RheumNow Podcast - Despite Corona (3.6.20) Save

It's the 03/06/2020. This is the RheumNow podcast, and I'm doctor Jack Cush, executive editor of rheumnow.com. This week, we're going to talk about the best biomarkers for Still's disease. No. It's not ferritin.

Misleading ANAs and where might you see those? And guess what? Fibromyalgia patients really are sick. We've got some evidence. Our first report is a study of two ninety five patients with giant cell arteritis.

In this particular study they looked for severe cranial ischemic complications of GCA. Turns out most of those were second nerve or visually related and in their analysis they showed a high risk of these ischemic cranial complications when the patient was older and when there was a history of jaw claudication. Both of those gave you basically over a threefold increased risk for these severe cranial ischemic complications. And guess what? They were in fact decreased when the patient had either PMR symptoms or a very, very high CRP.

I'm guessing the way to look at this data is that PMR symptoms and a high CRP were probably surrogates for patients getting treated more aggressively with steroids or more early with steroids, and that maybe instead the jaw claudication and age associated with larger vessel, large vessel complications of the disease. It's an interesting, set of data. We've been it would be nice to see if this gets repeated somewhere. We do ANAs all the time. We get consults for ANA all the time.

I don't know about you, in your long list of what causes a positive ANA that's not lupus and does not need to be followed by you, but high on my list is liver disease. You know, was an old American Journal of Medicine report about serologies in patients with liver disease showing surprisingly high levels of autoantibodies in patients with a variety of different liver diseases. We have a new report that does the same, and specifically looked at a large cohort and looked at the performance characteristics of the ANA test and showed that ninety one percent of patients with a systemic autoimmune disease had a positive ANA. We know that. The ANA is a poor man's measure for autoimmune disease, albeit not necessarily specific for lupus.

But if you have autoimmune hepatitis, the number is forty nine percent positive. Hepatitis B, hepatitis C ranges from fourteen to nineteen percent. Patients with hepatocellular carcinoma, almost twenty four percent of patients will have a positive ANA. The good news is that most of these ANAs are fairly low titer, meaning they're less than one in three twenty. And not surprisingly, there's a wide variety of patterns seen.

You should go to the report to read more about this, but again, this is a rock solid cause of a positive ANA. That's not gonna be due to lupus. NICE, that's the agency in The UK that oversees the, use of biologics and medicines in treatment of many diseases including rheumatoid arthritis. They did a cost analysis of how RA patients are treated, Looked at two zero five RA patients and compared the outcomes whether they were treated with combination DMARDs or the combination of biologic and methotrexate. Obviously, the biologic is much more expensive, the combination DMARDs not so, and yes, they found that you get similar clinical benefits with the cheaper agents, meaning combinations of DMARDs.

So it appears that you're gonna have to go through cheapy ville before you get to your happy drugs, the ones that are happily frequently advertised that you want to use because they're in your sample cabinet and whatnot. Again, there's not a lot of evidence that many of the therapies we use are clearly superior to everything else we also could use or used to use. So, in fact many meta analyses have basically said they're all the same, maybe with the exception of monotherapy anakinra and monotherapy hydroxychloroquine, everything else, especially when you talk about combinations, they're all about the same. So then it's up to you, the prescriber, and the patient's preference. Interesting data, those are the rules in The UK, they probably should apply here in The United States and Canada.

So we're going to talk about two main issues regarding RA patients that have to do with the lungs. One is a study of almost two hundred patients with rheumatoid arthritis who underwent polysomnography to look at their sleep and not surprisingly sleep apnea is not uncommon in patients with rheumatoid arthritis. Depending on your definition based on the AHI, an AHI of greater than 15, I believe was associated with a twenty three percent risk of developing sleep apnea, obstructive sleep apnea, that would merit treatment and CPAP and further evaluation. Makes me wonder whether or not that twenty three percent of RA patients with sleep apnea are the same twenty three percent, thirty three percent that have a lot of fatigue in the clinic. Often we think of fatigue as being an inflammation and disease associated phenomenon, when in fact, a fair amount of it could be related to bad sleep and sleep apnea.

Another interesting study looked at mortality in rheumatic disease patients. Over thirty five thousand patients were studied, followed for over sixteen years, and looked at all cause mortality in a number of different conditions. Not surprisingly, all cause mortality was increased in rheumatoid arthritis. Fifty two percent increase in all cause mortality with a relative risk of one point five two. You know what else was increased as far as all cause mortality?

Fibromyalgia, one point one nine, a nineteen percent increase in fibromyalgia patients. Also, widespread pain patients. Widespread pain, isn't that the same as fibromyalgia? Well, their risk of all cause mortality, relative risk was one point three eight, a thirty eight percent. So a nineteen to thirty eight percent increase in all cause mortality with chronic widespread pain diagnosis fibromyalgia or not.

Saying pain is not a good thing, pain may run with a lot of other comorbidities, I think we need to think about and listen to the pain of our patients with fibromyalgia and those who just have widespread pain and think outside the box a little on these people. Yes, they are sick. The Johnson County Osteoarthritis Project recently published report, a sixteen year follow-up of eight hundred patients with, hand OA. They found that, the patients who had, OA, they had found radiographic evidence of hand OA in three twenty seven out of eight hundred hand OA, radiographic hand OA was more likely with age being female and being Caucasian. Women were more likely than men to have hand OA and this was really true for DIPs.

And we kind of know that. It is more of a Caucasian disease than is African, than you'll see in African Americans. The ESPOSA study is a five European cohort study that looked at the associations with osteoarthritis and they found overall twenty seven percent of this fairly large group, multiple groups, had one or more falls presumably related to their osteoarthritis. Ten percent fell more than twice, calling them a recurrent faller. The risk was highest with knee OA and opioid analgesics were also associated with recurrent falls.

