RheumNow Week In Review - Do You Dig Shingrix%3F %284.13.2018%29 Save

Hi. It's the 04/13/2018. This is the RheumNow we can review. I'm doctor Jack Cush, executive editor of roomnow.com. This week, we have a lot of questions, a lot of talk about Shingrix.

And the question is, do you dig Shingrix? What in the world is Shingrix? What about maybe the most important study done in lupus this year, the Symbio study? And then why is rheumatology gonna get a lot harder by 2030? All this and more.

At the top, we have an interesting study about PPIs and rheumatoid arthritis. We did a review about PPIs because there's a lot of negative reports about the safety of proton pump inhibitors in general, but obviously we use a lot of them in our arthritis patients. And there's a lot about osteoporosis and the risk of kidney disease and a number of different things. It turns out many of warnings around PPIs are really rare, rare events, and hence really shouldn't call into question their safety unless the drug really isn't needed. Well, is an interesting study because it looks at a very large cohort of RA patients and matches them four to one, one RA to four controls not on PPIs, and looks at the risk of developing acute kidney injury.

And again, this is sort of an outcome study, not a lot in between, but nonetheless, it is shown that if have you rheumatoid arthritis and you're on PPI chronically, that you have a doubling of your risk of AKI, acute kidney injury. And the thing though is that it's a rare event, meaning that if you were on a PPI and had rheumatoid arthritis, the risk is two point two events per one thousand patient years, two point two per one thousand people. If you weren't on a PPI, your risk was zero point nine. So there's a doubling of the risk and that seems significant, but the risk is really low. The bottom line is if you need the PPI, you should probably be on it.

If you don't, this is a good reason maybe not to take it. Interesting data comes about, about early arthritis coming from The UK. Two cohorts over there over there, one in the Leeds Early Arthritis Clinic, the other one's called the ERAS study. And these are very large cohorts, one has four fifty four patients, the other one has eight ninety five, over thirteen hundred patients. And they looked at the outcomes of these people over time, specifically looking at how many achieved DMARD free, drug free remission.

Turns out, it wasn't nearly as great as you think it might be, given that they're early RA, they may have undifferentiated disease. Still in these two cohorts followed longitudinally, the risk of having DMARR free remission goes fifteen percent in the lead study and only nine point four percent in the ERAS study suggesting ten to fifteen percent will go into remission. That's kind of the number you should be quoting, in an early arthritis patient anyway. The risk of actually developing remission was seen most in those who had an acute onset, a short symptom duration, non smokers, and those that didn't have extensive x-ray damage, presumably erosions at the outset. And lastly, course, seronegativity.

They'd also looked at shared epitope and those who did not have the shared epitope alleles that we see on HLA, you know, the old Doctor four alleles, those also probably had a lower risk of developing of if you did not have those, you had a better chance of going into drug free remission. Shingrix, it is the new, approved, FDA approved vaccine for shingles. What is different from the old vaccine, Zostavax, that was a live virus vaccine. This is an inactive vaccine. It was approved this year, endorsed by the FDA, a marginal endorsement by the ACIP of, you know, like seven to five votes or something like that.

But nonetheless, the interesting data is that it has captured ninety percent of the shingles vaccine market, meaning that Zostavax really has taken a hit with the introduction of this new drug. Now it is about the same cost. They're both available. Virus, one is not. That's the Shingrix is not.

And it is indicated for those over the age of 50. It has to be given as two injections. The first one, the second one has to be either after two, but less than six months after the first. And again, it is more effective than Zostavax, the live virus, a lot more effective, especially in the elderly and not only as far as protection, but also in the prevention of post herpetic neuralgia. But it does have more nuisance side effects, more, you know, aches and pains and fevers and flu like stuff.

It does have the advantage of being, able to use it in patients on biologics, which you can't do with Zostavax, but you could do with Shingrix. Problem is it hasn't been studied and the company doesn't have any intentions of studying it. Although there are many of us, like Len Calabrese, myself, know, Bing Bingham and Jeff Curtis, all the vaccination guys who know a lot about the shingles data have all made pitches for this drug to be studied in our patients to learn more about it. Again, I would probably use it somewhat on a biologic if I needed to. But again, the question is, it's two shots versus one.

