The RheumNow Week In Review 18 August 2017 Save
The RheumNow Week In Review 18 August 2017 by Dr. Cush
Transcription
It's the 08/18/2017 and this is the Room Now we can review. I'm Doctor. Jack Cush, executive editor of roomnow.com and this week in the news we'll discuss rheumatologist testing, too much, too little. We'll discuss how to store etanercept and get away with it, and some interesting ideas about lupus and its management. We'll start off with lupus.
Survival numbers, as you know, have done very well since the 1990s with the advent of more aggressive therapies and better protocols on how to manage things like renal lupus. An analysis looking at survival in lupus patients basically showed that five year survival rates were highest in developed countries with high incomes. In fact, it was a greater than ninety five percent survival for both children and adults with lupus. The only thing that I could find negative was that survival in children with lupus was somewhat lower in low to moderate income countries, suggesting maybe it's an access issue there. Another study in lupus looked at criteria and recommendations.
This is an interesting group called SHARE that a bunch of experts got together and developed criteria for pediatric lupus and specifically they recommended that the diagnosis be done by the new SLIC criteria and not the old 11 criteria. They also recommended that newly diagnosed lupus in children, those children should have testing for complement deficiencies and ENA, they should have a chest x-ray and of course they should be referred to a rheumatologist. An analysis by Christina Chambers and her group from San Diego, they also run the Otis registries, looked at greater than three thousand patients with rheumatoid arthritis, psoriatic arthritis and Crohn's disease and compared them to normal controls. What they found was an increased risk of preterm birth and preeclampsia in RA and psoriatic arthritis patients. They did not find increased risk of depression in those patients, and the Crohn's patients did not have the same degree of risk as was seen in RA and PSA.
The downside to steroids was seen in an orthopedic study published in the Annals of Internal Medicine where they looked at the use of intra articular triamcinolone in one hundred and forty neoA patients. Half of them got triamcinolone, half of them received saline. They looked two years down the line and they found, as you would imagine, there were some short term benefits but long term there was no advantage in pain comparing those on the steroid and those who received placebo. But more importantly, those who received the steroid had a greater degree of cartilage loss over two years that was not seen in those on placebo or saline, suggesting that we may be doing more damage than we think if we're giving repeated intra articular steroids to such patients. A very bizarre report comes from Annals Internal Medicine where they looked at a 26 year old Filipino woman who had meningococcemia, severe sepsis, had amputation of both her hands and distal forearms.
Then at age 33, she underwent bilateral allogeneic forearm transplants with hands and as part of the immunotherapy, they gave the recipient some donor bone marrow infusions and then followed that up with tacrolimus. Later on, guess what, she develops rheumatoid arthritis. Neither the donor nor the recipient had a history of joint problems or a family history of arthritis or rheumatoid arthritis. Sort of shakes things up when you're considering the cause of this disease. A study looked at the stability of etanercept.
I don't know what you tell your patients, but most of my patients think it's a big ordeal to travel with this medicine and it really shouldn't be. Many of them are getting coolers and dry ice and letters from their priests and the government to travel with this medicine. It's just not worth it. What they really should be doing is one, taking the drug a few days early, three, four days early is perfectly acceptable, or three, four days late rather than travel with these contraptions. Or they could do what was suggested by this research that was just published that says that etanercept is stable at room temperature, 25 degrees centigrade plus or minus two degrees or 77 degrees Fahrenheit plus or minus two degrees centigrade, that's like 72 to 79, almost 80 degrees.
As long as it's stored under those conditions, all the forms of Etanercept are stable and good for thirty days. So that means that what I tell my patients is right. Either take it early or if you're going to travel with it, wrap it in a bubble wrap, put it in your purse, keep it cool and dark and out of the extremes of temperature and light and it's good for weeks. Obviously, what's not tested here is warming it up and then putting it back in the refrigerator. There are other studies not here that suggest that's not a good idea for the protein contained within the medicine, but that if it's kept out and used at room temperature within thirty days, still good, still has the same potency.
