The RheumNow Week In Review Baricitinib Splash %286.7.18%29 Save
The RheumNow Week In Review Baricitinib Splash %286.7.18%29 by Dr. Cush
Transcription
It's 06/07/2018. This is the RheumNow we can review. Hi, I'm Doctor. Jack Cush, executive editor of roomnow.com. This week in the news, we've got big time and small time FDA approvals in the past week.
Nurse practitioners and physician assistants are proliferating in both primary care and specialty care. And sons of gout, is it a rock band or a pro bands worry? First, we have some new information about how to treat fibromyalgia. There was an interesting meta analysis and literature review, if you will, on the topic of mirtazapine, also known as Remeron and its use in fibromyalgia. After a review of the literature, four studies were found that actually showed that mirtazapine can be effective in treating fibromyalgia in all of its aspects with significant improvements in pain, sleep, and quality of life.
I've often thought this is a very good drug for fibromyalgia in that obviously it's an effective antidepressant which can be used to manage pain, but at the same time has the useful side effect of sleep and therefore sort of a one two punch for patients who need a one two punch in a single pill. As you know, it comes in fifteen, thirty and forty five milligrams can be titrated up or down, usually is well tolerated. So it may be something you want to consider. It would be off label use, but so much of the drug use we use in fibromyalgia is off label. Consider it.
AbbVie announced this past week the results of its select early study is a head to head trial in methotrexate naive individuals who are randomized to receive either methotrexate or upadacitinib. It's a monotherapy trial and after twenty four weeks the ACR20 results were impressive. Methotrexate fifty nine percent, upa at both of its doses seventy eight and seventy nine percent, that's significantly different. The ACR 50s were significantly different as were the ACR 70s. ACR 70 methotrexate response rate at six months was sixteen percent, whereas the OOPA response rate was forty four to fifty percent for its two doses.
Again, highly effective, well tolerated, no more VTEs with OOPA, in fact, there were more VTE venous thromboembolic events with methotrexate than there was with the JAK-two inhibitor in this trial. So we'll look for more data on OOPA as it goes through the development process. The corona registry this week reported an interesting study from its 45,000 patient registry, impressive data looking at the outcomes of both psoriatic arthritis and rheumatoid arthritis over a ten year period 02/2013. And they basically showed that biologic, use rose during this period, not surprisingly, with sixty two percent of RA patients receiving a biologic and fifty two percent receiving a biologic in psoriatic arthritis. And with this rising use came increases in the outcomes as far as C.
Dye, HAC and other measures. And while all that's great, the disappointment in this study was that still with a growing use of more aggressive therapies, thirty five percent of RA patients and twenty five percent of PSA patients still have moderate to high disease activity suggesting that we may be aggressive, but maybe not aggressive enough. Again, we need to do something different and maybe it's not using new drugs that'll get us to better outcomes. Clearly, I'm an advocate for measuring and treat to target, but I think this needs to be considered. Again, we're doing well, but maybe not well enough.
The JBMR, this past week reported a single study, an interesting study, that was the collective single center experience looking at patients on teriparatide. And this was done in fifty three patients with severe osteoporosis. The observation was that hypomagnesemia was seen in thirty six percent of patients. Those were most likely to get it were those who were older and those who not surprisingly had a higher lower baseline magnesium level at the outset. This is something that often isn't discussed, it has been reported before and maybe should be looked at in patients who are being treated for severe osteoporosis.
Another interesting study comes in looking at the utility of rheumatoid factor and ACPA or CCP in patients who may, be preclinical for rheumatoid arthritis. That's usually first degree relatives who have seropositivity and you are following those people, they may have aches and pains but not yet quite have rheumatoid arthritis. This particular study from, William Robinson and others looked at 83 patients who went on to develop rheumatoid arthritis and looked at their prior serum samples and what was found. And what they found was that those who are double positive for rheumatoid factor and for ACPA are more likely to have significant elevations of multiple cytokines, multiple pro inflammatory cytokines and also have a faster time to develop rheumatoid arthritis suggesting that this double positive profile may not be, a good sign in patients who may be at risk, those with preclinical rheumatoid arthritis. The FDA approved this past week a drug called Consensi.
