EULAR 2019 Streaming Save

Hi. It's the 06/14/2019. This is the RheumNow podcast coming to you from Madrid, and you are 2019. I'm here at the convention center, sort of at the end of the day here. You're starting your day there in The United States and maybe somewhere else you're starting your day in the rest of the world.

A lot going on this week. We're only in day three. There's another big day tomorrow, Saturday. And I'm just gonna give you sort of my stream of consciousness about things that I've seen this week or something I'm looking forward to seeing. A few on the agenda.

Tomorrow, Saturday, Mark Genovese has a very novel presentation on a vagal nerve stimulator. As you know, this has previously been studied in a small fashion and shown to be effective. Vaginal nerve stimulation can lead to a decrease in TNF levels and when done in RA patients has led to clinical control of rheumatoid arthritis. He now presents the results of a larger study, uncontrolled, still a small study, and it's gonna show positive results. The final data we'll talk about next week, but it looks really interesting.

It's a novel way of actually doing it, and actually it's not that invasive to have this vagal nerve stimulator applied. Another interesting report was put forward yesterday on steroids. Actually, there's a lot on steroids at this meeting. Steroid weaning seems to be the general trend. Shows that actually steroid weaning in lupus patients, lupus patients who have inactive disease for many years on background Plaquenil and five milligrams of prednisone and totally inactive disease randomized in a clinical trial to either get off the steroids or stay on the steroids, guess what, they flare.

And then a low dose of steroids, five milligrams of prednisone or prednisolone in this case, is enough to keep the disease under control and hopefully not produce any side effects. Another big steroid study at this meeting was the use of low dose steroids in hand OA. Now, I'm a big believer in really low dose two, three, two point five milligrams of prednisone a day along with acetaminophen in hand OA, DIP, PIP disease for which there really is no good therapy. As you know there's a lot of failed therapies. So the recent October 2018 review in the Journal of Rheumatology showed you a meta analysis of 11 drugs, 11 studies that failed in HAND OA.

That includes all three TNF inhibitors, Enbrel, Humira, Remicade, two IL-one inhibitors, Methotrexate, and multiple studies with Hydroxychloroquine. All done in hand OA, mostly inflammatory E OA, but just even in garden variety hand OA. They all failed. The approved therapies for hand OA are what? Tylenol, nonsteroidals, pregabalin, curcumin works, and narcotics are used, but obviously not any better than acetaminophen or nonsteroidals.

So this particular study set out to look at the use of Prednisolone, ten milligrams a day. Fairly well designed, controlled trial. Took patients who were weaned off of their prior therapy, and to get in they had to have evidence of inflammation, redness of the DIPs, ultrasound evidence of synovitis or bone marrow edema on imaging. And the idea is that it wasn't garden variety, non inflammatory hand away, it was going to be those who had signs of inflammation. They gave them either placebo or ten milligrams of prednisolone, and guess what, they did great.

You know, showed clear separation from the placebo group, and then when they stopped the drug, they got worse again. So, I don't know what this proves. So while they got better clinically, the synovitis didn't approve, I don't think the bone marrow edema approved. And of course those are, those may be long term outcomes, but the pain outcome is a short term outcome. Maybe that's all prednisone is doing when it's given.

It's just another pain agent, it just happens to be in very low doses, maybe safe, in ten milligram doses, probably not safe. So I don't know if it's gonna change our thinking, but it's a novel study. Another interesting study came from Japan, a study of 74 patients with Takayasu's disease. In this particular study, and I don't know why they did this, they had about half their patients who were on statins. They were being treated with all sorts of standard therapies.

And when they looked at them over time and looked at relapse rates, turns out that the predictors of not having a relapse were number one, carotodynia, meaning carotid pain. Number two, and that would be in favor of relapse. LDL levels, actually in favor of relapse. Statin use against relapse. And I think there was one more.

But the idea is that statins in this particular cohort study showed to be protective and could be important adjunctive therapy in patients with vasculitis. Not usually on most of our therapeutic plans. I'd like to see more studies on this. So there's another interesting study that's going be presented tomorrow as a late breaking abstract Saturday morning. It's called the its nickname is Early Ample.

It is if you remember the Ample study, that's abatacip against adalimumab in patients with established RA giving very surprising results that abatacip works as fast as adalimumab for instance. In this particular study, it's a smaller subset study, it's only an 80 patient study, it's not really powered to give you a lot of good answers, but nonetheless, it's an important study because everybody enters into this trial has, is double positive for rheumatoid factor greater than I think a 100 and CCP greater than three times the upper limit of normal. They don't want sort of just barely positive, they want strongly positive individuals. And they then either randomize them to abatacep or adalimumab to see what happens. As you know, the data that's out there from abatacept suggests that seropositive patients respond better to abatacept.

