RheumNow Podcast- 2019 EULAR RA Guidelines (1.31.20) Save

It's the 01/31/2020. This is the Room Now podcast, and I'm doctor Jack Cush, executive editor of roomnow.com. This podcast is brought to you by Room Now Live. It's two days, sixteen hours of lectures, 23 lectures, 10 TED Talks, pre learning assignments, downloads, 25% or more Q and A time, unique downtown Fort Worth, two days away from work, 03/13/1415. Check it out.

This week in the podcast, a lot of good news. Let's start with a report from the corona registry. And it's interesting in that we know that there are a lot of things that can impair response to therapy in rheumatoid arthritis, obesity, comorbidity, disease severity, all these things are factors. Well, Corona tackled the question about comorbidity and obesity and looked at one drug, tocilizumab. They studied about 800 patients in their registry and they divided them up into those who had high comorbidity scores using the Charlson Comorbidity Index and those who had low comorbidity scores.

They had two cohorts and they looked at responsiveness to tocilizumab. Turns out comorbidity didn't make a difference, at least when it came to the use of tocilizumab. You know what else didn't make a difference? That would have been obesity. They used a BMI of greater than thirty and those who had a normal BMI of less than thirty and showed that obesity didn't impair responses to tocilizumab.

Now that's interesting because tocilizumab, as you know, is a weight based dosed biologic, meaning patients who are above a hundred kilograms need to be on weekly tocilizumab, one hundred and sixty two milligrams per week, if they're getting the sub q form, whereas those that are less than one hundred kilograms can get it every other week. And there is some data from some of their trials suggesting this trend, but nonetheless, this real world experience in Corona suggests that obesity may not impair responses, at least with tocilizumab. We do know obesity is a big problem with drug responsiveness for many biologic and for DMARDs, suggesting we should probably be treating obesity in RA as much as we should be treating it in OA. I found a nice report, an interesting report on something called GDF15, that's Growth Differentiation Factor 15. It's a cytokine, It's part of the TGF beta family.

It seems to be involved in regulating apoptosis and whatnot. And these particular investigators looked at it in inflammatory myositis patients. And they found in a cohort of thirty five patients with idiopathic inflammatory myopathy, that GDF15 levels were twice as high in those patients compared to normal healthy controls, suggesting this could be a marker of either damage or diagnosis. They talked about it as a potential biomarker. I think that's a long ways off.

You need to show how it performs over time, show that it has predictive value. And I think that maybe it has some utility. It also was high in patients with inclusion body myositis. So again, it's nice to see novel work being done in a difficult area like myositis, but again, biomarkers are a gigantic stretch. It gets thrown around a lot.

A biomarker is something that actually will help you predict what may happen. Most of the biomarkers that are out there now are about predicting the past, not about showing its utility in a prospective study, especially when done serially. So another nice bit of basic science research comes on the topic of gout, and that is possibly a new target for the treatment of gout, this new target being TAK1 standing for TGF beta activated kinase one. We do know that monosodium urate crystals is one of those substances that can activate the inflammasome and produce a lot of IL-one and then downstream cytokine and other mediators of inflammation in gout. In this particular research, they showed that MSU crystals are particularly effective at activating macrophages and fibroblasts to induce TAK1, and a TAK1 is instrumental in amplifying the release of IL-one beta, and then subsequently other cytokines like IL-six, IL-eight, and chemokines like CXCL-five.

So the idea is that could TAK1 be yet another target for the novel management of gout? It'd be nice to see this actually go into some sort of study, experimental in animals or real in patients, but we need I think drugs targeting TAK1. John Hanley wrote a nice paper about neuropsychiatric lupus, one of my favorite subjects. He has a large cohort of NP patients, neuropsychiatric lupus patients, eighteen twenty seven SLE patients specifically in whom using a rigid definition of, actually it's kind of a broad definition, but a well defined definition of neuropsychiatric lupus, it was found in fifty two percent of patients who have lupus have neuropsychiatric disease. This is not the first time this has been shown.

Other studies and ones that I've seen or I've done before show it actually is more than half of patients will have neuropsychiatric or cerebritis disease in the course of their lifetime. In this particular cohort, they found at least thirty one percent of those cases had neuropsychiatric disease directly attributable to lupus without being confounded by other factors that could have been involved. It turns out that the risk of neuropsychiatric disease is highest in the first two years of disease, and that sadly, actually the relative risk there was over six, but that there was a higher mortal risk, maybe a doubling of the mortality risk in people who had neuropsychiatric disease compared to those who did not, suggesting this is a particularly bad manifestation of lupus. So there was a study in the ID literature looking at the musculoskeletal side effects of TB treatment. A cohort of two sixty patients treated either with pyrazinamide or with fluoroquinolones for acute TB found a higher risk of joint pain, mostly knees and ankles with fluoroquinolones compared to pyrazinamide.

I didn't know that you could I certainly knew you could get tendon problems with the fluoroquinolones and that arthralgia has been reported, but at least in these TB patients, it's not inconsequential. Nearly thirty percent of patients on fluoroquinolones and about seventeen percent on pyrazinamide had, again, joint complaints. It took up to two months to develop this on fluoroquinolones, but much longer, one hundred and thirty eight days in patients on pyrazinamide. Half of them had hyperuricemia, but there were no well described events that would constitute or qualify as gout. So it's something to be concerned about when you see patients who are on anti TB therapy.

We are re reporting in a tweet form this time, what we had previously done about six months ago when this data first came out, the data was about the INTRACT trial. INTRACT, that's E N T R A C T E, is a head to head study of etanercept versus tocilizumab in patients with rheumatoid arthritis to find out what the risk of cardiovascular events might be. Certainly, we know RA patients have a higher risk of cardiovascular events, not necessarily higher with TNF inhibitors. In fact, there's been studies showing it's lowered by TNF inhibitors. But there's concern about tocilizumab, and you can say for that matter, JAK inhibitors, because they can increase your lipid levels.

