RheumNow Week In Review The Heart Attack Report %2811.2.18%29 Save
RheumNow Week In Review The Heart Attack Report %2811.2.18%29 by Dr. Cush
Transcription
It's the 11/02/2018. This is the RheumNow we can review. Hi. I'm doctor Jack Cush, executive editor of RheumNow. This week's edition is brought to you by rheumnow.live, an upcoming educational event in Fort Worth we'll tell you more about at the end of the show.
This week in the news, methotrexate in gout, new hope for Sjogren's patients, and how to count cells and know more about inflammation. At the top of the news, we didn't talk about this last week at the ACR with all the things we talked about, but there was an interesting late breaking abstract that was presented that garnered a lot of attention, not by me, I'm kind of a naysayer about this, but in doing my, reporting best, I think I should tell you about it. It's a small study in Sjogren's syndrome showing basically that leflunomide and hydroxychloroquine, yes, the combination may work in patients with primary Sjogren's syndrome. This was a late breaking abstract, it, did get attention, but it was only twenty nine patients. There was a two to one randomization to receive either placebo in nine patients or the combination of active therapy in twenty one patients who received standard doses of leflinamide and hydroxychloroquine.
At the end of the twenty four weeks, there was significantly greater responses in the active drug treatment group, nine out of twenty one or little less than half of those patients responded compared to only one out of the nine placebo patients. It's important to note the outcome measure here is a ESSDAI, that's the Sjogren's Syndrome New Disease Activity Index that seems to be fairly sensitive and specific, and a response in that study was an ESDAI score of three or more. So this is surprising because basically all of the therapies have failed in Sjogren's syndrome including biologics, including multiple trials of hydroxychloroquine, and yet many rheumatologists will try to use our standard immunosuppressive and anti inflammatory therapies to no avail in Sjogren's syndrome, which in my opinion is a train wreck that's already happened. Inflammation has already damaged those exocrine glands. Inflammation directed therapy is not going to change the outcomes, especially when looking at dry eyes, dry mouth, and it's uncertain what it would do to lung function.
But this is a small study, and I wouldn't encourage you to go out and use this right away. I would encourage you to look for trials in something like this right away. There is some biologic rationale for it. Again, a lot of excitement about it, but not by me. You figure it out for yourself.
We have the link if you wanna go and read more about it. This week in the news, a nice little review article talked about how you can use a CBC to actually assess whether patients have inflammation. Now, course, you already have those measures by using either a DAS score or CDI score, a DASH ESR or DAS CRP, CRPs and sed rates, why not? Well, there's something even more simple than that, and that's called the neutrophil to lymphocyte ratio. Also, the, measure that they actually quoted in here was the, I think, platelet to lymphocyte ratio, the PLR.
The neutrophil to lymphocyte ratio we've talked about before on RheumNow, there's a news article we wrote about this called, CBC Hidden Pearls that you can learn more about this, but basically take your neutrophil count and divide it by your lymph ocyte count. If it's greater than four, you'll likely have a significant amount of inflammation. In that review article, we also talk about the RDW being a useful tool that's up, not only in anemia, but also with inflammation. RDWs tend to be higher in whites than non whites and can be affected by a number of different things, but inflammation is part of the mix. So, this may be a useful marker.
It's been touted in other diseases, including vasculitis, including, RA, including lupus, in some patients. So it may be something that we should be looking into because it's certainly free, cheap, and easy, and maybe something you don't have to wait for. An interesting study looked at a large cohort, hundreds of thousands of patients in a nationwide database who had ST segment elevation MI, STEMIs, and non STEMI myocardial infarctions in the population, and amongst the population they identified two thousand lupus patients. They really looked at both STEMI and non STEMI outcomes for lupus patients and showed that lupus patients with myocardial infarction basically had the same outcomes as did non lupus patients who underwent the same type of myocardial infarction. That means their mortality rates were the same, rates of CABG and stents, adverse events, length of hospital stay, overall hospital costs, the same between lupus patients and non lupus patients, and that's probably important to note.
