The Future Of JAKs (6.5.20) Save
Dr Jack Cush reviews the news and journal reports from the past week on RheumNow.com
Transcription
It's the 06/05/2020. This is the RheumNow podcast, I'm doctor Jack Cush from roomnow.com. This week, new filings, new approvals, even new treatment guidelines, and yes, an update on hydroxychloroquine in COVID. We're gonna start with a reminder of good videos to watch this week, that would include Tuesday night rheumatology grand rounds with John Kay. This past Tuesday, fabulous lecture on biosimilars and what you need to know about it.
You can find it again on the website or on our YouTube channel. Also, a good video. I think it's good because a lot of people are looking at it. It's got thousands of views. That's the virtual video joint exam.
You can find that on the website and also on YouTube. It features me and my version. I don't think there is a right version of how to do telehealth. I think we're learning. I think that looking at others and how they do it could help how you do it.
How do you treat tuberculosis, latent tuberculosis? You know, we went over this a lot in the early 2000s and people are kind of set in their ways, but there have been some new studies about the best therapy for LTBI, latent tuberculosis infection, And the CDC has put those out. There's a Medscape article about it. You can go to the original CDC website to find the references, and we provide that to you. The CDC guidelines basically prefer three treatments.
Number one treatment. Again, latent tuberculosis is what? A positive TB test, whatever version you like to do. No signs and symptoms and a negative chest x-ray. No signs of active infection.
So the preferred treatment is not used to be INH nine months, more so than six months, and then rifampin. Now the standard is three HP. That's three months of once weekly INH plus once weekly rifapentine. Rifapentine nine hundred milligrams, INH nine hundred milligrams given once a week for twelve weeks. Real easy.
The next most preferred and the doses there you can find, but it's basically, as I said, it is different if you're less than fifty, kilograms in weight. The next best is four months of daily rifampin. That's sort of standard. That still works really, really well. And the third preferred is three months of daily INH plus rifampin, what's called three hour.
These regimens are preferred now because they're shorter, safer, have less liver toxicity, they are as effective, and they generally have higher completion rates, which is a real plus when trying to get latent TB treated. You can continue taking your TNF inhibitor or other biologic if that's the case. Interesting study from the Swedish Rheumatology Quality Register looked at a large number of rheumatoid, over forty six thousand rheumatoid, and assessed them for what the risk of venous thromboembolic events were. As has been shown by many others, they reconfirm that increasing disease activity increased the risk of VTE. We put that on the website.
It was just presented at It's interesting. We're gonna show you a lot of EULAR reports next week. I'll get to that in a minute. The DC VAS study looked at thirteen thirty eight patients with ANCA associated vasculitis to look at associations with outcomes. They showed that if you were over the age of 65 and had an ANCA associated vasculitis, you had a twofold higher risk of mortality.
Maybe that's not surprising, but I think it was. Higher damage indices, greater risk of CNS, cardiovascular, and renal disease was also higher in the older age group compared to those 65. So, again, will that color how you treat ANCA associated vasculitis? I think you have to be aggressive either way. Maybe you should worry a little bit more in the elderly.
Two new filings this week. AbbVie has filed applications with both the EMA and the FDA for upadacitinib RINVOQ, as a potential treatment for psoriatic arthritis. It's approved for rheumatoid arthritis, as you know, is not yet approved for psoriatic arthritis. I think the interesting thing here is where is the JAK inhibitor field going? What the indications going to be?
TOFA has what? RA, psoriatic arthritis, and ulcerative colitis. We know that there's a lot of JAK research going on with alopecia universalis and a lot of other skin diseases, including, skin lupus and dermatomyositis loop, with JAK inhibitors. You know, they may have a role in MAS and systemic JIA. Mean, I there's going to be in the end, lot of indications for JAK inhibitors, at least ipadacitinib, selective JAK1 inhibitors going after a second indication, that being psoriatic arthritis.
Aurinia, a new player in the market, has been developing voclosporin, a calciomerin inhibitor, for the treatment of lupus nephritis. Very, very smart here. They didn't go after lupus. They went after lupus nephritis, which is probably an easier endpoint. And that's all what the game the game is all about here, proving your endpoints so you can get a drug approved.
They have very good data presented a number of years ago by David Waffee and others that looks like this should be a good drug. They put the application in front of the FDA. It'll be interesting to see where that goes in the next, six to nine months. Another approval this week from the FDA for ixekizumab, also known as Taltz, for the treatment of non radiographic axial spondyloarthritis. The question is, do you have non radiographic axial spondyloarthritis?
