RheumNow Podcast Prevalence Of Methotrexate Toxicities (6.28.19) Save
RheumNow Podcast Prevalence Of Methotrexate Toxicities (6.28.19) by Dr. Cush
Transcription
It's It's the 06/28/2019. This is the RheumNow Weekend Review. I'm doctor Jack Cush, executive editor of roomnow.com. This week, we're gonna discuss neuropathies and lupus, what happens with infection when you do a joint replacement, And lastly, what's in shortage as far as the CDC is concerned? Our first report is a meta analysis of patients in methotrexate toxicity.
Doctor. Solomon and colleagues looked at a lot of studies, 20 randomized trials over almost 4,000 reports, and estimated that the rate of toxicity of, alopecia is one to five percent, one to four point nine percent with methotrexate and the risk of stomatitis with methotrexate is, guess, what do you think? If you guess twenty percent too high, five point seven to eight percent. I would say that alopecia is about on par and probably closer to one percent based on my years of practice. And the stomatitis, I think it varies on whether you're soliciting that report or not.
Again, since a this drug related stomatitis, it should be painful oral ulcers, not painless, and should be readily apparent. I think this number is a little lower than what I would expect, but nonetheless, it's what the data says from a very large number of studies. How do you manage this? Well, alopecia, I don't have a solution. When it rarely happens, I think your only choice is to stop the drug and find another option.
If you have stomatitis, I got a solution. As you know, I've talked about this before, but vitamin A every day. That's oral ulcerations are improved in seventy percent of people by taking eight thousand units of vitamin A every day. Do it, try it, you'll be surprised. Folic acid manipulation is not gonna help either of these situations.
And that's my experience and expertise on this. Also, there's a Cochrane analysis that would say the same thing. A Norway study of GCA patients looked at what happens to GCA patients as far as the risk of death. Now these are older patients getting a serious inflammatory vasculopathy. And you would think that that plus the drugs that they use, maybe there'd be a higher risk of death.
Well, when I looked at, almost eight 100 GCA patients and match that one to four against normal age match controls, they found no overall difference in survival between the two groups. They did have a higher rate of cardiovascular death in the GCA patients with about a thirty one percent increased risk or hazard ratio of one point three one. And strangely, unexpectedly, there's a lower risk of cancer death in patients who had GCA with a forty four percent drop or a hazard ratio of zero point five six. Maybe if you live this long and get this diagnosis, your immune system is not gonna give you cancer, but it is gonna give you GCA. That's just a theory, but it's hard to explain these results.
The cardiovascular death makes sense, inflammation, steroid use, etcetera. An Italian study looked at what happens when you take RA patients and put them into remission. They took almost 800 patients, seven ninety five RA patients, and studied them in as far as their clinical outcomes and what happened to them subsequently. What they did show was that achieving remission was associated with a significant reduction in subclinical atherosclerosis by seventy five percent. And amongst these patients who did well, eighty eight percent were on methotrexate and sixty percent were on biologics, suggesting again that if you control inflammation, there are downstream consequences to that, meaning there's going to be less cardiovascular disease, less atherosclerotic disease.
Disease. A nice study looked at neuropathies. You know, that neuropathies was actually a session at ULAAR and neuropathy and lupus. This particular study looked at twelve hundred patients with lupus and found that only seven percent had any one of the various kinds of peripheral nervous system disease, but I'll just call peripheral neuropathy. But really, of that seven percent, only two thirds of them were attributable to lupus.
The most common manifestation was a peripheral polyneuropathy seen in forty three percent of individuals. Those who are more likely to have peripheral neuropathies were elderly, they had higher disease activity as measured by the SLIC and the SLETE I2K And they were more likely to have Sjogren's, livatore, hypertension and diabetes. So again, suggesting maybe some of those are responsible for the neuropathy. But neuropathy really isn't that common a manifestation in lupus. You should probably think of drugs and these other comorbidities as causes for it when it happens.
A nice study looked at what happens with hip and knee replacement in almost three thousand RA patients and one hundred and twelve thousand patients that they saw that while the RA patients had more infections compared to OA patients, a thirty percent increased risk after having a hip or knee replacement. Turns out RA patients were actually had fewer VTEs, venous thromboembolic events compared to OA patients. If you had RA and you're on a biologic, you had a similar infectious risk, but actually VTE risk goes up suggesting maybe more inflammation from RA might drive that VTE risk and maybe there's a contribution by some of these drugs. Not just the, JAK inhibitors, we've seen VTE increases with TNF inhibitors as well. A study looked at what happens when you give psoriatic arthritis patients a loading dose of secukinumab or not.
