RheumNow Podcast A Grand New Year (1.4.19) Save
RheumNow Podcast A Grand New Year (1.4.19) by Dr. Cush
Transcription
This is the RheumNow podcast for 01/04/2019. Yes. It's the new year, and this podcast is brought to you by RheumNow live. So let's start out with a very happy New Year to all of you. I hope that you enjoyed the week off.
I wanted to start with some advice for the New Year. This I put out on the website. Number one, these are all lessons that take a long while to learn in life, and my favorite one is just show up. You'd be surprised what happens when you do show up. There are a million reasons not to show up, but when you do, you'll surprise yourself, you'll surprise others.
It's definitely the way to go. Number two, if you think you can, then you must do. You know, all too often, we talk ourselves out of things, including showing up, but there's a lot of stuff we can do, and we know we can do it. It's just a matter of pushing the button, moving forward, nose down, ass up, move forward. You can do it.
Number three, live each day as if it was your first or your last or your make or break day. Sounds kind of a hallmark, but, you know, honestly, if you really did actually take that approach, you'd be surprised what your day might be like. I have a friend who has a wonderful saying that I try to invoke when things aren't just so great, and that is best performance ever. That's the attitude she goes to work with. It's not that she's acting.
It's just that someday she needs to pull out that best performance so the rest of you don't know that she's having a tough day or having a great day for that matter. And let's end with teach, is where we're going to begin with on this week's news. Our first report is about chronic urticaria and osteoporosis. When I saw this, I couldn't understand the relationship here but it comes from an Israeli population based study and they took over eleven thousand almost twelve thousand people who had chronic urticaria compared them to sixty thousand controls and looked at the incidence of osteoporosis down the line. Turns out that those with chronic urticaria had a twenty three percent increase risk of developing osteoporosis and that when they segmented out the population who had been exposed to steroids it wasn't steroids that was causing the osteoporosis.
It tells you there's a lot more to osteoporosis than you might imagine and that you know with urticaria you have mast cells and other things going on that we know are going to be involved in bone health and so this is not surprising and is kind of teaches us a little bit more about osteoporosis than just a single significant association. A re analysis of the peglodecase data was published by Peter Lipsky and colleagues. This looked at the time to resolution of a TOFAS. You remember in those trials, two different trials that were published, forty percent of patients responded. Many patients had chronic refractory severe gout with TOFIS, TOFI that were really impressive and it turns out that resolution of TOFIS, they had a target TOFIS in this study, was more likely to be achieved by those who responded, and that was, seen in almost seventy percent of patients responded.
Only thirty percent of patients who didn't respond and only fourteen percent of patients who were on placebo in those clinical trials. The average time to resolution of a TOFIS was almost months, nine point nine months. So again, there's great benefit in really severe patients when this drug is used, but you need to be in it for the long haul, and need to be coaching the patient along on how to respond well and stay in, the therapeutic plan. An interesting series looked at vasculitis, IgA vasculitis specifically, and what happens in pregnancies, two forty seven pregnancies compared to five fifty six controls showing that those who had IgA vasculitis had no increase in infertility. It did not having pregnancy if you had IgA vasculitis did not necessarily induce more flares of disease, but like other autoimmune diseases, like rheumatoid, lupus, etc, that the, getting pregnant was often associated with more spontaneous abortions, some other complications like gestational hypertension and preterm delivery.
These were a little bit more frequent in patients who had IgA vasculitis. Again, there's a lesson to be learned here and even these rare patients who are often young and of childbearing potential. Still's disease can be complicated by pulmonary arterial hypertension. I've seen a lot of Still's disease because I want to see a lot of Still's disease and I advertise that and people send me patients. And I've seen two cases of pulmonary arterial hypertension.
I've seen this written about. There's an interesting review of forty one patients in the literature that we wrote this week and it shows that four point eight percent or five percent of those patients developed pulmonary arterial hypertension. It was often severe and has a small but significant mortality risk. So again, it's one of the unfortunate complications. I'm of the opinion that it could be the Still's disease, not ferreted out in their report but I'm interested in whether or not it could be related to IL-one inhibition or IL-one inhibitor use.
