It's TB land. I mean, the numbers are very different than The United States. The overall TB rate in The United States is about four cases per hundred thousand. You know, when you're in TV land, you know, places like Russia and, Southeast Asia, certain parts of South America, Central America, you know, it's one hundred, two hundred, three hundred. Well, it's like in that same range, two hundred, three hundred plus in South Africa.

And when they looked at they have a biologics registry there and they looked at the risk of developing TB amongst the patients who receive biologics. Well, the numbers are very high. The TB rate for biologic users was twelve forty, twelve forty per one hundred thousand. That's incredibly high compared to a very low number in patients who had never received a biologic. A third of these were extrapulmonary, two thirds were pulmonary.

These numbers were highest with monoclonal antibodies against TNF, where the number was sixteen eighty three. Half that number if you're using the receptor etanercept, and even lower, about a third of that number if using another MOA. Again, saying that patients who are might be at risk of TB should probably not be getting the monoclonal antibody TNF inhibitors, because that puts them at higher risk, especially if they're from countries where TB is a much higher rate than that seen in The United States, Canada, Great Britain, and certain parts of Australia. So, what about the risk of RA, or even better, the risk of ACBA? Nurses' health study actually does have some data, not just on diet, but even on a lot of other features.

They looked at two eighty four incident cases of RA and matched them against controls and showed that individuals who had asthma were at much higher risk of developing ACPA positivity, CCP antibody positivity, prior to the development of rheumatoid arthritis, and that was compared to controls. However, if you were an asthmatic and it did not necessarily increase your risk of getting RA, it just increased your risk of getting ACCA, which then later translated to a risk of RA. Again, speaking to the role of mucosal immunity, also the pulmonary microbiome. Janet Pope has written about this this week in talking about RA and the risk of RA. You might look at that article from this past week.

So yet another drug has failed in osteoarthritis of the hands. In this case, it was an erosive OA study. Patients had to have four or more DIPs, PIPs, one of which had to be red and swollen or have an ultrasound evidence of synovitis. And they went ahead and they gave these people actually that they gave them IL-one inhibition and an IL-one inhibitor is not on the market called Lutuximab. So, it doesn't really matter.

It's not going to make it to the market. At least drop for IL-one. This is a fairly large study, 110 erosive hand OA patients who showed no difference compared to placebo when it came to pain outcomes, even though those that were on IL-one had significant biochemical changes with a drop in IL-one and CRP and other inflammatory markers. So, again, a big pile of drugs that have failed in OA and inflammatory OA. You know, all the DMARDs have failed methotrexate, Plaquenil don't use it.

You know, a number of biologics have failed. Nothing seems to work here. We do need an intervention. This erosive OA maybe accounts for as much as four million Americans in The United States right now. So, need more right now.

What am I using? Acetaminophen in moderate to high doses, especially long acting, six fifty milligram acetaminophen, with two point five milligrams of prednisone, along with immobilization of problematic joints. If you've got a better option, study it or tell me about it, I'll give you credit. Speaking of HAND OA, another study looked at prednisone use in HAND OA. This was actually in Lancet this past week.

They tried to recruit 100 and fifty-sixty patients. One hundred and twelve patients were enrolled and either received placebo or ten milligrams of prednisolone for six weeks. They followed the patients for another six weeks thereafter, and what they showed was during the six weeks of prednisolone therapy, guess what? Pain scores went dramatically down in those on prednisolone and not those on placebo. However, when you stop the drug, pain reverted back to normal with no differences between the groups.

So, what does this tell you? Well, you could use steroids. You could use steroids for short term flares in OA, or you could do what I do, which is use a very low dose to try to chronically suppress inflammation in those problematic joints. Again, this is a very difficult area as far as treatment goes. Lastly, I don't know if you, have figured out what to tell your patients who want to know about CBD.

It's really a mess. This is what I tell mine. I tell them I shouldn't recommend it because there's not a lot of good biologic evidence and there's no clinical trial evidence that it works. However, the experience of my other patients says that six out of ten, seven out of 10 seem to think it does something. So there's a lot of buzz about this.

I'm not against it. I'm against the cost of it. And again, I don't think not just note about the safety of this. Anyway, this past week, the FDA came out with a warning letter to 15 of the manufacturers of CBD products, basically saying cease and desist from your ridiculous claims. They wanted to be very clear in saying that the FDA has not yet determined that cannabidiol or CBD is safe or effective.

They've heard the hearings, they're going over a lot of things. There are a lot of different preparations. It's taken a lot of different ways. There's a lot of safety signals out there. A lot of the products that are out there are actually illegally marketed and illegally made.

But there is the potential of some toxicity here, including liver injury, interaction with other drugs, drowsiness, diarrhea, changes in mood. Animal studies show there's problems with testes and scrotum development and testosterone levels. So a lot is still not known. And I wouldn't be a 100% behind this. I think you should warn your patients that they need to be judicious about this, and they need to try other maybe better proven remedies going forward.

Anyway, that's it for this week at RheumNow. Go to the website, check out these citations and others. Be sure to check out rheumnow.live. We have RheumNow live happening in February in beautiful downtown Fort Worth. We'll see you there.

Take care.