13 October 2017 The RheumNow Week In Review Save
13 October 2017 The RheumNow Week In Review by Dr. Cush
Transcription
It's the 10/13/2017, and this is the Room Now We Can Review. I'm Doctor. Jack Cush, executive editor of roomnow.com. A lot of good news on our website this week. At the top we have a report of an anti HIV antiviral drug that's been shown to have some anti fibrotic potential.
The drug is known as Nelfinavir. It's been studied elsewhere, but in culture it seems like it may have some effects on TGF beta-one. And what they did was they used a bleomycin induced animal model of systemic sclerosis, and when using this antiviral drug, they showed that they could decrease TGF beta one myofibroblast differentiation and pulmonary fibrosis in the animal model, suggesting that it may be a future useful therapy in patients with scleroderma. Hopefully more to come. A nice review was published in the last week about a very rare event, antimalarial cardiomyopathy.
I can't say I've ever seen it. I have seen antimalarial hydroxychloroquine myopathy, but cardiomyopathy I must say I haven't seen. This particular collection had forty seven cases, about fifteen each with lupus and rheumatoid arthritis. And not surprisingly, this was not a good outcome. Forty five percent mortality.
Patients, need to be thought of if they're on a high dose and a chronic dose of an antimalarial. Our most common one would be hydroxychloroquine. They tend to present as CHF or as syncope or, multiple levels AV block. So this should be thought of. It's a rare event but it could happen.
A study of almost fifteen hundred rheumatoid arthritis patients from the French Regat study looked at the incidence of serious infectious events and what the predictors were. I thought this was a little bit novel. Their SIE rate was as expected about four point nine per 100 patient years, but what they found was that the rate was higher in those who were taking leflunomide, those who had a high -twenty eight score, those were ACPA negative, and those with an absolute neutrophil count of greater than 5,000. Some those are expected. Why leflunomide?
Maybe it's because it's second or third line. Why ACPA negative? I'm not really that clear about. Certainly I can understand the high DAS scores because we do know that inflammation drives infectious risk. And then the ANC greater than 5,000 I find surprising, would think maybe neutropenia, lymphopenia, but in fact they found a high, ANC count.
Maybe such patients were primed in some way to get infection. Interesting observations, ones that should be replicated elsewhere. A prospective study looked at the success of withdrawing nonsteroidal therapy in RA patients who were in low disease activity state with a DAS of less than 3.2. They were able to achieve this in a sixteen week study I believe in eighty five percent of the patients and what importantly they did show was that there was no significant change patient reported outcomes and in -twenty eight scores. This was especially successful in those who had no swollen joints at baseline or at the time that they withdrew the drug.
So maybe that's the profile you're looking for if you nonsteroidal. Certainly many of our patients are going to do that with successful therapy anyway, but it's nice to have indicators where it may be successful. Uveitis may occur in adults who previously had JIA. A study of nineteen patients who had JIA onset nine years of age and the median adult age of uveitis onset was 26 years. Most of these did respond well to topical and or systemic therapies but might want to consider that uveitis could still occur in JIA even as an adult and certainly even suggest your patients have an ophthalmologist who will follow them intermittently, yearly, maybe twice yearly.
Wouldn't be a bad idea. Sort of review of the sensitivity and specificity of ultrasound in gout looked at 11 studies in nine thirty eight patients and came up with the following numbers. The sensitivity only sixty five percent, but yet the specificity was really quite high, which was almost ninety percent, eighty nine percent. So, there is certainly a real utility in using ultrasound in patients with suspected gout. It certainly may even supplant the use of crystal analysis, which is the gold standard.
A multicenter study of one hundred and thirty five JIA patients who were in good shape had achieved remission or LDAS and they stopped their biologic. Good idea. Seventy six percent of them flared. It was more likely to, have flared and not do well if they were in remission for less than two years. So the benchmark for biologic withdrawal in JIA would be being in remission for greater than two years and then consider it.
Most of these studies that are withdrawal studies have basically shown us patients want it, we'd love to simplify therapy, but really, rheumatoid arthritis, JIA, these are too complex a disorder to, really ever achieve drug withdrawal. Certainly dose, reduction, interval, lengthening, but to go off drugs, even when you're in remission is probably not a good idea for the majority of patients. A meta analysis of 38 studies looked at stem cell transplant in patients with PSS. The study was really messy, there's a lot of heterogeneity in the study, but overall suggested that there was improvement in both skin outcomes and lung FVC outcomes in these patients. It's hard to say what this means.