This is the combination of amlodipine and celecoxib for the treatment of both hypertension and osteoarthritis. Wait a second, you say, don't nonsteroidals cause hypertension Or do osteoarthritis patients have a higher rate of hypertension and may need, blood pressure medicines? Obviously, both could happen, but the combination in one pill, it's unbelievable. In fact, this is either brilliant or it's a special kind of stupid or actually I rephrased it in the tweet by saying it's an expensive brand of stupid. It's up to you to decide.
Between 02/2016, an interesting study appears that looks at the use of nurse practitioners and physician assistants in primary care. Again, an interest that just comes from JAMA, looked at the overall use of both of these advanced practice clinicians APCs in both rural and non rural environments. They show that over this time period of almost eight or nine years, the rates rose from about eighteen percent, fifteen percent to as high as twenty five percent. And there was higher in certain states where there were full scope practice laws for nurse practitioners, not in all states, but where there was the number was even higher. So, NPs and physician assistants are actually, excuse me, this is just a study of NPs, are growing in primary care.
I'm sure you could find the same for physician assistants. Another report that we had this week looked at both NPs and PAs, advanced practice providers in specialty care. This a JAMA article that I referred to, and what they found was again significant rates that on average about twenty five percent of specialty care practices are more likely to have APCs as part of their healthcare delivery. What they found was that, certain specialties were higher than others. In fact, across the board, amongst the medical and surgical subspecialties, were more NPEs being higher than there were PAs with the exception of a few surgical subspecialties where PAs are more popular and dermatology, which I found surprising where PAs are more popular than NPEs.
But nonetheless, the numbers are impressive and you should look at the citation to see where what specialties are being, having a growth of, APCs amongst their providers. They did not provide, individual information on specialties like rheumatology but we do know that that number has also gone up. Our number of APCs in the rheumatology field is estimated by the ACR to be I think somewhere around four seventy nationwide. Others say it may be much larger, but clearly this number is growing and for a lot of different reasons. It could be that there's a growth of these schools and they're graduating more people.
It could be the financial constraints that are being put upon practices, and that, APCs are a much more affordable option. Obviously, rheumatology at least, there's a shortage of rheumatologists that can be filled by, these providers. An interesting study, looked at the ability to predict progression in systemic sclerosis. This is what's called the SPAR model, S P A R, SP standing for pulse ox or SpO2 and R meaning arthritis. And in this particular study, two fifteen patients with mild interstitial lung disease, they follow them prospectively over time, looking at clinical parameters, looking at their PFTs and their pulse ox measures.
And what they showed was that the most predictive factors were just two, one, the presence of arthritis and two, the finding of a drop in the pulse ox below 94% after a six minute walk time. Two easy measures, obviously one you know because you're a rheumatologist, the six minute walk time is easily done as well and it's done with a pulse ox. So you'd use the time and you actually measure the PO2, something that might be considered and should be considered in clinical practice. The Sons of Gout study was published this past month. I thought it was a very interesting title, if not study.
What happened here was there was a UK cohort that followed the offspring of gout patients and they had a collection of 131 sons of gout who did not have clinical disease. And what they did was they examined them, they did blood tests on them, they did ultrasound in a number of joints. What they found was amongst these one hundred and thirty one asymptomatic sons of gout patients, two thirds of them had an elevated uric acid above six milligrams per deciliter. And that thirty percent had ultrasound evidence of a double contour sign suggesting that there were gout deposits going on in the joints of these individuals who were asymptomatic. What they found in their study were that the offspring that had a serum urate level less than five never had an abnormal MSK ultrasound for double contour sign but that when you went from, far less than five to five to six, twenty five percent or quarter or so, actually had ultrasonographic evidence of, ureter deposits on cartilage, suggesting that this is a preclinical form of gout and that these people could be followed and studied as well.
