The RheumNow Week in Review - 8 June 2017 Save
The RheumNow Week in Review - 8 June 2017 by Dr. Cush
Transcription
This is the RheumNow we can review. It's the 06/09/2017, and I'm Jack Cush, executive editor of roomnow.com with the highlights of this week's news at roomnow.com. The big news is going to be the following: The FDA gets tough on opioids. How about the methotrexate mavens fight back about alcohol? And how long is too long for long term bisphosphonate use?
These to follow. At the top of the news, you should all be aware of the AbbVie scholarship program. If you're not, this has been going on a number of years and AbbVie announced again its continuation of this program. I think it's important, that we know about this for our patients, especially our young patients. This is a grant program that issues $15,000 a year to applicants who apply, who have rheumatic diseases and want to further their secondary education.
It's a really nice program, it's designed specifically for those who have rheumatoid arthritis and serious rheumatic disease. It does not have to be a TNF inhibitor that they're taking, it could be any drug in any needy situation. The information that you will need can be found on the AbbVie website. An interesting report was seen this week where they looked at claims data, and looked at the comparative effects of allopurinol or febuxostat in reducing the, incidence of, renal disease. Now, obviously, this is going to be a population of individuals taking those drugs probably for gout and maybe some for, nephrolithiasis.
But looking at patients taking those drugs, and looking specifically at the onset of new renal disease which occurs in both gout and nephrolithiasis and theoretically the inhibition of uric acid and its production should lead to less renal disease over time. I think this sort of unbiased view, may be insightful and in fact what the claims data showed was that allopurinol was associated with I think about a twenty nine percent lower risk of, incidental renal disease. The hazard ratio was sixty one percent, so that makes it actually a thirty nine percent reduction. Interesting data. And I think it can coincide with the fact that most of us would use allopurinol first as opposed to fevuxostat.
A nice review of myositis in lupus patients shows that it's more likely to occur with the following constellation of symptoms: lupus rash, alopecia, pericarditis, vasculitis, serologies that would include SM and RNP and double stranded DNA autoantibodies, low platelets, low complements and neutropenia all being sort of associated with those who may be at higher risk for developing myositis with lupus. A nice review appears in the literature about myocarditis and the clinical associations that have been seen with it. Just as a review, myocarditis can be seen with sarcoidosis, Behcet syndrome, Churg Strauss, inflammatory myositis and lupus. A study from a few years ago, the Quest RA, I came across recently and I thought it was interesting because it talks to the comorbidities that occur with chronic inflammatory disease, in this case, rheumatoid arthritis. This is a multinational study of a large number of patients, tens of thousands, maybe 40,000 patients, and showed that the average rheumatoid arthritis patient has two or more comorbidities.
The most common ones being hypertension, osteoporosis, and osteoarthritis. It turns out that, fatigue, is commonly associated with the presence of comorbidity, as is disease activity. So, something that needs to be addressed, I don't think that we do a good job of addressing comorbidity. We assume it's going be managed by the primary care doctor, they assume we're managing it. The patient assumes that you're the smartest doctor in their mix of doctors, so they often don't go to their primary care doctor.
You do need to address comorbidity and how it's going to be managed. A nice review appeared in the literature about tofacitinib and its use in alopecia areata. As you know, it's an autoimmune disease, hair loss, a wide range of just sort of patchy hair loss to complete total body hair loss called alopecia universalis. And there's been reports in the past, about success when using tofacitinib often at high doses, ten mg twice a day. There are clinical trials going on right now that are looking at this, not just with, tofacitinib but other JAK inhibitors.
But we're at this point waiting for those results and this one, study looked at 13 patients who received tofacitinib at the usual dose that's currently available, five mg twice a day, in thirteen patients who had a variety of severity for alopecia areata. They showed about 50% regrowth after about four to five months. And this is sort of in keeping with some of the larger reports that have come out since the initial single case reports. The initial single case reports are very shocking as far as almost complete growth of hair, almost like this, when, they go on tofacitinib. The more, the larger case reports have shown a variable amount of hair improvement, although the majority do improve their hair growth.
