RheumNow Week In Review ACR Preview Edition %2810.19.18%29 Save

It's the 10/19/2018. This is the Room Now we can review. Hi. I'm doctor Jack Cush, executive editor of roomnow.com. This week in the news, does the Trump administration have a plan to reduce prices?

What about neuropathy with biologics? Is that a concern? And do drug holidays really work in those osteoporosis drugs? This and more. First, it's ACR week.

Tomorrow, we head to Chicago for the annual ACR convention. It's gonna be a big one. A lot going on. We're very excited about being there. RheumNow is gonna have expanded coverage that you can follow at a cr18.rheumnow.com or just look at your daily news feed from RheumNow and click through.

It'll take you to our microsite, and we have a lot of exciting things going on there. You'll have a lot of experts talking about the topics that you want to hear about. We're gonna have audio files, we're gonna have videos, we're gonna have panel discussions. You're really gonna like it. But first the news, drug induced interstitial lung disease.

You know, we do see this in rheumatology. Turns out amongst all interstitial lung diseases, it's only about five percent or less of all cases. When you look at the causes of this, cancer drugs, amiodarone, antibiotics, and yes, rheumatology drugs. Now, whether or not these rheumatology drugs are capable of causing interstitial lung disease is really debatable in my opinion because guess what? RA patients and other patients with rheumatic diseases, dermatomyositis, polymyositis, lupus, scleroderma, etc.

They get interstitial lung disease. And guess what? The drugs we use are often implicated. Hence, our TNF inhibitors capable of causing interstitial lung disease. Not in my opinion.

Same can be said for Orava and leflunomide, I mean, and other drugs. So again, it becomes a little bit complicated when looking at the capability of rheumatology drugs to cause interstitial lung disease. So the question you always must ask, is it the disease or is it the drug? It's sometimes not so clear. Turns out that there is no particular pattern radiographically or on CT scan that you can say, is very distinctive of drug induced interstitial lung disease.

Turns out though that the mortality rate is high in some studies over fifty percent. So the Federal Register came up with some new announcements this week about the Trump administration's plans to sort of level the playing field and to address in one way the drug pricing issue. They are going to, the plan is they're going to require drug makers who do direct to consumer advertising television ads for their drugs to actually list the drug prices in their ads. Make that a requirement. This is currently open for discussion and you'll obviously see a lot of discussion about this, a lot of pushback about this, but this is gonna be a big issue.

I mean, there's 25 companies running over 300 direct to consumer ads on television with over $3,000,000,000 in spending in the first nine months of 2018. So this is gonna be a hot ticket item. Will it change pricing? Will it drive competition? Will it force people to go into generics?

It'll be interesting to see how this actually plays out. The Toronto GLUPUS Clinic is known for a lot of good research and they've come up with a nice report on something that is really quite rare but we should know about, and that is antimalarial cardiomyotoxicity. And they have eight patients in their clinics. They reviewed them in this report that we have on our site. They're all endomyocardial biopsy proven.

Seven out of the eight patients had elevated CPKs. They tend to be older, they tend to have a long disease duration. They tend to have been on Plaquenil or hydroxychloroquine or the other anti malarials used for over twenty years. Half of them had very abnormal quantitative MRIs. The lab tests that were distinctive were cardiac troponin one, high CPK levels.

Again, there's a way of identifying these people. Turns out when you look at the endomyocardial biopsy, they tend to have very distinctive features with vacuolarization of the cardiomyocyte and curvilinear bodies which are also distinctive of antimalarial toxicity. One of their seven one of their eight patients died, others improved by just withdrawing the, antimalarial therapy. So, not common, but certainly serious and should be considered in patients who are having cardiac abnormalities. They often have conduction disturbances as well.

A very interesting study looks at the risk of developing peripheral neuropathy with TNF inhibitors. This is a claims database study looking at over sixty one thousand patients in the pharma metrics database and try to develop an association between the use of a TNF inhibitor and the risk of developing peripheral neuropathy. As you know, TNF inhibitors have been linked to demyelinating diseases, multiple sclerosis, even optic neuritis. And the question is, could they cause peripheral neuropathy? Well, use of a TNF inhibitor is not associated with peripheral neuropathy, but when they looked at it in other ways, they showed that patients who were multiple users of TNF inhibitors that the relative risk rose from anywhere from three to four and that was significant.

So the question is, does repeated use of TNF inhibitors make for a higher risk of peripheral neuropathy or do patients who are severe enough disease to get repeated TNF inhibitors, meaning they're refractory bad disease, does that give you peripheral neuropathy? So again, is really muddied. Is it the disease or is it the drug? Again, I think that when you look at, and we've looked at this in the past, while TNF inhibitors have the publicized risk, the label risk of causing a demyelinating disorder, turns out demyelinating disorders happen with all the biologics and none is actually better than the other as far as safety. The ones that look the best are the ones that are newer biologics have the least amount of data.

This gets reported commonly. Is it part and parcel of rheumatoid disease or psoriatic disease? It's really not known. So again, this is a very murky area, and I personally would not stop a TNF inhibitor for someone who is developing peripheral neuropathy. Would look more towards the disease and other well known causes.

Another interesting study looks at the association between TNF inhibitors and sarcoidosis. You know, there's, do those drugs work in sarcoidosis? You know, the first line therapy, steroids, second line therapy, methotrexate, third line is said to be biologics including TNF inhibitors. Turns out the data isn't very good when I looked at it a long time ago. It was only good for really severe sarcoid, ocular sarcoid and whatnot.

