RheumNow Podcast – Good Time Charlie…. (10.16.20) Save

It's the 10/16/2020. This is the RheumNow podcast. Hi, I'm doctor Jack Cush, executive editor of roomnow.com. This week, the podcast is brought to you by our coverage of virtual twenty twenty ACR's annual meeting. You give us two hours, we'll give you the meeting.

Today, we're gonna talk about head to head trials. In a head to head trial, you need to have a winner and a loser, don't you? Or do you? More on that in a minute. Let's start off with a study about lupus and remission.

An interesting study, a retrospective study of almost two sixty lupus patients looked at those who achieved a definition of the, of low disease activity state called the LLDAS, the lupus low low disease activity state. In their cohort, they found that over eighty percent of patients, were in such a state, and of those eighty percent were in remission and twenty percent had active disease. When they looked at the different components of the LLDAS, they looked at one, which was a subjective assessment of activity by the patient called the SLAC. If you had low disease activity, patient impression of low disease activity, of six or six, of less than six, that was fifty six patients compared to the remaining patients who felt like they were not. Even though they were LL DAS patients, they had a slack score of six or higher, and they call those discordant.

The point being here, if you were a discordant patient, meaning you're an LL DAS, but a patient didn't think so, what kind of patient was that? Well, in their analysis, such patients had a history of, or current active arthritis, fibromyalgia, and taking steroids. That might be, a reluctant and reticent bunch. Something to be thinking about when your patient doesn't think they're doing as well as you think they're doing. Could it be their arthritis, their fibromyalgia, or that they're on steroids?

Juvenile localized scleroderma, morphia, linear disease. I've learned from our dermatologists at UT Southwestern that this is actually a quite treatable bunch. And there's a lot of successful trials out there, including a lot of success with methotrexate, but a lot of other drugs including mycophenolate. In this particular study, an analysis of, oh, it was a good group, I think it was like 40 in each group, patients either responded to methotrexate and the ones who didn't went on to mycophenolate. And then they did an analysis of those that were methotrexate refractory and on mycophenolate, or those who are methotrexate responsive.

Turns out the patients who are on methotrexate and responsive were more likely to have facial linear scleroderma, the coupe de sabre and facial linear scleroderma. Kinda interesting because those that needed to be treated with mycophenolate had another sub had other subtypes including pansclerotic morphia and a mixed, localized subtype. Again, they both had the same, degree of disease and length of disease. They both had, inactivity of more than ninety percent at nine years. But nonetheless, the it seems like these different subtypes may respond to drugs differently.

Good to know. There's an interesting study that we has been going for years now called the U Star Study, it's a European, League study of patients with systemic sclerosis, and they have patients in that who have significant interstitial lung disease. In this cohort of eight twenty six patients, they found that, SSC ILD was progressive in up to twenty seven percent of patients. And progressive was defined as having, moderate, meaning a greater than 5% change in FVC, or severe FVC decline of more than 10% over a twelve month period. Turns out that the patients who are going to have progressive or more aggressive, SSC ILD, were likely to be male, have a higher modified Rodnan Skin score, and have evidence of reflux and dysphasia.

So we do know that more skin score is associated with more severe organ disease. We do know that other organ disease portends other organ disease like GI, you can get more lung or more renal. And males, I think that's been seen in several other studies. So, again, that's, an interesting combination that you might I mean, there's enough to worry about with scleroderma, and ILD is a really poor outcome. It may be the second poorest, maybe the first poorest outcome, with a close competition with, ILD and renal disease.

I found interesting study that we've sort of talked about in the past about COVID and outcomes in our patients. This is a Spanish study of one hundred and twenty three patients who had a rheumatic disease and developed COVID-nineteen infection, and that fifty four of their patients were hospitalized, Predictors of being admitted and being in the hospital was being, maybe older, actually, the overall their patients had an average age of, almost 70, and about twenty two percent of those who are hospitalized died. But again, being hospitalized or not, older, autoimmune disease more likely to be hospitalized than inflammatory arthritis, an odds ratio of three point five five. But turns out DMARR therapy did not distinguish between those who require hospitalization and not. That's been seen in other studies.