I'm not saying that every person who has a child should undergo ultrasound, but it may be an interesting way of looking further into the early pathogenesis of gout and maybe how we progress from preclinical disease to actually clinically manifest gout. And then there's an interesting study that comes from the Toronto Lupus Study. This is a cohort of patients were diagnosed with lupus, two sixty seven patients. This is a study led by colleagues in Toronto, and what they described was a a small cohort of patients who had sustained remission and were off of drugs after the onset of their lupus. So to get to this point, you actually had to have a sleet eye of zero, and you had to be in remission for greater than ten years and be off of all drugs.
What they found that was after ten years, was it number twenty seven or ten percent of patients were able to achieve remission, as defined in the study, that they had seven point five percent who had sustained remission and were off of all drugs for a mean of eighteen years. Now amongst those people, that went into remission after ten years, it turns out that seven out of the twenty seven actually had a relapse and these were generally after ten years of being quiescent. Four of them developing arthritis, one with anti phospholipid syndrome, and two with lymphadenopathy, suggesting that even though you can go into remission, it may not stay in remission, and that these patients need to be followed chronically over time. And lastly, the FDA approved last Friday when we went to press on our last edition of the room now we can review, the FDA approved in the morning baricitinib at the low dose of two milligrams once a day. This is, now the second JAK inhibitor to be on the market.
It's certainly a major advance in therapeutics for rheumatoid arthritis. And in this article that we, did on Friday and then updated on Monday, we review some of the finer points, regarding the use of this drug. So number one, it was recommended by the Arthritis Advisory Committee to approve this drug. Number two, there are box warnings for serious infections, TB, risk of cancer and lymphoma and the risk of venous thromboembolic events including DVT and PE. It can be used as monotherapy or in combination.
The dose is two milligrams once a day. There are no data about dose ranging. Actually the drug was approved based on, studies involving twelve fifty three patients. The one limitation here is that patients need to have failed one or more TNF inhibitors. You need to be on the lookout for lymphopenia, neutropenia, anemia, hyperlipidemia.
You need to have a TB test prior to use. It is not recommended for patients who have moderate to severe, renal disease or severe renal impairment, and the risk of zoster is about one to one point four percent. That's it for this week at roomnow.com. Go to the website to find these citations and read more. Be sure to follow us next week when we'll be reporting from EULAR with a lot of good new information from EULAR.
Take care and thanks.
Nurse practitioners and physician assistants are proliferating in both primary care and specialty care. And sons of gout, is it a rock band or a pro bands worry? First, we have some new information about how to treat fibromyalgia. There was an interesting meta analysis and literature review, if you will, on the topic of mirtazapine, also known as Remeron and its use in fibromyalgia. After a review of the literature, four studies were found that actually showed that mirtazapine can be effective in treating fibromyalgia in all of its aspects with significant improvements in pain, sleep, and quality of life.
I've often thought this is a very good drug for fibromyalgia in that obviously it's an effective antidepressant which can be used to manage pain, but at the same time has the useful side effect of sleep and therefore sort of a one two punch for patients who need a one two punch in a single pill. As you know, it comes in fifteen, thirty and forty five milligrams can be titrated up or down, usually is well tolerated. So it may be something you want to consider. It would be off label use, but so much of the drug use we use in fibromyalgia is off label. Consider it.
AbbVie announced this past week the results of its select early study is a head to head trial in methotrexate naive individuals who are randomized to receive either methotrexate or upadacitinib. It's a monotherapy trial and after twenty four weeks the ACR20 results were impressive. Methotrexate fifty nine percent, upa at both of its doses seventy eight and seventy nine percent, that's significantly different. The ACR 50s were significantly different as were the ACR 70s. ACR 70 methotrexate response rate at six months was sixteen percent, whereas the OOPA response rate was forty four to fifty percent for its two doses.
Again, highly effective, well tolerated, no more VTEs with OOPA, in fact, there were more VTE venous thromboembolic events with methotrexate than there was with the JAK-two inhibitor in this trial. So we'll look for more data on OOPA as it goes through the development process. The corona registry this week reported an interesting study from its 45,000 patient registry, impressive data looking at the outcomes of both psoriatic arthritis and rheumatoid arthritis over a ten year period 02/2013. And they basically showed that biologic, use rose during this period, not surprisingly, with sixty two percent of RA patients receiving a biologic and fifty two percent receiving a biologic in psoriatic arthritis. And with this rising use came increases in the outcomes as far as C.