It's gonna be hard to know in patients like this because they're so rare and many of them will receive IL-one inhibition. Many those who receive IL-one inhibition will not develop pulmonary arterial hypertension so anyway it's just a thought. AbbVie has submitted its application to the FDA for upadacitinib, its JAK1 inhibitor once a day to the FDA and EMA for a new indication that being severe moderate to severe rheumatoid arthritis is now going to go under undergo review. We'll see what happens in 2019 for this other JAK inhibitor. There are two other interesting reports that we wrote about this week.
One was the use of a JAK inhibitor tofacitinib in a patient with severe refractory cutaneous sarcoidosis. The patient had previously been tried on multiple drugs without success And because of the idea that they have found in sarcoid lesions evidence of JAK and STAT activation, they went ahead and used the JAK inhibitor and showed really significant benefits not only with regard to the clinical outcome and also with regard to the histologic outcomes that was seen, but they also showed that JAK STAT signaling was down regulated in the patient who was treated. Now this is an N of one trial, I wouldn't run out and treat every patient with this but I think it is an important lesson that, the JAK inhibitors are certainly going to be useful in other disorders and this may well be one of them. This kind of research will probably lend to another early phase two trial is what we'd like to see because right now who's managing sarcoidosis? Especially the difficult cases.
I find a lot of pulmonary doctors don't want to manage it, that many rheumatologists are forced into management but they're not yet comfortable in treating sarcoidosis. So it's, I think it'd be nice if we receive research in this area. Another interesting area that I've seen with with JAK inhibitors and with tofacitinib is control of patients with systemic onset Still's disease. Now again, it's not that's an IL-one, IL -six disease, there's a little IL-six activity with the JAK inhibitors, not much in the way IL-one but there's a lot of interferon activity and that may benefit Still's disease patients. It's also been shown and in a report or two that it does benefit Still's disease and that it may also benefit patients with the macrophage activation syndrome.
So again those are all case reports. Again you want to look for that literature, you want to look for that research going down the road. So what else have we got left? We got one more report and this one last report has to do with the risk of sleep apnea in gout patients. This was not necessarily surprising.
I've seen some of this literature before and it actually goes both ways, meaning that in this particular study that we started out with coming from a UK clinical practice database, a large number of patients with sleep apnea, sixteen thousand patients were compared to four to one, four controls for every one patient basically. At a median follow-up for almost six years they showed that a much higher rate, almost twice the rate of sleep apnea patients develop incident gout over time. And then when they've done all the math and corrections and multivariate analysis, the hazard ratio after one or two years was one point six four, a sixty four percent increase risk. It was also seen in patients at earlier dates, was also seen in patients who are both obese and those who are non obese. So that's kind of a nice association.
Does, sleep apnea cause gout or does people get sleep apnea also get gout? And so reverse has also been seen by, Singh in Cleveland who had a report, earlier last year I believe that showed Medicare population patients with gout had a higher risk of sleep apnea. So again, we know that sleep apnea and gout have the same sort of strange bedfellows of metabolic syndrome, obesity, diabetes, etcetera, and those also happen to be risk factors for developing, both of those conditions. So again, it's instructive to, in your management of patients with either condition. So, we'll end with, some of the, I'll point you to the year in review which we published today or yesterday on on RheumNow.
I think you'll find it an interesting read. I go over my top 10 news items for the year. I'll give you a quick rundown before I send you off to bed. Number one, new drugs. The FDA has 59 new drugs this year, another record that you should look at.
The immune checkpoint inhibitors are a big ticket item for rheumatologists. Two surveys I've done in large audiences recently showed that half rheumatologists have seen patients with musculoskeletal and autoimmune events associated with these immune checkpoint inhibitors, and it's something you need to be familiar with if you haven't yet seen that. I think a big event is going to be Sandoz versus Amgen currently in court on the patent issue of Enbrel versus Irelzi. You know, we have six biosimilars in the marketplace, but very little use. I think this particular case, which should be decided on sometime in 2019 may actually flip the switch on biosimilars in The United States or delay it even further for that matter.