Another study from The UK looked at what rheumatoid do when they're given a prescription. Specifically, a study from the National Rheumatoid Arthritis Society in The UK showed that only one in three RA patients would pick up a prescription that was sent to the pharmacy for them. It goes along with a lot of the data that says that up to half of patients don't fill prescriptions that are sent to the pharmacy for them. The main reason here was that of cost where in The UK the medicine is not costly and there are programs for cheaper medicine. There is an announcement this week that the tocilizumab study in scleroderma, the next phase, I think this is a phase two study, phase three trial, excuse me, has completed enrollment, and we'll see the results of that.
You know the first study that was done, the FASTINate study, that was a phase two trial. It looked very encouraging. They need this phase three trial to get the indication for use in scleroderma. This will have skin and lung outcomes. We're going need another year or more to get those results.
How much testing is enough? You know, one day I was seeing a patient, a 26 year old a 36 year old with new onset, a few weeks six weeks, ten weeks, doesn't really matter, of polyarthralgias in her hands. On exam, she has tenderness in her MCPs and PIPs. I did the tests I thought were reasonable and I thought, What would my colleagues do? And so I did a Twitter poll on this and within twenty four hours I had 106 responses and there were four choices there.
Just do a Sedrate and CRP or Sedrate CRP and test for rheumatoid arthritis or Sedrate CRP ANA, RF, NCCP, or lastly, Sedrate CRP and hepatitis serologies? The answers to me were a bit surprising. The answers were that fifty eight percent of rheumatologists, almost sixty percent, wanted everything, including the ANA. Why ANA? I have no idea.
The next most common answer was a sed rate, CRP, rheumatoid factor, and CCP at seventeen percent. Only nine percent did what I did, which is to order a sed rate and a CRP, and that's it. Of course, everybody gets a chem profile and a complete blood count. Now interestingly, this generated a lot of discussion online and rheumatologists generally want everything and then they want to figure it out the second visit. That's really not smart medicine.
You have to read my view on this on the website to see why the prudent thing to do is to just do testing as was required. You're supposed to use these tests to confirm a diagnosis. This patient did not have rheumatoid arthritis by any criteria. She had MCP tenderness and a little bit of PIP tenderness with only six joints involved, but nothing to show forth. There was no synovitis or enthesitis or periarticular involvement.
There was no other features of rheumatoid arthritis. This is going to likely burn out in most people. Having rheumatoid factor CCP, I don't believe is going to make you treat her any differently and it's not going to give her a diagnosis and she's not going to have pre clinical RA at that point. So anyway, you read and you can comment if you like any further. Two studies look at back pain and chronic pain showing things that we commonly use don't work at all.
First, gabapentinoids. That includes pregabalin and gabapentin. A number of studies, I think it was 26 studies were analyzed to see what the effects of that were on many different kinds of pain, and that included neuropathic pain and that's a marijuana study. I'm sorry. This was actually six studies, three done in pregabalin, three done in gabapentin, basically showing no benefits.
In fact, the pregabalin showed worse pain and yet we use a lot of these drugs in trying to manage chronic pain. Another study with marijuana and cannabinoids looked at 27 published studies and its ability to control chronic pain, what is often used for in states where it's legal, and they studied neuropathic pain, pain from MS, pain from cancer and other causes including rheumatic pain really showed no benefit. In most of these studies, both with the gabapentinoids and with marijuana there were more toxicities than there were benefits. I've heard others discuss gabapentinoids that if they went in front of the FDA today they would not get approved given the hurdles that are required to get a drug approved today. They are on the market as a sort of social wave of having importance and trying to manage the needs of many who advocate strongly for marijuana.