It's about the same money, maybe a little bit more, but really about the same cost. The coverage is about the same. You could use it in more people, but it's got more side effects. So the question is, do you date Shingrix? At least as far as sales, it's dominating the market.

We don't know what it's doing in rheumatoid arthritis in the rheumatology space. Interesting data comes from Ireland where there's actually new laws about developing new care centers and streamlined care for pediatric rheumatology patients. Unfortunately, this hasn't yet taken place and they've seen a significant delay in, pediatric, patients getting in to see pediatric rheumatologists. There's right now nine zero two patients waiting for an appointment with a rheumatologist, pediatric rheumatologist, whereas it was only three zero two in 2017, a year ago. So there's a delay in this and the bottom line is that they're having a problem there in getting their pediatric rheumatology patients seen by the pediatric rheumatology specialist.

Guess what? The same thing is I think going on here in The United States. If you review the data about the availability of pediatric rheumatology in The United States, it's abysmal. I mean, it's a geographic maldistribution. There is, you know, eight states with one, I think it's five states with one pediatric rheumatologist and eight states with none at all.

There's a lot in Southern California and New York, but everywhere in between, it's really, really suffering. So we need more pediatric rheumatologists, we need more adults to take on the responsibility of caring these kids because there's a lot of kids who do need care here in The United States and also in Ireland. Interesting data comes from one of these advocacy groups that looks at pharma spending, and they just released data about the pharma spending habits when it comes to patient advocacy groups. In 2015, pharma gave $116,000,000 to, groups like the Arthritis Foundation, the Crohn's and Colitis Foundation, etc. And some wonder whether or not that's a conflict of interest.

Interestingly, there's one group that's called Patients for Biologic Safety and Access, and not surprisingly, they oppose the introduction or the forced use of biosimilars, and they've received $9,100,000 from drug companies who stand to gain from such a stance. There's a lot of money being thrown around here and we'd like to think the nonprofits are behaving in a responsible manner. But that's sort of what those reports about. And if you want to read more about it, there's links and you can follow the numbers and build your own conspiracy. What about lupus and the risk to lupus patients?

Well, an interesting study looks at the comorbidity burden. This actually comes from Leslie Crawford's group at Vanderbilt University, where they have a novel way of looking at the phenome, meaning the way the disease is expressed, in a large number of individuals that they've tracked using electronic health records, like almost 2,000,000 people and whatnot. They've narrowed it down to a few 100 patients with lupus and specifically looked at lupus patients who are African American, those were Caucasian, and then African Americans who didn't have lupus. And what they found was that African Americans have a significantly higher burden of comorbidities compared to the comparator groups. In fact, there's like somewhere between a four and tenfold increased odds of having, both cardiovascular disease, renal disease, and infections suggesting that this is a population, we know this population has more aggressive disease than does Caucasian disease.

But again, it's the comorbidities that may kill them as much as lupus may kill them. I always like to say that for lupus patient gets admitted to the hospital, it's more likely they're there for a medical reason than for lupus unless it's a CNS presentation. That just means really that there's a lot of comorbidity that happens in lupus that we need to be aware of and we need to develop preventative strategies towards. Well, the SymBio study, I teased about this at the outset. This was probably the most important and impactful paper that was presented at EULAR in 2017.

This is a group from Leiden University in The Netherlands and what they did was they took an interest in trying to figure out why lupus patients get the manifestations that they do. That they do know from studies that immune complex drive a lot of auto reactive B cells and that there's a lot of NETosis going on and NETs lead give rise to auto antibodies including ANAs and whatnot. And they think that this could be tied in with the pathogenesis of the disorder. So they set out to affect the outcomes by trying to target these auto reactive plasma cells, by giving patients who have very severe refractory lupus, rituximab at the outset, two infusions thousand milligrams two weeks apart, followed by regular infusions of belimumab given over a six month period. So they put this to the test, were looking at clinical outcomes, safety outcomes and immunologic outcomes.