The fourth item opioid crisis continues, it's just plain ugly out there and of course the people who lose the most and being victimized are the deserved pain patients who really do need strong pain management. You don't know JAK. JAK inhibitors are going to get big in 2019 and beyond with now we have the growth of of ofacitinib but now the growth of baricitinib drug improved in 2018 and then newer ones coming down the pipeline. The ACR Hot Topic my decision was it was the same PSA study methotrexate versus etanercept versus the combination. Read what I wrote to see what I wrote.
The lupus trials on fire, ustekinumab, baricitinib are looking good in lupus and ifrolimab looked good in phase two but crashed and burned in phase three but yet it's still in development. We have a lot of new exciting new drugs in lupus including tick inhibitors BTK inhibitors voclosporin the calcineurin inhibitor. The all that is unknown about about medical marijuana, I think you should read this paragraph again. Medical marijuana is approved nationwide in Canada soon to follow in Mexico and is currently approved in 21 states in The United States for medical use and another 10 states for medical and recreational use. This is an economic, social and political windfall, but an evidence based disaster.
Number nine, the walk of shame on expensive drugs. I'll just say the names. You go to the website to find out the price. The drugs that we're talking about here is Cupramine. That's an eye opener.
Actar, you know about that. But what about drugs like Duexis and Vimovo, and how do they compare to, the combination of diclofenac and misoprostol. And lastly, senolytics. Some new research on senolytics is appearing more and more in applications in multiple disorders but in our case arthritis and specifically osteoarthritis. I think you should look at it, it's kind of an interesting area.
That's it for this week, RheumNow and I think you should go to the website to find out more about these particular citations and get the references and read on. Be sure to look at the roomnow.live that's roomnow.live website to find out more about our big meeting coming up in March. You know, rheumatologists like us want to go to meetings that are a good use of our time. This is a weekend meeting. It's two days.
It's very affordable. It's got the world's best speakers. You're gonna be able to have day long conversations with those delivering the You can talk to them during the during the lecture, after the lecture, in a panel discussion, during the breaks, for the rest of the day or next day that they're there. I think you'll find it interesting. So, again, rheumnow.live.
Be there. See you next week.
I wanted to start with some advice for the New Year. This I put out on the website. Number one, these are all lessons that take a long while to learn in life, and my favorite one is just show up. You'd be surprised what happens when you do show up. There are a million reasons not to show up, but when you do, you'll surprise yourself, you'll surprise others.
It's definitely the way to go. Number two, if you think you can, then you must do. You know, all too often, we talk ourselves out of things, including showing up, but there's a lot of stuff we can do, and we know we can do it. It's just a matter of pushing the button, moving forward, nose down, ass up, move forward. You can do it.
Number three, live each day as if it was your first or your last or your make or break day. Sounds kind of a hallmark, but, you know, honestly, if you really did actually take that approach, you'd be surprised what your day might be like. I have a friend who has a wonderful saying that I try to invoke when things aren't just so great, and that is best performance ever. That's the attitude she goes to work with. It's not that she's acting.
It's just that someday she needs to pull out that best performance so the rest of you don't know that she's having a tough day or having a great day for that matter. And let's end with teach, is where we're going to begin with on this week's news. Our first report is about chronic urticaria and osteoporosis. When I saw this, I couldn't understand the relationship here but it comes from an Israeli population based study and they took over eleven thousand almost twelve thousand people who had chronic urticaria compared them to sixty thousand controls and looked at the incidence of osteoporosis down the line. Turns out that those with chronic urticaria had a twenty three percent increase risk of developing osteoporosis and that when they segmented out the population who had been exposed to steroids it wasn't steroids that was causing the osteoporosis.
It tells you there's a lot more to osteoporosis than you might imagine and that you know with urticaria you have mast cells and other things going on that we know are going to be involved in bone health and so this is not surprising and is kind of teaches us a little bit more about osteoporosis than just a single significant association. A re analysis of the peglodecase data was published by Peter Lipsky and colleagues. This looked at the time to resolution of a TOFAS. You remember in those trials, two different trials that were published, forty percent of patients responded. Many patients had chronic refractory severe gout with TOFIS, TOFI that were really impressive and it turns out that resolution of TOFIS, they had a target TOFIS in this study, was more likely to be achieved by those who responded, and that was, seen in almost seventy percent of patients responded.