I don't live in a state where we can use cannabinoids other than by prescription and by pill. Lastly, there's two more. Psoriatic arthritis, if you have comorbidity, guess what? You're going to have probably worse disease and you're less likely to respond to DMARD and biologic therapy. Analysis of a good cohort of patients with from the Dan BioRegistry, think it was seventeen hundred plus PSA patients and they looked at the influence of comorbidities.
If you had a Charlson comorbidity index of two or higher, suggesting you had two or more comorbidities, you are more likely to have higher baseline disease activity and you're also more likely to have depression. Down the line, you're also more likely to not respond to drug intervention suggesting again the importance of comorbidity in psoriatic disease. Surprising because most of us recognize this but most of us certainly don't want to treat it and we assume it's going to be done by the primary care. Oops, that may not happen. We need another strategy for managing comorbidities amongst our rheumatology patients.
Lastly, a published report from Calabrese, Cavanaugh and Ellipsky looked at the safety of peglodecase in the clinical trials where it's been given. Peglodecase came out in 2010, I thought was very much a game changer when you started looking at some of the data and some of the pictures of patients with severe tophaceous gout remitting with tophite resolving. But yet there has been a concern about the safety of pegvodecase IV, especially IV infusion reactions. They looked at all of the IV infusion reactions. They looked at anaphylaxis rates using an NIH criteria for anaphylaxis and overall they showed that the number of infusion reactions, only about six point seven percent of patients had IV infusion reactions.
The number of anaphylaxis cases I think was incredibly low, was zero point three percent looking at all patients. But what they found interesting in this particular study and analysis was that the ones who had the most infusion reactions were the non responders and that was twelve percent non responders and two percent if you were getting the drug every four weeks or it was nine point eight percent in non responders and zero point five percent in responders if you were getting the drug every two weeks. The authors went on to say that if we kept an eye on the guidelines and used the drug as it's described and discontinued the drug when the serum uric acid level rose, especially above eight, that you would avoid one non response and two infusion reactions and ultimately anaphylaxis. That's it for this week on roomnow.com. You can go to the website and see these links and read up more on this information.
You can also not only see the RheumNow we can review but listen to it on iTunes and Soundhound. If you go to the social media icons on our website, you can click on one of those and find the podcast for you to listen to in the future. Have a good weekend and we'll see you next week.
Survival numbers, as you know, have done very well since the 1990s with the advent of more aggressive therapies and better protocols on how to manage things like renal lupus. An analysis looking at survival in lupus patients basically showed that five year survival rates were highest in developed countries with high incomes. In fact, it was a greater than ninety five percent survival for both children and adults with lupus. The only thing that I could find negative was that survival in children with lupus was somewhat lower in low to moderate income countries, suggesting maybe it's an access issue there. Another study in lupus looked at criteria and recommendations.
This is an interesting group called SHARE that a bunch of experts got together and developed criteria for pediatric lupus and specifically they recommended that the diagnosis be done by the new SLIC criteria and not the old 11 criteria. They also recommended that newly diagnosed lupus in children, those children should have testing for complement deficiencies and ENA, they should have a chest x-ray and of course they should be referred to a rheumatologist. An analysis by Christina Chambers and her group from San Diego, they also run the Otis registries, looked at greater than three thousand patients with rheumatoid arthritis, psoriatic arthritis and Crohn's disease and compared them to normal controls. What they found was an increased risk of preterm birth and preeclampsia in RA and psoriatic arthritis patients. They did not find increased risk of depression in those patients, and the Crohn's patients did not have the same degree of risk as was seen in RA and PSA.
The downside to steroids was seen in an orthopedic study published in the Annals of Internal Medicine where they looked at the use of intra articular triamcinolone in one hundred and forty neoA patients. Half of them got triamcinolone, half of them received saline. They looked two years down the line and they found, as you would imagine, there were some short term benefits but long term there was no advantage in pain comparing those on the steroid and those who received placebo. But more importantly, those who received the steroid had a greater degree of cartilage loss over two years that was not seen in those on placebo or saline, suggesting that we may be doing more damage than we think if we're giving repeated intra articular steroids to such patients. A very bizarre report comes from Annals Internal Medicine where they looked at a 26 year old Filipino woman who had meningococcemia, severe sepsis, had amputation of both her hands and distal forearms.