Dye, HAC and other measures. And while all that's great, the disappointment in this study was that still with a growing use of more aggressive therapies, thirty five percent of RA patients and twenty five percent of PSA patients still have moderate to high disease activity suggesting that we may be aggressive, but maybe not aggressive enough. Again, we need to do something different and maybe it's not using new drugs that'll get us to better outcomes. Clearly, I'm an advocate for measuring and treat to target, but I think this needs to be considered. Again, we're doing well, but maybe not well enough.
The JBMR, this past week reported a single study, an interesting study, that was the collective single center experience looking at patients on teriparatide. And this was done in fifty three patients with severe osteoporosis. The observation was that hypomagnesemia was seen in thirty six percent of patients. Those were most likely to get it were those who were older and those who not surprisingly had a higher lower baseline magnesium level at the outset. This is something that often isn't discussed, it has been reported before and maybe should be looked at in patients who are being treated for severe osteoporosis.
Another interesting study comes in looking at the utility of rheumatoid factor and ACPA or CCP in patients who may, be preclinical for rheumatoid arthritis. That's usually first degree relatives who have seropositivity and you are following those people, they may have aches and pains but not yet quite have rheumatoid arthritis. This particular study from, William Robinson and others looked at 83 patients who went on to develop rheumatoid arthritis and looked at their prior serum samples and what was found. And what they found was that those who are double positive for rheumatoid factor and for ACPA are more likely to have significant elevations of multiple cytokines, multiple pro inflammatory cytokines and also have a faster time to develop rheumatoid arthritis suggesting that this double positive profile may not be, a good sign in patients who may be at risk, those with preclinical rheumatoid arthritis. The FDA approved this past week a drug called Consensi.
This is the combination of amlodipine and celecoxib for the treatment of both hypertension and osteoarthritis. Wait a second, you say, don't nonsteroidals cause hypertension Or do osteoarthritis patients have a higher rate of hypertension and may need, blood pressure medicines? Obviously, both could happen, but the combination in one pill, it's unbelievable. In fact, this is either brilliant or it's a special kind of stupid or actually I rephrased it in the tweet by saying it's an expensive brand of stupid. It's up to you to decide.
Between 02/2016, an interesting study appears that looks at the use of nurse practitioners and physician assistants in primary care. Again, an interest that just comes from JAMA, looked at the overall use of both of these advanced practice clinicians APCs in both rural and non rural environments. They show that over this time period of almost eight or nine years, the rates rose from about eighteen percent, fifteen percent to as high as twenty five percent. And there was higher in certain states where there were full scope practice laws for nurse practitioners, not in all states, but where there was the number was even higher. So, NPs and physician assistants are actually, excuse me, this is just a study of NPs, are growing in primary care.
I'm sure you could find the same for physician assistants. Another report that we had this week looked at both NPs and PAs, advanced practice providers in specialty care. This a JAMA article that I referred to, and what they found was again significant rates that on average about twenty five percent of specialty care practices are more likely to have APCs as part of their healthcare delivery. What they found was that, certain specialties were higher than others. In fact, across the board, amongst the medical and surgical subspecialties, were more NPEs being higher than there were PAs with the exception of a few surgical subspecialties where PAs are more popular and dermatology, which I found surprising where PAs are more popular than NPEs.
But nonetheless, the numbers are impressive and you should look at the citation to see where what specialties are being, having a growth of, APCs amongst their providers. They did not provide, individual information on specialties like rheumatology but we do know that that number has also gone up. Our number of APCs in the rheumatology field is estimated by the ACR to be I think somewhere around four seventy nationwide. Others say it may be much larger, but clearly this number is growing and for a lot of different reasons. It could be that there's a growth of these schools and they're graduating more people.
