RheumNow Podcast - Corona Increases RA Risk (3.13.20) Save

It's the 03/13/2020. This is the RheumNow podcast. Hi. I'm doctor Jack Cush, executive editor of rheumnow.com. Today is RheumNow live day.

You can tune in by going to the website roomnow.live and register and consume the online content half day on Friday, all day Saturday, Sunday morning, sixteen hours of CME, you can be there. This week, a number of interesting reports. Let's start with a report about, TYK2 inhibitors and their potential role in spondylitis. Bob Inman has a very nice report in, I think it's Journal of Clinical Investigation, and it shows that TYK2 inhibition could be the next new big thing for patients with spondyloarthritis and ankylosing spondylitis. He points out in that report that patients who are treated with TNF inhibitors, the AS patients, you know, there's not a lot of evidence that they are good at retarding x-ray progression in spondylitis.

For that matter, there's not a lot of great evidence that even IL-seventeen inhibitors will do that. There is some, but it's not consistent, it's not overwhelming, and of course the problem is it takes a long time to develop X-ray changes and most of the studies done thus far have been short term. So his investigations were getting at the root of maybe why we could do better by having other targets other than TNF and IL-seventeen. And using an animal model, including a knockout model of a TYK2, they showed that by inhibiting TYK2, you can block IL-twenty three and also the production of IL-twenty two that could not only leads to clinical improvement, but also radiographic benefits in a rodent model. Now, again, there's some limitations to that, but I think the main point of the paper was that merely inhibiting IL-seventeen may not be the right path way, and you may not be able to do that effectively through IL-twenty three inhibition that you can subsequently inhibit IL-seventeen.

That, actually JAK inhibition is much more effective at inhibiting IL-seventeen than is TIC inhibition for instance. So again, think this is nice basic science sort of research that will help maybe guide future therapies. A corona evaluation of their almost twenty five thousand RA patients shows that thirty two patients thirty two percent of RA patients have Sjogren's Syndrome, suggesting that there's an overall incidence of about point three zero or thirty percent. It's a little bit, it's either about the same or a little bit below what has been quoted elsewhere. And we know that secondary Sjogren's is a very prevalent condition in many of the autoimmune diseases.

You know, Norman Talal once told me that the most common autoimmune disease that rheumatologists treat is Sjogren's because of the large number of primary Sjogren's patients and then an even larger number of secondary Sjogren's patients, and that may well be true. In this particular study, Sjogren's was associated with increasing disease duration, age, being female, being seropositive, and having an extreme or high disease activity. Such patients were more likely to have more comorbidities and more extra articular manifestations. This report seems to confirm a lot of what's already been known and what is in textbooks. So we are going to talk about seropositivity at RheumNow Live.

I got a lecture on that talking about the relative value of, rheumatoid factor, CCP, and also some of the newer rheumatoid tests including anti carbamylated P antibodies, what's called CAR P antibodies. An interesting study came across this week, comparing a 179 RA patients, twenty one percent of whom had a history of ILD or evidence of ILD, interstitial lung disease, and the remainder did not. And when they compared the serologic profiles of such patients, they showed that the presence of anti CAR P antibodies was associated with a 3.4 increased risk of interstitial lung disease. Now, we do know that CCP has been associated with chronic lung disease, and in some cases interstitial lung disease. It's interesting to note that CAR P antibodies, also seems to have the same characteristics.

So, it's something maybe it may be another reason why you might want to do CAR P antibodies, which are generally not widely available but are gaining some momentum, at least in research studies. So, there's a large, study from British Columbia that looked at what happens when you get pregnant with rheumatic disease. They compared, rheumatic disease patients, I think it was like a hundred and sixty with a hundred and eighty pregnancies, and these are DMARD, or biologic exposed pregnancies. And they compared to six thousand people, RA patients not, actually not RA, but not DMARD exposed patients. They showed that when you look at common DMARDs, Plaquenil, Azathioprine, Sulfazalazine, when those were used either at the time of conception or during the pregnancy, was no untoward outcomes.

There was no problems as far as the birth of those children or small gestational weight children. They did have an interesting analysis and there's I wouldn't say that they had very strong numbers to make this claim, but nonetheless, they did show first trimester exposure to methotrexate yielded an increased odds of congenital anomalies with an an adjusted odds ratio of six point six with a very wide interval, confidence interval 1.1 to 37.8. Again, that would need to be repeated in other studies, maybe better powered studies. You know, most of the studies actually have not shown methotrexate to increase the risk of congenital anomalies when, patients become pregnant on the drug. This is one that says it is.