These are patients with inflammatory back pain, don't have, radiographic evidence of sacroiliitis, and hence you need to prove that it's a non radiographic axial SpA either by having inflammatory back pain with either an elevated CRP or, MR evidence of sacroiliac inflammation. As you know, this is now the second drug approved for non radiographic axial SpA. The first approved was cerdulizumab, also known as Cimzia. Now we have two in the marketplace. This is an advantage for patients, is an advantage for the doctors who in the past have had to treat these patients with other agents or to be think about creative coding here to get them approved.
Now you have data from from, these trials and these drugs. The, execizumab data was approved based on what's called the COAST X or COAST 10 trial. ACE has 40 responses of thirty percent versus thirteen percent in placebo. That's significant because it's a higher level response, the ACE has 40, not the ACE has 20 we're looking at here. And the dose is eighty milligrams given subcutaneously once a week.
Looks like the same side effects and issues, in spondylitis as there will be in other conditions such as psoriatic disease. So, interesting reports this week from a number of interesting reports this week from Lancet. One, that masks, distance, and eyewear are the preventative measures for the COVID-nineteen infection. Not surprising, but they put together the meta analysis data that shows you why the numbers are what they are. For instance, physical distancing.
It's hard it's actually, the benefit starts at one meter, and it gets progressively better when you get to two meters. That's why people recommend six feet. But it is actually quite good at one meter being significant. Second, masks. Wearing a mask, prevents the infection.
If you don't wear a mask, seventeen percent risk of infection. If you do wear a mask, three percent risk of infection. And eyewear. Everybody forgets about eyewear, significant data about the protective effects of eyewear in preventing the coronavirus infection. So hydroxychloroquine is in the news nonstop.
The big report came this week from the New England Journal showing that the use of hydroxychloroquine as prophylaxis did not work. In this particular study, it was a placebo controlled trial. It was done in The United States and in Manitoba and other places in Canada. Eight hundred and twenty one patients were asymptomatic but were exposed physically, by distance and by time. And from the time they were treated, there was a certain window which they could be get on the drug or get on placebo.
They were given a course of high dose hydroxychloroquine, and then looked at outcomes twelve weeks later. At the end of twelve weeks, the risk of being a seroconverter or evidence of a positive infection by nasal swab or blood test, I guess, was almost twelve percent, eleven point eight percent with hydroxychloroquine and fourteen percent with placebo, meaning they were not statistically different, meaning there was no benefit of taking hydroxychloroquine. The number needed to benefit to prevent an infection would be forty two, again, suggesting this is probably not a good use of hydroxychloroquine. And but there was, not surprisingly, more adverse events with hydroxychloroquine, forty percent of people, versus placebo, seventeen percent. There was not serious side effects, were no deaths, were no cardiovascular, were no serious adverse events, these were sort of minor nuisance side effects.
And then lastly, The Lancet, yesterday or day before issued a retraction. It's not a full retraction. It's an expression of concern. Boy, if you wanted to know my expression of concern list, it'd be really long. So we're not gonna go into that.
We will say that Lancet issued an expression of concern to the readership because there have been many scientific, concerns that have been voiced about their hydroxychloroquine, chloroquine paper we talked about last time where it showed there were more deaths in people who were taking hydroxychloroquine. And again, I think everybody over, interpreted that study. In that study, the I think the odds ratio or hazard ratio was one point three six if you're on antimalarial as far as death. So it looked like, yes, it caused more deaths, but it doesn't say why. And really the better explanation is that the drug caused the death was that people who were sicker were more likely to get chloroquine or hydroxychloroquine.
This wasn't a randomized controlled trial, this was a use trial and looking at outcomes. So not surprisingly, sicker patients are gonna get more aggressive and sometimes off label unproven therapies. And that's been the case for a lot of the hydroxychloroquine data. In fact, a lot of hydroxychloroquine data, which is damning for the drug, really is damning for the drug being given to sick patients with comorbidities, cardiovascular comorbidities, and they're the ones who have had bad outcomes including cardiovascular death. It's probably the comorbidities and not the drug that's the blame, but you're not gonna know because these are not well done studies that can actually answer the question.
Anyway, interesting data nonetheless. I don't think they're gonna fully retract it. They're gonna come up with a few editorials that will better explain the results for people and for the, the media who has jumped all over that, somewhat inappropriate in my opinion. EULAR has started. We've been reporting on EULAR for the last few days.
We've decided that we're going to delay our EULAR reports till next week till Monday. And next week, you're gonna see a EULAR report every day from RheumNow. The first day is gonna be a report on rheumatoid arthritis. Second day is gonna be, psoriatic arthritis and spondyloarthritis, so on and so forth. The whole week is gonna feature ULAAR content.
We've got a few good reporters out there. We're following the Twitter feed. A lot of interesting stuff at ULAAR. Watch the website. Click on the links.
