RheumNow Podcast Dos And Donts In Spondylitis (9.5.19) Save

This is the Room Now podcast for 09/05/2019. Hi. I'm doctor Jack Cush, executive editor of rheumnow.com. This week in the news, alcohol being the straw that breaks the camel's back in ankylosing spondylitis, Sort of a bad pun. What about a phase twothree turnaround for a new lupus drug?

And there are new drugs and there's a new approval and a new approach for patients with ankylosing spondylitis and axial spondyloarthritis. Let's start with a discussion on gout and the utility of dual energy CT scans to identify urate deposits. That's deck scanning. The question is, where do they fit? Turns out they haven't seemed to perform all that well in making the diagnosis of patients or in fitting into classification criteria.

In this one particular study, they looked at a cohort of almost 90 patients who had undiagnosed mono or oligoarthritis and saw what the utility of Dex scanning was going to be. It turns out that Dex scans did not add to the ability to classify patients as having gout, Did not add anything over usual clinical criteria such as history, uric acid elevation or identification of MSU crystal. So, thus far this seems to be a good research tool, maybe not one for regular use. We need more research on this. Sugar free or sugar drinks, are these good for you or not?

Well, an impressive study, impressive by numbers, almost a half billion people from 10 European countries were studied and looked at mortality rates according to how many soft drinks one consumed. Turns out that having an increased amount of drinks, soft drinks, two or more per day was associated with an increase in all cause mortality in this very large cohort. The question is, what kind of soft drinks? Well, if they were sweetened soft drinks, it turns out that sweetened soft drinks, high fructose sugars containing soft drinks, was associated with almost a sixty percent increase in digestive deaths. That was very significant.

It turns out that artificially sweetened diet drinks was also associated with significant risk of deaths, in this case, circulatory deaths, with about a fifty two percent increase. Now, is it the NutraSweet that's killing people, or is it the NutraSweet that's a sort of surrogate marker for people who probably have unhealthy lifestyles and are thinking, I can offset the nutritional value of two slices of pizza with a diet coke and I'm breaking even. Well, not really. Diet coke is really a marker for unhealthy lifestyles would be my guess. But, soft drinks are not a good thing in one's diet.

An analysis of smoking and RA, you know, there's a lot of data that says RA certainly can be worsened by smoking, that increases the risk of smoking, especially in people who have a shared epitope. And the question is, what if you took smoking away? Would smoking cessation lead to better improvement of RA? Turns out a Cochrane review on this subject, pretty extensive, found almost no studies that really dealt with it. Two studies that dealt with it, and even they didn't look at it very well.

Very few patients have been studied in this regard. This would be a great project, a very quotable publication for anyone that wanted to make a big name for themselves. Look at whether smoking cessation not compared to not, or some other control group would lead to better outcomes and improvement in clinical parameters of RA, work on it. It's your next ACR project for next year. A study of ankylosing spondylitis patients looked at the association with alcohol and ankylosing spondylitis.

I thought this was odd, but a study of two seventy eight axial spondyloarthritis patients, they divided them up into those who were alcohol drinkers and those who didn't consume alcohol. And it turns out that alcohol consumption was associated with an increase in spinal progression as measured by the MSAS scores. And this was over, I think, a two or three year, two year period. So, if you had a greater than two unit change, that was felt to be progression. And again, was seen in sixty percent of alcohol drinkers, but only twenty nine percent of those who didn't drink alcohol.

Again, this is a surprising first time finding. Is it possible? Well, if you look at the history of ankylosing spondylitis and axial spondyloarthritis, alcohol does seem to play a role in progression. It does seem to play a role in death. Patients with ankylosing spondylitis are more likely to have alcohol related deaths and accidents than other people, and that was sort of a strange finding.