Something that we often teach about, but there's a little bit of data that you can point to from this citation that we found, I think from the Korean literature, Korean researchers I should say, and that shows that rheumatoid factor we know goes up with chronic liver disease, especially with hepatitis C infection. But we supposedly think that the ACBA positivity or CCP antibody positivity should not go up in those people, and that's what this one large study of almost 300 patients shows that only amongst HCV positive patients, meaning there's no arthritis in play here. They just looked at hepatitis C infected individuals and looked at seropositivity. They found forty seven percent had a positive rheumatoid factor, but that less than one percent one percent had a positive CCP antibody. High high titer positive rheumatoid factor in nine percent, again, titer positive ACPA one percent.
It is safe to say that ACPA should not go up with liver infection and liver disease, whereas rheumatoid factor may go up. An interesting study from Taiwan looked at what happens to, a large cohort of psoriasis patients, especially psoriasis patients who have hypertension, over four thousand patients followed for five years, showed that these patients are not only at a higher risk of cardiovascular outcomes, they have a higher risk of cardiovascular procedures and surgery, and this was more so seen in patients with psoriatic arthritis and those with severe psoriasis. Again, to that diagnosis being a significant risk factor for cardiovascular disease, suggesting that your psoriasis and psoriatic arthritis patients really need multidisciplinary management and comorbidity management. It's very important. A late breaking report, late breaking abstract nine, L09 from the ACR looked at the risk of venous thromboembolic events and specifically looked at a Medicare dataset of over 50,000 claims made and specifically looked at the RA patients and tried to assess those RA patients who are on tofacitinib and those RA patients who are on any TNF inhibitor and what was the overall risk of venous thromboembolic event, and that includes both deep vein thrombosis and or, pulmonary embolism.
As was seen in previous research on this, RA patients are at a higher risk. Turns out that, RA patients on these drugs tend to have risks that are about that of the population risk, a little higher than the population risk, about zero point five events per one 100 patient years. The hazard ratio was not different between tofacitinib and, any TNF inhibitor, has a ratio being 1.33, but the confidence intervals being wide at 0.78 to 2.24, suggesting that the rates were higher in RA patients, not higher on one drug versus another, higher with age. Older age groups tend to have more of these events and we know age is a risk factor for venous thromboembolic events. Another I thought important abstract that were not previously covered by us, from the ACR is the abstract by, Jeff Peterson's group in Washington where they reported on their collective experience of 10 patients undergoing peglodecase therapy.
As you know, the big issue with peglodecase these days is, it works. It's tremendously, effective in patients with a large total body urate load. It drops your uric acid levels from elevated to basically nothing right quick as we say in Texas. But the big limiting factor there is not every patient responds and that some patients the hindered response seems to be related to the immunogenicity against the PEGylated portion of the molecule, so anti PEG antibodies. When that happens, you'll get anti PEG antibodies interfering with the tests and the uric acid levels will rise and whatnot.
Anyway, the question in play right now is whether or not you should use immunosuppression when you're giving peglodecase to lower the immunogenicity of the drug and therefore improve the success of the therapy. Well, in their single center, uncontrolled, all 10 patients got methotrexate at the usual doses of around fifteen milligrams per week, and basically they had a response in all patients and no patients were found to have an immunogenic response or loss of efficacy. There was no subsequent rise in serum uric acid level suggesting this was an effective way to maximize therapy with pegilodecase in patients with chronic refractory gout. There are trials, there's been reports in the literature, from Michael Pillinger and a few others using azathioprine for that same purpose. There is a trial that's underway with Ken Sag in Alabama using peglodecase but using background mycophenolate to suppress responses.
I want to remind you that the earliest trials with infliximab, the CA2 antibody done by Tiny Mani and others, their very early trials showed that they could suppress the immune responses in patients by using methotrexate at low doses seven point five, and other therapies that we commonly use. Methotrexate is not particularly novel here, but it is important that this be considered. Antiphospholipid antibodies in myocardial infarction, an interesting study in the cardiology journals looks at a large Australian cohort of over eight hundred first new MIs and found eleven percent of their MIs had elevated. These are not arthritis patients, not lupus patients, these are MI patients. Eleven percent of their patients had elevated antiphospholipid antibodies against both cardiolipin and beta-two glycoprotein-one, and this was more than 10 times controls.