In this particular study, this is a future four study, believe, three forty one patients were randomized to either a loading dose of secukinumab or not everybody got one hundred and fifty milligrams in the usual dose. And at week sixteen, the ACR 20 responses were the same forty one and thirty nine percent, whether you were getting it with or without the loading dose. Although the ones with the loading dose did have a slightly earlier response, were no other differences in outcome. This is a lot like other studies in rheumatology where we forego the loading dose, the screwiness of the loading dose, you know, milligrams on Arava before you do twenty milligrams every day. I mean, again, these things rheumatologists quickly discard because if anything, they are an inconvenience and they may add more to the toxicity profile and don't seem to detract from the efficacy profile of these drugs as they're developed.
So this is what I'm doing in practice. I'm not usually giving an IV loading dose of secukinumab. I don't know if you saw the tweet last Friday, but I want to remind you included in this report that the CDC has put out a warning that the PPD that's supplied by one of the main manufacturers is gonna be in short supply for the next three to six months. The company that makes this, the product was called, Aplisol. The other one, Tubersol, is actually still available.
The Apisol that you use to do skin testing or PPD skin testing is gonna be not available. CDC recommendations in this situation are to either use an IGRA, an IGRA test, FERON or the TP spot, prioritize who needs a skin test and switching, but they recommend that if you switch from skin tested PPD or PPD to skin testing, you might notice some conversions that may require some interpretation. So one might have been negative now it's a low positive. Does it mean anything? Again, it has to require interpretation in light of any recent exposure in light of the magnitude of response it's seen.
Again, if you're not sure what to do talk to your ID or TB specialist. A quote that comes from this MMWR paper says clinicians should assess test results based on a person's likelihood of infection and risk for progression to TB disease if infected. I think those are very sage comments. Two more reports, three more reports. DMARDs success with myositis related interstitial lung disease.
This a report from Johns Hopkins and their myositis, cohort. About a 100 patients they reviewed who are either treated with azathioprine or mycophenolate. The outcomes were the same, especially as far as the pulmonary outcomes. Were looking here, they were looking myositis associated interstitial lung disease. So when it looked at FVC responses over a two to five year period, patients did better when they were on DMARDs.
They had lower, amount of steroid use, and they were equally effective. Where there was a slight difference between them was that, azathioprine might have been slightly better at steroids bearing compared to mycophenolate, and that azathioprine group unlike the microphenylene group, actually did have a reduction in DLCO, percentage after two to five years. Another nice study looked at the use of steroids in polymyalgia rheumatica and giant cell arteritis showing quite convincingly that in this very large cohort that steroid use increases infectious risk. So overall, they saw that about fifty five percent of patients with either diagnosis had an infection, one infection in the five years of follow-up, And that continued use of steroids was associated with not only increase in infection, but increase of hospitalization and death from infection. The infectious risk at one year on steroids was eighteen percent, at five years fifty four percent, at ten years seventy seven percent.
Thank God we have an alternative to steroids in PMR. Well, certainly in GCA. PMR, I think that that'll happen sometime soon. And lastly, a report from yesterday, mortality in the elderly. I think that this is sort of obvious, but we should think about this.
The data basically says that a significant number, thirty percent of patients over the age of 65 will have a fall in the next year. That that fall is associated with significant morbidity, mortality and healthcare utilization that really needs to be dealt with. In this CDC report published in the MMWR shows that individuals 75, the number of falls has increased substantially between 2000 and 2016. Specifically, they've increased from eighty six hundred to twenty five thousand per year. The crude mortality rate doubled from fifty one deaths per 100,000 to a hundred and twenty two deaths per 100,000 in 2016.
And at this rate of fall is sort of correlated with the age of the individual. So at age 75 to 79, the risk of death from fall is forty two per one hundred thousand. But if you look at individuals over the age of 95, the risk is six hundred per one hundred thousand. Yikes, more than a tenfold increased risk. Again, it's obvious the elderly, are at risk for falls, they hurt, they get weaker because they get weaker, they do less, because they do less, they get weaker, they get, then they hurt more, and then when they try to do something, they don't have the strength and they fall.
I think that what we should be preaching with all of our patients over the age of 65, certainly over the age of 75, is strength is your number one drug. If you're stronger, you're gonna have less problems with pain. If you're stronger, you're gonna be more independent. If you're stronger, you're have less likely a chance of falling and God forbid, dying from that fall. That's it for this week at RheumNow.