And the results were astounding. These people had really severe disease, mean, gigantically severe disease, they had an average sleet eye score of 18. To put that in perspective, to get into a lupus trial, have to have a sleet eye score usually of more than four or more than eight. They had an average of 18. They were all on mycophenolate, had failed other therapies, and they go on the study on and sixty milligrams of prednisone and then the Rituxan followed by the Balimumab.

So in the end, at the end of twenty four weeks, were significant reductions in auto antibodies, significant reductions in in vitro net ptosis activity as again measured in vitro. And then they also had, you know, no new safety signals, but the numbers that they saw were astounding. Sleet Eye went down from an average of eighteen to two. Eighty percent of people were able to achieve a low disease activity state in lupus. You know, more than half these patients had nephritis and proteinuria dropped dramatically.

Almost everybody was able to drop their corticosteroid dose significantly. Almost everybody was able to go off of mycophenolate. Again, the results were astounding. There were some mild infections, there were three cases of hypogammaglutidemia. This is dramatic.

Of course, it's also uncontrolled. These were really severe people using two drugs that I must say I'm not a big fan of because, you know rituximab trials failed in spite you all thinking that rituximab is a miracle drug in lupus. There's no data to support that really other than the state I'm showing you here. It's a lot of collective open label experience with a reporting bias and this too could be a reporting bias. Also, belimumab, the margin of benefit in belimumab is small compared to those on placebo.

And then who do you give belimumab to when you don't know what else to do? I don't like these. Anyway, these investigators found what seems to be a really smart use of the drug. Turns out when you give rituximab, there's a gigantic rise in circulating bliss. It turns out then if you inhibit that with belimumab, that goes way down, patients get better.

We need to see more studies like this. This is a I think a very important trial. Also important is the finally published ACR Manpower report that's published in this month's Arthritis Care and Research. And it's a very important study. It tells us that right now as of 2015, we are operating in a deficit.

When you look at the current supply and demand, looking at full time employees, FTEs that are capable of taking care of patients, that includes rheumatologists, but also, advanced practice providers like physician assistants and nurse practitioners, that we are down seven hundred right now. Then with an aging population, with the, a growing number of people with arthritis and the retirement of many white 60 year old rheumatology, hey that's me. No, I'm not retiring. A tsunami of older white rheumatologists retiring. And then along with a shift more women going into the marketplace and they but they may not work a full year.

What if they have a child and took time off for their families? Less men, more foreign graduates. There are geographic distribution problems here. We're going to be down in 2030 by over 4,000 rheumatologists to provide the current care that we're supposed to be providing. So this is a big issue and one that the College is going to have to tackle and you as an individual need to think about and talk to your leaders, talk to your friends.

We need to solve this because I want rheumatology to continue to be an incredibly attractive discipline to go into. And we need to make it attractive. We need to make it as as interesting and scientific and as touchy feely as it is and why we all love it. Lastly, a report from Megan Claus and a number of investigators, which if you read all of them in the middle of some guy named Cush, that talks about the collective experience with cerdulizumab in women exposed to cerdulizumab during pregnancy. As you know, was a preliminary report that came out with a few 100 cases, already in publication.

This is a follow-up report, that looks looks at over eleven hundred cerdulizumab exposed pregnancies for which they have great data on five hundred and thirty eight known outcomes. Eighty five percent live births, eight percent miscarriages, elective abortions in five percent, zero point nine percent or only five stillbirths. All in all, there were eight congenital malformations for a rate of one point seven. You know, a general population, that number is hard to come by, but it's about three to six percent of normal people having supposedly normal children. Again, three to six percent congenital malformations are seen.

So this is below even that seen in the normals and they did compare these results to normals. There are no other controls to look at. Of these patients that were exposed, the vast majority were for Crohn's disease and rheumatoid arthritis, a few hundred each. The vast majority eighty one percent had first trimester exposures, but, nearly half forty four percent or so had exposure to cerdulizumab throughout pregnancy. That tends to happen more in Crohn's disease than it does happen in RA.

But this is very encouraging data, that's come out about cerdulizumab and again it's used in women who wish to become pregnant, and its safety. I guess that means we have to sign off. See you next week at RheumNow.