Speaking of interstitial lung disease, Jeff Sparks group at the Brigham, has an interesting cohort. They presented this at last year's ACR, I believe, and now it's in print. It's a study of almost 200 patients that, they're following with RA and who had chest CTs done. And they found that lung disease is common, and it happens regardless of whether you're seropositive or not. Clearly, having RA lung disease imparts a higher risk of morbidity, but certainly an even higher risk of mortality, a five fold higher risk of mortality if you have, RA lung disease.

Overall, they found RA lung disease in twenty eight percent of patients, sixteen percent of whom had ILD, fourteen percent had, bronchiectasis, almost ten percent with pleural disease. Again, the thing that goes against all my teaching and what I was taught was that if you had RA lung disease, including ILD, you were just as likely to be seropositive as seronegative. Or put the other way, seropositive patients had a risk of RA lung disease twenty nine percent. Seronegatives at risk of RA lung disease twenty eight percent, it don't matter. RA lung disease can affect in both subgroups, and you shouldn't use seropositivity as a risk factor for lung disease.

So, who gets remission and how do you call it? And what should you hang your hat on? Of course, rheumatologists say, know it when I see it. But, you know, there are the criteria and if you're living a treat to target existence as I do, then, you should know the criteria and live by, an outcome measure. The ACR boolean criteria on remission is maybe the most stringent.

And there's, four criteria for that, patient global, TJC, SJC, and CRP. An interesting study, a meta analysis of almost 6,000 patients, 6,000 patients, 11 from 11 clinical trials, looked at whether you could accurately define remission and outcomes by dropping one of those four, specifically dropping patient global assessment. And just going with TJC, SJC, and CRP, more discrete variables. So having all four variables is a 4V definition, three variables dropping the global, outcomes was a 3V, three variable outcome TJC, SJC and CRP in milligrams per deciliter all being equal to or less than one. They found out the three V was just as good as the four V in predicting X-ray outcomes, maybe a little less so with functional outcomes, but still was pretty darn good.

So I think that speaks to again, measure something, stick to it, you'll do well in managing your patients. So, I thought an interesting study comes from a Swiss study looking at non radiographic axial SpA patients. As you know, the definition of non radiographic axial SpA are those who meet axSpA criteria for having inflammatory back pain and they have the other features of axSpA. But non radiographic axial SpA does not have radiographic evidence of sacroiliitis. And instead, you have to confirm that or might confirm that with an MR evidence or an elevated CRP.

In this Swiss study that compared men and women with non radiographic axial SpA, women had a longer delay in the diagnosis, not unlike that seen in other axSpA. They did have higher disease activity and more enthesitis. They were less likely to be B27 and more worrisome is they had a significantly lower TNF responder rate, meaning if when given a TNF inhibitor, they were about 80% lower in their ability to respond TNF inhibitors compared to men with non radiographic axial SpA. I find that worrisome. So, how about this?

Some gotta win, some gotta lose. RheumGoodTimeRuneNow's got the news. I should stay away from music. Head to head study, someone's gotta win, someone's gotta lose. The Select Choice study was published this week in the New England Journal.

Abitacep head to head against ubus, upadacitinib in patients, RA patients, moderate to severe disease, active disease who had failed at least a TNF inhibitor, that had to be on a background DMARD. Over six hundred patients were randomized to one arm or another twelve week outcome, and guess which one wins? You're wrong. Doesn't matter which one you chose. Actually, upadacitinib was the more effective therapy.

Multiple parameters at twelve weeks showing upadacitinib was better than primary endpoint was, the difference in dash 28 CRP, also dash 28 CRP remission levels, less than 2.6. Upadacitinib was better than abatacitinib. But wait, there's more. Abatacitinib was better than upadacitinib when it came to safety. There were more SAEs with upadacitinib than there were with abatacitinib.