Only thirty percent of patients who didn't respond and only fourteen percent of patients who were on placebo in those clinical trials. The average time to resolution of a TOFIS was almost months, nine point nine months. So again, there's great benefit in really severe patients when this drug is used, but you need to be in it for the long haul, and need to be coaching the patient along on how to respond well and stay in, the therapeutic plan. An interesting series looked at vasculitis, IgA vasculitis specifically, and what happens in pregnancies, two forty seven pregnancies compared to five fifty six controls showing that those who had IgA vasculitis had no increase in infertility. It did not having pregnancy if you had IgA vasculitis did not necessarily induce more flares of disease, but like other autoimmune diseases, like rheumatoid, lupus, etc, that the, getting pregnant was often associated with more spontaneous abortions, some other complications like gestational hypertension and preterm delivery.
These were a little bit more frequent in patients who had IgA vasculitis. Again, there's a lesson to be learned here and even these rare patients who are often young and of childbearing potential. Still's disease can be complicated by pulmonary arterial hypertension. I've seen a lot of Still's disease because I want to see a lot of Still's disease and I advertise that and people send me patients. And I've seen two cases of pulmonary arterial hypertension.
I've seen this written about. There's an interesting review of forty one patients in the literature that we wrote this week and it shows that four point eight percent or five percent of those patients developed pulmonary arterial hypertension. It was often severe and has a small but significant mortality risk. So again, it's one of the unfortunate complications. I'm of the opinion that it could be the Still's disease, not ferreted out in their report but I'm interested in whether or not it could be related to IL-one inhibition or IL-one inhibitor use.
It's gonna be hard to know in patients like this because they're so rare and many of them will receive IL-one inhibition. Many those who receive IL-one inhibition will not develop pulmonary arterial hypertension so anyway it's just a thought. AbbVie has submitted its application to the FDA for upadacitinib, its JAK1 inhibitor once a day to the FDA and EMA for a new indication that being severe moderate to severe rheumatoid arthritis is now going to go under undergo review. We'll see what happens in 2019 for this other JAK inhibitor. There are two other interesting reports that we wrote about this week.
One was the use of a JAK inhibitor tofacitinib in a patient with severe refractory cutaneous sarcoidosis. The patient had previously been tried on multiple drugs without success And because of the idea that they have found in sarcoid lesions evidence of JAK and STAT activation, they went ahead and used the JAK inhibitor and showed really significant benefits not only with regard to the clinical outcome and also with regard to the histologic outcomes that was seen, but they also showed that JAK STAT signaling was down regulated in the patient who was treated. Now this is an N of one trial, I wouldn't run out and treat every patient with this but I think it is an important lesson that, the JAK inhibitors are certainly going to be useful in other disorders and this may well be one of them. This kind of research will probably lend to another early phase two trial is what we'd like to see because right now who's managing sarcoidosis? Especially the difficult cases.
I find a lot of pulmonary doctors don't want to manage it, that many rheumatologists are forced into management but they're not yet comfortable in treating sarcoidosis. So it's, I think it'd be nice if we receive research in this area. Another interesting area that I've seen with with JAK inhibitors and with tofacitinib is control of patients with systemic onset Still's disease. Now again, it's not that's an IL-one, IL -six disease, there's a little IL-six activity with the JAK inhibitors, not much in the way IL-one but there's a lot of interferon activity and that may benefit Still's disease patients. It's also been shown and in a report or two that it does benefit Still's disease and that it may also benefit patients with the macrophage activation syndrome.
So again those are all case reports. Again you want to look for that literature, you want to look for that research going down the road. So what else have we got left? We got one more report and this one last report has to do with the risk of sleep apnea in gout patients. This was not necessarily surprising.