Well, this meta analysis, 65 studies, five randomized controlled trials, over 15 patients basically says there's really no good data about the efficacy or utility of a TNF inhibitor specifically in sarcoid, specifically for etanercept, galimumab, and cerdulizumab. However, there is some evidence to suggest, albeit limited evidence, to suggest that infliximab may have benefits in cases of pulmonary sarcoid skin ocular CNS and multisystem sarcoid. A little bit less evidence for adalimumab with some efficacy in skin and ocular sarcoidosis. So I wouldn't look to this to be prime therapy for patients who have problematic sarcoidosis, because the data isn't very good. You can look at it yourself, but we have a link on the website.

Diabetics, you know, are actually at higher risk of developing hip fracture. Would they also be at higher risk of developing, other fractures? Well, meta analysis over five million people and fifty thousand fractures occurring in diabetics shows that there's a thirty percent increase in ankle fractures, the relative risk being one point three zero and that was significant, and a fifteen percent decrease in wrist fractures, relative risk of zero point eight five in diabetic patients. Turns out that these numbers are about the same that you would see with obesity. So it's probably mediated through that mechanism more so than being drug specific.

But again, diabetics may be higher risk of certain fractures now, not just hip but also ankle. Lower risk for lower risk for wrist. ASBMR reported a study in a 100 and fifty thousand individuals from Southern California and their use of bisphosphonates and the use of a drug holiday. Turns out that when I looked at patients who are on a bisphosphonate for at least three to five years and then went on a drug holiday, they showed that in the first year, there was a forty four percent reduction in the risk of atypical femoral fractures. Mind you, this risk is really, really low anyway, so a forty four percent reduction takes you from really, really low to forty four percent less, really, really low.

Meaning like these are one in a thousand kind of risks. Turns out that the longer the drug holiday between years one and four, the risk went down eighty percent. That's kinda interesting. The bottom line about drug holiday and bisphosphonates are that if you need the bisphosphonate, going on drug holiday is idiotic. However, if you're osteopenic or on the borderline, you've been on them for several years, it probably does make some sense to avoid these very unpleasant, very rare side effects of atypical femoral fractures and or osteonecrosis of the jaw.

We have two nice review papers on the website that we highlight an update on immune checkpoint inhibitors from, recent issue of JAMA. As you know, these checkpoint inhibitors are out there blocking CTLA-four, PD one or PD L one, and includes drugs like nivolumab or pembrolizumab. There's a whole bunch of other ones that are all part of that UMAB stuff that's going on. And we do know now that with widespread use of these and they have 14 different indications, these are major additions, have dramatically improved survival, a number of different and very difficult to treat cancers that there are these rare events where autoimmune phenomenon shown. Have This includes colitis and up to twenty five percent of patients on ipilimumab and less than five percent of patients on the PD-one and PD L1 monotherapy.

Pneumonitis two to two to five percent, cutaneous features up to thirty percent, very rarely including things like toxic epineural necrolysis. Patients with apophysitis, hypothyroidism, hepatitis, myositis, and myocarditis are out there. There's also a report in today or yesterday's New England Journal, was a nice debate about the use of medical marijuana. You should look at it. We sort of summarize it real quickly.

The doctor Benjamin Kaplan in favor of use of medical marijuana is someone who has refractory severe disease in the case that they presented to a patient who had complex regional pain syndrome and and was not responsive to narcotics. He says that, you know, these are proven regimens for the relief of allodynia and chronic pain. They could be used as a replacement for opioids. They may also alleviate the distress of not having a response. And it turns out that, again, for control of moderate and, for getting moderate analgesia, reducing allodynia, muscle relaxation, reducing stress, this was a good choice.

He was in favor. Against it, doctor Edgar Rose from the Brigham and Women's basically says, you know, marijuana's gone run amok. It's almost being talked about in 30 to 50 states right now. Problem is there's a lot of anecdotal information, not a lot of data. And he points out that the data in favor of efficacy and safety is quite limited.

Turns out that the effects of cannabinoids are roughly similar to that of codeine, and that the side effects are not, minuscule sedation, dizziness, dry mouth, dysphoria, short term memory loss. There are long term effects leading including psychosis and schizophrenia that you have to worry about in some patients. He points out that this particular patient that they presented as the example case had not received beyond her opioid therapy and all the things she failed. This patient really didn't receive a comprehensive program, which is the standard of care now that would include multidisciplinary pain management, psychologic therapy, rehab, pain specialty care, cognitive behavioral therapy, etc. There's a lot of other things that can be done in patients before jumping into cannabinoids.

The interesting thing about this particular debate, New England Journal actually had also a poll going from the readers, and when I did it, yesterday morning, it was only, it's not much more, almost 2,000 patients, but yesterday was twelve hundred patients or more. 70% of the readers favored the use of cannabinoids, in opioid refractory cases such as this. Very interesting. Well, that's it for this week. Make sure you go to the website to check out these citations and learn more about these interesting reports.

Come by, RheumNow. Come by our booth at C 12. That's right down the center aisle on your way to Amgen and AbbVie. You can see us. We're gonna be on your left hand side.

If you come by the booth, you can get a RheumNow pen. You can get the rheumatology card, laminated board certification, two sides, special printing. It's got everything you wanna know. You can get a handful of gout stop cards. This is for either for you if you wanna learn about gout or for your patients.

We have other treats, and and we have great people at the booth. We're gonna be doing some very interesting panel discussions in the booth. We're gonna be doing some interviews there. You'll learn if you just stop by our booth. We'll see you at ACR.

Travel safe.