RheumNow Podcast - MTX Vs. Etanercept In Psoriatic Arthritis (2.15.19) Save
RheumNow Podcast - MTX Vs. Etanercept In Psoriatic Arthritis (2.15.19) by Dr. Cush
Transcription
Hi. It's the 02/15/2019. This is the RheumNow podcast. I'm Doctor. Cush coming to you from RWCS in Maui where we've had a very exciting meeting, really good proceedings.
You can follow that on RheumNow. You can follow that on the rwcs.com website. That's rwcs.com, and a lot of good content. Today in the news, we're gonna talk about what happens when you combine PSA with tempo that equals SEEM. Is there such a thing as ANA negative lupus?
I think we have some genetic information about that. And should RA be managed by genetics, seropositivity, lifestyle? Are those important? All that and more. At the top of the news, we're going talk about a study that comes, from a large database of pediatric lupus patients.
And they specifically looked at almost, six thousand SLE admissions, and compared that to other controls. But what they showed in this fifty six seventy nine hundred SLE admissions, these are kids with lupus, They showed that twelve point four percent of them had pericardial effusion at admission. So PCE, what was that associated with? It was actually associated with a higher rate of mortality, and a very significant two point five fold higher risk of mortality if you were admitted with pericardial effusion. Now, again, these are hospital records.
People would have done an echo for a reason. These were not everybody being scanned or ultrasound for pericardial effusion, but this is a fairly high number, twelve point five percent with a two point five higher risk of death and a one point five higher risk of readmission in the next thirty days, suggesting that serositis on admission is a poor prognostic finding in pediatric lupus. Another lupus study looked at what happens when you use contraceptives. In fact, what they looked at, a thousand lupus patients in our registry showed that the combined use of hormonal contraceptive or the use of combined hormonal contraceptives was really low, only eight percent. And nearly half of those took them, were taking them in the face of possible contraindications.
So that number was eight percent was lower than the general population. And that if you consider the fact that even of those, many of them had contraindications, there's a large unmet need. So the contraindications, what would that have been? Was mostly anti phospholipid syndrome, hypertension, migraine with R twenty two percent. So the point here is that there's a large unmet need as far as how to use contraceptive agents in patients with lupus.
And guess what? The next few months you're going to see guidelines coming out from the ACR, a paper by Lisa Samaritano and a reproductive health group that looked at new guidelines on how to manage rheumatic disease in people who are pregnant. Look for that. It's coming out in the next few months. An interesting study looked at the genetics of individuals and how it associates with disease.
So using what was called Mendelian randomization methods, this very large study of a UK data bank of patients showed that uric acid was associated with gout. No big surprises. But it would also show that uric acid was associated with reductions in renal function as measured by the estimated GFR, nor with an overall diagnosis of CKD. So we know we worry about this association and how to treat patients with renal disease. It is not a genetically programmed thing.
It is not inherent to uric acid. So again, the association was not between uric acid and EGFR and CKD risk, telling you consequences but not necessarily due to serum uric acid. An interesting study looked at the association between biologics and serious infectious events. This is a claims data association, and it looked at what happens after you take your first TNF inhibitor, what your next choice is, and then what the risk of infection may be. So it already starts out with a defined population that has higher risk.
They've already moved on from their first to their next TNF inhibitor. Turns out that when you use tocilizumab after failing one TNF inhibitor, there's no higher risk of infection. However, the SIAE risk was higher in tocilizumab compared to TNF or abatacep otherwise. So if you've just failed one TNF, but for being initiated on a biologic, not failing a TNF inhibitor, but being initiated on a biologic, choosing tocilizumab first was associated with a statistically higher risk of SIE. Again, this is very large data.
It's claims data. It's a little confusing, and most of you have to use a TNF inhibitor as your first biologic anyway. So this could be a reporting bias and a selection bias as to who gets on tocilizumab, agent as first drug. Maybe they have other issues and contraindications. So I'm not sure that it means tocilizumab has a much higher risk, but I want to be aware of this report.
I think you should be aware of there's probably holes in the data. And I think that, you know, in my opinion, other reports that we've done, most of the biologics have roughly the same risk of a serious infectious event. An interesting look at lupus patients looked at patients who have different cytokine profiles. They sort of subset of lupus patients, whether they had a higher or lower levels of interferon alpha or interferon gamma, I should say, TNF alpha, IL-twelve 23. And they basically then looked at, let me go back.
