RheumNow Podcast You Owe Me A DEXA (3.15.19) Save

It's the 03/15/2019 and this is the Room Now podcast. Hi, I'm Doctor. Jack Cush, executive editor of roomnow.com. And this week in the news, a change in blockbuster drug sales, higher dropout rates on TNF inhibitors, is that possible and in what disease? And where's that DEXA you owe me?

Let's start with that report. Almost three thousand patients in a single center who are older, over the age of 50 went to the ER and were diagnosed with a vertebral fracture. These were new vertebral fractures. Again, this is a study that was done between 02/2014. And the shocking thing is for this large number of people who went to the ER found to have a vertebral fracture, how they were treated subsequently is sort of shocking.

Actually, data was like ninety eight percent of people did not have a DEXA in the two years prior, so maybe they missed it and maybe they weren't watching for it. Again, they're over the age of 50, I think the mean age was over 60. And also in the year after the index vertebral fracture, they did not have a DEXA scan ordered. More importantly, only seven percent actually went on to receive anti resorptive therapy, five percent in the first year, two percent in the second year, and in the next two years, almost forty percent of these people went on to have another fracture. This should be a knee jerk reaction.

Just saw a patient with this the other day. In this case, it was a metatarsal fracture in someone who's a postmenopausal woman, happened six months ago, no bone density, no osteoporosis assessment, no treatment for osteoporosis. So this is a large deficit, I don't know why this happens. We as rheumatologists need to spread the word. List came out this week of the top selling drugs of twenty eighteen worldwide.

At top of the list is AbbVie's Humira with $19,900,000,000 in worldwide sales. There are other, drugs that we use in our specialty. Number six on the list was rituximab or rituxan at 6,900,000,000 and number 10 on the list was stalara or ustekinumab at 5,200,000,000. Noticeably absent are the other two TNF inhibitors, Enbrel and Remicade have fallen off the list. The times they are changing.

I think that most of those changes in those drugs falling off the list have to do with worldwide use of biosimilars, not necessarily happening here in The United States. If we looked at top 10 selling drugs in The United States, I'm sure those would still be on the list, at least Enbrel would. But times they are changing, partly biosimilar, partly the use of these drugs is being challenged in other disciplines, especially psoriasis and psoriatic arthritis by other agents, IL-twelve twenty three inhibitors, IL-seventeen inhibitors, again, times they are changing. An interesting study, looked at, the association of progressive skin fibrosis in scleroderma patients and what happens to lung function. This is over one thousand patients in the U Star cohort and they define progression of their skin disease as greater than five modified Rodman skin units change in one year.

They call that a rapid progression benchmark and they looked at those people and those people were more likely to have significant decline in lung function and all cause mortality in that follow-up period. We've already known that patients who you worry about are those who have rapidly changing skin, that's always been taught, here's another measure of that that says the same thing. They didn't give you other measures that would also have been correlated with rapidly declining lung function and or all cause mortality. An interesting study comes from the Osteoarthritis Initiative that shows that if you can lose weight and they defined it as greater than 5% of your baseline BMI in obese or overweight patients, they looked at them over an eight year period and they found that the patients who lost weight by diet or diet and exercise had a significant decline in knee cartilage loss over this eight year period. This wasn't seen in the individuals who lost weight by exercise alone, kind of interesting there.

Maybe it has to do with muscle mass in those people, I'm not really sure. But this is sort of encouraging data for you who are advising your patients, weight loss is the way to treat osteoarthritis, that may be the most condor protective disease modifying measure one can employ in someone with osteoarthritis of the knee. The COBRA data, as you remember, the study back from, gosh, I think it was the late or early 90s, which looked at early RA patients who were treated either with sulfasalazine or the combination of sulfasalazine and high dose prednisolone weaned down over a six month period. What they showed in that, twenty three year follow-up of those patients was they had basically a long term survival, to that of the general population suggesting that early aggressive therapy has a survival benefit in patients with rheumatoid arthritis. More interesting data comes from the corona registry where they looked at chronic opioid use in their RA cohort, they showed that it doubled between the years of 2002 to 2015 from seven point four to almost seventeen percent.