And the question is, is that a reflection of what's going on with inflammation or does that sort of reflex increase in lipid levels in at least twenty percent of patients result in a cardiovascular or some other cardiac risk? They took patients who were at risk, three thousand and eighty patients, and randomized them to atosolizumab and etanercept at standard doses and found no increased risk of major adverse cardiac events, MACE events, when comparing tocilizumab to etanercept, the hazard ratio is one point zero five with overlapping intervals that overlap one. So again, I think this is comforting data for those of you who use tocilizumab and IL-six inhibitors. And again, we like to see this kind of data done with the JAK inhibitors as well. So there's an administrative claims study that was reported recently from Canada and British Columbia that looked at the benefits of Plaquenil in SLE patients.

And they showed that the risk of studying almost fifteen hundred patients with lupus, they found for over almost five years, I guess, that there was a lower risk of developing type two diabetes if you were on Plaquenil compared to lupus patients not on Plaquenil. Now lupus patients themselves are not particularly at any increased risk for diabetes, type two diabetes, but it turns out that, and this has been reported before, that there may be an anti diabetic effect of hydroxychloroquine when given chronically over time. Add this to the many, many benefits of hydroxychloroquine therapy in patients with lupus and even patients without lupus. So there are the new ACR and ULAR guide, it's actually, sorry, just ACR guidelines on the treatment of osteoarthritis of the hip and knee. You can review those, we've reported on those previously.

I specifically was looking at the issue of balance. And I've had a few patients recently where the falls was their complaint. And the question is, is it because they're elderly and they've developed a new neurologic condition or dementia? Or is it because they have osteoarthritis and pain? And it turns out there are a number of studies that show that osteoarthritis patients who have OA of hip and knee are much higher risk of falls and balance issues.

And the ACR guidelines do make a conditional recommendation for balance exercises in patients who have knee OA. They didn't really comment on that with regard to hip OA. So there is some data that would support that. One study, a systematic review of actually 11 studies show that knee OA patients are significantly higher risk of falls. There's our current AC and R paper that's on your desk that shows that knee OA patients who also have back pain have a doubling of their risk of falls.

This is a big problem. And I think that, you know, this is where physical therapy needs to be aggressively employed to teach patients how not to fall, to teach them how to fall and to deal with their balance issues so that they don't fall. And lastly, there's the ULAR guidelines for the management of lupus, I'm sorry, of rheumatoid arthritis. These are the twenty nineteen ULAR recommendations for the management of rheumatoid arthritis. We published it.

It's a good read. It's a fast read compared to reading the paper. There are five overarching principles. There are 12 new recommendations. Many of these mirror the recommendations from 2016, but there's a few new notable additions that I think bear mentioning.

And the overarching principles that again states that rheumatologists should be the specialists who are primarily involved in the care and management of RA. To do it without a rheumatologist on board is probably a gigantic mistake. Rheumatologists do it better and we're happier to do so. Specific recommendations, DMARDs should be started as soon as the diagnosis of RA is made. There's no waffling, there's no well, symptomatic management, DMARDs, DMARDs, DMARDs.

Second is that monitoring needs to be done and a treat to target strategy needs to be employed. Methotrexate should be the first DMARDs used unless it is contraindicated and it is the anchor drug upon which all other drugs can be added. They make a case for short term glucocorticoid therapies when initiating or changing your DMARR therapy. And I think that that's sort to me a bit of a surprise that they say it's considered, it's not mandatory, but they say you should at least consider it. I think many of us do.

They say that if you don't treat, if you don't achieve your target goal and you're using methotrexate or another conventional DMARD, that in the absence of a poor prognostic indicator, it's okay to then try a second conventional DMARD. So it's okay to go from methotrexate to sulfasalazine or from methotrexate to Arava or from Arava to sulfasalazine. But it is the presence of poor prognostic indicators that should drive the use of more aggressive therapies. What is that? As you know, that's erosions, many joints, extra articular manifestations.

We wrote about it in the article. If you have poor prognostic indicator and you fail a methotrexate or a conventional DMARD, then a biologic DMARD or a targeted synthetic DMARD like the JAK inhibitors should be added at that point. They say that when you're using those drugs, they should be combined with a conventional DMARD like methotrexate. And if someone fails a biologic DMARD or a targeted synthetic or JAK inhibitor, that they should be changed to another biologic DMARD or targeted synthetic. If you fail your first TNF inhibitor, what do you do as a second drug?

They say patients may receive an agent with another DMARD with another MOA or second TNF inhibitor. This differs from the prior additions where they said it didn't matter, but here they wanna put another MOA ahead of a TNF inhibitor, second TNF inhibitor based on the literature, which is seeming to stack up and say that after your first TNF inhibitor, going to a second and third may not be your best choice, going to another MOA may be your best choice. They say if you're doing well and in persistent remission, that tapering the biologic DMARD or their targeted synthetic may be appropriate. However, that if you do make that choice, there is a reasonable risk of flares in such patients. And similarly, if you're in remission, tapering a conventional DMARD should be considered.

They seem to think that when tapering therapies to go after them is not wise. It may be better instead to have dose reduction or a change in dosing interval so the patient takes less, but it still remains on the drug and doesn't flare or doesn't experience worsening of radiographic outcomes. That's it for this week on the podcast. Tune in to the podcast next week. Tell your friends about it.

You can rate us on iTunes. You can listen to us or watch us online. Be sure to check out room now. Live. We'll see you next week.