The RheumNow Week in Review - 17 November 2017 Save
The RheumNow Week in Review - 17 November 2017 by Dr. Cush
Transcription
Hi. I'm Jack Cush, executive editor of roomnow.com. It's the 11/17/2017, and this is the RheumNow we can review. A lot of good news this week after the ACR. It still comes in.
There's still actually a number of things on our website you may wanna look at, including videos and reports that summarize what happened at the ACR. But we did cover a lot of new news that came across the, wire, and I'll fill you in on that. So I don't know if you saw this, and I don't know if it's important to you, but bunch of cardiologists, the American Heart Association got together and they've redefined hypertension. Again, this is something, it's a comorbidity, it's important. We see it in our patients.
We channel patients with hypertension back to their primary care doctors, we treat hypertension. The new definition is one hundred and thirty over eighty, it's no longer one hundred forty over ninety, and this is based on data that says that, lower blood pressures have less overall risk for heart and stroke and things like that. So again, the number's lower. It's sort of like a treat to target sort of message, isn't it? In the last, what, fifteen years, the Australians have developed a registry looking at their RA patients, specifically almost around three thousand seven hundred RA patients, had an interesting report that looked at steroid use.
What they did show was that starting in sort of five year blocks in 2001, that steroid use back then was, as much as fifty five percent, and that when you go out as far as 2015, steroid use amongst RA patients had dropped almost sixteen percent down to thirty nine percent of their patients. Patients who are more likely to be on steroids included those that were on DMARDs and nonsteroidals and opioids, those with higher activity, those with lower pain scores, those with worse HACs. Interestingly, steroid use was not associated with biologics. Does that mean that patients on biologics are better controlled and don't need steroids? Certainly, you would suggest a channeling bias for steroid use amongst those who are more aggressively treated DMARDs and pain medicines and nonsteroidal.
So it is interesting to note how, A, steroids use has changed, and then also maybe that, more, even more aggressive therapy may be associated with less use. A nice report in the Journal of Clinical Investigation came out this past week on IL-seventeen producing alpha beta cells, T cells, being found at the sites of lesions that have resolved. So specifically, took psoriasis patients and they biopsied and analyzed skin that had previously had active skin disease to see if there were resident cells. And in fact, they did find these T cell clones that had psoriasis specific antigen receptors on them that was seen in previously lesional skin suggesting that that these T cells reside there and don't go away very easily, that they are probably part of the pathogenesis of the disorder. So it's a nice advance, tells you something about the pathogenesis, IL-seventeen, and maybe how, we need to modify our treatment, especially after we've done well and resolved the lesions.
A very, controversial report, it was a news item, it was done by, an analysis done by a group that was not CMS, but they came up with, after analyzing the data, they came up with this statement that, the settlement between AbbVie and Amgen regarding the use of Amgen's adalimumab biosimilar called Amjevita, is going to affect the cost of care here in The United States. Specifically, the settlement says that AMGEVITA, the adalimumab biosimilar, can be sold in Europe beginning October 2018, but that it would not be sold in The United States until 01/01/2023. This not making it available in The United States is now estimated to cost the US Centers of Medicare and Medicaid CMS 1,480,000,000, 1,000,000,001 half dollars, and the savings they would might have otherwise realized had the biosimilar been available. Now, are obviously other adalimumab biosimilars that will come into play, but these are just some conservative estimates based on the effects of taking Amjavida out of the mix. So, again, biosimilars are going be a hot issue and money is going to be a very hot issue going forward.
Another very hot issue, I don't know if you saw this, but the FDA issued a warning, a safety warning just yesterday, and we reported it, but it's a tweet, because I don't know the full data, but the FDA safety alert is over febuxostat, saying that there may be an increased risk of cardiac death with vobuxostat, and compared to allopurinol. And this is based on a, 6,000 patient safety trial that's in play that, has shown a signal there. The FDA says, we're studying it, but we want to put the information out there and let you know about it. Now, again, cardiac deaths, increased cardiac deaths are part and parcel of dealing with a gout population. And in fact, in the development trials for febuxostat, prior to, or about the time they submitted their NDA, that patients on febuxostat had a zero point eight percent, risk of a cardiovascular event, ATPCO adjudicated events, and that it was four times higher than that seen with allopurinol, is only zero point two percent.
