RheumNow Podcast A Tofa Two - Fer (4.12.19) Save

It's the 04/12/2019. This is the RheumNow podcast. Hi, I'm doctor Jack Cush, executive editor of roomnow.com, co chair of roomnow.live, which is now available on demand on our website. You know, we had RoomNow live on the twenty third, twenty fourth, twenty second, roughly almost two weeks ago. Great successful meeting.

Again, unlike any other great sessions, fabulous faculty, great attendees, lots of discussion. You can be a part of it on demand. Go to roomnow.live, click on register, and click on not the live meeting, but the online meeting. And once you register, you can pick and choose a la carte whether you want to listen to the whole session on lupus, including a thirty minute discussion with the faculty, or whether you want to listen a la carte on lectures on GPA and GCA and PSA and all those acronyms which we love in rheumatology. Again, fabulous meeting.

I can't be more pleased with the outcome. I think you will be too when you look at some of the content. So you say, Jack, why so happy? Well, actually I'm not. I'm really quite depressed.

One of my reports is about using a biologic in fibromyalgia. What? You know what's depressing? Not fellowship numbers and not NSAID users. Let's start at the top.

An interesting study looked at the accuracy of primary care doctors making a diagnosis of gout. This was published in J Rheum recently. It's a 12 center study where they actually applied criteria, I think there's a Mexico and Netherlands criteria for the diagnosis of gout, and they looked at primary care patients and they used codes for gout and they applied the criteria and amongst a large data set they found that between seventy one and eighty percent, depending on the criteria, of those primary care diagnosed gout patients actually met criteria. I think the authors intended the study to say, Hey, congratulations, looks like we may be able to use primary care diagnosed gout in our studies, however that works. I look at the data and say, why would you not get gout right the first time, every time, everybody professes to know how to diagnose gout, but yet there's a lot of misdiagnosis.

And by these studies, at least twenty to twenty nine percent misdiagnosis in the primary care sector. So again, there's a gigantic unmet need in gout. It's eight times more prevalent than rheumatoid arthritis, probably two to three times more prevalent than, spondyloarthritis. Again, we need more help, and more education. Depression, an interesting study, not published in our room literature, but it's a meta analysis looking at the effects of anti inflammatory therapy on a cohort of over six thousand six hundred depression patients to see what the outcomes were and they looked at anti inflammatory therapies meaning NSAIDs, steroids, statins, cytokine inhibitors and minocycline and showed in many of these cases like 36 studies like 17 studies showed that nonsteroidals, had a positive effect that, cytokine inhibitors in 12 studies had a positive effect.

What's the positive effect? It actually made antidepressant therapies more effective, almost as if it's adjunctive therapy, which really calls into question what in the world is going on here? Does that mean that maybe they are better managed, more likely to take their medicine or does that mean the inflammation plays a role in major depressive disorders? And interestingly the use of these anti inflammatory therapies again led mostly by nonsteroidals, did not have an increased, risk of side effects in these patients. I found it compelling and interesting research.

MMWR has published again their sort of annual yearly report that the TB rate is in fact going down. For 2017 to 2018 it dropped one point three percent. Now the rate is two point eight per one hundred thousand patients, or persons. So again, just some perspective, the, in the past it's always said that, places like The UK, Canada, Australia, US about four per one hundred thousand, but The US rate is dropping steadily at this one to two to three percent rate per year, and that's sort of a good thing, but it says that we'll never truly eradicate TB given these rates of change. RA patients probably have a rate of around six.

RA patients on biologics, it goes up to about ten. But if you're from TB land where the background risk is one hundred and fifty to three hundred cases being on a TNF inhibitor goes way up. Anyway, some perspective on gout numbers I think is helpful. Also helpful is the good news about what's happening in rheumatology fellowship. Richard Panish and colleagues published a report looking at the growth of the Rheumatology Fellowship programs in The United States showing that between 2000, before 2013, the rates were going down sort of at a steady rate.

But since 2014, the numbers have gone way up. In fact, there's been a 44% increase in the number of US fellowship training positions for rheumatology going from two thirty to three thirty two as our current number. That's the number we train and graduate every year. This is, the rate of growth here is more than any other subspecialty. That means that there's actually more demand for our specialty as compared to the available slots.

There's more US grads going into rheumatology and the salaries are actually much higher than a lot of other specialties. Think the salary as we reported in RheumNow a few years ago was $62,000 a year as a a fellow. I think I should go back and do my fellowship make some money. An interesting study comes from the US Veterans Administration looking at their RA cohort and, those patients starting on methotrexate and what was their ultimate outcomes. Basically, they showed that only twenty percent, twenty one percent were started on a biologic within two years.

Now this is surprising me because in most of your practices, upwards of around sixty percent of most US doctors have their RA patients on a biologic and that's usually after they get on methotrexate. And in the VA system in The United States, there isn't a lot of restriction on use. Yes, you must start methotrexate, but you can get on a biologic without a lot of rigmarole and look that word up. But this, I think the data that we see here is what we've seen in other sources that the people who don't get biologic therapies were more likely to be elderly, an eighty percent reduction if you compare those 80 to those 50. Patients with comorbidities, those who have heart failure, cancer and actually non Caucasians have a lower risk of twenty percent lower risk of getting on a biologic.

This is data published in J Rheum in patients between 2,000 five and twenty sixteen. This is relatively recent data so, again, there's always been this problem of the elderly not being treated aggressively, confounded by comorbidities or reasons and not use aggressive therapies. I don't ascribe to that belief. I think we should be watching for how we prescribe therapies, especially in the elderly, especially in our veterans. This is the depressing study I talked about.

