RheumNow Podcast Believe In Vitamin D Or Rituximab (9.20.19) Save

It's the 09/20/2019. This is the RheumNow podcast. Hi, I'm Doctor. Jack Cush, executive editor of rheumnow.com. You know, I got a lot on my mind.

I got a chip on my shoulder. I'm going get a lot of stuff off my chest today. We're going to talk about Rheum's and their love for vitamin D. We also love that rituximab thing, especially when it's been used in diseases for which it's been proven to not work. And everybody knows statins are good for the heart, but did you know it's also good for the knees?

Here are these reports. Let's start with ankylosing spondylitis and the risk of hypertension if you use a nonsteroidal. Now, we know that nonsteroidals can increase blood pressure. We should be mentioning that as an adverse effect of the drug that happens in some. Patients with brittle hypertension should be monitored for blood pressure changes when starting a nonsteroidal or when switching nonsteroidals.

Hypertension is not a part of ankylosing spondylitis and a large prospective cohort study of ankylosing spondylitis patients looked at a subset, specifically six twenty eight patients who did not have hypertension at baseline and followed them forward based on whether or not they received certain therapies and whether or not they received, or developed incident hypertension. So overall, two hundred of these six twenty eight were treated with nonsteroidals continuously and one hundred and twenty nine of them developed incident hypertension. After adjustment for a lot of covariates, the actual hazard ratio was twelve percent higher, significantly higher, but only twelve percent higher in people in enclosing spondylitis patients who were given nonsteroidals, suggesting that this should be something you should discuss with your patients. This should be something that you look for in your patients. The Southern Sweden is noted for its many different registries that are really of excellent quality.

The Southern Sweden Registry on Vasculitis looked at the risk of cancer. Specifically, they looked at the risk of cancer in patients who had ANCA associated vasculitis, which as you would expect, would include patients with GPA, EPA, and microscopic polyangiitis MPA. Overall, they followed one hundred and ninety five patients for up to eight years, and they showed that there was an overall increase in cancer risk in patients with AAV and associated vasculitis with a two point six fold higher rate in these patients compared to controls. That meant that the SIR, this is the SIR compared to the normal population, for squamous cell cancer was 12 fold higher, for bladder cancer four fold higher, and for pancreatic cancer seven fold higher, SIR is seven. This is sort of surprising, would have expected maybe some increase in these patients.

Of course, they didn't fair it out whether it's related to their drugs. They did show some interesting data that said if you receive cyclophosphamide at a total dose of less than ten grams, you did not have an increased risk of cancer. Certainly there we might consider bladder cancer, urogenital cancers in people on chronic cyclophosphamide. But if you were at less than ten grams total, then it was less likely. So again, this is something we do need to talk to patients about.

Something that you don't see or hear much about is pregnancy in scleroderma. So, often the cohort sizes are small. There certainly are patients who are of childbearing age who do come down with scleroderma, many of whom are female. So it's not surprising that there's some data out there. This is a meta analysis of up to 16 different studies that comes up with some of the, I think some instructive data that you can advise patients on.

Turns out that systemic sclerosis patients do have a higher risk of miscarriages, about sixty percent higher. A threefold or a three point two odds ratio, increased risk of intrauterine growth retardation, and a twofold increase in preterm births. We also had about a three fold or 3.8 fold increase in low birth weight newborns. Discardino patients also had a three fold increased risk of gestational height, sorry about that, gestational hypertension and, two to three fold more, C sections being done. This is as much as what you see with really, active RA patients or any active inflammatory disease.

So pregnancy is not going to necessarily be an easy, venture in patients with systemic sclerosis. Obviously, you'd want them to be in the best possible shape before they get pregnant, but it's unclear as to whether disease activity plays any role in any of these occurrences. There was no mention of a higher rate of fetal malformations in scleroderma. That may have to do also with the fact that there's often, not a lot of therapy going on here, or certainly no therapies that we would deem to be risky. The osteoarthritis initiative has come up with a lot of interesting outcome, results from their very large prospective study.

In this recent report, they looked at statins and what happens in patients who, are in the osteoarthritis initiative. They found six zero two patients who were on statins and had a control group. They examined eight thirty two knees overall, and they found that patients in the OA initiative who had Heberden's nodes and other evidence of osteoarthritis who were on statins, they actually showed a significant reduction in knee joint, joint space narrowing, and the progression of joint space narrowing, that statins may play some protective role in knee osteoarthritis. This is good news because in that age group, a lot of patients are going to have hyperlipidemia and may need to be on statins as well. So this is, I think, something that's encouraging for those patients.

Another bit of interesting evidence about osteoarthritis comes from British Columbia, where they looked at administrative claims data and studied, the role of nonsteroidals in osteoarthritis patients and what that may do to overall cardiovascular risk. What they found was, not surprisingly, older osteoarthritis patients did have a significantly higher rate of cardiovascular disease and outcomes compared to age matched controls who didn't have osteoarthritis. That rate was twenty three percent higher in osteoarthritis. The question is, how much of that is related to their therapies and specifically how much of that is related to the use of nonsteroidal anti inflammatory drugs. Their calculations show that forty one percent of this overall increased risk was attributable to nonsteroidal use continuously, suggesting that something you might have to worry about in patients who have, again, osteoarthritis.

I tend not to use a lot of nonsteroidals in elderly patients for their osteoarthritis to try to minimize it. I think other analgesic therapies work just as well. I'm a big believer in a long acting acetaminophen, tramadol. I don't use narcotics. Lifestyle management, obviously very important here.