Complete hair growth is seen in less than fifty percent. But again, that fifty percent number, of responders or degree of response seems to be common. This is probably gonna be a dose related effect but we need to see the results of the clinical trials. That's probably going to happen, late this year, early next year. There are also some interesting reports in the area of JAK inhibitors where, case reports on tofacitinib and another JAK inhibitor called, roloxacitinib used in other conditions, where those have been used in refractory cases of dermatomyositis and have yielded surprisingly good results.
This is leading several of the manufacturers to develop clinical trials in dermatomyositis. They'll probably be open label, they'll probably be small, but nonetheless that is a research that's much needed going forward. Certainly, we do need more options for our patients who have dermatomyositis. Metformin has been often used lately with regard to, as an adjunctive agent. It may have effects on IL-seventeen and T-seventeen cells.
A recent study which looks at the effects of metformin and its effects on the gut microbiome, and how it may work in diabetes. So, while there are lot of postulates about metformin working, it seems that a lot of its effect may be mediated by a change in the gut microbiome. In fact, taking the, fecal transplants of metformin, altered microbiota has actually improved the glucose tolerance in animal models. So, a sort of surprising result but, a novel finding for metformin for both diabetes and maybe even for its use in autoimmune disease like psoriasis. The FDA, came up with recent news just yesterday suggesting that, Opana extended release, a long acting opioid be removed from the market by its manufacturer Endo Pharmaceuticals.
They did not mandate this, they have suggested this. Opana, a long acting, drug has been often abused. It's been out of the market since 2006. People would crush it to get a faster effect, a higher high, so to speak. And in the years since its approval the manufacturer has tried to make it more tamper resistant but that has not been met with much success.
A recent, review by an advisory committee suggested that the risks far outweigh the benefits and that the newer drugs that are being approved as long acting opioids are much more tamper resistant. So, the FDA has gone forward and said that this should be removed, and it's going to be a voluntary removal. We'll wait and see what the manufacturer says. If they don't comply, it's likely that the FDA will take further steps to take it off the market. A nice debate, can be seen in the correspondence section of the current edition of Annals of Rheumatic Disease.
Mike Weinblatt and, Joel Kremer wrote a letter to the editor, specifically to the authors, of a paper that was published earlier in the year, by, oh, I forget the name, a group of authors, looked at a UK database and commented on, how safe it was to take alcohol while you were on methotrexate. And what they found, what they recommended was that, if you looked at those people who took 14 less alcoholic units per week, the incidence of methotrexate hepatotoxicity as defined as a threefold or higher elevation in transaminases, was not significantly higher and it was only when you went above 14 drinks per week, fourteen units per week, that you were seeing higher in numbers. Well, in response to this, the gentleman who developed the guidelines on methotrexate use, Joel Kramer, Mike Weinblatt, there were others. Grecia Alecon was the lead author on that paper. They've come out and wrote a nice reply back saying, It wasn't too long ago that we were worried about the liver and we were doing liver biopsies regularly in these patients.
And they said that, you know, it was erroneous for the authors to take an arbitrary cut off of threefold higher elevations as some indicator of liver damage. They pointed out, Weinblatt and Kremer, that the stringency in which they made their definitions, they had histologic evidence that complete medical records. And again, there was a conservative guideline regarding, alcohol. This move to allow more liberal use of alcohol, which I sort of believe in, actually is really not yet based on any good evidence. So, they sort of chastised the authors for, their suggestions that it's okay to do that.
The authors actually agreed with much of the points made by Kramer and Weinblatt, although they said they wanted something more practical and pragmatic and that they say that, they're not advocating that patients drink fourteen units a week but that there should be a conversation between the patient and the prescribing physician. And then, we have a few more things in the news. I guess biosimilar reports came out this week. This was our fifth installment of biosimilars and what's new in the world of biosimilars. As you know, in April there was a new infliximab, biosimilar called Renflexis made by, Sampson Bioepis, the same people who make those exploding telephones.