We're gonna send you an email every day saying RA report, lupus report, etcetera. Click on there and read the content. I think you'll get something out of it. It's a new way of learning. This is a virtual meeting, so we're learning how to do this just like everybody else.
Hope you're doing well. To carry cells, go to the website to check out these links and more. We'll talk next week.
You can find it again on the website or on our YouTube channel. Also, a good video. I think it's good because a lot of people are looking at it. It's got thousands of views. That's the virtual video joint exam.
You can find that on the website and also on YouTube. It features me and my version. I don't think there is a right version of how to do telehealth. I think we're learning. I think that looking at others and how they do it could help how you do it.
How do you treat tuberculosis, latent tuberculosis? You know, we went over this a lot in the early 2000s and people are kind of set in their ways, but there have been some new studies about the best therapy for LTBI, latent tuberculosis infection, And the CDC has put those out. There's a Medscape article about it. You can go to the original CDC website to find the references, and we provide that to you. The CDC guidelines basically prefer three treatments.
Number one treatment. Again, latent tuberculosis is what? A positive TB test, whatever version you like to do. No signs and symptoms and a negative chest x-ray. No signs of active infection.
So the preferred treatment is not used to be INH nine months, more so than six months, and then rifampin. Now the standard is three HP. That's three months of once weekly INH plus once weekly rifapentine. Rifapentine nine hundred milligrams, INH nine hundred milligrams given once a week for twelve weeks. Real easy.
The next most preferred and the doses there you can find, but it's basically, as I said, it is different if you're less than fifty, kilograms in weight. The next best is four months of daily rifampin. That's sort of standard. That still works really, really well. And the third preferred is three months of daily INH plus rifampin, what's called three hour.
These regimens are preferred now because they're shorter, safer, have less liver toxicity, they are as effective, and they generally have higher completion rates, which is a real plus when trying to get latent TB treated. You can continue taking your TNF inhibitor or other biologic if that's the case. Interesting study from the Swedish Rheumatology Quality Register looked at a large number of rheumatoid, over forty six thousand rheumatoid, and assessed them for what the risk of venous thromboembolic events were. As has been shown by many others, they reconfirm that increasing disease activity increased the risk of VTE. We put that on the website.
It was just presented at It's interesting. We're gonna show you a lot of EULAR reports next week. I'll get to that in a minute. The DC VAS study looked at thirteen thirty eight patients with ANCA associated vasculitis to look at associations with outcomes. They showed that if you were over the age of 65 and had an ANCA associated vasculitis, you had a twofold higher risk of mortality.
Maybe that's not surprising, but I think it was. Higher damage indices, greater risk of CNS, cardiovascular, and renal disease was also higher in the older age group compared to those 65. So, again, will that color how you treat ANCA associated vasculitis? I think you have to be aggressive either way. Maybe you should worry a little bit more in the elderly.
Two new filings this week. AbbVie has filed applications with both the EMA and the FDA for upadacitinib RINVOQ, as a potential treatment for psoriatic arthritis. It's approved for rheumatoid arthritis, as you know, is not yet approved for psoriatic arthritis. I think the interesting thing here is where is the JAK inhibitor field going? What the indications going to be?
TOFA has what? RA, psoriatic arthritis, and ulcerative colitis. We know that there's a lot of JAK research going on with alopecia universalis and a lot of other skin diseases, including, skin lupus and dermatomyositis loop, with JAK inhibitors. You know, they may have a role in MAS and systemic JIA. Mean, I there's going to be in the end, lot of indications for JAK inhibitors, at least ipadacitinib, selective JAK1 inhibitors going after a second indication, that being psoriatic arthritis.
Aurinia, a new player in the market, has been developing voclosporin, a calciomerin inhibitor, for the treatment of lupus nephritis. Very, very smart here. They didn't go after lupus. They went after lupus nephritis, which is probably an easier endpoint. And that's all what the game the game is all about here, proving your endpoints so you can get a drug approved.
They have very good data presented a number of years ago by David Waffee and others that looks like this should be a good drug. They put the application in front of the FDA. It'll be interesting to see where that goes in the next, six to nine months. Another approval this week from the FDA for ixekizumab, also known as Taltz, for the treatment of non radiographic axial spondyloarthritis. The question is, do you have non radiographic axial spondyloarthritis?
These are patients with inflammatory back pain, don't have, radiographic evidence of sacroiliitis, and hence you need to prove that it's a non radiographic axial SpA either by having inflammatory back pain with either an elevated CRP or, MR evidence of sacroiliac inflammation. As you know, this is now the second drug approved for non radiographic axial SpA. The first approved was cerdulizumab, also known as Cimzia. Now we have two in the marketplace. This is an advantage for patients, is an advantage for the doctors who in the past have had to treat these patients with other agents or to be think about creative coding here to get them approved.
