The RheumNow Week In Review - 8 September 2017 Save
The RheumNow Week In Review - 8 September 2017 by Dr. Cush
Transcription
Hi. It's 09/08/2017. It's the RheumNow we can review, and I'm doctor Jack Cush, executive editor of rheumnow.com. Bad news this week about opioids. Does that not ever stop?
Surprising shocking news about fibromyalgia, the inflammatory disorder. And do rheumatologists pay lip service to ACR ULA criteria, or do they really mean something? At the top of the news, we have a report, of a study of a hundred and ninety two patients with chronic fatigue syndrome. You know, that's the, MECFS, the myalgic encephalitis chronic fatigue syndrome story. And they assayed a large number of them and also a large number of controls looking at cytokine production by these people, using sera.
And, and they found a surprising number of pro inflammatory cytokines being upregulated in patients with chronic fatigue syndrome. Now, again, none of us think of this as a inflammatory disorder, yet they find high TGF beta levels, low resistant levels, and all in all, 17 cytokines that were elevated, and may indicate some degree of inflammation, if not immunologic activation. This includes four or five different chemokines, IL four, IL five, IL seven, IL 13, IL 17 f, a number of growth factors including G CSF and GM CSF. Again, what it means, and the showing that these correlate to some degree with activity is a bit surprising. So, you know, maybe it would be good for rheumatology to learn that fibromyalgia isn't just a simple pain disorder or pain amplification disorder and may have alternative approaches because lord knows we need one.
A number of studies actually looked at methotrexate and methotrexate dosing. So specifically between 2004 and 2014, the use of methotrexate in biologics rose substantially. Methotrexate from forty to sixty four percent, biologics from two percent to over twenty four percent in this particular cohort, twenty seven percent. But during that same period, the rate of orthopedic surgery of the hip and knee declined significantly dropping from seventy two to fifty one per one thousand patient years, suggesting that more effective therapy is leading to a shift in cost away from hospitalizations and surgeries and towards more expensive biologic and combination therapies. Another study about methotrexate dosing looked at patients in a large cohort and those who achieved optimal dosing.
And optimal dosing was defined as being on ten milligrams of methotrexate per week within three months of presentation. These are early RA patients, by the way. And then at six months being on twenty milligrams per week unless they had a contraindication. And what they did show that those who had optimal dosing did have, as you would expect, significant improvement in clinical and functional parameters, but no improvement in radiographic parameters suggesting that, again, maybe we do need more than just methotrexate alone, the age old question. A study of two hundred and thirty consecutive SLE patients in a nephrology journal looked at the comparative value of protein to creatinine ratios, PCR, and twenty four hour urine collections for protein, in lupus patients.
They followed these patients serially, they basically showed, that of the ninety five patients who had an had both of these abnormal at the outset, over time, the protein to creatinine ratio was not a good surrogate. In fact, it was, said insufficient in its accuracy compared to the twenty four hour, protein assessment. So I don't know how I don't rely on that in my practice, but I don't know some people do, spot protein creatinine ratios as a measure. I think it's a quick and dirty, but I don't think it's accurate. And that was then a study would would sort of back that up.
Claims data looked at RA and the incidence of RA over a ten year period and found RA to be slightly increased in this ten year period affecting between one point two eight and one point three six million adults in The United States or roughly about zero point five percent of all adults. As you know, it changes with age. It changes with more and more common in women, etcetera. But these were numbers as as late as 2014, somewhat of a change, and I think somewhat of a decrease as far as the overall prevalence numbers. Pruritus is a common accompaniment to psoriasis.
It affects about eighty percent of patients. And in a particular study that was published, they looked at a meta analysis of of over 13 trials, and they tried to look at the drugs that had an impact on pruritus as an outcome. And, surprisingly to me, the only ones that actually did, affect pruritus were IL-seventeen inhibitors, the JAK inhibitors, adalimumab, and aprimelast. It wasn't shown for the other TNF inhibitors on the market or other ones including resusukinumab in this story. I would imagine it must, but anyway, this particular study said no.