The biggest predictors of chronic use of opioids was severe pain, not surprisingly, also antidepressant use, high disease activity and high disability. It's the antidepressant use and the high disability that worries me, maybe that's where some of the inappropriate use of opioids, might be, happening these days. It's something we need to worry about. We certainly know patients with depression, fibromyalgia and whatnot, use of opioids in that population is not wise. So there's an interesting study that came out this week also from, Atul Diadar and his colleagues looking at persistence on TNF inhibitors in patients with ankylosing spondylitis.

So they took a claims database cohort, they identified over a thousand patients, thirteen seventy two ankylosing spondylitis patients between two thousand and nine and 2013 and looked at a two year window from the time they started on their TNF inhibitor, to the time that they stopped or whether they continued. The sad and bad news in the study is at two years, only one third of patients were still taking the TNF inhibitor that they started with. Twenty six percent switched to another TNF inhibitor that seems reasonable. That means that two years fifty percent are on a TNF inhibitor. However, forty one percent stopped the TNF inhibitor and did not restart it.

That's problematic. The idea here of course, with aggressive therapy in this cohort would be not only to improve signs and symptoms and function, and pain, but also to improve long term outcomes including radiographic outcomes, damage, fusion, etc. Not going to be a change if they're not on persistent therapy. So is this because of the nature of ankylosing spondylitis patients being mostly male, maybe more non compliant? Again, they didn't look at it because this claims data that they looked at, but I think it's a worrisome data.

Again, dropout rate on TNF inhibitors in rheumatoid arthritis tends to be about ten percent a year or fifty percent at five years. This is a two years where you wouldn't expect to see more than dropout of thirty at the most forty percent, but really about thirty percent, they have sixty seven percent dropout at the end of two years. That's not good. That's actually a sixty percent because it's only forty one percent stopped. So anyway, but the bottom line is the numbers aren't really encouraging at all.

ULA came out with guidelines for the management of juvenile localized scleroderma patients with morphia or linear scleroderma. We had a number of guidelines out this week, Brazilian guidelines for myopathies, the Swedish guidelines for giant cell arteritis, you can look at those. I chose just to highlight the juvenile localized scleroderma, where they say that when these patients are identified, they need to be referred to a pediatric rheumatologist, that there's a more liberal recommendation regarding use of imaging, either ultrasound of lesions and or MRI of the musculoskeletal system. Then if you have lesions of the head and face, especially the Coupe de Sables, lesion that you need to do MRIs of the brain, but if it involves other parts of the face, ENT and ophthalmological recommendations and dental recommendations are also recommended. The mainstay of therapy is the early use of steroids if they're in the early inflammatory phase, but then everybody should be put on methotrexate at the same time they're put on steroids or put on methotrexate and if not methotrexate looks like the second preferred drug there is mycophenolate where they're seeing good outcomes with regard to the skin lesions over time.

Lastly, tramadol, was in the news this week, JAMA reports showing that tramadol use may be associated with increased mortality. And this is an osteoarthritis patients and eighty eight thousand eighty nine thousand patients with osteoarthritis were either given initial first time use of tramadol and they compared that to several different nonsteroidals about forty thousand and even a cohort with codeine. They showed that compared to nonsteroidal use tramadol use was associated with a hazard ratio of one point seven one to two point zero four increased risk of mortality. Now is that real? Is this confounded by indication?

Turns out when you compare tramadol to codeine users, there was no difference in the overall mortality rates, but then is that higher too? I think this is sort of a big question mark, it needs to be repeated and studied in a different manner, but it's worrisome and I think that maybe the take home message here isn't that tramadol causes death, but that patients with osteoarthritis that require narcotic therapies or more aggressive therapies are in a different class as far as risk, and ultimate outcomes. There probably needs to be a better algorithm for managing such patients, one that we can all agree on. That's it for this week, go to the website to look at these links and more. Be sure to check out roomnow.live, our big meeting is next week, you can register online and view it free from home, or you can come to Fort Worth and join in the fun.

We'll see you next week.