I've seen some of this literature before and it actually goes both ways, meaning that in this particular study that we started out with coming from a UK clinical practice database, a large number of patients with sleep apnea, sixteen thousand patients were compared to four to one, four controls for every one patient basically. At a median follow-up for almost six years they showed that a much higher rate, almost twice the rate of sleep apnea patients develop incident gout over time. And then when they've done all the math and corrections and multivariate analysis, the hazard ratio after one or two years was one point six four, a sixty four percent increase risk. It was also seen in patients at earlier dates, was also seen in patients who are both obese and those who are non obese. So that's kind of a nice association.
Does, sleep apnea cause gout or does people get sleep apnea also get gout? And so reverse has also been seen by, Singh in Cleveland who had a report, earlier last year I believe that showed Medicare population patients with gout had a higher risk of sleep apnea. So again, we know that sleep apnea and gout have the same sort of strange bedfellows of metabolic syndrome, obesity, diabetes, etcetera, and those also happen to be risk factors for developing, both of those conditions. So again, it's instructive to, in your management of patients with either condition. So, we'll end with, some of the, I'll point you to the year in review which we published today or yesterday on on RheumNow.
I think you'll find it an interesting read. I go over my top 10 news items for the year. I'll give you a quick rundown before I send you off to bed. Number one, new drugs. The FDA has 59 new drugs this year, another record that you should look at.
The immune checkpoint inhibitors are a big ticket item for rheumatologists. Two surveys I've done in large audiences recently showed that half rheumatologists have seen patients with musculoskeletal and autoimmune events associated with these immune checkpoint inhibitors, and it's something you need to be familiar with if you haven't yet seen that. I think a big event is going to be Sandoz versus Amgen currently in court on the patent issue of Enbrel versus Irelzi. You know, we have six biosimilars in the marketplace, but very little use. I think this particular case, which should be decided on sometime in 2019 may actually flip the switch on biosimilars in The United States or delay it even further for that matter.
The fourth item opioid crisis continues, it's just plain ugly out there and of course the people who lose the most and being victimized are the deserved pain patients who really do need strong pain management. You don't know JAK. JAK inhibitors are going to get big in 2019 and beyond with now we have the growth of of ofacitinib but now the growth of baricitinib drug improved in 2018 and then newer ones coming down the pipeline. The ACR Hot Topic my decision was it was the same PSA study methotrexate versus etanercept versus the combination. Read what I wrote to see what I wrote.
The lupus trials on fire, ustekinumab, baricitinib are looking good in lupus and ifrolimab looked good in phase two but crashed and burned in phase three but yet it's still in development. We have a lot of new exciting new drugs in lupus including tick inhibitors BTK inhibitors voclosporin the calcineurin inhibitor. The all that is unknown about about medical marijuana, I think you should read this paragraph again. Medical marijuana is approved nationwide in Canada soon to follow in Mexico and is currently approved in 21 states in The United States for medical use and another 10 states for medical and recreational use. This is an economic, social and political windfall, but an evidence based disaster.
Number nine, the walk of shame on expensive drugs. I'll just say the names. You go to the website to find out the price. The drugs that we're talking about here is Cupramine. That's an eye opener.
Actar, you know about that. But what about drugs like Duexis and Vimovo, and how do they compare to, the combination of diclofenac and misoprostol. And lastly, senolytics. Some new research on senolytics is appearing more and more in applications in multiple disorders but in our case arthritis and specifically osteoarthritis. I think you should look at it, it's kind of an interesting area.
That's it for this week, RheumNow and I think you should go to the website to find out more about these particular citations and get the references and read on. Be sure to look at the roomnow.live that's roomnow.live website to find out more about our big meeting coming up in March. You know, rheumatologists like us want to go to meetings that are a good use of our time. This is a weekend meeting. It's two days.
It's very affordable. It's got the world's best speakers. You're gonna be able to have day long conversations with those delivering the You can talk to them during the during the lecture, after the lecture, in a panel discussion, during the breaks, for the rest of the day or next day that they're there. I think you'll find it interesting. So, again, rheumnow.live.
Be there. See you next week.
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