It's the IL-seventeen inhibitors which are more dominant therapies in the dermatology and psoriasis world. Despite the need to do TB testing with IL-seventeen inhibitors, it's required. It's in the label. It should be noted a recent report showed that, biologically, in vitro studies suggest that IL-seventeen is not important in granuloma formation and maintenance, and therefore, in animal models or not animal models, in vitro models, there is no reactivation of TB with use of IL-seventeen inhibition. And that's backed up by the clinical data since the, these drugs have been in clinical trials and studied in multiple multiple IL-seventeen inhibitors.
In the one year results in randomized controlled trials, they did not show any new cases of TB or reactivation of TB in patients going into those trials. So even though you gotta do the test, it's like other drugs, other situations where you have to do the test, but really there is no risk with abatacept, rituximab, anakinra, a number of other drugs. So let me just check my battery here. There we go. Yeah.
We're human here. So, a hundred fifty three RA patients, twenty three percent had anemia. The only drugs that are shown to significantly affect anemia was tocilizumab, not tofacitinib, not DMARDs, not other non TNF biologics. There's four interesting reports and news articles on the website this week, including new recommendations on on ultrasound use from EULAR, but also new recommendations on biosimilar use from John Kay and a number of of colleagues, throughout the world who are sort of expert in this area. They developed a task force.
They looked at this. They came up with, 13 overarching principles and recommendation. Of those thirteen, ten of them were grade d evidence, meaning that they were expert opinion. So that's one of the problems of guidelines where we are when you're not ready to really write good guidelines. But nonetheless, they are helpful and are instructive, and the other three do have evidence to back them up.
They include that in situations where they should be used, biosimilars should be used just as the bio originator should be. Same indication, same use. As there is no good evidence of immunogenicity that's different between these drugs, there's no indication and need for anti drug antibodies to be drawn with biosimilars. And then in situations where there have been single switch studies, going from the originator to a biosimilar, there's been no downside. Now that's interchangeability, and there are new guidelines interchangeability, and no drug currently has an indication for interchangeability, but the existing evidence suggests that that can happen.
There's no reason to suggest that changing from one bio originator to biosimilar to another biosimilar back to bio originator should produce any issues. But, again, the FDA has new guidelines. The EMA has guidelines on that as well. There is a report about rheumatoid arthritis augmenting cardiovascular risk. A study from 13 centers, 5,600 plus patients followed for over nearly six years showed that cardiovascular events, and these are people who are not at risk, RA patients with no history of cardiovascular disease, that twenty one percent of males and eleven percent of females developed a cardiovascular event, includes things like angina and MI, etcetera, and some cardiac deaths.
And that when they looked at the risk factors for these cardiovascular events, as you would expect, traditional cardiovascular risk factors, hypertension, smoking, hyperlipidemia were major risk factors but and accounted for about seventy percent of these events. However, the remaining thirty percent could be accounted for by rheumatoid arthritis itself. And if the risk imposed by rheumatoid arthritis, about equal to that imposed by hyperlipidemia. Breaking bad and fentanyl. You should look at this article.
It's quite shocking. As you know, that, you know, in a five year period, opioid related deaths doubled in in Ohio, and the and and early on, was a lot of heroin use that was contributing to this as we were getting more restrictive with the use of drugs like hydrocodone, OxyContin, even tramadol. So there's a lot of unexpected heroin used out there. More recently, it's fentanyl. And not only just fentanyl, but analogs of fentanyl that are, you know, adulterated fentanyl that are leading to, compounds that are hard to detect in laboratory assays.
Nonetheless, in 2017 alone, the numbers are a bit shocking. Ninety percent of all of the unintentional overdose deaths in Ohio were due to fentanyl or fentanyl analogs. This is a major problem. And lastly, do rheumatologists, use ACR and ULA criteria? We asked four questions of almost 300 US and non US rheumatologists, and they all pretty much behave the same.