This led to a delay in the approval of febuxostat and the company had to do another large study to look at cardiovascular outcomes and this was called the CONFIRM study. This involved, I think almost two thousand patients and then in the CONFIRM study they saw a flip of that data. Only zero point three percent, zero point two percent had cardiovascular events with febuxostat and, double that with allopurinol zero point four percent. That led to the drug being approved, but obviously part of the approval mandated further study, ongoing study, and that must be this ongoing 6,000 patient trial that we'll be investigating further. But the question is, is this real?
Do you need to worry about this? Or is this basically, is part of the landscape that you have when managing patients with gout, especially those patients who previously did not do well on former therapies? Again, this is one of the confusing and hard parts of managing gout and also, dealing with gout research. An interesting report came out showing a paradox, in PSA, and by that, large cohort of UK patients looked at the risk of developing psoriatic arthritis in the general population. And it was shown that if you smoke, have a twenty seven percent significantly higher risk of developing psoriatic arthritis.
However, if you smoke and you have psoriasis, there's a lower risk. It's not significantly lower, it's only a nine percent lower risk. But the question is, is this what's the deal with this paradox? Again, think there's a lot of ways to look at this. My view is that smoking causes psoriatic disease, and whether it be skin or joints.
So, if you already have psoriasis, there's probably not much contribution and there may be some protection through mechanisms not otherwise understood. But if you are someone who doesn't have psoriatic disease, normal control in the population and you smoke, yes, you may be at higher risk for psoriatic arthritis, mainly mediated through a higher risk of psoriasis. A meta analysis of six studies, 8,000 controls, 3,000 patients shows that vitamin C intake is associated with a lower risk of hip fracture, a twenty seven percent lower risk in fact. In this study, it was shown that a fifty milligram per day increase in vitamin C intake lowered the risk of hip fracture by as much as five percent. So, simple, easy, patients love to take vitamins, recommend vitamin C, especially to your women who are post menopausal.
I found an interesting study about pregabalin improving hand osteoarthritis, a randomized control trial. And interestingly, it wasn't a large trial, but it was a good sized trial. But in this trial, they showed that pregabalin, but not duloxetine, was able to lower the pain scores and improve the function scores in patients with hand OA. To me hand OA is the most frustrating disease out there. It's highly prevalent.
There's nothing that works, especially if they have erosive inflammatory OA. There's really very few options for our patients. My best treatment is really Tylenol and a low dose prednisone and that's about it. So anyway, we'll have to see if that pans out in future studies. Yeah, my video is still going here.
Three more reports. Stroke is increasing in arthritis. This is important because we know that RA increases cardiovascular risk, increases the risk of venous thromboembolic events, but does it increase the risk of stroke? This study from Israel says yes, about a ten percent increased risk. Methotrexate doubles the risk of hepatotoxicity in psoriasis patients.
This is not really surprising for most of us. We know this to be true, but in this study that looked at large cohorts, it was seen that if you have psoriasis, it doubles your risk of liver disease, including serious liver disease, but the same was not seen in methotrexate. With RA patients, I'm sorry, same was not seen in RA patients on methotrexate. RA patients without methotrexate have a higher risk of liver disease, presumably inflammation mediated, but if you give them methotrexate, their risk of liver disease does not go up, in fact it goes down. So, again, psoriasis patients, psoriatic arthritis patients are uniquely, at risk for liver disease when taking methotrexate, another reason why it probably shouldn't be used, in addition to the fact that it doesn't even work, in my opinion, and very few studies would actually say that it does.
Lastly, thiopurines and anti TNF drugs causing an increased risk in cancer. This was a large study looking specifically at lymphoma risk, and what they showed is that with thiopurine monotherapy, the hazard ratio is 2.6, significantly elevated. With anti TNF monotherapy in IBD, significantly increased, 2.4. And if you use combination, it was increased, to 6.1. That's thiopurine plus a TNF inhibitor.
Again, they're comparing patients on TNF to those not on TNF, with IBD. This is not rheumatoid arthritis or any arthritis. And what's unique about this data is that, usually in RA, where there's very good data, a lot of data on this, when you compare those on TNF to those not on TNF, the number isn't really increased. It's actually around one because it's RA that drives most of the risk of lymphoma, specifically lymphoma. And then the higher rates of lymphoma, leukemia, etcetera, are when you compare RA patients on drug to the general population where there's a two to six fold higher risk of a cancer, more mostly lymphoma.
So this is unique. This is one of the study, a few studies that says that there might be a lymphoma risk associated with a TNF inhibitor use, recognize it is being seen in the IBD population, not rheumatoid arthritis, psoriatic arthritis, or ankylosing spondylitis. I think it's an important report. We still are worried about this. We need to look at this, but I think the data still is pretty strong that you should be treating the arthritis and let someone else take care of any cancers that might occur.