Go to the website. You can check out these citations and more. Next week, July, Independence Day in The United States, we're on vacation. We're gonna be having the best of EULAR on display all week. Hope you enjoy that.
We'll see you in two weeks. Enjoy.
Doctor. Solomon and colleagues looked at a lot of studies, 20 randomized trials over almost 4,000 reports, and estimated that the rate of toxicity of, alopecia is one to five percent, one to four point nine percent with methotrexate and the risk of stomatitis with methotrexate is, guess, what do you think? If you guess twenty percent too high, five point seven to eight percent. I would say that alopecia is about on par and probably closer to one percent based on my years of practice. And the stomatitis, I think it varies on whether you're soliciting that report or not.
Again, since a this drug related stomatitis, it should be painful oral ulcers, not painless, and should be readily apparent. I think this number is a little lower than what I would expect, but nonetheless, it's what the data says from a very large number of studies. How do you manage this? Well, alopecia, I don't have a solution. When it rarely happens, I think your only choice is to stop the drug and find another option.
If you have stomatitis, I got a solution. As you know, I've talked about this before, but vitamin A every day. That's oral ulcerations are improved in seventy percent of people by taking eight thousand units of vitamin A every day. Do it, try it, you'll be surprised. Folic acid manipulation is not gonna help either of these situations.
And that's my experience and expertise on this. Also, there's a Cochrane analysis that would say the same thing. A Norway study of GCA patients looked at what happens to GCA patients as far as the risk of death. Now these are older patients getting a serious inflammatory vasculopathy. And you would think that that plus the drugs that they use, maybe there'd be a higher risk of death.
Well, when I looked at, almost eight 100 GCA patients and match that one to four against normal age match controls, they found no overall difference in survival between the two groups. They did have a higher rate of cardiovascular death in the GCA patients with about a thirty one percent increased risk or hazard ratio of one point three one. And strangely, unexpectedly, there's a lower risk of cancer death in patients who had GCA with a forty four percent drop or a hazard ratio of zero point five six. Maybe if you live this long and get this diagnosis, your immune system is not gonna give you cancer, but it is gonna give you GCA. That's just a theory, but it's hard to explain these results.
The cardiovascular death makes sense, inflammation, steroid use, etcetera. An Italian study looked at what happens when you take RA patients and put them into remission. They took almost 800 patients, seven ninety five RA patients, and studied them in as far as their clinical outcomes and what happened to them subsequently. What they did show was that achieving remission was associated with a significant reduction in subclinical atherosclerosis by seventy five percent. And amongst these patients who did well, eighty eight percent were on methotrexate and sixty percent were on biologics, suggesting again that if you control inflammation, there are downstream consequences to that, meaning there's going to be less cardiovascular disease, less atherosclerotic disease.
Disease. A nice study looked at neuropathies. You know, that neuropathies was actually a session at ULAAR and neuropathy and lupus. This particular study looked at twelve hundred patients with lupus and found that only seven percent had any one of the various kinds of peripheral nervous system disease, but I'll just call peripheral neuropathy. But really, of that seven percent, only two thirds of them were attributable to lupus.
The most common manifestation was a peripheral polyneuropathy seen in forty three percent of individuals. Those who are more likely to have peripheral neuropathies were elderly, they had higher disease activity as measured by the SLIC and the SLETE I2K And they were more likely to have Sjogren's, livatore, hypertension and diabetes. So again, suggesting maybe some of those are responsible for the neuropathy. But neuropathy really isn't that common a manifestation in lupus. You should probably think of drugs and these other comorbidities as causes for it when it happens.
A nice study looked at what happens with hip and knee replacement in almost three thousand RA patients and one hundred and twelve thousand patients that they saw that while the RA patients had more infections compared to OA patients, a thirty percent increased risk after having a hip or knee replacement. Turns out RA patients were actually had fewer VTEs, venous thromboembolic events compared to OA patients. If you had RA and you're on a biologic, you had a similar infectious risk, but actually VTE risk goes up suggesting maybe more inflammation from RA might drive that VTE risk and maybe there's a contribution by some of these drugs. Not just the, JAK inhibitors, we've seen VTE increases with TNF inhibitors as well. A study looked at what happens when you give psoriatic arthritis patients a loading dose of secukinumab or not.