Shockingly, when asked how you diagnosed RA, fifty two percent said that they use ACR UR criteria, the new ACR UR criteria to make the diagnosis, and the others use clinical parameters. However, when asked how they put them to use, they, number one, didn't actually know that the number of points you get for either a high titer rheumatoid factor or high titer CCP was three points, only thirty percent got that right. And it was the same in The US as opposed to non US. Moreover, when we asked how you define remission and do you rely at all on ACR UR criteria for remission, Less than less than eight percent, did. Everybody used, you know, whatever their own clinical acumen was.
I know it when I see it. No swollen joints, that sort of thing. So they actually forty percent were clinical parameters. No swollen joints, no standing joints. Forty five percent were in favor of a metric defined remission like a rapid less than three, etcetera.
And then lastly, the number that actually use treatment guidelines, the ICR UR treatment guidelines published in 2015 from, a number of our colleagues, less than twenty four percent rely on those in making treatment decisions. So there is this discordance out there about how important these are and doesn't seem like they have a lot of traction. And I'm not sure if that's a good thing or a bad thing because in fact most rheumatologists are doing pretty well in how they manage these patients. I wanna close with an announcement about Doctor. Hugo Jason, one of my mentors, one of the first faculty members I had at UT Southwestern who recently passed on on 08/24/2017.
Yugo, has a he was one of the triple threats in medicine. One of those guys that taught, saw patients, did research, and ultimately ran a division, was an administrator as well, had a lifelong career in academic medicine and rheumatology and was one of the giants, did a lot of work in B cells and rheumatoid factor and was highly respected throughout the rheumatology world. His loss is a great one. He's had a lot of people like me who he mentored. He was my first week in Parkland's rheumatology clinic.
You know, Jason told me, We don't prescribe these new drugs. We let other people and then the the drug in name was was paroxacam, Feldene. It just come out. It was being pushed by the manufacturer. Well, we don't use brand new drugs here.
We let other people use new drugs, we learn from them. He also taught me to be cautious about the use of methotrexate back in 1984, and, and, you know, conservatism has its place, especially for trainees in training programs. Thank God for people like you, Jason. May you rest in peace. That's it for this week in roomnow.com.
Go to the website. Look at our our citations and read more if you like. Be sure to follow us at ACR two thousand seventeen San Diego. We got a lot of stuff coming your way. That's it for this week.
Goodbye.
Surprising shocking news about fibromyalgia, the inflammatory disorder. And do rheumatologists pay lip service to ACR ULA criteria, or do they really mean something? At the top of the news, we have a report, of a study of a hundred and ninety two patients with chronic fatigue syndrome. You know, that's the, MECFS, the myalgic encephalitis chronic fatigue syndrome story. And they assayed a large number of them and also a large number of controls looking at cytokine production by these people, using sera.
And, and they found a surprising number of pro inflammatory cytokines being upregulated in patients with chronic fatigue syndrome. Now, again, none of us think of this as a inflammatory disorder, yet they find high TGF beta levels, low resistant levels, and all in all, 17 cytokines that were elevated, and may indicate some degree of inflammation, if not immunologic activation. This includes four or five different chemokines, IL four, IL five, IL seven, IL 13, IL 17 f, a number of growth factors including G CSF and GM CSF. Again, what it means, and the showing that these correlate to some degree with activity is a bit surprising. So, you know, maybe it would be good for rheumatology to learn that fibromyalgia isn't just a simple pain disorder or pain amplification disorder and may have alternative approaches because lord knows we need one.
A number of studies actually looked at methotrexate and methotrexate dosing. So specifically between 2004 and 2014, the use of methotrexate in biologics rose substantially. Methotrexate from forty to sixty four percent, biologics from two percent to over twenty four percent in this particular cohort, twenty seven percent. But during that same period, the rate of orthopedic surgery of the hip and knee declined significantly dropping from seventy two to fifty one per one thousand patient years, suggesting that more effective therapy is leading to a shift in cost away from hospitalizations and surgeries and towards more expensive biologic and combination therapies. Another study about methotrexate dosing looked at patients in a large cohort and those who achieved optimal dosing.