This is certainly a reporting bias, a review of the successful cases reported in the literature. My own N of one experience is that the patient did fabulously well with very aggressive disease. The patient did not go unscarred did have significant lung and renal disease even after this but they halted the disease in my case. So again, this may be something to consider while we're waiting for something to work in scleroderma. A study of thirty one thousand four hundred and sixty five patients on urate lowering therapy a claims data study showed that the risk of renal disease was lower with allopurinol compared to febuxostat.
In fact, it was thirty nine percent lower. And I think that not surprisingly, it would make sense that higher doses are associated with higher risks, especially allopurinol, not necessarily with febuxostat. An interesting report about the use of rituximab and Henoch Schonline purpura, as you know, a difficult disorder, often refractory. You're not supposed to use DMARDs and biologics. Nothing seems to really affect the outcomes here.
But in this cohort of twenty one patients with refractory HENOX SHO line purpura, they were treated with standard doses of rituximab. Twenty out of twenty one achieved remission, as manifest as less proteinuria, lower BVAS, the Birmingham Vasculitis Activity Scores, lower CRP levels, yet there still was a thirty five percent relapse. So is this an advance, something to maybe consider? It might be for those people who have refractory disease, that are on too high a dose of steroids and are steroid dependent, it might be a reasonable option. I don't know if you're bothered by the current state of affairs with narcotic use in The United States, but I am.
I can understand the hysteria and the legislative changes and the difficulty, and the restrictions that are imposed. What bothers me greatly is that patients who need pain medicine are not getting pain medicine and that's because most rheumatologists are not writing it, most family practitioners are not writing for narcotics, and even a lot of the pain management physicians are trying to write for less of these narcotics. This is all made worse by news that as of January 1 Cigna will stop covering the OxyContin. So I think you're going see more of these measures and the question is who is going to protect the patient who really does need a narcotic agent? I want to congratulate and thank all of the physician assistants out there.
I just found out today that this was Physician Assistant Week and I think we should acknowledge our physician assistants, give them a great big pat on the back for the great work they do with us. You know, I did a survey this last month and published the results this week on how we need more physician assistants and nurse practitioners, the data is pretty staggering. Half of us are using physician extenders, more than half have never used or don't know about physician extenders, and when asked who would you want to work with and what your preferences are, rheumatologists, not surprisingly you want to see more young rheumatologists enter the marketplace. Then as secondary choice, yes we'll take more NPs and PAs if necessary, but there's a gigantic manpower shortage. As of 2015, I think it was 4,500 rheumatologists in The United States and that's going to drop significantly by 2020 to somewhere in the 3,000 to maybe 3,500.
The problem is the shortage is not going to be made up by our training programs. There's a problem with our training programs. Some are expanding. Some don't have the funds to expand. You have to get approval to do this.
There are a lot of programs stopped seeing training fellows a long time ago, so replacing the need with more rheumatologists is going to be almost impossible. Rheumatologists need to get on board with physician extenders. If you read the article, you'll see some of the evidence that's pretty overwhelming about how good they are in covering your patients. They're not restricted. They see all patients.
They do mostly outpatient care. The biggest problem with physician extenders has been their education. Most of them receive just on the job training. Almost none of them have gone through any specific curriculum or certification course and the ACR needs to step up and develop a rheumatologist, NPPA, committee to develop these resources and develop the training and take seriously what is going to be part of our future in delivering care for the millions who are going to have musculoskeletal conditions in the next two decades. You can find that citation on the website.
Lastly, there's a new drug that was approved last Friday, in fact, by the FDA. It's called ZILRETTA. It is a combination drug. It's a triamcinolone acetate that's been mixed with a vehicle that increases the duration of effects to weeks to months. So a single injection priced at almost $1,000 per injection is now available for those who have osteoarthritis of the knee.
This company has provided some data, I put it in the article, showing the cost efficacy of this very expensive version of a very cheap drug. Will it be worth it? Will rheumatologists use it? Hard to say, but we'll look and see what you do. That's it for this, week in roomnow.com and the week in review.