It could be the financial constraints that are being put upon practices, and that, APCs are a much more affordable option. Obviously, rheumatology at least, there's a shortage of rheumatologists that can be filled by, these providers. An interesting study, looked at the ability to predict progression in systemic sclerosis. This is what's called the SPAR model, S P A R, SP standing for pulse ox or SpO2 and R meaning arthritis. And in this particular study, two fifteen patients with mild interstitial lung disease, they follow them prospectively over time, looking at clinical parameters, looking at their PFTs and their pulse ox measures.
And what they showed was that the most predictive factors were just two, one, the presence of arthritis and two, the finding of a drop in the pulse ox below 94% after a six minute walk time. Two easy measures, obviously one you know because you're a rheumatologist, the six minute walk time is easily done as well and it's done with a pulse ox. So you'd use the time and you actually measure the PO2, something that might be considered and should be considered in clinical practice. The Sons of Gout study was published this past month. I thought it was a very interesting title, if not study.
What happened here was there was a UK cohort that followed the offspring of gout patients and they had a collection of 131 sons of gout who did not have clinical disease. And what they did was they examined them, they did blood tests on them, they did ultrasound in a number of joints. What they found was amongst these one hundred and thirty one asymptomatic sons of gout patients, two thirds of them had an elevated uric acid above six milligrams per deciliter. And that thirty percent had ultrasound evidence of a double contour sign suggesting that there were gout deposits going on in the joints of these individuals who were asymptomatic. What they found in their study were that the offspring that had a serum urate level less than five never had an abnormal MSK ultrasound for double contour sign but that when you went from, far less than five to five to six, twenty five percent or quarter or so, actually had ultrasonographic evidence of, ureter deposits on cartilage, suggesting that this is a preclinical form of gout and that these people could be followed and studied as well.
I'm not saying that every person who has a child should undergo ultrasound, but it may be an interesting way of looking further into the early pathogenesis of gout and maybe how we progress from preclinical disease to actually clinically manifest gout. And then there's an interesting study that comes from the Toronto Lupus Study. This is a cohort of patients were diagnosed with lupus, two sixty seven patients. This is a study led by colleagues in Toronto, and what they described was a a small cohort of patients who had sustained remission and were off of drugs after the onset of their lupus. So to get to this point, you actually had to have a sleet eye of zero, and you had to be in remission for greater than ten years and be off of all drugs.
What they found that was after ten years, was it number twenty seven or ten percent of patients were able to achieve remission, as defined in the study, that they had seven point five percent who had sustained remission and were off of all drugs for a mean of eighteen years. Now amongst those people, that went into remission after ten years, it turns out that seven out of the twenty seven actually had a relapse and these were generally after ten years of being quiescent. Four of them developing arthritis, one with anti phospholipid syndrome, and two with lymphadenopathy, suggesting that even though you can go into remission, it may not stay in remission, and that these patients need to be followed chronically over time. And lastly, the FDA approved last Friday when we went to press on our last edition of the room now we can review, the FDA approved in the morning baricitinib at the low dose of two milligrams once a day. This is, now the second JAK inhibitor to be on the market.
It's certainly a major advance in therapeutics for rheumatoid arthritis. And in this article that we, did on Friday and then updated on Monday, we review some of the finer points, regarding the use of this drug. So number one, it was recommended by the Arthritis Advisory Committee to approve this drug. Number two, there are box warnings for serious infections, TB, risk of cancer and lymphoma and the risk of venous thromboembolic events including DVT and PE. It can be used as monotherapy or in combination.
The dose is two milligrams once a day. There are no data about dose ranging. Actually the drug was approved based on, studies involving twelve fifty three patients. The one limitation here is that patients need to have failed one or more TNF inhibitors. You need to be on the lookout for lymphopenia, neutropenia, anemia, hyperlipidemia.
You need to have a TB test prior to use. It is not recommended for patients who have moderate to severe, renal disease or severe renal impairment, and the risk of zoster is about one to one point four percent. That's it for this week at roomnow.com. Go to the website to find these citations and read more. Be sure to follow us next week when we'll be reporting from EULAR with a lot of good new information from EULAR.
Take care and thanks.
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