It's possible that this is not just alcohol as a lifestyle issue, but there might be something to alcohol in leading to progression. Now, know alcohol to be sort of an anti inflammatory therapy, not prescribable by the way, but it does show in peripheral arthritis to be somewhat protective. In axial disease, not so much. What's the value of vasodilator therapy in patients with systemic sclerosis? Well, clearly we know it reduces the risk of renal crisis, reduces the risk of renal demise and other bad outcomes.

A study of six zero one patients with systemic sclerosis, four forty eight on vasodilators, one hundred and fifty three not vasodilator therapy was associated with a lower risk of arrhythmias, especially ventricular arrhythmias, and that was protective. It also looked at aspirin. Patients who had aspirin use in systemic sclerosis had fewer heart block and had fewer need for pacemakers in the future, suggesting that these probably should be a part of scleroderma therapy. Know, we don't know what to do with scleroderma. We're looking for the next great drug.

Know, maybe tocilizumab will be approved for stomach sclerosis, maybe not. But, you know, right now we don't have anything. The way I treat my patients, everybody goes on low dose aspirin, everyone goes on a low dose of a statin, everyone should be on either a calcium channel blocker or some other form of vasodilator therapy. And I'm waiting for the next great hope. Lupus patients we know do well when their disease is doing well and they get pregnant.

Their pregnancy outcomes are good. Hence what we often do is we keep them on therapy to keep them stable. We certainly know from past research that hydroxychloroquine is highly effective in pregnancy and in lupus. Better pregnancy outcomes, less APS problems. I mean, it's just sort of the great tonic for lupus, especially during pregnancy.

In this one particular study that we quoted this week, three seventy six pregnancies in two eighty four women, hydroxychloroquine was used in about a quarter of patients prior to pregnancy. I'm not sure why it's not closer to one hundred percent of patients prior to pregnancy. But then during pregnancy, discontinuations were very frequent. Seventeen percent in the first trimester, thirty percent in the first trimester, ten percent second trimester, twenty six percent third trimester. But, you know, it's just sort of surprising that most people haven't caught on to the fact that most people with lupus should be on hydroxychloroquine.

There's almost very little downside. And that if you're pregnant, you should be on it and stay on it throughout the pregnancy. Other good news for lupus patients came this week with anifrolimab. Anifrolimab, as you know, is a drug that's been in development in phase two and phase three trials. It is a type one interferon inhibitor and it's being developed for lupus.

As you know, the first anaprolimab study, a phase two looked fabulous. Reported by Doctor. Furey and colleagues at EULAR two years ago looked great. Earlier this year, the phase three studies came out and boy, they did not look good at all. They failed to meet their primary endpoint.

They looked good in a few things, but not most things. Not an uncommon story. Looking great in phase two, failing in phase three. Well, they report their second phase three trial this week. No exact data, but in this phase three trial, a fairly large phase three trial with a week fifty two outcome, AstraZeneca reported that it met its primary endpoint, which was a Bicla endpoint, and they expect to present this data at an upcoming medical conference.

I assume it might be a late breaking abstract at ACR. I don't know that to be a fact. I have no inside information, but look for that. This is good news. I think that a lot of people had a lot of hope for anaprolimab and what it may do in lupus as adjunctive therapy.

So, we have a number of biosimilars. As you know, I think in RA we have 28 biologics for RA and I think that 19 of them are biosimilar. Actually, it's 28 approved therapies. I think 19 of them are biologics. I think 10 of the 19 or nine of the 19 are biosimilars.

Yet, we're not using that much in the way of biosimilars. One of the first ones approved was CTP-thirteen, which was called Inflectra here, REMSMA in Europe. And this comes from Celltrion And it's been out on the market and seems to do well in Europe and in The United States. Now, the drug CTP-one hundred thirty or REMSEM is being developed not as an IV Remicade like therapy, but as a sub Q therapy. The data was presented at EULAR, forty eight patients.

The data between the sub q and the IV version was exactly the same, comparable. This is sort of exciting new news. I think we mentioned this during EULAR, but I put it up because it's interesting. When you take an IV therapy that is approved for the originator drug like Remicade and then the biosimilar drug like CTP-thirteen or its multiple versions including Inflectra, you get all the indications, right? You just do one study, you get all the indications.