In this particular study, this is a future four study, believe, three forty one patients were randomized to either a loading dose of secukinumab or not everybody got one hundred and fifty milligrams in the usual dose. And at week sixteen, the ACR 20 responses were the same forty one and thirty nine percent, whether you were getting it with or without the loading dose. Although the ones with the loading dose did have a slightly earlier response, were no other differences in outcome. This is a lot like other studies in rheumatology where we forego the loading dose, the screwiness of the loading dose, you know, milligrams on Arava before you do twenty milligrams every day. I mean, again, these things rheumatologists quickly discard because if anything, they are an inconvenience and they may add more to the toxicity profile and don't seem to detract from the efficacy profile of these drugs as they're developed.
So this is what I'm doing in practice. I'm not usually giving an IV loading dose of secukinumab. I don't know if you saw the tweet last Friday, but I want to remind you included in this report that the CDC has put out a warning that the PPD that's supplied by one of the main manufacturers is gonna be in short supply for the next three to six months. The company that makes this, the product was called, Aplisol. The other one, Tubersol, is actually still available.
The Apisol that you use to do skin testing or PPD skin testing is gonna be not available. CDC recommendations in this situation are to either use an IGRA, an IGRA test, FERON or the TP spot, prioritize who needs a skin test and switching, but they recommend that if you switch from skin tested PPD or PPD to skin testing, you might notice some conversions that may require some interpretation. So one might have been negative now it's a low positive. Does it mean anything? Again, it has to require interpretation in light of any recent exposure in light of the magnitude of response it's seen.
Again, if you're not sure what to do talk to your ID or TB specialist. A quote that comes from this MMWR paper says clinicians should assess test results based on a person's likelihood of infection and risk for progression to TB disease if infected. I think those are very sage comments. Two more reports, three more reports. DMARDs success with myositis related interstitial lung disease.
This a report from Johns Hopkins and their myositis, cohort. About a 100 patients they reviewed who are either treated with azathioprine or mycophenolate. The outcomes were the same, especially as far as the pulmonary outcomes. Were looking here, they were looking myositis associated interstitial lung disease. So when it looked at FVC responses over a two to five year period, patients did better when they were on DMARDs.
They had lower, amount of steroid use, and they were equally effective. Where there was a slight difference between them was that, azathioprine might have been slightly better at steroids bearing compared to mycophenolate, and that azathioprine group unlike the microphenylene group, actually did have a reduction in DLCO, percentage after two to five years. Another nice study looked at the use of steroids in polymyalgia rheumatica and giant cell arteritis showing quite convincingly that in this very large cohort that steroid use increases infectious risk. So overall, they saw that about fifty five percent of patients with either diagnosis had an infection, one infection in the five years of follow-up, And that continued use of steroids was associated with not only increase in infection, but increase of hospitalization and death from infection. The infectious risk at one year on steroids was eighteen percent, at five years fifty four percent, at ten years seventy seven percent.
Thank God we have an alternative to steroids in PMR. Well, certainly in GCA. PMR, I think that that'll happen sometime soon. And lastly, a report from yesterday, mortality in the elderly. I think that this is sort of obvious, but we should think about this.
The data basically says that a significant number, thirty percent of patients over the age of 65 will have a fall in the next year. That that fall is associated with significant morbidity, mortality and healthcare utilization that really needs to be dealt with. In this CDC report published in the MMWR shows that individuals 75, the number of falls has increased substantially between 2000 and 2016. Specifically, they've increased from eighty six hundred to twenty five thousand per year. The crude mortality rate doubled from fifty one deaths per 100,000 to a hundred and twenty two deaths per 100,000 in 2016.
And at this rate of fall is sort of correlated with the age of the individual. So at age 75 to 79, the risk of death from fall is forty two per one hundred thousand. But if you look at individuals over the age of 95, the risk is six hundred per one hundred thousand. Yikes, more than a tenfold increased risk. Again, it's obvious the elderly, are at risk for falls, they hurt, they get weaker because they get weaker, they do less, because they do less, they get weaker, they get, then they hurt more, and then when they try to do something, they don't have the strength and they fall.
I think that what we should be preaching with all of our patients over the age of 65, certainly over the age of 75, is strength is your number one drug. If you're stronger, you're gonna have less problems with pain. If you're stronger, you're gonna be more independent. If you're stronger, you're have less likely a chance of falling and God forbid, dying from that fall. That's it for this week at RheumNow.
Go to the website. You can check out these citations and more. Next week, July, Independence Day in The United States, we're on vacation. We're gonna be having the best of EULAR on display all week. Hope you enjoy that.
We'll see you in two weeks. Enjoy.
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