Go to the website, check out the citations, read more on a lot of this good news. We'll to you next week. Goodbye.
The drug is known as Nelfinavir. It's been studied elsewhere, but in culture it seems like it may have some effects on TGF beta-one. And what they did was they used a bleomycin induced animal model of systemic sclerosis, and when using this antiviral drug, they showed that they could decrease TGF beta one myofibroblast differentiation and pulmonary fibrosis in the animal model, suggesting that it may be a future useful therapy in patients with scleroderma. Hopefully more to come. A nice review was published in the last week about a very rare event, antimalarial cardiomyopathy.
I can't say I've ever seen it. I have seen antimalarial hydroxychloroquine myopathy, but cardiomyopathy I must say I haven't seen. This particular collection had forty seven cases, about fifteen each with lupus and rheumatoid arthritis. And not surprisingly, this was not a good outcome. Forty five percent mortality.
Patients, need to be thought of if they're on a high dose and a chronic dose of an antimalarial. Our most common one would be hydroxychloroquine. They tend to present as CHF or as syncope or, multiple levels AV block. So this should be thought of. It's a rare event but it could happen.
A study of almost fifteen hundred rheumatoid arthritis patients from the French Regat study looked at the incidence of serious infectious events and what the predictors were. I thought this was a little bit novel. Their SIE rate was as expected about four point nine per 100 patient years, but what they found was that the rate was higher in those who were taking leflunomide, those who had a high -twenty eight score, those were ACPA negative, and those with an absolute neutrophil count of greater than 5,000. Some those are expected. Why leflunomide?
Maybe it's because it's second or third line. Why ACPA negative? I'm not really that clear about. Certainly I can understand the high DAS scores because we do know that inflammation drives infectious risk. And then the ANC greater than 5,000 I find surprising, would think maybe neutropenia, lymphopenia, but in fact they found a high, ANC count.
Maybe such patients were primed in some way to get infection. Interesting observations, ones that should be replicated elsewhere. A prospective study looked at the success of withdrawing nonsteroidal therapy in RA patients who were in low disease activity state with a DAS of less than 3.2. They were able to achieve this in a sixteen week study I believe in eighty five percent of the patients and what importantly they did show was that there was no significant change patient reported outcomes and in -twenty eight scores. This was especially successful in those who had no swollen joints at baseline or at the time that they withdrew the drug.
So maybe that's the profile you're looking for if you nonsteroidal. Certainly many of our patients are going to do that with successful therapy anyway, but it's nice to have indicators where it may be successful. Uveitis may occur in adults who previously had JIA. A study of nineteen patients who had JIA onset nine years of age and the median adult age of uveitis onset was 26 years. Most of these did respond well to topical and or systemic therapies but might want to consider that uveitis could still occur in JIA even as an adult and certainly even suggest your patients have an ophthalmologist who will follow them intermittently, yearly, maybe twice yearly.
Wouldn't be a bad idea. Sort of review of the sensitivity and specificity of ultrasound in gout looked at 11 studies in nine thirty eight patients and came up with the following numbers. The sensitivity only sixty five percent, but yet the specificity was really quite high, which was almost ninety percent, eighty nine percent. So, there is certainly a real utility in using ultrasound in patients with suspected gout. It certainly may even supplant the use of crystal analysis, which is the gold standard.
A multicenter study of one hundred and thirty five JIA patients who were in good shape had achieved remission or LDAS and they stopped their biologic. Good idea. Seventy six percent of them flared. It was more likely to, have flared and not do well if they were in remission for less than two years. So the benchmark for biologic withdrawal in JIA would be being in remission for greater than two years and then consider it.
Most of these studies that are withdrawal studies have basically shown us patients want it, we'd love to simplify therapy, but really, rheumatoid arthritis, JIA, these are too complex a disorder to, really ever achieve drug withdrawal. Certainly dose, reduction, interval, lengthening, but to go off drugs, even when you're in remission is probably not a good idea for the majority of patients. A meta analysis of 38 studies looked at stem cell transplant in patients with PSS. The study was really messy, there's a lot of heterogeneity in the study, but overall suggested that there was improvement in both skin outcomes and lung FVC outcomes in these patients. It's hard to say what this means.