Again, pain knee OA, we talked about this before, is a frequent risk factor for falls. Patients who are in this category should be sent to physical therapy for training on how to fall, how not to hurt themselves during fall, to carefully consider the need for a walking assist device. We do not use enough physical therapy and occupational therapy in our patients, in our clinics. Speaking about the global we, not you and me, we are of course perfect. What's the best biomarker for Still's disease?

I've been saying this for years because I've been taught this by some very, very smart pediatric rheumatologists, Virginia Pasquale, Lynn Panero at the University of Texas Southwestern, and they've taught me that aldolase is the biomarker for patients with Still's disease, whether it's a kid or whether it's an adult. Turns out it's also a great biomarker for all the IL-one responsive auto inflammatory disorders. And guess what? The aldolase is sky high and the CPK is rock solid normal. So this has been backed up by a recent report that was in the literature.

You can go and find the citation showing the exact same thing. Now there are lot of biomarkers that have been thrown around about Still's disease, and I'm sorry folks, ferritin is only elevated in fifty percent of patients with active systemic Still's disease. Hyperferonemia is probably less than twenty percent, probably less than ten percent. That's like the 10,000, 20,000 ferritins. Again, it's not what most people don't believe that, but that's in fact what the data is.

There's good data suggesting LDH might be a good biomarker, better data saying that the CRP is a good biomarker. Even better is that the neutrophil to lymphocyte ratio, an NLR of greater than three or greater than five is a very good biomarker for Still's, but now you should be looking at the aldolase. Vitamin D, you know I hate vitamin D because it's associated with everything, yet there's no proof that giving vitamin fixes anything truly, consistently, argue with me when you see me, knock me down, make me take your vitamin D pills. Anyway, nice study of two thirty two post menopausal women shows that vitamin D deficiency is associated with lumbar disc disease and low back pain. That's not surprising but it's kind of interesting.

Now of course if you give lots of vitamin D will you prevent that from happening? I don't think so but nonetheless those of you who love vitamin D will love this report. Find it, print it out, put it on your favorite paper wall. The FDA has recently gone ahead and accepted the BLA, the regulatory application for the nerve growth factor drug called Tanezumab. It's been in a number of phase two and phase three trials.

They're going to evaluate this drug as a potential new treatment for chronic pain related to moderate to severe osteoarthritis. That's going to be osteoarthritis of the hip and knee. We'll see what else. You know, are some issues with this drug early on in that being a nerve growth factor inhibitor really modulates pain downward, but patients who had really severe stage three and four Kellgren damage in the hip and knee were rapidly progressing to joint destruction, joint replacement, and people were thinking oh my goodness this is causing a Charcot joint. Well the FDA put a moratorium on those studies, studied the issue, had a hearing on the issue, and then reinitiated the study saying well no, it's a little bit, it's not quite a Charcot joint, nonetheless there should be warnings about using this kind of therapy in people with advanced, very advanced disease.

It is an effective therapy it seems in the clinical trials. We'll see how it fares when the FDA puts it under the microscope. Two more reports. A venom peptide steroid conjugate has been studied in a collagen induced model of rheumatoid arthritis in rats and they looked at peptide. These are cysteine rich peptides which have been found to traffic really preferentially to cartilage in joints.

And they proved that as part of their studies, they took these cysteine rich peptides and linked it to one of two different steroids, either dexamethasone or triamcinolone, and showed that it can be an effective way of delivering steroid to the joint with minimal toxicity. Of course, the rats never complain, That's the problem with rat studies. But nonetheless, other measurable toxicities were not seen. The more effective combination was the one that involved triamcinolone as its conjugate. So it seems to be a novel way of delivering targeted therapy, in this case steroid targeted therapy, in arthritis.

Now, whether this can be extended to humans, we'll see. Hopefully someone will jump all over this. Our last report, I think a very interesting report from the, nurses health study. As you know, it's a prospective cohort of over 205,000 women followed. And in this particular analysis they showed that prior asthma or COPD leads to an increased risk of incident rheumatoid arthritis and then that risk is not necessarily related to smoking, although being a former smoker does potentiate things quite a bit.

So in this large two hundred thousand subject cohort, fifteen thousand had asthma to begin with, three thousand five hundred had COPD, and along the way a thousand and sixty developed incident RA. The risk of developing RA if you had prior asthma was one point five three or fifty three percent increase, and if you had COPD it was one point eight nine or an eighty nine percent, almost a doubling of the risk if you had COPD. The asthma related risk was not was also seen in people who did not smoke. So this is very interesting data, you know, University of Colorado and Mike Hollars have also studied the risk of lung disease in preclinical RA and shown that there's sometimes subclinical evidence of airway inflammatory disease in people with preclinical RA, so this is probably an important part of the puzzle that leads to clinically manifest RA. The puzzle being driven by first the genetics, second by environmental exposures that develop autoantibodies, and then autoantibodies in the presence of maybe lung disease could be all the keys one needs to develop rheumatoid arthritis.

That's it for this week on the podcast. Be sure to go to roomnow.live and register. Today, we're announcing open registration for the free online access to roomnowlive, which will start next Friday afternoon. Go to the website roomnow.live. Choose to either register to attend the meeting in Fort Worth, still a few seats left, or to watch this from home whether you're in New York, New Zealand, or New Braunfels, Texas.

Again, I think that you'll find the online experience to be just as good as the in person experience, but people in person get to go to Fort Worth, hang out with their friends, be with the faculty, have dinner and lunch with the faculty, etc. That's it for this week. We are having our RheumNow live meeting in spite of corona, and there's no reason to not come. Everything's working fine. Texas Department of Health, the Fort Worth and Dallas Department of Health say travel should be as normal.

We are on. We'll see you next week at RheumNow Live.