RheumNow Podcast Drug Ad Transparency (6.7.19) Save

It's the 06/07/2019. This is the RheumNow podcast, and I'm Doctor. Jack Cush, executive editor of rheumnow.com. This week in the news, low remission rates from TNF inhibitors. Is that possible?

Next, drug ads are about to get uglier. And lastly, stem cell clinics, they're getting slapped around by the feds. That's our first report. We talked about this week the two announcements from the FDA that they have gone after these stem cell clinics. As you may have noticed, these clinics are sort of rapidly proliferating.

The whole field of regenerative medicine has become a sort of a scam. Most of these stem cell therapies that are being done are not true pluripotential cells, but instead are the patient's own cells, including fat cells that are being extracted, spun down, tricked up and injected back into the patient usually for a good cash dollar. Well, the FDA is very concerned about this. They've actually been watching it and then this week they came out with two different sort of actions. One sending an untitled letter to a group of clinics called R3 Stem Cell.

An untitled letter is sort of like a mild warning letter, but nonetheless it's coming from the FDA, warning these people that their claims of birth tissue products that are helpful for all kinds of ailments from lumbago to God knows what else are without scientific merit and need to stop. And then the FDA was also involved in a legal case and it's against The US stem cell clinics and they were won the case basically because the clinic was sort of found guilty for promoting again adulterated and misbranded stem cell preparations. Supposedly, this was in Florida, three patients ended up blind from these therapies. So again, it's good to know that the FDA is watching these therapies. I would strongly recommend against most of this and there really is no science behind it.

So is transparency finally coming? Will drug prices really be on TV? Well, looks like it's going to happen. The Health and Human Services led by secretary Alex Azar and the Trump administration has finalized regulations that now say drug companies who advertise drug ads on TV will have to disclose the price of medications especially if that medication is going to cost the patient more than $35 a month. So you can imagine what's going to happen.

All these blockbuster drugs, especially the biologic drugs, are gigantically expensive and they're making a lot of money with direct to consumer advertising DTC. Well, know, it used to be that these ads were confusing because they look good, patients were skipping through the fields of Lilly and smiling and eating tortellini with their family. And all the while the language says death and mayhem and greasy diarrhea are going to happen. So it's sort of confusing the patients, especially people don't even have these diseases. But now it's going to get more interesting because also in all that lawyer droppings as Artie Cavanaugh calls it, is going to be the price of the drug that's going to inform the public just how expensive these drugs are and why they can the companies, I guess, can advertise them regularly.

It's gonna be an interesting, year ahead. An interesting study comes from Korea where they looked at the risk of opportunistic infection in RA patients, especially new incident cases of rheumatoid arthritis. They use their national claims database to analyze this risk, and they showed that the risk of opportunistic infections which they define the study was actually higher in patients with early RA, fourteen percent higher, not a big bump, but surprising that would happen at early RA. You assume that the bad things that happen in RA usually are established disease, long standing disease, highly immunosuppressed individuals, and many early RA patients are, usually treated aggressively. Well, could be that these opportunistic infections are occurring because patients may not be getting treated early, or may not be getting treated early and aggressively.

The infections that they noticed here were specifically a zoster risk twelve percent increase and a candidiasis risk at twenty two point four fold increase risk. Risk factors for developing an opportunistic infection include advancing age, higher steroid doses, comorbidities, all of them contributing to the risk of these kinds of infections. Again, the risk here of opportunistic infections usually like one in ten thousand or certainly more than one in a thousand, usually around one in ten thousand, three in ten thousand, that sort of thing. So these are relatively rare events. The CDC came up with new guidelines this week about, TB testing only in health care workers.

I thought it was interesting. It might be a useful read to you if you would like to follow what's going on with TB testing. They do say, as you would expect, all health care personnel need to be tested for TB and that usually can be a skin test or it can be a QuantiFERON or an IGRA, Interferon gamma releasing assay. But what they is a little bit different on this one that I pointed out is that for people who have otherwise low risk after undergoing a TB risk assessment, there is no need for ongoing annual testing or serial testing for TB in the absence of increasing risk, exposures, etc. So this is sort of important for you and as you consider how you manage your patients with biologics who need TB testing, this idiotic policy that says that you need to have annual testing, that's just plain wrong.

Again, there's no need for it. It was first advocated by the American Academy of Dermatology for psoriasis patients. I don't know what data they were looking at, but it makes no sense to do annual testing. It does make sense to do testing, repeat testing when risk changes, meaning exposure, travel to a foreign country, exposure, etc. I think it makes sense to do a second test after the first test was initially negative because there is somewhere between a five and ten percent risk of patients who were previously found to be negative at inception upon retesting are found to be positive suggesting that some of those people had were anergic meaning that inflammation that was making their test negative when in fact they should have been positive when you corrected their inflammation they got the ability back to generate gamma interferon or even a skin test.