This is certainly a reporting bias, a review of the successful cases reported in the literature. My own N of one experience is that the patient did fabulously well with very aggressive disease. The patient did not go unscarred did have significant lung and renal disease even after this but they halted the disease in my case. So again, this may be something to consider while we're waiting for something to work in scleroderma. A study of thirty one thousand four hundred and sixty five patients on urate lowering therapy a claims data study showed that the risk of renal disease was lower with allopurinol compared to febuxostat.
In fact, it was thirty nine percent lower. And I think that not surprisingly, it would make sense that higher doses are associated with higher risks, especially allopurinol, not necessarily with febuxostat. An interesting report about the use of rituximab and Henoch Schonline purpura, as you know, a difficult disorder, often refractory. You're not supposed to use DMARDs and biologics. Nothing seems to really affect the outcomes here.
But in this cohort of twenty one patients with refractory HENOX SHO line purpura, they were treated with standard doses of rituximab. Twenty out of twenty one achieved remission, as manifest as less proteinuria, lower BVAS, the Birmingham Vasculitis Activity Scores, lower CRP levels, yet there still was a thirty five percent relapse. So is this an advance, something to maybe consider? It might be for those people who have refractory disease, that are on too high a dose of steroids and are steroid dependent, it might be a reasonable option. I don't know if you're bothered by the current state of affairs with narcotic use in The United States, but I am.
I can understand the hysteria and the legislative changes and the difficulty, and the restrictions that are imposed. What bothers me greatly is that patients who need pain medicine are not getting pain medicine and that's because most rheumatologists are not writing it, most family practitioners are not writing for narcotics, and even a lot of the pain management physicians are trying to write for less of these narcotics. This is all made worse by news that as of January 1 Cigna will stop covering the OxyContin. So I think you're going see more of these measures and the question is who is going to protect the patient who really does need a narcotic agent? I want to congratulate and thank all of the physician assistants out there.
I just found out today that this was Physician Assistant Week and I think we should acknowledge our physician assistants, give them a great big pat on the back for the great work they do with us. You know, I did a survey this last month and published the results this week on how we need more physician assistants and nurse practitioners, the data is pretty staggering. Half of us are using physician extenders, more than half have never used or don't know about physician extenders, and when asked who would you want to work with and what your preferences are, rheumatologists, not surprisingly you want to see more young rheumatologists enter the marketplace. Then as secondary choice, yes we'll take more NPs and PAs if necessary, but there's a gigantic manpower shortage. As of 2015, I think it was 4,500 rheumatologists in The United States and that's going to drop significantly by 2020 to somewhere in the 3,000 to maybe 3,500.
The problem is the shortage is not going to be made up by our training programs. There's a problem with our training programs. Some are expanding. Some don't have the funds to expand. You have to get approval to do this.
There are a lot of programs stopped seeing training fellows a long time ago, so replacing the need with more rheumatologists is going to be almost impossible. Rheumatologists need to get on board with physician extenders. If you read the article, you'll see some of the evidence that's pretty overwhelming about how good they are in covering your patients. They're not restricted. They see all patients.
They do mostly outpatient care. The biggest problem with physician extenders has been their education. Most of them receive just on the job training. Almost none of them have gone through any specific curriculum or certification course and the ACR needs to step up and develop a rheumatologist, NPPA, committee to develop these resources and develop the training and take seriously what is going to be part of our future in delivering care for the millions who are going to have musculoskeletal conditions in the next two decades. You can find that citation on the website.
Lastly, there's a new drug that was approved last Friday, in fact, by the FDA. It's called ZILRETTA. It is a combination drug. It's a triamcinolone acetate that's been mixed with a vehicle that increases the duration of effects to weeks to months. So a single injection priced at almost $1,000 per injection is now available for those who have osteoarthritis of the knee.
This company has provided some data, I put it in the article, showing the cost efficacy of this very expensive version of a very cheap drug. Will it be worth it? Will rheumatologists use it? Hard to say, but we'll look and see what you do. That's it for this, week in roomnow.com and the week in review.
Go to the website, check out the citations, read more on a lot of this good news. We'll to you next week. Goodbye.
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