So what about vitamin D? Rheumatologists love vitamin D. When I talk trash about vitamin D, they get in my face, call me a heretic or a mutineer or something like that. And, so I throw up vitamin D literature whenever I can, especially when it looks bad because it makes me look good. But this actually is kind of interesting.

It's a meta analysis of vitamin D and its role in lupus. As you know, vitamin D is very important in metabolic bone disease and what happens with bone. It's also very important as far as immune function. It's important in T cell, growth. It's important in B cell activity, the generation of autoantibodies, what plasma cells are going to do.

Vitamin D is actually very important. And based on the data, the immune function data, you would postulate that vitamin D treatment or deficiency should play an important role in lupus. Because of this, there's actually been a few trials of high dose vitamin D intervention in active lupus. Unfortunately And they didn't show any. I was involved in one with the NIH and it was really disappointing in what was seen, even though I think it's a fairly well designed trial.

But these trials are hard to do and that's why there's not many of them. So in this particular instance, the study that we're looking at was a meta analysis of vitamin D and its role in lupus. Specifically, showed that overall lupus patients have low vitamin D levels, not surprising. Moreover, there are even lower in patients with very high SLETE EYE scores. SLETE EYE is greater than 10 tend to have the lowest vitamin D levels.

They also showed that a deficiency of vitamin D was associated with an increased risk of lupus, meaning a big risk, like a 4.3, fold increased risk of developing lupus if you are, hypo vitaminosis D. I think it's E56.9 for those of you who are doing the ICD-ten, scoring. And lastly, vitamin D levels were inversely correlated with SLETEI in some studies with a correlation coefficient of minus 0.5, not tremendously strong, but strong enough to get my attention. So again, I take vitamin D every day. I take two thousand units.

Have I ever measured my vitamin D levels? No, I'm sure they're low. I'm a white guy. I live indoors. I work indoors.

I'm not plowing the fields, but I want all the benefits and none of the hassle of vitamin D. So I'm taking it every day. But again, I want to see a trial where vitamin D intervention and use fixes something, whether it's lumbago, itchy teeth, or fracture rates. I'm looking at that kind of data. But this does say vitamin D is important in lupus and we should pay attention to that.

What else do we love in lupus? We love rituximab. Oh God, we love rituximab. We're not using an RA where it's been proven to work. And we are using lupus where it's proven to not work.

But yes, because of our frustration with lupus and our therapies, we often use a lot of rituximab despite uncontrolled data that shows that it works. This particular report was, guess what, uncontrolled data, one hundred and forty seven patients who were treated with rituximab from a few centers and basically showed that there were better outcomes with rituximab, especially when patients had received fewer DMARDs or biologics prior to the use of rituximab and had lower C4 levels. Well, more than half the patients in this study had received either, mycophenolate, azathioprine, hydroxychloroquine, and a third had been treated with Citoxan or methotrexate. So a healthy number of people in this trial had received lots of therapy, which meant that it wasn't going to work as well in those. Why did it work with low C4?

Maybe active disease, maybe it would work. It didn't work as well in patients who had predominant musculoskeletal or arthritis outcomes or arthritis problems. So again, if you like to use rituximab, there is uncontrolled data out there to support you. Good luck with that. I don't use much of it.

I use it by the way, think it's great for, you know, autoimmune hemolytic anemia, ITP, fabulous responses. But for a lot of what ails our lupus patients, including seborrheitis, nephritis, skin disease, generally not great responses in my hands. What about Plaquenil toxicity, chloroquine toxicity? A single center analysis, I think over three fifty patients looked at the three twenty six patients followed for almost thirteen years, showed that the risk of retinal toxicity was five point five percent. That's low, thankfully.

But you know what? See, any of this in my practice, maybe I'm not following people long enough, Maybe or I'm not using enough hydroxychloroquine. What you should know is that none of these events occurred in the first five years of antimalarial use. The earliest one that was reported was eight years of use and the longest one was after thirty three years of use. So obviously it's cumulative dose and over time this seems to go up higher.

It did show a slightly higher rate of retinal toxicity in those who had renal disease, and it was slightly less in Caucasians. Ninety patients with lupus given an immunosuppressive in Japan were given either a placebo or Zostavax. That's the live virus vaccine for herpes zoster. Can you do that? Can you give an active lupus patient on immunosuppressive a live virus vaccine?

This study says yes. They showed significantly higher VZV anti varicella zoster virus IgG levels and all kinds of other measures to show that they were properly immunized in those who took the vaccine versus those who took the placebo. They showed more injection site reactions with the Zostavax compared to placebo. Only a few people flared two in one group, one another doesn't really matter, but there were no cases of post vaccination, cutaneous or otherwise zoster events suggesting you can use this in that situation. Lastly, an important report from the ACR from the Simple Task Initiative that looked at their it's an annual survey.

There's over 1,500 patients basically coming up with a headline that more than half the patients that we're treating cannot afford the treatments that we're giving them. So ninety percent of these people in this study had health insurance, but only about sixty percent said they had a hard time affording their medications or treatments in the last year. Half the patients were required by their insurance companies to participate in step therapy. And we know that's kind of idiotic and the ACRs come out against that. Twenty five percent say that their out of pocket costs are greater than $1,000 and six percent say it's greater than $5,000 a year.

The good news is that sixty percent of people in this study done by the ACR were seeing a rheumatologist. It's a little bit of a biased sample. I like that number, but you know, in my rant on the war on RA, I said every rheumatoid should be followed and seen by a rheumatologist. We're getting there. The problem is two thirds had to wait more than thirty days to get an appointment.

We got to step up. And lastly, two thirds of their patients, other patients said they were limited in their activity because of their arthritis. That's it. This is this week's report. Tune in next week for another one.