And this is now the fourth TNF inhibitor to be on the market, the fifth biosimilar in The United States to be approved. That's sort of a landmark for this, in the last few months. Obviously, some really nice, literature reports. The Dan Bio study looked at, switching, the North Switch study which we wrote about on our site is covered in here. There's a nice review, new guidelines that could be put forward by, the EMA.
There's a new biosimilar guideline that's put out for physicians in the EU, but I think for those of you who are looking for some new instructive overviews, that might be a nice one to look at. And lastly, something we hinted at but we're going to follow closer is the, Supreme Court case of Amgen versus Sandoz where they're at this level of Supreme Court asking questions about how long one company has to give another company notice before they market their new biosimilar, and there are some patent issues. This is overall being called the patent dance, so you might want to look into that and watch for more information about that going forward. The last report we have today is, a higher risk of fracture in women, older women who are taking bisphosphonates. This is a study from the Women's Health Initiative, over 5,000 women followed prospectively.
They looked at their bisphosphonate use and whether they were on it for two years, and then compared that to those who were on bisphosphonates for three to five, six to nine, ten to thirteen years. They showed that, those that were taking bisphosphonates for ten to thirteen years had a twenty nine percent higher risk of any and all fractures. When they looked at individual fractures, vertebral and non vertebral, it wasn't significant but for all fractures it was significant. The hazard ratio was one point two nine, and suggested significant. So, clearly it says that, you know, really long prolonged use of bisphosphonates may not be a good use.
And obviously you need to make that decision based on how much they need the bisphosphonate or other, therapies that will build up bone. So, a nice, instructive report from the Women's Health Initiative. That's it for this week at roomnow.com. You can go to the website to find the links to these reports and read more about these reports. You can listen to this as a podcast from iTunes or we'll post the link from Soundhound.
Please be sure to give us a really high rating so that we can win an Academy Award, Tony, Katie Award, whatever awards they're giving out this day for the Internet. We'll see you next week.
These to follow. At the top of the news, you should all be aware of the AbbVie scholarship program. If you're not, this has been going on a number of years and AbbVie announced again its continuation of this program. I think it's important, that we know about this for our patients, especially our young patients. This is a grant program that issues $15,000 a year to applicants who apply, who have rheumatic diseases and want to further their secondary education.
It's a really nice program, it's designed specifically for those who have rheumatoid arthritis and serious rheumatic disease. It does not have to be a TNF inhibitor that they're taking, it could be any drug in any needy situation. The information that you will need can be found on the AbbVie website. An interesting report was seen this week where they looked at claims data, and looked at the comparative effects of allopurinol or febuxostat in reducing the, incidence of, renal disease. Now, obviously, this is going to be a population of individuals taking those drugs probably for gout and maybe some for, nephrolithiasis.
But looking at patients taking those drugs, and looking specifically at the onset of new renal disease which occurs in both gout and nephrolithiasis and theoretically the inhibition of uric acid and its production should lead to less renal disease over time. I think this sort of unbiased view, may be insightful and in fact what the claims data showed was that allopurinol was associated with I think about a twenty nine percent lower risk of, incidental renal disease. The hazard ratio was sixty one percent, so that makes it actually a thirty nine percent reduction. Interesting data. And I think it can coincide with the fact that most of us would use allopurinol first as opposed to fevuxostat.