One hundred and fifty one patients with that other acronym fibromyalgia, Myalgic Encephalomyelitischronic fatigue syndrome, patients were treated with rituximab or placebo. What? Why would you even do this study? Well, I'll give you one reason why and one of the early studies on biologics, did look at the use of rituximab in patients with Sjogren's syndrome. Then I don't know about you, but the data says the fifty percent of Sjogren's patients have fibromyalgia.

My clinic it's more like seventy but in this study of B cell inhibition in Sjogren's syndrome it didn't work. Nothing really seems to work in Sjogren's syndrome but they did show a reduction in pain and tender points in that study study as a sub analysis. Maybe that was the fuel to do this idiotic study. Sorry, my opinion. But obviously it failed and maybe you shouldn't be using biologics and or B cell inhibitors in patients with fibromyalgia.

Who would think fibromyalgia is an immunologic mediated disease is really on a limb that's going to break really quick? Don't make this mistake. Analysis of an early RA cohort three thirty patients I found was really interesting. Care RA is the name of the study. They looked at patient reported outcomes.

Basically they showed that and they were looking at whether or not it's the initial regimen you get that predicts the outcome or, and the outcome here being patient reported outcome measures or whether it was the, how fast you responded. And in their study, they showed it really was how fast you responded that had the greatest impact on long term outcomes as reported by the patients. The numbers here are a telltale. Primary non responders nine percent, secondary nonresponders twenty eight percent. Twenty one percent were delayed responders to whatever therapy and they had like it was like COBRA.

It was like that was the division in therapies, but forty two percent were early persistent responders, meaning they responded within twelve weeks and the response persisted. Those are the ones who did the best. That's what you want. You want to hit a home run. You should know what our current therapies if you're doing well within six no more than twelve weeks and make decisions accordingly.

Here's Tufa, Tofa, a Tufa on Tofa. A Tufa Tufa. I thought it was a good idea, maybe not. A long term study on, tofacitinib, and actually long term open label extension of patients in tofacitinib trials show some very interesting data. It showed that though in general there was a general a mild decrease in lymphocyte counts over time, for the most part not significant dropping on an average of I think it was like around 400 cells or something like that.

But the number in total who actually developed some degree of lymphopenia was, twenty four percent at two years, suggesting you really should be looking at not just the white count, which is a risk factor with JAK inhibitors, but really looking at the absolute lymphocyte count. Turns out it's the absolute lymphocyte count less than 500 that was associated with a higher risk of serious infections and a higher risk of herpes zoster infections. The ones who were more likely to get this number less than 500 and ALC less than 500 were those who had a beginning amount of lymphopenia or low ALCs. The elderly, those on higher doses of TOFA which we don't don't use in rheumatoid arthritis, and those also on methotrexate. The bottom line here is you need to be monitoring for ALC at baseline and Q3 months thereafter.

Number two on TOFA, this was a study of four thousand eight hundred, no four thousand four hundred and eighty one patients long term safety following that cohort over nine to ten years, sixteen thousand patients of patient, patient years of exposure. They found again after a mean of nine, median of nine point five years fifty two percent discontinued TOFA, four percent very low number for insufficient response, twenty four percent for adverse events, a big gap in the other seventy percent. Incidence rates were pretty low for adverse events three point four per 100 patient years led by, that was the rate for zoster three point four per 100 patient years, two point four for SIEs, zero point eight per 100 patient years for cancer, zero point four for MACE, zero point three for mortality. And that's a fairly good safety profile for tofacitinib, but like our other therapies at, ten years fifty percent of patients are taking, the drug. That's not bad.

Another study looked at zoster. We just mentioned that the risk of zoster is higher with TOFA thirty three point four per one patient years or thirty four per one thousand patients. A meta analysis of zoster incidents in patients with psoriasis and psoriatic arthritis finds that there's a higher risk for herpes zoster in those psoriasis and psoriatic patients taking steroids, tofacitinib, and the biologic plus a DMARD. Turns out that monotherapy with a biologic or monotherapy with DMARD was not associated with a higher risk of herpes zoster in psoriatic patients. An interesting study, appear I think this just yesterday in, or this week in adults internal medicine looking at, the utility of dietary supplements on overall outcomes.

In that study, it showed that patients who were, taking dietary supplements really had no change in their overall mortality rates, and that mortality really was unaffected by dietary supplements taken in pill form. When they looked at other things like diet and whatnot, there were some small changes. It turns out that, calcium intake, mainly in the form of supplements, was associated with a slightly higher risk of cancer in analysis. This week the big news from the FDA was the approval of Romelosizumab. Say that three times fast, Romelosizumab, Romelosizumab, Romelosizumab, I'm practicing.

Evenity is the name, the trade name for the drug. This drug was developed by Amgen in conjunction with UCB as you know. It had a few hiccups. They had some early phase two trials that looked really good but then they hit a phase two trial where there was an increased risk of cardiovascular events. This led to a complete response letter meaning the FDA had to get together with the company to revise their plan, analyses, get some more data.

In fact, they did, they did more and more studies and now here in 2019 the drug is going to be approved, but approved for, women at high risk, women with postmenopausal osteoporosis who are at high risk for fractures. So it's not for all postmenopausal osteoporosis, just a few. ILD is in the news. I mean, it seems to be a lot in the news. It turns out that patients with ILD seem to have, number one, it's growing in frequency.

Number two, it's associated with disease activity. Number three, it's associated with mortality. That's it for this week on RheumNow. Tune in next week for more good reports. Go to the website to check out these citations and more.

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