RheumNow ACR Week In Review The ACR Wrap - Up Show %2810.26.18%29 Save

Hi. It's the 10/26/2018. This is the RheumNow ACR week in review. Today, we're gonna wrap up the ACR, which just finished up yesterday in Chicago. Was in a great week.

The weather was reasonable, a little chilly at night. Chicago was a great host town with a lot of interesting things to see and do if you didn't go to the meeting. But I was at the meeting the whole time starting Saturday and got home on Thursday and, exhausted from a tremendous amount of information walking and whatnot. Again, a lot of eye opening research, fabulous people, leaders in the field, exhibits, guidelines, sessions that were really stimulating, a great poster floor, of course, never ending supply of cups of small coffee and long lines to get those cups of small coffee. My highlights for this past week at ACR twenty eighteen.

First would be the acr18.roomnow.com, website. You should go there. We posted this week with a faculty of like 16 people, four or five different topic editors guiding us, doing a lot of interesting work. We posted over a thousand pieces of content that includes tweets, videos, news articles, panel discussions, quotes, pictures, etc. Take a look at it.

I think it's a very large website with information, but you can navigate your way, find the content you want in a number of different ways either by clicking on the header boxes on the top on rheumatoid arthritis, PSA, AS, gout or OP, or click on the day that you wanted to see day one, day two, day three. You can actually, there are category buttons that are designated for special areas like TNF inhibitors, RA, gout, ankylosing spondylitis, and just narrow down your choices to what you may see. And you can certainly use a search field to find the content you may want. While you're on the site, I think the things that you should look at are the roundtable panel discussions. We had a number of them, think there are nine or 10 of them.

My favorites were the PSA, the gout, and the spondyloarthritis ones. I thought that the discussion was lively and really stimulating. I think if you're gonna look at our videos, we got a ton of them. Be careful be sure to look at Catherine Dow's video on the great debate between Jim Rosenbaum and Michelle Petrie. Doctor Rachel Tate doing an exhibitor floor shakedown or smackdown.

She rates the coffee, she rates the boots. It's pretty interesting. Doctor. Sam Whittle on the Scott trial, Doctor. David Liu on, immune related adverse events with checkpoint inhibitors, really good videos.

There are many to choose from, but start there. And then lastly, when you're on the site, when you're on the sub pages for RAPSA, AS, gout and osteoporosis, scan down and look at these little circles in the corner of these tiles which are talking heads. These are KOL experts in the area providing expert commentary. I think you'll find it really interesting. So my highlights, tanezumab and osteoarthritis, you know, this is the nerve growth factor inhibitor.

These have been bouncing around a while. This is a late breaker, late l 20 abstract. I think over many hundreds, 700 patients, the endpoint being forty weeks showing the two point five milligrams sub q does very well, escalation of dose doesn't seem to add much, safety profile being very good. These have been held up by the FDA in the past because of basically studying patients with really bad osteoarthritis, taking away their pain to a significant degree that they go on and damage their osteoarthritis joints and there's progression. So obviously, be careful about who we give this to, but it is effective at relieving pain and it is a whole new modality.

There are lot of other new modalities vying for the title of being disease modifying, drugs for osteoarthritis. I don't think we're quite there yet, and the methotrexate trial in knee OA largely was a failure as would have been expected. A lot of JAK activity, not me, the JAK inhibitors, I think the updates on JAKs look good. The baricitinib long term data looked really interesting. I think that more importantly, safety data specifically, their cardiovascular data and VTE data reported by Doctor.

Mike Weinblatt was interesting. They looked at almost 3,500 patients over I think six years and basically showed no increase in MACE major cardiac events or in acute thrombotic events and then they showed the long term data on VTE, venous thromboembolism, whether it be PE or DVT was not significantly different than what you see in the background rate for RA patients. The RA patients are at increased risk for venous thromboembolic events to the tune of about point five events per one hundred patient years and that's what their long term data showed, zero point five three events per 100 patient years. Again, they had a little concern in the earliest one of their trials in the placebo controlled portion where it seemed like a little higher, but that didn't pan out with big data and long term data. There were other analyses of obesity and its effects on JAK therapy, specifically looking at baricitinib and tofacitinib.