A nice review of myositis in lupus patients shows that it's more likely to occur with the following constellation of symptoms: lupus rash, alopecia, pericarditis, vasculitis, serologies that would include SM and RNP and double stranded DNA autoantibodies, low platelets, low complements and neutropenia all being sort of associated with those who may be at higher risk for developing myositis with lupus. A nice review appears in the literature about myocarditis and the clinical associations that have been seen with it. Just as a review, myocarditis can be seen with sarcoidosis, Behcet syndrome, Churg Strauss, inflammatory myositis and lupus. A study from a few years ago, the Quest RA, I came across recently and I thought it was interesting because it talks to the comorbidities that occur with chronic inflammatory disease, in this case, rheumatoid arthritis. This is a multinational study of a large number of patients, tens of thousands, maybe 40,000 patients, and showed that the average rheumatoid arthritis patient has two or more comorbidities.
The most common ones being hypertension, osteoporosis, and osteoarthritis. It turns out that, fatigue, is commonly associated with the presence of comorbidity, as is disease activity. So, something that needs to be addressed, I don't think that we do a good job of addressing comorbidity. We assume it's going be managed by the primary care doctor, they assume we're managing it. The patient assumes that you're the smartest doctor in their mix of doctors, so they often don't go to their primary care doctor.
You do need to address comorbidity and how it's going to be managed. A nice review appeared in the literature about tofacitinib and its use in alopecia areata. As you know, it's an autoimmune disease, hair loss, a wide range of just sort of patchy hair loss to complete total body hair loss called alopecia universalis. And there's been reports in the past, about success when using tofacitinib often at high doses, ten mg twice a day. There are clinical trials going on right now that are looking at this, not just with, tofacitinib but other JAK inhibitors.
But we're at this point waiting for those results and this one, study looked at 13 patients who received tofacitinib at the usual dose that's currently available, five mg twice a day, in thirteen patients who had a variety of severity for alopecia areata. They showed about 50% regrowth after about four to five months. And this is sort of in keeping with some of the larger reports that have come out since the initial single case reports. The initial single case reports are very shocking as far as almost complete growth of hair, almost like this, when, they go on tofacitinib. The more, the larger case reports have shown a variable amount of hair improvement, although the majority do improve their hair growth.
Complete hair growth is seen in less than fifty percent. But again, that fifty percent number, of responders or degree of response seems to be common. This is probably gonna be a dose related effect but we need to see the results of the clinical trials. That's probably going to happen, late this year, early next year. There are also some interesting reports in the area of JAK inhibitors where, case reports on tofacitinib and another JAK inhibitor called, roloxacitinib used in other conditions, where those have been used in refractory cases of dermatomyositis and have yielded surprisingly good results.
This is leading several of the manufacturers to develop clinical trials in dermatomyositis. They'll probably be open label, they'll probably be small, but nonetheless that is a research that's much needed going forward. Certainly, we do need more options for our patients who have dermatomyositis. Metformin has been often used lately with regard to, as an adjunctive agent. It may have effects on IL-seventeen and T-seventeen cells.
A recent study which looks at the effects of metformin and its effects on the gut microbiome, and how it may work in diabetes. So, while there are lot of postulates about metformin working, it seems that a lot of its effect may be mediated by a change in the gut microbiome. In fact, taking the, fecal transplants of metformin, altered microbiota has actually improved the glucose tolerance in animal models. So, a sort of surprising result but, a novel finding for metformin for both diabetes and maybe even for its use in autoimmune disease like psoriasis. The FDA, came up with recent news just yesterday suggesting that, Opana extended release, a long acting opioid be removed from the market by its manufacturer Endo Pharmaceuticals.
They did not mandate this, they have suggested this. Opana, a long acting, drug has been often abused. It's been out of the market since 2006. People would crush it to get a faster effect, a higher high, so to speak. And in the years since its approval the manufacturer has tried to make it more tamper resistant but that has not been met with much success.
A recent, review by an advisory committee suggested that the risks far outweigh the benefits and that the newer drugs that are being approved as long acting opioids are much more tamper resistant. So, the FDA has gone forward and said that this should be removed, and it's going to be a voluntary removal. We'll wait and see what the manufacturer says. If they don't comply, it's likely that the FDA will take further steps to take it off the market. A nice debate, can be seen in the correspondence section of the current edition of Annals of Rheumatic Disease.