And in this study, and that's why they enrolled seropositive patients. It turns out that wasn't seropositivity that they looked at here, they looked at the shared epitope. And you only had to have one allele, you could be either homozygous or heterozygous, and it turns out that the real separation in outcomes was seen in those people who had the shared epitope. So that result may explain why some patients who have, seropositivity, don't always respond better to abatacip or rituximab. There's data to suggest that.

There's also some data from Europe and Japan that says it doesn't work. And maybe this variability in data may relate to the frequency of the shared epitope. If it were true, maybe you could have a therapeutic advantage if you knew whether they were seropositive and had the share epitope. Again, I'm not saying rush out nor do shared epitope, I like the idea that it's getting closer to being able to predict who's going to respond to therapy. A few more, TRAPS.

As you know, the T cell receptor associated periodic syndrome is a P55 type one TNF receptor genetic rearrangement that leads to periodic fevers. These people often have two, three, sometimes four weeks of fever at a time and they go into remission, they recur, they're at risk for other kinds of systemic complications. There's a registry in Europe called the Euro Fever Registry that takes on all auto inflammatory patients. And it turns out they have two ninety one patients that they report on in this particular abstract. What was interesting about this abstract, they show you a few different rearrangements that are associated with certain outcomes, but most importantly, what drugs seem to work.

And I don't know if you remember the data, but because this is a TNF receptor deal, they've tried TNF inhibitors and it turns out that etanercept does work and that's historically the drug you should use because infliximab did not. Why that was wasn't entirely clear. Well the data from this two ninety patient cohort suggests that etanercept doesn't work really well at all. I mean there's a low success rate and a low dropout rate. It's really IL-one inhibitors that work really really well here.

And if you have someone with traps, that's the drug of therapy beyond the initial use of steroids of course. So that's kind of a new revelation from UR twenty nineteen and the Euro Fever Registry. So there's a nice set of papers from a group of investigators that looked at, from Pennsylvania and Boston, that looked at predictors of psoriatic arthritis. The bottom line is that skin severity. The more severe the skin disease, the higher risk you might have of developing psoriatic arthritis.

The other ones, which are often in play, but I'm surprised that it would shine through in this particular report, or data analysis of large numbers of patients was that patients who have obesity and depression are also at greater risk. And you know, comorbidity is a big issue in psoriatic disease and also in psoriatic arthritis. Well, turns out it may also be a risk factor for developing psoriatic arthritis. Three more. RA is getting milder.

Investigators from Lund have a longitudinal database, an RA database in Sweden, and it's like almost 7,000 patients. They assess people over different ten year intervals and showed that over that interval joint counts, swollen joint counts, tender joint counts are going down, sed rates, CRPs are going down, patient global, vision global are going up, and what's also going down is the time from symptom onset to the diagnosis, suggesting the patients are being referred earlier and being diagnosed earlier and getting in the hands of rheumatologists earlier. So therefore, maybe that's the reason why RA is in fact getting milder. There may be other factors, but I think this is one nice explanation of something we may be seeing. There was a negative report about Abitazep and Sjogren's Syndrome.

As you know, there's a lot of work in Sjogren's Syndrome trying to find adjunctive therapy, a DMAR therapy, a biologic therapy, and all these sort of crashed and burned. Rituximab failed, Plaquenil failed multiple times, Methotrexate doesn't work, while Avatacin was studied here in two different studies and shown not to be effective. And then my last report is on new drugs. There's a new IL-twenty three that's in place approved for use in psoriasis. It's called Tildrekizumab.

It's been studied in psoriatic arthritis. Looks good, you'll see more studies on that and maybe that'll get approved in the future. That'll be the third IL-twenty three inhibitor out in the marketplace. And then februchnib, a novel approach, a BTK inhibitor. These have been tried before with some unsuccess.

This one actually was tried and compared head to head to Adalimumab where it showed kind of similar results. And I'd say it's encouraging at this point, but it's very early. Their primary endpoint here was ACR fifty and both adalimumab and venbrutinib achieve like thirty five to forty percent ACR 50s here and there is no placebo control. But it's a new therapeutic approach to rheumatoid arthritis. That's it for this week on the RheumNow podcast.

Tune in next week for more information, more information about EULAR twenty nineteen. You can go and look at all the reports from RheumNow and our coverage of the meeting by going to ur19.roomnow.com and you'll see pages and pages and pages. We have a special focus on gout that you could look at. We have a lot of good abstracts here on gout as well. Take care.