The German rabbit registry looked at a large number of patients, over 500 patients, six month outcomes in over 200 patients and showed number one, that if you were obese in that registry, are more likely to have the higher disease activity, and that if you were obese, you were going to have less drug response to a JAK inhibitor. That's been seen with all the biologics, that's been seen with DMARDs, now it's been shown for, patients with tofacitinib and baricitinib suggesting obesity is the co conspirator in managing RA therapy. You may be doing fine using the right drugs, but if you're not addressing lifestyle issues, and physical therapy issues and maybe even surgical issues, you're failing the patient. This is a really big issue in RA management. There was another interesting analysis of the risk of venous thromboembolic events in patients on tofacitinib versus, TNF inhibitors basically showing no statistically significant difference.

But when you looked at the dataset, young people tended to have very, low rates in that zero point five per one hundred patient years or less. Older people tended to have higher events, almost double that event. This is very much an age related phenomenon and may not be due to the drug. But again, we'll continue to watch this. Other JAKs, there's a lot of new JAK inhibitors.

There's pefacitinib, which was reported by Tom Takeuchi and Professor Tanaka from Japan showing fairly good early data with this, I think largely JAK3 inhibitor. Filgotinib, a very selective JAK1 inhibitor being developed for rheumatoid arthritis. But Philip Meiss presented a plenary session, using filgotinib in psoriatic arthritis patients, one hundred and thirty patients treated for I think the fourteen weeks was the endpoint, showing an ACR 20 of eighty percent placebo response rate of thirty three percent. Safety profile looked very, very good in this very short term early phase study in psoriatic arthritis, that's filgotinib, again being developed for RAN PSA. Then again, we have the abstracts, on the newer JAK, the upadacitinib, another JAK1 inhibitor being touted as monotherapy.

When tested as monotherapy in methotrexate naive patients, almost a thousand patients, it outperformed methotrexate alone and placebo, basically showing fifteen and thirty milligrams, were fifty five percent or so versus those that were on just methotrexate at twenty three percent. And again, these are these are relatively early RA patients. They also had X-ray data that showed that the change in Sharpe score was lower for the OOPA fifteen and thirty milligram groups. The select change therapy study also showed very good data for OOPA, that's very encouraging, Then abstract eight eighty six looked at what happens when you change patients who are on adalimumab to baricitinib, that's the extension of the BEAM trial, thirteen hundred patients with methotrexate incomplete responses who went on to receive either baricitinib, adalimumab or placebo. After the endpoint, the adalimumab patients crossed over and did very, very well on, in open label on baricitinib.

There's a lot of new data on old drugs and their indications. So ustekinumab in lupus presented by Ron Van Vollenhaven showed and that was published in New England Journal recently as week 24 data. Now they're showing you, one year data, I guess, that says actually one hundred two. Well, that's two year data showing that patients who crossed over in that trial to receive ustekinumab continue to do very well as far as the lupus outcome measures SRI-four. Only a minority of patients in that trial had, nephritis of fifteen percent or so.

So it's hard to know what's going to happen with really severe lupus, what happens with serologic parameters, those are going to be sub analyses that will come forward. Aprimilast, as we know approved for psoriasis psoriatic arthritis being tested and developed in Behcet's. Now we have a newer and large Phase three trial that basically mirrors the earlier Phase two trial that appeared in New England Journal, that's encouraging. Baricitinib in SLE, that's also appeared in the literature. We have the long term extension data showing great data that was, done by, Dan Wallace and colleagues.