Now you have data from from, these trials and these drugs. The, execizumab data was approved based on what's called the COAST X or COAST 10 trial. ACE has 40 responses of thirty percent versus thirteen percent in placebo. That's significant because it's a higher level response, the ACE has 40, not the ACE has 20 we're looking at here. And the dose is eighty milligrams given subcutaneously once a week.
Looks like the same side effects and issues, in spondylitis as there will be in other conditions such as psoriatic disease. So, interesting reports this week from a number of interesting reports this week from Lancet. One, that masks, distance, and eyewear are the preventative measures for the COVID-nineteen infection. Not surprising, but they put together the meta analysis data that shows you why the numbers are what they are. For instance, physical distancing.
It's hard it's actually, the benefit starts at one meter, and it gets progressively better when you get to two meters. That's why people recommend six feet. But it is actually quite good at one meter being significant. Second, masks. Wearing a mask, prevents the infection.
If you don't wear a mask, seventeen percent risk of infection. If you do wear a mask, three percent risk of infection. And eyewear. Everybody forgets about eyewear, significant data about the protective effects of eyewear in preventing the coronavirus infection. So hydroxychloroquine is in the news nonstop.
The big report came this week from the New England Journal showing that the use of hydroxychloroquine as prophylaxis did not work. In this particular study, it was a placebo controlled trial. It was done in The United States and in Manitoba and other places in Canada. Eight hundred and twenty one patients were asymptomatic but were exposed physically, by distance and by time. And from the time they were treated, there was a certain window which they could be get on the drug or get on placebo.
They were given a course of high dose hydroxychloroquine, and then looked at outcomes twelve weeks later. At the end of twelve weeks, the risk of being a seroconverter or evidence of a positive infection by nasal swab or blood test, I guess, was almost twelve percent, eleven point eight percent with hydroxychloroquine and fourteen percent with placebo, meaning they were not statistically different, meaning there was no benefit of taking hydroxychloroquine. The number needed to benefit to prevent an infection would be forty two, again, suggesting this is probably not a good use of hydroxychloroquine. And but there was, not surprisingly, more adverse events with hydroxychloroquine, forty percent of people, versus placebo, seventeen percent. There was not serious side effects, were no deaths, were no cardiovascular, were no serious adverse events, these were sort of minor nuisance side effects.
And then lastly, The Lancet, yesterday or day before issued a retraction. It's not a full retraction. It's an expression of concern. Boy, if you wanted to know my expression of concern list, it'd be really long. So we're not gonna go into that.
We will say that Lancet issued an expression of concern to the readership because there have been many scientific, concerns that have been voiced about their hydroxychloroquine, chloroquine paper we talked about last time where it showed there were more deaths in people who were taking hydroxychloroquine. And again, I think everybody over, interpreted that study. In that study, the I think the odds ratio or hazard ratio was one point three six if you're on antimalarial as far as death. So it looked like, yes, it caused more deaths, but it doesn't say why. And really the better explanation is that the drug caused the death was that people who were sicker were more likely to get chloroquine or hydroxychloroquine.
This wasn't a randomized controlled trial, this was a use trial and looking at outcomes. So not surprisingly, sicker patients are gonna get more aggressive and sometimes off label unproven therapies. And that's been the case for a lot of the hydroxychloroquine data. In fact, a lot of hydroxychloroquine data, which is damning for the drug, really is damning for the drug being given to sick patients with comorbidities, cardiovascular comorbidities, and they're the ones who have had bad outcomes including cardiovascular death. It's probably the comorbidities and not the drug that's the blame, but you're not gonna know because these are not well done studies that can actually answer the question.
Anyway, interesting data nonetheless. I don't think they're gonna fully retract it. They're gonna come up with a few editorials that will better explain the results for people and for the, the media who has jumped all over that, somewhat inappropriate in my opinion. EULAR has started. We've been reporting on EULAR for the last few days.
We've decided that we're going to delay our EULAR reports till next week till Monday. And next week, you're gonna see a EULAR report every day from RheumNow. The first day is gonna be a report on rheumatoid arthritis. Second day is gonna be, psoriatic arthritis and spondyloarthritis, so on and so forth. The whole week is gonna feature ULAAR content.
We've got a few good reporters out there. We're following the Twitter feed. A lot of interesting stuff at ULAAR. Watch the website. Click on the links.
We're gonna send you an email every day saying RA report, lupus report, etcetera. Click on there and read the content. I think you'll get something out of it. It's a new way of learning. This is a virtual meeting, so we're learning how to do this just like everybody else.
Hope you're doing well. To carry cells, go to the website to check out these links and more. We'll talk next week.
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