But it has to be used and dosed the same way as it is in RA therapy with the originator drug. But here, they're making it a subcutaneous therapy. So, they're changing the way it's being used. Can this drug be approved as subcutaneous therapy? It turns out it can.

Happened earlier this year. The breast cancer drug Herceptin has a biosimilar approved as an IV biosimilar as Herceptin is. Also recently approved in March as a sub q. You have to go through some extra steps, but you don't have to develop this as a brand new biologic. I think this is an exciting advance.

So, maybe look for that in the future. Another interesting study that we reported earlier at one of the big meetings, but now comes out in publication, is the INTRACT study. It compares tocilizumab to etanercept in looking at cardiovascular risk. They took patients with seropositive RA through over 3,000 patients and gave them open label, and they also had to have a cardiovascular risk factor to get in, by the way. And they gave them either etanercept or tocilizumab as open label therapy and they looked at cardiovascular event rates.

Turns out that they were about the same. As you would expect, etanercept had no increase in lipids, but the reason they're doing the study is tocilizumab and other IL-six inhibitors do increase lipids. In this case, about a 10 to 13% increase in LDL, HDL and triglycerides compared to the TNF inhibitor. There was one hundred and sixty one MACE events, about balanced between tocilizumab and etanercept. Hence, the hazard ratio for MACE event with tocilizumab was really 1.05.

No different than etanercept. So, these are the similar outcomes. There's no increased risk of cardiovascular outcomes in a drug that may increase lipids. That's a surprising finding. But a consistent finding we're seeing now both in open label claims based studies.

Turns out in this study there were a few more adverse events in those on tocilizumab compared to eshanercept, a few more SIEs, 4.5 versus 3.2 events per 100 patient years, and eight versus one gastrointestinal perforations, tocilizumab versus etanercept, but that was not significant. So, again, this is a positive, study. It tells us a lot about the safety of using tocilizumab and that we don't have to worry about an added risk for cardiovascular events, especially when given to patients with cardiovascular risk factors. As we reported at the beginning of last week, ixekizumab or Taltz was approved by the FDA for use in ankylosing spondylitis and radiographic axial SPA. This is based on their studies that were done phase two and phase three.

You know, the company reminds us there's one point six million Americans who have ankylosing spondylitis and the shocking statistic that only fifteen percent of such patients are receiving biosimilars. There is a sort of an unmet need there, probably more patients. Yes, ankylosing spondylitis and spondylitis does get better with nonsteroidals, but there's a lot that don't. Certainly a lot more than are currently on just on the nonsteroidals. So, there is no box warning for this drug.

As usual, warnings for TB and serious infection and of course you know about the risk of colitis that can happen either worsening colitis or de novo new IBD occurring in patients who receive IL-seventeen inhibitors. The last report is from the ACR Spartan, new guidelines and recommendations for treatment of ankylosing spondylitis and non radiographic axial spondyloarthritis, non radiographic axial spondyloarthritis, for which only UCB has done the work, but there'll be more companies looking for that indication coming up. Again, that's the surprising thing. There's guidelines here for non radiographic axial spondyloarthritis. And the algorithm is nonsteroidals first, TNF inhibitors second, TNF inhibitors before IL-seventeen inhibitors, IL-seventeen inhibitors before JAK inhibitors like tofacitinib.

Now, they included a discussion of tofacitinib when there's really no likelihood or in my opinion that TOFA will be, or any JAK inhibitor will be approved for spondyloarthritis remains to be seen. But I guess because there's been some work in the area, they included it in the list. Tune in and check out the reference to see the guidelines as they're being put forth from the ECR and SPARTAN. So, that's it for the Room Now Weekend Review, the Room Now podcast. You can go to the website, click on the links and find out more information on these exciting studies.

We'll talk to you next week. Take care.