This was an important and significant suggest if you don't have an etiology for a myocardial infarction, testing for antiphospholipid antibodies would be reasonable. Lastly, we have a nice little review on a spotlight on interstitial lung disease from ACR. A few interesting reports. The highlights of that include, two abstracts, one from, two abstracts from Jeff Sparks' group and the brass database, which one showed that disease activity, was associated with an increased risk of interstitial lung disease, increased risk to the tune of about two and a half fold higher, clearly being a risk factor for interstitial lung disease. Also, one of his fellows, Doctor.
Huang, looked at their experience with CT chests in their RA population over 1,500 patients and showed that seropositive RA patients did not have a lock or exclusivity on lung disease. Turns out that seronegative patients had a significant amount of lung findings including the lung nodules, being equally present in RF negative and RF positive patients around forty percent. Interstitial lung disease, sixteen and fifteen percent for seronegative and seropositive patients, and pleural effusion same thing about nine percent, ten percent suggesting that do not exclude the possibility of lung disease being related to RA just because they're seronegative. Maybe the most important report was the plenary session report about this, MUC5B or MUC5B promoter variant RS35705950 being associated with an increased risk of interstitial lung disease, about a two to fivefold increased risk in RA patients. This promoter, variant is not seen in RA patients, not associated with RA, but it is associated with interstitial lung disease.
It is not seen in systemic sclerosis, but it may be seen in other disorders. It seems to be associated with the UIP pattern of ILD, and I think that's important. Lastly, I wanna tell you about the most important thing that we're working on here at, RheumNow, and that is RheumNow Live. This is our first CME conference. It's going to occur February '20 04/2019 in beautiful downtown Fort Worth, Texas at the Worthington Hotel.
It's going be an event depart. I really would ask you to look at this. The program was developed by you, the RheumNow readership in our needs assessment. A lot of what we took from you is what's been in the design of this program. This is going to be a highly interactive audience between the faculty, the moderators, and the audience.
There's an app that we're going to be using to cross communicate and interact with the faculty. We have sessions devoted to drug safety, orthopedics, rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, systemic lupus, and, I'm leaving out one, but that's enough. I think there's about seven or eight main sessions. Then in between the main sessions, which are two hours long, three and a half hour lectures, one half hour group discussion, panel discussion with the faculty. Between those two hour segments, we're going to have TED like talks, which are going to be just fabulous.
I encourage you to go to roomnow.live to learn more about this meeting. That's it for this week on roomnow.com. We'll see you next week. Have a good weekend.
This week in the news, methotrexate in gout, new hope for Sjogren's patients, and how to count cells and know more about inflammation. At the top of the news, we didn't talk about this last week at the ACR with all the things we talked about, but there was an interesting late breaking abstract that was presented that garnered a lot of attention, not by me, I'm kind of a naysayer about this, but in doing my, reporting best, I think I should tell you about it. It's a small study in Sjogren's syndrome showing basically that leflunomide and hydroxychloroquine, yes, the combination may work in patients with primary Sjogren's syndrome. This was a late breaking abstract, it, did get attention, but it was only twenty nine patients. There was a two to one randomization to receive either placebo in nine patients or the combination of active therapy in twenty one patients who received standard doses of leflinamide and hydroxychloroquine.
At the end of the twenty four weeks, there was significantly greater responses in the active drug treatment group, nine out of twenty one or little less than half of those patients responded compared to only one out of the nine placebo patients. It's important to note the outcome measure here is a ESSDAI, that's the Sjogren's Syndrome New Disease Activity Index that seems to be fairly sensitive and specific, and a response in that study was an ESDAI score of three or more. So this is surprising because basically all of the therapies have failed in Sjogren's syndrome including biologics, including multiple trials of hydroxychloroquine, and yet many rheumatologists will try to use our standard immunosuppressive and anti inflammatory therapies to no avail in Sjogren's syndrome, which in my opinion is a train wreck that's already happened. Inflammation has already damaged those exocrine glands. Inflammation directed therapy is not going to change the outcomes, especially when looking at dry eyes, dry mouth, and it's uncertain what it would do to lung function.
But this is a small study, and I wouldn't encourage you to go out and use this right away. I would encourage you to look for trials in something like this right away. There is some biologic rationale for it. Again, a lot of excitement about it, but not by me. You figure it out for yourself.