Then lastly, the focus study, this is the second study of larger Phase three study of tocilizumab in systemic sclerosis. The primary endpoint in that trial was the modified Rodnan skin scores and it failed. It didn't actually improve skin thickness as measured by Rodnan scores, but it did improve lung function, showed preservation of lung function as measured by forced vital capacity. So it was a win on one hand but failed the primary endpoint. The weakness here is the primary endpoint is a gigantic weakness.

Anyone who does scleroderma trials, says that that's not the best measure. It may change too easily and tends to change heroin over time anyway. Of course, that's a real problem for us clinicians because we're treating scleroderma, skin thickness. It's the one thing we see and worry about most, we of course we worry about underlying organ damage, but that's hard to assess. The problem is we need different and better outcome measures in scleroderma just like we need better outcome measures in lupus.

I think the high point of the meeting that might change practice for a lot of people was the data from McGill University about high dose influenza vaccination in RA patients. It was a plenary session. It compared standard dose vaccination to high dose vaccination in RA patients. RA patients are a two to three fold higher risk of getting influenza, yet less than forty percent of patients with RA are being vaccinated every year. We're not very good at doing that, and there's a lot of misconceptions about vaccination.

It is safe, it does work most of the time, it clearly reduces death rates, and it should be used. But nonetheless, the data here, two sixty seven patients followed over two different flu seasons compared the two and clearly RA patients and regardless of the background therapy that they were on, they actually had a two-three fold better protection looking at seroconversion rates and what is your protection rates than those that getting the standard dose therapy. While it may be harder to get and maybe more expensive, it seems like it is worth going out of the way to use this vaccination form in our RA patients. You have to be careful however about all vaccinations and patients on rituximab, they need to be vaccinated before they get their rituximab or at least six months after or whenever they reconstitute their B cells before they get their vaccination. There was a lot of guidelines being, put forth from this meeting.

I'm part of the reproductive health guidelines that was really interesting, a very long session, very well run by Lisa Samaritano and the guidelines leadership group. Incredible data you'll be seeing coming forth on how to best manage patients with rheumatic disease who either wish to get pregnant or may get pregnant. A few of the smartest things I heard was number one, you need to ask of all your patients of childbearing potential at every visit, what's their intention with regard to pregnancy, what's their plan? That needs to be done because if there isn't a plan, then you're in trouble because half of all pregnancies are unexpected. The other issue is that it's paramount to work on disease activity and worry more about that than worry about the potential for, damage by the drugs you're using to control disease activity.

Lastly, it's almost carte blanche on males on what drugs you can use. Cytotoxic is probably not, but methotrexate TNF inhibitors, anything, it doesn't matter, males can stay on that drug and still be part of a teen that's trying to get pregnant. Look for the guidelines. There's AS and Spartan guidelines that are in draft form that are coming out. These are interesting, although I worry about what happens after the initial stages when you say that you can go from a TNF inhibitor to then adding in an IL-seventeen inhibitor or tofacitinib.

They put tofacitinib in the list. I have no idea why. Scant, weak, early data, the sponsor doesn't even going after it until this happened, to allow tofacitinib to be in the mix. I think that that was a gigantic mistake. So it tells you that guidelines are not infallible.

And then Peter Merkel had a session about new draft criteria for large vessel vasculitis, look for that coming forward. To wrap up with a few other measures, IL-seventeen inhibitors look really good, ixekizumab and ankylosing spondylitis presented by Desiree Vanderheide, abstract eighteen sixty four, very impressive ASAS 40 results, fifty two percent, ixekizumab, the IL-seventeen inhibitor versus forty eight percent on, adalimumab and thirty six percent on placebo. Actually, it's thirty six percent on adalimumab and eighteen percent on placebo. A really impressive data. There was good data, comforting data about the long term response in measure three.

Then lastly, radiologists aren't that good at reading MRI reports. You gotta read them yourself. You gotta look for erosions. That's abstract six fifty one. That's it for this week.

Tune in next week. It was a great ACR. We'll see you at the next ACR.