And optimal dosing was defined as being on ten milligrams of methotrexate per week within three months of presentation. These are early RA patients, by the way. And then at six months being on twenty milligrams per week unless they had a contraindication. And what they did show that those who had optimal dosing did have, as you would expect, significant improvement in clinical and functional parameters, but no improvement in radiographic parameters suggesting that, again, maybe we do need more than just methotrexate alone, the age old question. A study of two hundred and thirty consecutive SLE patients in a nephrology journal looked at the comparative value of protein to creatinine ratios, PCR, and twenty four hour urine collections for protein, in lupus patients.
They followed these patients serially, they basically showed, that of the ninety five patients who had an had both of these abnormal at the outset, over time, the protein to creatinine ratio was not a good surrogate. In fact, it was, said insufficient in its accuracy compared to the twenty four hour, protein assessment. So I don't know how I don't rely on that in my practice, but I don't know some people do, spot protein creatinine ratios as a measure. I think it's a quick and dirty, but I don't think it's accurate. And that was then a study would would sort of back that up.
Claims data looked at RA and the incidence of RA over a ten year period and found RA to be slightly increased in this ten year period affecting between one point two eight and one point three six million adults in The United States or roughly about zero point five percent of all adults. As you know, it changes with age. It changes with more and more common in women, etcetera. But these were numbers as as late as 2014, somewhat of a change, and I think somewhat of a decrease as far as the overall prevalence numbers. Pruritus is a common accompaniment to psoriasis.
It affects about eighty percent of patients. And in a particular study that was published, they looked at a meta analysis of of over 13 trials, and they tried to look at the drugs that had an impact on pruritus as an outcome. And, surprisingly to me, the only ones that actually did, affect pruritus were IL-seventeen inhibitors, the JAK inhibitors, adalimumab, and aprimelast. It wasn't shown for the other TNF inhibitors on the market or other ones including resusukinumab in this story. I would imagine it must, but anyway, this particular study said no.
It's the IL-seventeen inhibitors which are more dominant therapies in the dermatology and psoriasis world. Despite the need to do TB testing with IL-seventeen inhibitors, it's required. It's in the label. It should be noted a recent report showed that, biologically, in vitro studies suggest that IL-seventeen is not important in granuloma formation and maintenance, and therefore, in animal models or not animal models, in vitro models, there is no reactivation of TB with use of IL-seventeen inhibition. And that's backed up by the clinical data since the, these drugs have been in clinical trials and studied in multiple multiple IL-seventeen inhibitors.
In the one year results in randomized controlled trials, they did not show any new cases of TB or reactivation of TB in patients going into those trials. So even though you gotta do the test, it's like other drugs, other situations where you have to do the test, but really there is no risk with abatacept, rituximab, anakinra, a number of other drugs. So let me just check my battery here. There we go. Yeah.
We're human here. So, a hundred fifty three RA patients, twenty three percent had anemia. The only drugs that are shown to significantly affect anemia was tocilizumab, not tofacitinib, not DMARDs, not other non TNF biologics. There's four interesting reports and news articles on the website this week, including new recommendations on on ultrasound use from EULAR, but also new recommendations on biosimilar use from John Kay and a number of of colleagues, throughout the world who are sort of expert in this area. They developed a task force.
They looked at this. They came up with, 13 overarching principles and recommendation. Of those thirteen, ten of them were grade d evidence, meaning that they were expert opinion. So that's one of the problems of guidelines where we are when you're not ready to really write good guidelines. But nonetheless, they are helpful and are instructive, and the other three do have evidence to back them up.
They include that in situations where they should be used, biosimilars should be used just as the bio originator should be. Same indication, same use. As there is no good evidence of immunogenicity that's different between these drugs, there's no indication and need for anti drug antibodies to be drawn with biosimilars. And then in situations where there have been single switch studies, going from the originator to a biosimilar, there's been no downside. Now that's interchangeability, and there are new guidelines interchangeability, and no drug currently has an indication for interchangeability, but the existing evidence suggests that that can happen.