So again, once maybe twice and only when risk changes. That's how it should work for patients. For us healthcare workers once is maybe all you need. An interesting report came out about metformin use in a mouse model of Sjogren's syndrome. This is the, NOD, mouse that actually has, examples of salivary inflammation, salivary flow is decreased, etcetera.

Well, when they gave these these mice metformin, have you ever seen the size of a metformin pill? It's actually about the size of a mouse's head. So I'm not sure how this is gonna work out in the lab, but I'd like to see that video. Nonetheless, when they gave metformin to these, this mouse model, they actually had a reduction in salivary inflammation by histologically, an improvement in salivary flow, and reductions in IL six TNF and IL 17 levels by mRNA assessment. So again, by affecting supposedly, t effect, suppressor suppressor effector t cells and b cell differentiation, they showed improvement in these mice.

Well, I don't know about you, but nothing seems to work in Sjogren's in my adult patients, and I don't think my adult patients are going to approximate the biology of these mice. But nonetheless, this is nice biologic information. It is far far far far far from being applicable to adult patients with Sjogren's. I mean, how many are already on metformin? Has no one observed this in their clinic?

You might want to look at this if you have a large cohort and have some time on your hands. The UK clinical practice database is often used to assess a number of different outcomes. It's a reliable general practice database of hundreds of thousands of patients. In this particular survey, they looked at match pairs of sixty two thousand patients who had a history of gout and those who did not have a history of gout and they specifically looked at the issue of venous thromboembolic events. That's right DVT, pulmonary embolism, etc.

And in this particular study, they showed that there was about a twenty five percent increased risk. And it was a significant increase in gout patients compared to non gout patients. And this was by the way not affected by those who were taking urate lowering therapy such as allopurinol. And the other strange thing was it was mainly seen in outpatients, was not significant when they looked at inpatients who had gout versus those who didn't have gout. But maybe the sobering statistic here is not that there was a twenty five percent increase in gout, maybe you could suspect that because inflammation drives VTE risk, but that the numbers were relatively low.

The event rates were zero point three seven versus zero point two seven per 100 patient years. That's about what the background population risk is in you and I. You know, RA patients are up to point six and then when it's a drug effect, it's gonna be like much higher than that one point o per 100 patient years. So the numbers were modest, maybe it reflects The UK population, but it was increased. It's not unexpected but I put it out there because a lot of talk about VTE these days and who's at risk.

We do know that patients with inflammation, and that's RA and spondyloarthritis and psoriatic arthritis even lupus patients etc are at risk certainly cancer patients, hyperviscosity patients, other risk factors for, thrombotic disease, but gout, could they be on the list? The British Biologics Registry is an important registry. They have over fourteen thousand RA patients who've been started on TNF inhibitors starting I think in 2001. They did a recent analysis of their patients who were started on TNF inhibitors from 2001 to 2013, looking at the number of people who would develop what they called sustained remission or sustained LDA, low disease activity state, as determined by, the cutoffs with a -twenty eight ESR. The bad news is here that, and again the sustained remission meant that it had to be, more than two consecutive visits, more than six months of achieving remission numbers, or, low disease activity state numbers and that this will happen within a three year period.

So maybe it's a little hard because you have to do it more than one visit and sustain it for six months, but the numbers were not good. The numbers were fifteen percent of RA patients have a sustained remission and twenty six percent get LDA. So all combined, that number I guess could be thirty, forty one percent. But that means there's a lot of people on TNF inhibitors, first TNF inhibitors who in fact are not achieving a really good response. Again, this started in 2001 and ended 2013, maybe they're doing better today, but some of the things that you could take from this one the predictors of who was going to achieve a remission or an LDA, was those on adalimumab compared to etanercept.

Patients with high patient global scores or high patient, swollen joint counts, not tender joint counts, swollen joint counts, non smokers, never smokers and those who went on combinations of methotrexate and TNF inhibitors. Inhibitors. The interesting thing is that during the period of the study from 2001 to 2013 there was an increasing rate of those achieving remission LDAA. So those achieving remission went up from fourteen percent to twenty two percent by 2013. At the same time, methotrexate use also increased from fifty six percent to sixty four percent by 2013.

And maybe good news, but maybe not, was that there's a shorter time from rheumatologic consultation to the initiation of a TNF inhibitor, a 40% reduction in time. However, it went from ten years from consultation to biologic to six years and that's not good at all. But then again, this reflex went on in the last fifteen years rather than today. Hopefully we're doing better. Really controversial data comes from actually the UK rheumatology meeting that was held recently and an abstract that was presented there.