We have the link if you wanna go and read more about it. This week in the news, a nice little review article talked about how you can use a CBC to actually assess whether patients have inflammation. Now, course, you already have those measures by using either a DAS score or CDI score, a DASH ESR or DAS CRP, CRPs and sed rates, why not? Well, there's something even more simple than that, and that's called the neutrophil to lymphocyte ratio. Also, the, measure that they actually quoted in here was the, I think, platelet to lymphocyte ratio, the PLR.
The neutrophil to lymphocyte ratio we've talked about before on RheumNow, there's a news article we wrote about this called, CBC Hidden Pearls that you can learn more about this, but basically take your neutrophil count and divide it by your lymph ocyte count. If it's greater than four, you'll likely have a significant amount of inflammation. In that review article, we also talk about the RDW being a useful tool that's up, not only in anemia, but also with inflammation. RDWs tend to be higher in whites than non whites and can be affected by a number of different things, but inflammation is part of the mix. So, this may be a useful marker.
It's been touted in other diseases, including vasculitis, including, RA, including lupus, in some patients. So it may be something that we should be looking into because it's certainly free, cheap, and easy, and maybe something you don't have to wait for. An interesting study looked at a large cohort, hundreds of thousands of patients in a nationwide database who had ST segment elevation MI, STEMIs, and non STEMI myocardial infarctions in the population, and amongst the population they identified two thousand lupus patients. They really looked at both STEMI and non STEMI outcomes for lupus patients and showed that lupus patients with myocardial infarction basically had the same outcomes as did non lupus patients who underwent the same type of myocardial infarction. That means their mortality rates were the same, rates of CABG and stents, adverse events, length of hospital stay, overall hospital costs, the same between lupus patients and non lupus patients, and that's probably important to note.
Something that we often teach about, but there's a little bit of data that you can point to from this citation that we found, I think from the Korean literature, Korean researchers I should say, and that shows that rheumatoid factor we know goes up with chronic liver disease, especially with hepatitis C infection. But we supposedly think that the ACBA positivity or CCP antibody positivity should not go up in those people, and that's what this one large study of almost 300 patients shows that only amongst HCV positive patients, meaning there's no arthritis in play here. They just looked at hepatitis C infected individuals and looked at seropositivity. They found forty seven percent had a positive rheumatoid factor, but that less than one percent one percent had a positive CCP antibody. High high titer positive rheumatoid factor in nine percent, again, titer positive ACPA one percent.
It is safe to say that ACPA should not go up with liver infection and liver disease, whereas rheumatoid factor may go up. An interesting study from Taiwan looked at what happens to, a large cohort of psoriasis patients, especially psoriasis patients who have hypertension, over four thousand patients followed for five years, showed that these patients are not only at a higher risk of cardiovascular outcomes, they have a higher risk of cardiovascular procedures and surgery, and this was more so seen in patients with psoriatic arthritis and those with severe psoriasis. Again, to that diagnosis being a significant risk factor for cardiovascular disease, suggesting that your psoriasis and psoriatic arthritis patients really need multidisciplinary management and comorbidity management. It's very important. A late breaking report, late breaking abstract nine, L09 from the ACR looked at the risk of venous thromboembolic events and specifically looked at a Medicare dataset of over 50,000 claims made and specifically looked at the RA patients and tried to assess those RA patients who are on tofacitinib and those RA patients who are on any TNF inhibitor and what was the overall risk of venous thromboembolic event, and that includes both deep vein thrombosis and or, pulmonary embolism.
As was seen in previous research on this, RA patients are at a higher risk. Turns out that, RA patients on these drugs tend to have risks that are about that of the population risk, a little higher than the population risk, about zero point five events per one 100 patient years. The hazard ratio was not different between tofacitinib and, any TNF inhibitor, has a ratio being 1.33, but the confidence intervals being wide at 0.78 to 2.24, suggesting that the rates were higher in RA patients, not higher on one drug versus another, higher with age. Older age groups tend to have more of these events and we know age is a risk factor for venous thromboembolic events. Another I thought important abstract that were not previously covered by us, from the ACR is the abstract by, Jeff Peterson's group in Washington where they reported on their collective experience of 10 patients undergoing peglodecase therapy.