That's it for this week on RheumNow. Go to the website, see the links. Tune in next week. Thank you, and bye.
There's still actually a number of things on our website you may wanna look at, including videos and reports that summarize what happened at the ACR. But we did cover a lot of new news that came across the, wire, and I'll fill you in on that. So I don't know if you saw this, and I don't know if it's important to you, but bunch of cardiologists, the American Heart Association got together and they've redefined hypertension. Again, this is something, it's a comorbidity, it's important. We see it in our patients.
We channel patients with hypertension back to their primary care doctors, we treat hypertension. The new definition is one hundred and thirty over eighty, it's no longer one hundred forty over ninety, and this is based on data that says that, lower blood pressures have less overall risk for heart and stroke and things like that. So again, the number's lower. It's sort of like a treat to target sort of message, isn't it? In the last, what, fifteen years, the Australians have developed a registry looking at their RA patients, specifically almost around three thousand seven hundred RA patients, had an interesting report that looked at steroid use.
What they did show was that starting in sort of five year blocks in 2001, that steroid use back then was, as much as fifty five percent, and that when you go out as far as 2015, steroid use amongst RA patients had dropped almost sixteen percent down to thirty nine percent of their patients. Patients who are more likely to be on steroids included those that were on DMARDs and nonsteroidals and opioids, those with higher activity, those with lower pain scores, those with worse HACs. Interestingly, steroid use was not associated with biologics. Does that mean that patients on biologics are better controlled and don't need steroids? Certainly, you would suggest a channeling bias for steroid use amongst those who are more aggressively treated DMARDs and pain medicines and nonsteroidal.
So it is interesting to note how, A, steroids use has changed, and then also maybe that, more, even more aggressive therapy may be associated with less use. A nice report in the Journal of Clinical Investigation came out this past week on IL-seventeen producing alpha beta cells, T cells, being found at the sites of lesions that have resolved. So specifically, took psoriasis patients and they biopsied and analyzed skin that had previously had active skin disease to see if there were resident cells. And in fact, they did find these T cell clones that had psoriasis specific antigen receptors on them that was seen in previously lesional skin suggesting that that these T cells reside there and don't go away very easily, that they are probably part of the pathogenesis of the disorder. So it's a nice advance, tells you something about the pathogenesis, IL-seventeen, and maybe how, we need to modify our treatment, especially after we've done well and resolved the lesions.
A very, controversial report, it was a news item, it was done by, an analysis done by a group that was not CMS, but they came up with, after analyzing the data, they came up with this statement that, the settlement between AbbVie and Amgen regarding the use of Amgen's adalimumab biosimilar called Amjevita, is going to affect the cost of care here in The United States. Specifically, the settlement says that AMGEVITA, the adalimumab biosimilar, can be sold in Europe beginning October 2018, but that it would not be sold in The United States until 01/01/2023. This not making it available in The United States is now estimated to cost the US Centers of Medicare and Medicaid CMS 1,480,000,000, 1,000,000,001 half dollars, and the savings they would might have otherwise realized had the biosimilar been available. Now, are obviously other adalimumab biosimilars that will come into play, but these are just some conservative estimates based on the effects of taking Amjavida out of the mix. So, again, biosimilars are going be a hot issue and money is going to be a very hot issue going forward.
Another very hot issue, I don't know if you saw this, but the FDA issued a warning, a safety warning just yesterday, and we reported it, but it's a tweet, because I don't know the full data, but the FDA safety alert is over febuxostat, saying that there may be an increased risk of cardiac death with vobuxostat, and compared to allopurinol. And this is based on a, 6,000 patient safety trial that's in play that, has shown a signal there. The FDA says, we're studying it, but we want to put the information out there and let you know about it. Now, again, cardiac deaths, increased cardiac deaths are part and parcel of dealing with a gout population. And in fact, in the development trials for febuxostat, prior to, or about the time they submitted their NDA, that patients on febuxostat had a zero point eight percent, risk of a cardiovascular event, ATPCO adjudicated events, and that it was four times higher than that seen with allopurinol, is only zero point two percent.
This led to a delay in the approval of febuxostat and the company had to do another large study to look at cardiovascular outcomes and this was called the CONFIRM study. This involved, I think almost two thousand patients and then in the CONFIRM study they saw a flip of that data. Only zero point three percent, zero point two percent had cardiovascular events with febuxostat and, double that with allopurinol zero point four percent. That led to the drug being approved, but obviously part of the approval mandated further study, ongoing study, and that must be this ongoing 6,000 patient trial that we'll be investigating further. But the question is, is this real?