There's no reason to suggest that changing from one bio originator to biosimilar to another biosimilar back to bio originator should produce any issues. But, again, the FDA has new guidelines. The EMA has guidelines on that as well. There is a report about rheumatoid arthritis augmenting cardiovascular risk. A study from 13 centers, 5,600 plus patients followed for over nearly six years showed that cardiovascular events, and these are people who are not at risk, RA patients with no history of cardiovascular disease, that twenty one percent of males and eleven percent of females developed a cardiovascular event, includes things like angina and MI, etcetera, and some cardiac deaths.
And that when they looked at the risk factors for these cardiovascular events, as you would expect, traditional cardiovascular risk factors, hypertension, smoking, hyperlipidemia were major risk factors but and accounted for about seventy percent of these events. However, the remaining thirty percent could be accounted for by rheumatoid arthritis itself. And if the risk imposed by rheumatoid arthritis, about equal to that imposed by hyperlipidemia. Breaking bad and fentanyl. You should look at this article.
It's quite shocking. As you know, that, you know, in a five year period, opioid related deaths doubled in in Ohio, and the and and early on, was a lot of heroin use that was contributing to this as we were getting more restrictive with the use of drugs like hydrocodone, OxyContin, even tramadol. So there's a lot of unexpected heroin used out there. More recently, it's fentanyl. And not only just fentanyl, but analogs of fentanyl that are, you know, adulterated fentanyl that are leading to, compounds that are hard to detect in laboratory assays.
Nonetheless, in 2017 alone, the numbers are a bit shocking. Ninety percent of all of the unintentional overdose deaths in Ohio were due to fentanyl or fentanyl analogs. This is a major problem. And lastly, do rheumatologists, use ACR and ULA criteria? We asked four questions of almost 300 US and non US rheumatologists, and they all pretty much behave the same.
Shockingly, when asked how you diagnosed RA, fifty two percent said that they use ACR UR criteria, the new ACR UR criteria to make the diagnosis, and the others use clinical parameters. However, when asked how they put them to use, they, number one, didn't actually know that the number of points you get for either a high titer rheumatoid factor or high titer CCP was three points, only thirty percent got that right. And it was the same in The US as opposed to non US. Moreover, when we asked how you define remission and do you rely at all on ACR UR criteria for remission, Less than less than eight percent, did. Everybody used, you know, whatever their own clinical acumen was.
I know it when I see it. No swollen joints, that sort of thing. So they actually forty percent were clinical parameters. No swollen joints, no standing joints. Forty five percent were in favor of a metric defined remission like a rapid less than three, etcetera.
And then lastly, the number that actually use treatment guidelines, the ICR UR treatment guidelines published in 2015 from, a number of our colleagues, less than twenty four percent rely on those in making treatment decisions. So there is this discordance out there about how important these are and doesn't seem like they have a lot of traction. And I'm not sure if that's a good thing or a bad thing because in fact most rheumatologists are doing pretty well in how they manage these patients. I wanna close with an announcement about Doctor. Hugo Jason, one of my mentors, one of the first faculty members I had at UT Southwestern who recently passed on on 08/24/2017.
Yugo, has a he was one of the triple threats in medicine. One of those guys that taught, saw patients, did research, and ultimately ran a division, was an administrator as well, had a lifelong career in academic medicine and rheumatology and was one of the giants, did a lot of work in B cells and rheumatoid factor and was highly respected throughout the rheumatology world. His loss is a great one. He's had a lot of people like me who he mentored. He was my first week in Parkland's rheumatology clinic.
You know, Jason told me, We don't prescribe these new drugs. We let other people and then the the drug in name was was paroxacam, Feldene. It just come out. It was being pushed by the manufacturer. Well, we don't use brand new drugs here.
We let other people use new drugs, we learn from them. He also taught me to be cautious about the use of methotrexate back in 1984, and, and, you know, conservatism has its place, especially for trainees in training programs. Thank God for people like you, Jason. May you rest in peace. That's it for this week in roomnow.com.
Go to the website. Look at our our citations and read more if you like. Be sure to follow us at ACR two thousand seventeen San Diego. We got a lot of stuff coming your way. That's it for this week.
Goodbye.
If you are a health practitioner, you may Login/Register to comment.
Due to the nature of these comment forums, only health practitioners are allowed to comment at this time.