As you know, the big issue with peglodecase these days is, it works. It's tremendously, effective in patients with a large total body urate load. It drops your uric acid levels from elevated to basically nothing right quick as we say in Texas. But the big limiting factor there is not every patient responds and that some patients the hindered response seems to be related to the immunogenicity against the PEGylated portion of the molecule, so anti PEG antibodies. When that happens, you'll get anti PEG antibodies interfering with the tests and the uric acid levels will rise and whatnot.
Anyway, the question in play right now is whether or not you should use immunosuppression when you're giving peglodecase to lower the immunogenicity of the drug and therefore improve the success of the therapy. Well, in their single center, uncontrolled, all 10 patients got methotrexate at the usual doses of around fifteen milligrams per week, and basically they had a response in all patients and no patients were found to have an immunogenic response or loss of efficacy. There was no subsequent rise in serum uric acid level suggesting this was an effective way to maximize therapy with pegilodecase in patients with chronic refractory gout. There are trials, there's been reports in the literature, from Michael Pillinger and a few others using azathioprine for that same purpose. There is a trial that's underway with Ken Sag in Alabama using peglodecase but using background mycophenolate to suppress responses.
I want to remind you that the earliest trials with infliximab, the CA2 antibody done by Tiny Mani and others, their very early trials showed that they could suppress the immune responses in patients by using methotrexate at low doses seven point five, and other therapies that we commonly use. Methotrexate is not particularly novel here, but it is important that this be considered. Antiphospholipid antibodies in myocardial infarction, an interesting study in the cardiology journals looks at a large Australian cohort of over eight hundred first new MIs and found eleven percent of their MIs had elevated. These are not arthritis patients, not lupus patients, these are MI patients. Eleven percent of their patients had elevated antiphospholipid antibodies against both cardiolipin and beta-two glycoprotein-one, and this was more than 10 times controls.
This was an important and significant suggest if you don't have an etiology for a myocardial infarction, testing for antiphospholipid antibodies would be reasonable. Lastly, we have a nice little review on a spotlight on interstitial lung disease from ACR. A few interesting reports. The highlights of that include, two abstracts, one from, two abstracts from Jeff Sparks' group and the brass database, which one showed that disease activity, was associated with an increased risk of interstitial lung disease, increased risk to the tune of about two and a half fold higher, clearly being a risk factor for interstitial lung disease. Also, one of his fellows, Doctor.
Huang, looked at their experience with CT chests in their RA population over 1,500 patients and showed that seropositive RA patients did not have a lock or exclusivity on lung disease. Turns out that seronegative patients had a significant amount of lung findings including the lung nodules, being equally present in RF negative and RF positive patients around forty percent. Interstitial lung disease, sixteen and fifteen percent for seronegative and seropositive patients, and pleural effusion same thing about nine percent, ten percent suggesting that do not exclude the possibility of lung disease being related to RA just because they're seronegative. Maybe the most important report was the plenary session report about this, MUC5B or MUC5B promoter variant RS35705950 being associated with an increased risk of interstitial lung disease, about a two to fivefold increased risk in RA patients. This promoter, variant is not seen in RA patients, not associated with RA, but it is associated with interstitial lung disease.
It is not seen in systemic sclerosis, but it may be seen in other disorders. It seems to be associated with the UIP pattern of ILD, and I think that's important. Lastly, I wanna tell you about the most important thing that we're working on here at, RheumNow, and that is RheumNow Live. This is our first CME conference. It's going to occur February '20 04/2019 in beautiful downtown Fort Worth, Texas at the Worthington Hotel.
It's going be an event depart. I really would ask you to look at this. The program was developed by you, the RheumNow readership in our needs assessment. A lot of what we took from you is what's been in the design of this program. This is going to be a highly interactive audience between the faculty, the moderators, and the audience.
There's an app that we're going to be using to cross communicate and interact with the faculty. We have sessions devoted to drug safety, orthopedics, rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, systemic lupus, and, I'm leaving out one, but that's enough. I think there's about seven or eight main sessions. Then in between the main sessions, which are two hours long, three and a half hour lectures, one half hour group discussion, panel discussion with the faculty. Between those two hour segments, we're going to have TED like talks, which are going to be just fabulous.
I encourage you to go to roomnow.live to learn more about this meeting. That's it for this week on roomnow.com. We'll see you next week. Have a good weekend.
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