They subset of their lupus patients based on whether or not they're positive for SSA, SSV, RNP, APL, and the other group being multiple autoantibodies. And then they looked at cytokine profiles in those different groups. They found out amongst all the patients who were in those different groups, they roughly had the same cytokine derangements and abnormalities, nothing revealing. What they did find was ANA negative patients were clearly different. They had much lower levels of interferon alpha, TNF alpha, interferon gamma, IL12, IL23 antibodies, I'm sorry, levels.
So the point here is that there's something not too different about most lupus patients, but very different about ANA negative lupus patients suggesting I think that that really is a disorder or not lupus. And I think there's been a lot of questions recently about lupus patients and the impreciseness of ANAs. I've always thought there is no such thing as ANA negative lupus anymore, and I know there's a few cases out there, but if you've diagnosed this in more than two people in your large cohort, you're making a wrong diagnosis. You're diagnosing fibromyalgia, and calling it lupus because I think this is incredibly rare. But I think we need to see more research like this that says in this case there is in fact a cytokine difference.
Some interesting reports that we wrote articles about this week on RheumNow. One was the, lack of an added value of an MRI, in guiding therapy. This is an RA study. It's been just published. It's 200 patients who are randomized to either conventional management or management that was guided by MRIs, point being that you had to have no marrow edema and no progression, etcetera.
And the interesting thing about the studies was enrolled people who had relatively controlled disease. They had to have a DAS 28 CR of less than 3.2. And it turns out that whether you were managed according to MRI or according to conventional management techniques, the outcomes were the same. The remission rates were very high in both eighty five and eighty eight percent respectively. And similarly, lack of x-ray progression was high in sixty six and sixty two percent.
Again, suggesting that using the much finer, much more sensitive measure of MRI to guide therapy probably is not a good idea. This data is in line with the Arctic study and something called the TASER study that we've written about, saying that while those tests are good for diagnosis and maybe even staging some people, they're not good tools to guide therapy. An interesting study comes from Laura's group, again about this subject was smoking and the shared epitope, the HLADR beta one epitope in seropositive RA and its predictive value. As you know, he's published that smoking is a very bad factor, especially in patients who are HLA Doctor beta one positive. In this particular study, they subsetted out the patients according to whether they had rheumatoid factor and CCP and showed that if you had both rheumatoid factor and CCP and you were a smoker, your odds of getting RA were now tenfold higher than all the controls.
And that was much higher than even patients who were rheumatoid factor but CCP negative. Someone in between were the patients who were CCP positive and rheumatoid factor negative, they seemed to have half that rate. The bottom line on this is that double positive is a bad risk factor and it's probably not a bad risk factor for people with established disease, it's probably a bad risk factor for people who have preclinical RA as well. And our last report is the SEEM study. The SEEM study was almost nine hundred patients who had psoriatic arthritis, somewhat early, mean disease duration around, median disease duration around three years.
And they had psoriatic arthritis and they were relatively naive to therapy and they were randomized to either receive methotrexate or etanercept or both, the combination. That is basically the tempo study design used in rheumatoid arthritis. And in the end, at twenty four weeks, the outcomes of eight fifty one patients by the way, The ACR twenty results were fifty one percent for methotrexate, sixty one percent for etanercept and not much different when it was methotrexate plus etanercept sixty five percent. So surprise here was that the combination wasn't better than both. Surprise here was that etanercept is equal to etanercept plus methotrexate, meaning that methotrexate doesn't add anything once you're using etanercept.
The surprise here was that methotrexate did better than everybody expected, including me. I'm a big disbeliever in methotrexate's efficacy in methotrexate based on the data that's already been out there, which is poor, and based on my own experience. But in this study, you know, fifty percent of patients respond to methotrexate and that's somewhat encouraging. The high end responses were also different. ACR 70 responses fourteen percent with methotrexate, twenty nine percent double that in etanercept and about the same twenty eight percent if you're on the combination.
So there is an advantage of etanercept over methotrexate. The data here suggests methotrexate may play a role in some patients with psoriatic arthritis. So that's it for this week on RheumNow and our podcast. Make sure you go to the website. You can click on these links to learn more.