Then at age 33, she underwent bilateral allogeneic forearm transplants with hands and as part of the immunotherapy, they gave the recipient some donor bone marrow infusions and then followed that up with tacrolimus. Later on, guess what, she develops rheumatoid arthritis. Neither the donor nor the recipient had a history of joint problems or a family history of arthritis or rheumatoid arthritis. Sort of shakes things up when you're considering the cause of this disease. A study looked at the stability of etanercept.
I don't know what you tell your patients, but most of my patients think it's a big ordeal to travel with this medicine and it really shouldn't be. Many of them are getting coolers and dry ice and letters from their priests and the government to travel with this medicine. It's just not worth it. What they really should be doing is one, taking the drug a few days early, three, four days early is perfectly acceptable, or three, four days late rather than travel with these contraptions. Or they could do what was suggested by this research that was just published that says that etanercept is stable at room temperature, 25 degrees centigrade plus or minus two degrees or 77 degrees Fahrenheit plus or minus two degrees centigrade, that's like 72 to 79, almost 80 degrees.
As long as it's stored under those conditions, all the forms of Etanercept are stable and good for thirty days. So that means that what I tell my patients is right. Either take it early or if you're going to travel with it, wrap it in a bubble wrap, put it in your purse, keep it cool and dark and out of the extremes of temperature and light and it's good for weeks. Obviously, what's not tested here is warming it up and then putting it back in the refrigerator. There are other studies not here that suggest that's not a good idea for the protein contained within the medicine, but that if it's kept out and used at room temperature within thirty days, still good, still has the same potency.
Another study from The UK looked at what rheumatoid do when they're given a prescription. Specifically, a study from the National Rheumatoid Arthritis Society in The UK showed that only one in three RA patients would pick up a prescription that was sent to the pharmacy for them. It goes along with a lot of the data that says that up to half of patients don't fill prescriptions that are sent to the pharmacy for them. The main reason here was that of cost where in The UK the medicine is not costly and there are programs for cheaper medicine. There is an announcement this week that the tocilizumab study in scleroderma, the next phase, I think this is a phase two study, phase three trial, excuse me, has completed enrollment, and we'll see the results of that.
You know the first study that was done, the FASTINate study, that was a phase two trial. It looked very encouraging. They need this phase three trial to get the indication for use in scleroderma. This will have skin and lung outcomes. We're going need another year or more to get those results.
How much testing is enough? You know, one day I was seeing a patient, a 26 year old a 36 year old with new onset, a few weeks six weeks, ten weeks, doesn't really matter, of polyarthralgias in her hands. On exam, she has tenderness in her MCPs and PIPs. I did the tests I thought were reasonable and I thought, What would my colleagues do? And so I did a Twitter poll on this and within twenty four hours I had 106 responses and there were four choices there.
Just do a Sedrate and CRP or Sedrate CRP and test for rheumatoid arthritis or Sedrate CRP ANA, RF, NCCP, or lastly, Sedrate CRP and hepatitis serologies? The answers to me were a bit surprising. The answers were that fifty eight percent of rheumatologists, almost sixty percent, wanted everything, including the ANA. Why ANA? I have no idea.
The next most common answer was a sed rate, CRP, rheumatoid factor, and CCP at seventeen percent. Only nine percent did what I did, which is to order a sed rate and a CRP, and that's it. Of course, everybody gets a chem profile and a complete blood count. Now interestingly, this generated a lot of discussion online and rheumatologists generally want everything and then they want to figure it out the second visit. That's really not smart medicine.