You should look at the recent guidelines from the American College of Rheumatology. Lead author on that is Lisa Samaritano in the current edition of Arthritis and Rheumatology and it actually addresses this issue of the safety of methotrexate in and around pregnancy. A very surprising result comes from a UK population based study basically saying that vaccination against seasonal flu influenza does not yield the expected benefits. So this is a very large population based study, shows that the people who are most likely to receive the flu vaccine were those who are older and those who had more, medical problems. But when they made a lot of corrections, they showed that those who received seasonal influenza vaccination, they did not have a substantial or significant reduction in either hospitalizations or mortality, especially amongst the elderly.

This basically says we may need to rethink some of our thinking about, how we vaccinate, who we vaccinate, and how this best gets done. So there was another study that looked at those who are more likely to quit smoking if they had rheumatoid arthritis. So this is an analysis of two different health care systems specifically looking at electronic health record data and combined they had three thousand five hundred plus patients, five hundred of whom were smokers, active smokers. Nearly thirty percent of them had quit smoking over the prior seven and a half years. They found that people who are more likely to quit were people who were new to the healthcare system and also those that were in rural communities as opposed to those who were in more urban areas, and that seropositive patients were less likely to quit.

This is kind of distressing because I don't see either of these as being any of these as being great opportunities for us to seize upon, and we clearly know that our patients who do smoke, who have rheumatoid arthritis need to quit. So it still means you're going to have to work even harder to bring that end to to reality in your patients who are smokers. Ron Van Vollenhoven was the lead author in the first study of ustekinumab and SLE. As you remember, that was a highly effective study. They now have reported the one year results in that trial.

In the first six months, patients received either placebo or ustekinumab, and a and it was blinded, and they had sixty two percent SRI four responses on ustekinumab versus thirty three percent on placebo. Turns out that when you look at the data out to a year, the, s r I four SRI four responses, the lupus responses are maintained at over sixty three percent for those who continued on ustekinumab and those who crossed over from placebo to receive ustekinumab caught up, suggesting again this looks like a highly effective therapy. The Korean national study looked at the incidence of RA and what may be causing RA. Is this not timely? Guess what causes RA?

Three to excuse me, six to seven weeks following an active upper respiratory infection with the coronavirus. Yeah. The coronavirus or parainfluenza or what was called metapneumovirus was associated with an increased risk of incident RA in a population based study from Korea. This these results were more likely in women and in the elderly. So if we get into a real, you know, sticky wicket with this whole coronavirus, we could be seeing a lot more rheumatoid arthritis.

Is it not bad enough? Lastly, the EMA, the European Medicines Agency that oversees the regulatory approval of drugs in the throughout the European Union has issued its final recommendations regarding tofacitinib. As you remember back in November, there were the warnings, from the EMA based on a safety study done by Pfizer comparing, adalimumab to, low dose or high dose tofacitinib in high risk RA patients looking to see what the safety of the drug is. Unfortunately, the high dose tofacitinib ten milligram BID, not approved for anything we treat, only approved for, ulcerative colitis. That high dose was associated with increased risk of VTE events and cardiovascular death.

When they reviewed all the data, they made the following recommendations, which are, I must say, severe and maybe even a bit ridiculous. These recommendations are in the label for this drug tofacitinib in the European Union. This has not changed The US label and these are not what's in The US label. In The US label, for all the JAK inhibitors, is a warning about the risk and that you may not want to use these drugs and people have a prior history of VTE venous thromboembolic events. However, in the European warning it says do not use the ten milligram BID dose.

If you must use it, it's with risk. Second, do not use this drug if a patient has a high risk for thromboembolic events. That would include patients with myocardial infarction, CHF, cancer, a history of a clotting disorder. If that's not enough, people who are on hormone replacement therapy or are taking hormonal contraceptives, people who are immobile, people who are undergoing major recent surgery, don't give them tofacitinib. Moreover, they have a conditional warning against use of this drug in people who are older, have diabetes, who are obese with a BMI greater than thirty, who are smokers and hypertensive.

Basically, can't use it in anybody in Europe. Again, I think this is going a little bit overboard. I think using good common sense in people who have a history or high risk of ETU as you determine, maybe shouldn't go on this drug when they have other options. So patients are doing great on these drugs and you now find out this information about what to do. You need to have a discussion about the benefits of stopping such medicine, what's working versus the hazards of continuing.

It's got to be a one on one decision. That's it for this week on the RheumNow podcast. Tune in next week. Tune in next week to hear more about RheumNow live. See you then.