I made it a feature article because I think it's kind of novel. Pro inflammatory diets can actually increase CRP levels and increase the risk of developing rheumatoid arthritis. There's a lot out there that the pro inflammatory diet is high in carbohydrates, in gluten, etc. The paleo diet, Mediterranean diet, gluten free diet, those are anti inflammatory diets and you know there's a lot of nonsense talk about this but then again maybe it works. I actually recommend this to my patients who have psoriatic or spondyloarthritis, diseases.

Not so much in my hands seeing anything in my RA patients or newly diagnosed RA patients. Anyway, this particular study was novel in that it looked at a large cohort, I think the number is 25,000 patients entering into what was called an epic database. Epic was a sort of cancer prospective study, and as part of that study at baseline, they made them do, a dietary survey. The dietary inflammatory index was calculated from that, the DII. This is a calculation that says that certain substances may provoke, pro inflammatory biomarkers so that you could come up with basically a measure of an inflammatory or non inflammatory diet.

Then they took their 25,000 and cross referenced that with the NOR database, it's an early RA database in The UK, and they found a hundred and fifty nine new cases, incident RA cases, and looked at the influence of diet on developing RA. Now they know from other studies that were done that, diets that have high DII scores, pro inflammatory diets are capable of increasing CRP levels and increasing IL-six levels. And then when they applied the same score and compared the upper quartile to the lowest quartile, they showed that the risk of developing RA was actually increased in those who had the highest quartile of inflammatory design and it was a ninety percent increase in the onset risk of RA compared to those who, didn't get RA. So the bad news is that when they adjusted this for age, sex and BMI, the significance of this which was less than point zero one was now lost and now as we had was an odd ratio of one point three five or thirty five percent risk risk or a trend for for such a risk, but it was not significant with a p value of 0.2. So I think it's interesting.

We may see more about this in the future. Lastly, I'll throw it out there that the FDA had a public hearing on CBD oil. Cannabidiol, as you know, is out on the market widely, metastasizing throughout our cities whether it's legal or not. Again, supposedly safe because it doesn't have the high associated with cannabis and that's because there is no THC. In fact, actually you're allowed to have up to 0.3 THC in the CBD oil preparations.

Again, this is a product of the concern by the FDA, former commissioner Gottlieb, new commissioner Sharpless, talking about unregulated, these drugs are really unknown, and are they food drugs? Are they drugs? Are they food products? Again, they're concerned about that. And so they had this hearing.

It was an open public hearing. There were a number of presentations by academicians and researchers, but it was an open forum. All the companies, all the patients, all their negative stories, all their positive stories were aired out. And again, it's hard to say where this is going. What you need to know from this is that in the last from 2014 to 2017 CBD product sales increased up to tripled up to 367,000,000 in sales in 2017 and it is estimated that in the next six years by 2025 it's going to be a 16 to $22,000,000,000 market.

The reason this has had its surge is that Congress passed the bill I think it was in 2018, that basically made growing hemp an okay thing. Somewhere back in history the legislature outlawed hemp and you know I believe someone told me that the Declaration of Independence is written on hemp. Oh, was all the people who are making paper mills and paper products and cutting down trees and it's like the, I don't know who did it, the rich people from the early parts of this century, the Astors or God knows who, but they lobbied hard and had hemp taken out of the mix so that trees became the product for paper. Well, hemp and all the things that hemp can do have been illegal until this bill was passed and now it says that hemp it's a free for all. You can grow all you want as long as the product contains less than 0.3% THC.

As you know, the claims around around this are sort of nonsense, ridiculous, anxiety, Alzheimer's, fibromyalgia, pain, again, lumbago, itchy teeth, Lord knows what else. They heard from a large number of people. There is no takeaway from this at this point. The FDA is taking it in. They'll probably convene another meeting before they act on this, but they heard from mothers and marketers, researchers, business people and consumer advocates who were both for it and against it, lawyers, academic researchers.

The only thing that came out of this as a certainty is that the FDA reinforced the point that CBD oil is not to be allowed in food, drinks and or supplements. And again, it's now being I think judged as a food supplement not necessarily a drug. We'll see where this goes but again that just happened last Friday on May 31. That's it for this week at RheumNow, make sure you follow us next week we're going to be at ULAAR having some limited coverage of the meeting, we'll be broadcasting, publishing, doing podcasts and a whole bunch of videos from Wednesday, Thursday, Friday and the Saturday, last day of the meeting, we'll actually publish on Monday, the June 17. Tune in.

Talk to you next week.