Mike Weinblatt and, Joel Kremer wrote a letter to the editor, specifically to the authors, of a paper that was published earlier in the year, by, oh, I forget the name, a group of authors, looked at a UK database and commented on, how safe it was to take alcohol while you were on methotrexate. And what they found, what they recommended was that, if you looked at those people who took 14 less alcoholic units per week, the incidence of methotrexate hepatotoxicity as defined as a threefold or higher elevation in transaminases, was not significantly higher and it was only when you went above 14 drinks per week, fourteen units per week, that you were seeing higher in numbers. Well, in response to this, the gentleman who developed the guidelines on methotrexate use, Joel Kramer, Mike Weinblatt, there were others. Grecia Alecon was the lead author on that paper. They've come out and wrote a nice reply back saying, It wasn't too long ago that we were worried about the liver and we were doing liver biopsies regularly in these patients.
And they said that, you know, it was erroneous for the authors to take an arbitrary cut off of threefold higher elevations as some indicator of liver damage. They pointed out, Weinblatt and Kremer, that the stringency in which they made their definitions, they had histologic evidence that complete medical records. And again, there was a conservative guideline regarding, alcohol. This move to allow more liberal use of alcohol, which I sort of believe in, actually is really not yet based on any good evidence. So, they sort of chastised the authors for, their suggestions that it's okay to do that.
The authors actually agreed with much of the points made by Kramer and Weinblatt, although they said they wanted something more practical and pragmatic and that they say that, they're not advocating that patients drink fourteen units a week but that there should be a conversation between the patient and the prescribing physician. And then, we have a few more things in the news. I guess biosimilar reports came out this week. This was our fifth installment of biosimilars and what's new in the world of biosimilars. As you know, in April there was a new infliximab, biosimilar called Renflexis made by, Sampson Bioepis, the same people who make those exploding telephones.
And this is now the fourth TNF inhibitor to be on the market, the fifth biosimilar in The United States to be approved. That's sort of a landmark for this, in the last few months. Obviously, some really nice, literature reports. The Dan Bio study looked at, switching, the North Switch study which we wrote about on our site is covered in here. There's a nice review, new guidelines that could be put forward by, the EMA.
There's a new biosimilar guideline that's put out for physicians in the EU, but I think for those of you who are looking for some new instructive overviews, that might be a nice one to look at. And lastly, something we hinted at but we're going to follow closer is the, Supreme Court case of Amgen versus Sandoz where they're at this level of Supreme Court asking questions about how long one company has to give another company notice before they market their new biosimilar, and there are some patent issues. This is overall being called the patent dance, so you might want to look into that and watch for more information about that going forward. The last report we have today is, a higher risk of fracture in women, older women who are taking bisphosphonates. This is a study from the Women's Health Initiative, over 5,000 women followed prospectively.
They looked at their bisphosphonate use and whether they were on it for two years, and then compared that to those who were on bisphosphonates for three to five, six to nine, ten to thirteen years. They showed that, those that were taking bisphosphonates for ten to thirteen years had a twenty nine percent higher risk of any and all fractures. When they looked at individual fractures, vertebral and non vertebral, it wasn't significant but for all fractures it was significant. The hazard ratio was one point two nine, and suggested significant. So, clearly it says that, you know, really long prolonged use of bisphosphonates may not be a good use.
And obviously you need to make that decision based on how much they need the bisphosphonate or other, therapies that will build up bone. So, a nice, instructive report from the Women's Health Initiative. That's it for this week at roomnow.com. You can go to the website to find the links to these reports and read more about these reports. You can listen to this as a podcast from iTunes or we'll post the link from Soundhound.
Please be sure to give us a really high rating so that we can win an Academy Award, Tony, Katie Award, whatever awards they're giving out this day for the Internet. We'll see you next week.
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