Do you need to worry about this? Or is this basically, is part of the landscape that you have when managing patients with gout, especially those patients who previously did not do well on former therapies? Again, this is one of the confusing and hard parts of managing gout and also, dealing with gout research. An interesting report came out showing a paradox, in PSA, and by that, large cohort of UK patients looked at the risk of developing psoriatic arthritis in the general population. And it was shown that if you smoke, have a twenty seven percent significantly higher risk of developing psoriatic arthritis.
However, if you smoke and you have psoriasis, there's a lower risk. It's not significantly lower, it's only a nine percent lower risk. But the question is, is this what's the deal with this paradox? Again, think there's a lot of ways to look at this. My view is that smoking causes psoriatic disease, and whether it be skin or joints.
So, if you already have psoriasis, there's probably not much contribution and there may be some protection through mechanisms not otherwise understood. But if you are someone who doesn't have psoriatic disease, normal control in the population and you smoke, yes, you may be at higher risk for psoriatic arthritis, mainly mediated through a higher risk of psoriasis. A meta analysis of six studies, 8,000 controls, 3,000 patients shows that vitamin C intake is associated with a lower risk of hip fracture, a twenty seven percent lower risk in fact. In this study, it was shown that a fifty milligram per day increase in vitamin C intake lowered the risk of hip fracture by as much as five percent. So, simple, easy, patients love to take vitamins, recommend vitamin C, especially to your women who are post menopausal.
I found an interesting study about pregabalin improving hand osteoarthritis, a randomized control trial. And interestingly, it wasn't a large trial, but it was a good sized trial. But in this trial, they showed that pregabalin, but not duloxetine, was able to lower the pain scores and improve the function scores in patients with hand OA. To me hand OA is the most frustrating disease out there. It's highly prevalent.
There's nothing that works, especially if they have erosive inflammatory OA. There's really very few options for our patients. My best treatment is really Tylenol and a low dose prednisone and that's about it. So anyway, we'll have to see if that pans out in future studies. Yeah, my video is still going here.
Three more reports. Stroke is increasing in arthritis. This is important because we know that RA increases cardiovascular risk, increases the risk of venous thromboembolic events, but does it increase the risk of stroke? This study from Israel says yes, about a ten percent increased risk. Methotrexate doubles the risk of hepatotoxicity in psoriasis patients.
This is not really surprising for most of us. We know this to be true, but in this study that looked at large cohorts, it was seen that if you have psoriasis, it doubles your risk of liver disease, including serious liver disease, but the same was not seen in methotrexate. With RA patients, I'm sorry, same was not seen in RA patients on methotrexate. RA patients without methotrexate have a higher risk of liver disease, presumably inflammation mediated, but if you give them methotrexate, their risk of liver disease does not go up, in fact it goes down. So, again, psoriasis patients, psoriatic arthritis patients are uniquely, at risk for liver disease when taking methotrexate, another reason why it probably shouldn't be used, in addition to the fact that it doesn't even work, in my opinion, and very few studies would actually say that it does.
Lastly, thiopurines and anti TNF drugs causing an increased risk in cancer. This was a large study looking specifically at lymphoma risk, and what they showed is that with thiopurine monotherapy, the hazard ratio is 2.6, significantly elevated. With anti TNF monotherapy in IBD, significantly increased, 2.4. And if you use combination, it was increased, to 6.1. That's thiopurine plus a TNF inhibitor.
Again, they're comparing patients on TNF to those not on TNF, with IBD. This is not rheumatoid arthritis or any arthritis. And what's unique about this data is that, usually in RA, where there's very good data, a lot of data on this, when you compare those on TNF to those not on TNF, the number isn't really increased. It's actually around one because it's RA that drives most of the risk of lymphoma, specifically lymphoma. And then the higher rates of lymphoma, leukemia, etcetera, are when you compare RA patients on drug to the general population where there's a two to six fold higher risk of a cancer, more mostly lymphoma.
So this is unique. This is one of the study, a few studies that says that there might be a lymphoma risk associated with a TNF inhibitor use, recognize it is being seen in the IBD population, not rheumatoid arthritis, psoriatic arthritis, or ankylosing spondylitis. I think it's an important report. We still are worried about this. We need to look at this, but I think the data still is pretty strong that you should be treating the arthritis and let someone else take care of any cancers that might occur.
That's it for this week on RheumNow. Go to the website, see the links. Tune in next week. Thank you, and bye.
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