Make sure you go and check out rheumnow.live. It is a real unique event. I think it's going to be an opportunity for you to lead, teach, and integrate with your peers and researchers. In RoomNow Live, you're going to be the program. You are the focus of the program.
Check it out at the website. Thank you very much.
You can follow that on RheumNow. You can follow that on the rwcs.com website. That's rwcs.com, and a lot of good content. Today in the news, we're gonna talk about what happens when you combine PSA with tempo that equals SEEM. Is there such a thing as ANA negative lupus?
I think we have some genetic information about that. And should RA be managed by genetics, seropositivity, lifestyle? Are those important? All that and more. At the top of the news, we're going talk about a study that comes, from a large database of pediatric lupus patients.
And they specifically looked at almost, six thousand SLE admissions, and compared that to other controls. But what they showed in this fifty six seventy nine hundred SLE admissions, these are kids with lupus, They showed that twelve point four percent of them had pericardial effusion at admission. So PCE, what was that associated with? It was actually associated with a higher rate of mortality, and a very significant two point five fold higher risk of mortality if you were admitted with pericardial effusion. Now, again, these are hospital records.
People would have done an echo for a reason. These were not everybody being scanned or ultrasound for pericardial effusion, but this is a fairly high number, twelve point five percent with a two point five higher risk of death and a one point five higher risk of readmission in the next thirty days, suggesting that serositis on admission is a poor prognostic finding in pediatric lupus. Another lupus study looked at what happens when you use contraceptives. In fact, what they looked at, a thousand lupus patients in our registry showed that the combined use of hormonal contraceptive or the use of combined hormonal contraceptives was really low, only eight percent. And nearly half of those took them, were taking them in the face of possible contraindications.
So that number was eight percent was lower than the general population. And that if you consider the fact that even of those, many of them had contraindications, there's a large unmet need. So the contraindications, what would that have been? Was mostly anti phospholipid syndrome, hypertension, migraine with R twenty two percent. So the point here is that there's a large unmet need as far as how to use contraceptive agents in patients with lupus.
And guess what? The next few months you're going to see guidelines coming out from the ACR, a paper by Lisa Samaritano and a reproductive health group that looked at new guidelines on how to manage rheumatic disease in people who are pregnant. Look for that. It's coming out in the next few months. An interesting study looked at the genetics of individuals and how it associates with disease.
So using what was called Mendelian randomization methods, this very large study of a UK data bank of patients showed that uric acid was associated with gout. No big surprises. But it would also show that uric acid was associated with reductions in renal function as measured by the estimated GFR, nor with an overall diagnosis of CKD. So we know we worry about this association and how to treat patients with renal disease. It is not a genetically programmed thing.
It is not inherent to uric acid. So again, the association was not between uric acid and EGFR and CKD risk, telling you consequences but not necessarily due to serum uric acid. An interesting study looked at the association between biologics and serious infectious events. This is a claims data association, and it looked at what happens after you take your first TNF inhibitor, what your next choice is, and then what the risk of infection may be. So it already starts out with a defined population that has higher risk.
They've already moved on from their first to their next TNF inhibitor. Turns out that when you use tocilizumab after failing one TNF inhibitor, there's no higher risk of infection. However, the SIAE risk was higher in tocilizumab compared to TNF or abatacep otherwise. So if you've just failed one TNF, but for being initiated on a biologic, not failing a TNF inhibitor, but being initiated on a biologic, choosing tocilizumab first was associated with a statistically higher risk of SIE. Again, this is very large data.
It's claims data. It's a little confusing, and most of you have to use a TNF inhibitor as your first biologic anyway. So this could be a reporting bias and a selection bias as to who gets on tocilizumab, agent as first drug. Maybe they have other issues and contraindications. So I'm not sure that it means tocilizumab has a much higher risk, but I want to be aware of this report.
I think you should be aware of there's probably holes in the data. And I think that, you know, in my opinion, other reports that we've done, most of the biologics have roughly the same risk of a serious infectious event. An interesting look at lupus patients looked at patients who have different cytokine profiles. They sort of subset of lupus patients, whether they had a higher or lower levels of interferon alpha or interferon gamma, I should say, TNF alpha, IL-twelve 23. And they basically then looked at, let me go back.