You have to read my view on this on the website to see why the prudent thing to do is to just do testing as was required. You're supposed to use these tests to confirm a diagnosis. This patient did not have rheumatoid arthritis by any criteria. She had MCP tenderness and a little bit of PIP tenderness with only six joints involved, but nothing to show forth. There was no synovitis or enthesitis or periarticular involvement.
There was no other features of rheumatoid arthritis. This is going to likely burn out in most people. Having rheumatoid factor CCP, I don't believe is going to make you treat her any differently and it's not going to give her a diagnosis and she's not going to have pre clinical RA at that point. So anyway, you read and you can comment if you like any further. Two studies look at back pain and chronic pain showing things that we commonly use don't work at all.
First, gabapentinoids. That includes pregabalin and gabapentin. A number of studies, I think it was 26 studies were analyzed to see what the effects of that were on many different kinds of pain, and that included neuropathic pain and that's a marijuana study. I'm sorry. This was actually six studies, three done in pregabalin, three done in gabapentin, basically showing no benefits.
In fact, the pregabalin showed worse pain and yet we use a lot of these drugs in trying to manage chronic pain. Another study with marijuana and cannabinoids looked at 27 published studies and its ability to control chronic pain, what is often used for in states where it's legal, and they studied neuropathic pain, pain from MS, pain from cancer and other causes including rheumatic pain really showed no benefit. In most of these studies, both with the gabapentinoids and with marijuana there were more toxicities than there were benefits. I've heard others discuss gabapentinoids that if they went in front of the FDA today they would not get approved given the hurdles that are required to get a drug approved today. They are on the market as a sort of social wave of having importance and trying to manage the needs of many who advocate strongly for marijuana.
I don't live in a state where we can use cannabinoids other than by prescription and by pill. Lastly, there's two more. Psoriatic arthritis, if you have comorbidity, guess what? You're going to have probably worse disease and you're less likely to respond to DMARD and biologic therapy. Analysis of a good cohort of patients with from the Dan BioRegistry, think it was seventeen hundred plus PSA patients and they looked at the influence of comorbidities.
If you had a Charlson comorbidity index of two or higher, suggesting you had two or more comorbidities, you are more likely to have higher baseline disease activity and you're also more likely to have depression. Down the line, you're also more likely to not respond to drug intervention suggesting again the importance of comorbidity in psoriatic disease. Surprising because most of us recognize this but most of us certainly don't want to treat it and we assume it's going to be done by the primary care. Oops, that may not happen. We need another strategy for managing comorbidities amongst our rheumatology patients.
Lastly, a published report from Calabrese, Cavanaugh and Ellipsky looked at the safety of peglodecase in the clinical trials where it's been given. Peglodecase came out in 2010, I thought was very much a game changer when you started looking at some of the data and some of the pictures of patients with severe tophaceous gout remitting with tophite resolving. But yet there has been a concern about the safety of pegvodecase IV, especially IV infusion reactions. They looked at all of the IV infusion reactions. They looked at anaphylaxis rates using an NIH criteria for anaphylaxis and overall they showed that the number of infusion reactions, only about six point seven percent of patients had IV infusion reactions.
The number of anaphylaxis cases I think was incredibly low, was zero point three percent looking at all patients. But what they found interesting in this particular study and analysis was that the ones who had the most infusion reactions were the non responders and that was twelve percent non responders and two percent if you were getting the drug every four weeks or it was nine point eight percent in non responders and zero point five percent in responders if you were getting the drug every two weeks. The authors went on to say that if we kept an eye on the guidelines and used the drug as it's described and discontinued the drug when the serum uric acid level rose, especially above eight, that you would avoid one non response and two infusion reactions and ultimately anaphylaxis. That's it for this week on roomnow.com. You can go to the website and see these links and read up more on this information.
You can also not only see the RheumNow we can review but listen to it on iTunes and Soundhound. If you go to the social media icons on our website, you can click on one of those and find the podcast for you to listen to in the future. Have a good weekend and we'll see you next week.
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