Ten versus five serious adverse events, including the one death and thromboembolic events and a few other things. That's kind of kind of worrisome. Where else would this be different? Well, interestingly, surprisingly, upadacitinib had like twenty three, instances of liver enzyme elevation, and it was like ten or five with abatacitinib. Upadacitinib had more grade three and four lymphopenia or anemia versus the abatacept.

So, really confusing, they both kind of win. Abatacept wins on the safety outcome, upadacitinib wins on the efficacy outcome. What are you looking for in your patient who has refractory TNF refractory, active RA? I think it's a really interesting exercise, I would like to know what rheumatologists think. You know what, I'm going do a Twitter poll on this, look for it.

I hope you're on Twitter. A few articles this week about thrombotic risk in RA, a very nice analysis about the thrombotic risk of arterial and venous thrombosis with tofacitinib, we covered that, gives you all the data from the clinical trial experience says that there is an increased risk, it's really small, really, really small, but it's, you know, again, it's significant and it's seen in the RA, the psoriasis, the PSA, drug development programs, it looks like it's the same in other registries as well. But I want to talk first about the, I guess, the Swedish national study about thrombotic risk in RA being related to disease activity. Their study of forty six thousand RA patients followed between two thousand and six and twenty eighteen, they showed that there was almost a doubling of the venous thromboembolic risk in RA patients in their popul in this population based study. The risk was increased by having activity, such that patients who were in remission had the lowest risk of VTE zero point five percent, whereas those who had, DAS28 ESR of high disease activity had a one point zero eight percent increased risk or basically a two fold increased risk just related to activity.

So we know RA imparts risk, we know activity adds to that risk, we know that RA patients in clinical trials have had VTEs, some related to drugs, some not. Again, I think you need to be aware of some of these numbers. The risks are about five per thousand, three per thousand in you and me, five per thousand, six per thousand in an RA, and then about eight, six to eight per thousand in RA patient on a JAK inhibitor. Well, or maybe it's a little bit higher when you're when you have these activities. So, the point is that it's still a low risk.

But maybe you shouldn't use a JAK inhibitor in someone who already has a high risk if they have a prior history of VTE, then you'd want to avoid it. Again, multiple studies have shown as was shown in our papers this week, that if you have pre existing VT, pre existing cardiovascular disease or risk factors for VTE, you're more likely to get it if you're on a JAK inhibitor. Let's end with, a bit of news we talked about before, but I want to underscore it because it's it's news for our time, and that is COVID transmission from the young to the old. You know, we reported, two weeks ago, I think that MMR said that the most common age group being hospitalized right now for COVID was twenty to twenty nine year olds. This recent report from MMWR says, when there's a spike in the elderly with COVID in a population, you can look back and see that there was a pre existing, that the spike in a younger age group preceded its appearance in an older age group.

This comes from studies of 707, seven sixty seven counties in The US that are called hotspots, where the rates are going up and they meet a certain criteria, and these are PCR confirmed diagnoses. The bottom line here is of course that, that, an increase in the percentage of positive tests in older age groups is likely to result in their being hospitalized, have more severe disease and possibly death. And it's all being driven by the younger population who are running around without masks and going back to college and, you know, having COVID parties and whatnot. This is one of the reasons why we're about to hit the second wave of COVID. And if you think COVID's gonna be over by the end of the year or by March year, you're sorely wrong.

It's gonna go on for another year or two, and I'm invoking the wisdom of, our friend Kevin Winthrop, who I heard lecture this past week. He thinks there's too many things that are lining up against us that this is gonna continue for some time to come. So be vigilant. Please wear your masks and, and take care of yourselves. So who sang that song, Good Chime Charlie's Got the Blues?

Shall I do it again? Some gotta win. Some no. You don't want me to. You don't know who's who's saying that, do you?

It was Danny O'Keefe. Who's Danny O'Keefe? He's a one hit wonder, but boy, that was a good song. Again, RheumNow, our coverage, come for the education, stay for our perspectives, you're gonna love it. We'll talk next week.