They subset of their lupus patients based on whether or not they're positive for SSA, SSV, RNP, APL, and the other group being multiple autoantibodies. And then they looked at cytokine profiles in those different groups. They found out amongst all the patients who were in those different groups, they roughly had the same cytokine derangements and abnormalities, nothing revealing. What they did find was ANA negative patients were clearly different. They had much lower levels of interferon alpha, TNF alpha, interferon gamma, IL12, IL23 antibodies, I'm sorry, levels.
So the point here is that there's something not too different about most lupus patients, but very different about ANA negative lupus patients suggesting I think that that really is a disorder or not lupus. And I think there's been a lot of questions recently about lupus patients and the impreciseness of ANAs. I've always thought there is no such thing as ANA negative lupus anymore, and I know there's a few cases out there, but if you've diagnosed this in more than two people in your large cohort, you're making a wrong diagnosis. You're diagnosing fibromyalgia, and calling it lupus because I think this is incredibly rare. But I think we need to see more research like this that says in this case there is in fact a cytokine difference.
Some interesting reports that we wrote articles about this week on RheumNow. One was the, lack of an added value of an MRI, in guiding therapy. This is an RA study. It's been just published. It's 200 patients who are randomized to either conventional management or management that was guided by MRIs, point being that you had to have no marrow edema and no progression, etcetera.
And the interesting thing about the studies was enrolled people who had relatively controlled disease. They had to have a DAS 28 CR of less than 3.2. And it turns out that whether you were managed according to MRI or according to conventional management techniques, the outcomes were the same. The remission rates were very high in both eighty five and eighty eight percent respectively. And similarly, lack of x-ray progression was high in sixty six and sixty two percent.
Again, suggesting that using the much finer, much more sensitive measure of MRI to guide therapy probably is not a good idea. This data is in line with the Arctic study and something called the TASER study that we've written about, saying that while those tests are good for diagnosis and maybe even staging some people, they're not good tools to guide therapy. An interesting study comes from Laura's group, again about this subject was smoking and the shared epitope, the HLADR beta one epitope in seropositive RA and its predictive value. As you know, he's published that smoking is a very bad factor, especially in patients who are HLA Doctor beta one positive. In this particular study, they subsetted out the patients according to whether they had rheumatoid factor and CCP and showed that if you had both rheumatoid factor and CCP and you were a smoker, your odds of getting RA were now tenfold higher than all the controls.
And that was much higher than even patients who were rheumatoid factor but CCP negative. Someone in between were the patients who were CCP positive and rheumatoid factor negative, they seemed to have half that rate. The bottom line on this is that double positive is a bad risk factor and it's probably not a bad risk factor for people with established disease, it's probably a bad risk factor for people who have preclinical RA as well. And our last report is the SEEM study. The SEEM study was almost nine hundred patients who had psoriatic arthritis, somewhat early, mean disease duration around, median disease duration around three years.
And they had psoriatic arthritis and they were relatively naive to therapy and they were randomized to either receive methotrexate or etanercept or both, the combination. That is basically the tempo study design used in rheumatoid arthritis. And in the end, at twenty four weeks, the outcomes of eight fifty one patients by the way, The ACR twenty results were fifty one percent for methotrexate, sixty one percent for etanercept and not much different when it was methotrexate plus etanercept sixty five percent. So surprise here was that the combination wasn't better than both. Surprise here was that etanercept is equal to etanercept plus methotrexate, meaning that methotrexate doesn't add anything once you're using etanercept.
The surprise here was that methotrexate did better than everybody expected, including me. I'm a big disbeliever in methotrexate's efficacy in methotrexate based on the data that's already been out there, which is poor, and based on my own experience. But in this study, you know, fifty percent of patients respond to methotrexate and that's somewhat encouraging. The high end responses were also different. ACR 70 responses fourteen percent with methotrexate, twenty nine percent double that in etanercept and about the same twenty eight percent if you're on the combination.
So there is an advantage of etanercept over methotrexate. The data here suggests methotrexate may play a role in some patients with psoriatic arthritis. So that's it for this week on RheumNow and our podcast. Make sure you go to the website. You can click on these links to learn more.
Make sure you go and check out rheumnow.live. It is a real unique event. I think it's going to be an opportunity for you to lead, teach, and integrate with your peers and researchers. In RoomNow Live, you're going to be the program. You are the focus of the program.
Check it out at the website. Thank you very much.
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