RheumNow Podcast- Best Biologics (2.7.20) Save
RheumNow Podcast- Best Biologics (2.7.20) by Dr. Cush
Transcription
It's the 02/07/2020. This is the RheumNow podcast, and I'm doctor Jack Cush, executive editor of rheumnow.com. Heads up on head drop. What do you do with your itchy, scratchy urticaria patients, and what do they really have? And oops, found that synovial fluid in my lab coat pocket.
How long has it been there? Oh my goodness. Is it still good? Let's start off with that report, which is an interesting analysis of 30 synovial fluid samples, 18 with CPPD, 12 with MSU gout. And they took the samples and stored them in either EDTA or heparinized tubes, and then they left them in either the refrigerator or at room temperature and assessed their viability of those crystals at days one, three, and seven.
Guess what? MSU crystals are hard to kill. I mean, they were basically ninety two percent viable for out to seven was it seven seven days when they were at room temperature and a 100% viable when they were refrigerated. Again, they're really durable. CPB CPPD or the calcium pyrophosphate crystals are less durable.
They do pretty well, but they don't do well at room temperature compared to the refrigerator. They do better in in the refrigerator, And they don't do well in EDTA. So optimal CPB CPPD results are seen when they're in heparinized tubes and refrigerated. At room temperature, the viability goes down by 33%. Only 67% were able to identify the crystal at seven days.
Still's disease and how do you assess when they're gonna have a flare? Most of us would point to ferritin. I You have to stop doing that by the way. Ferritin is really nice and dramatic, but only in a small number of Still's patients. Fifty percent of Still's patients will have an elevated ferritin.
Ninety five percent will have an elevated CRP and sed rate. Which one you're gonna look at? Hyperferonemia is fabulous, but it's not that frequently seen and it's got other causes for that too. Anyway, Tom Takeuchi's group in Japan studied seventy five patients with Still's disease over a time period and they looked at FLAIR biomarkers. Of the seventy five patients, twenty five were not taking so tocilizumab than they previously had been.
Six were on others were on other drugs. They looked at AOSD flares and what happened to Sedrate, CRP, and ferritin. Guess what? When you flared with Still's disease, Sedrate, CRP, and ferritin were significantly elevated and were dynamic in patients who, were not on tocilizumab. But when they were on tocilizumab, guess what?
Not quite so good. Tocilizumab blunted the response of SED rate, CRP, and ferritin. On the other hand, white blood cell count and LDH levels rose whether you're on tocilizumab or not, and they were both quite dynamic. So they put forward that if you're following patients with Still's, white blood cell count, LDH in everyone, CRP and ferritin are helpful, but recognize they may drop or may not be as impactful in patients who are on the IL six inhibitor tocilizumab. A nice Canadian study comes out of Calgary, and I had put this up because I it's the kind of stuff we see all the time, and it's what do you do with ANA positive individuals?
It's a study from I think 2015, and they basically have this triage system at the university there, and they identified over a three year period six hundred and forty three patients who were referred because of a positive ANA. About half the patients were seen by a rheumatologist, and this is what they came up with. Twenty five percent, twenty four percent had the ANA that was due to an ANA associated rheumatic condition, you know, lupus, myositis, etcetera. Next, twenty six percent had no disease, no nothing, no known cause. Third, thirty nine percent had another rheumatic condition and they were quite vague about that.
Eleven percent failed to meet these autoimmune rheumatic disease criteria. I'm not sure what that was. What they didn't put in there was the number of people that had an ANA due to other disease associations that are not autoimmune or rheumatic. That would include, obviously, the number one, which is thyroid disease, cancer, hepatitis, chronic renal disease, chronic lung disease, some drugs, etcetera, pregnancy, there are a number of things obviously, renal failure. But nonetheless, I think it's an interesting interesting study.
And it actually says that not all ANA consults are gonna be nonsense. Maybe as many twenty five percent will have a real disease. Difficult RA and its management comes up quite often. We're often at a loss for what is left in choices. Timely comes a report on the utility of tacrolimus in patients with rheumatoid arthritis.
And meta analyses of five different studies shows that the odds of achieving an ACR twenty response were significantly higher with tacrolimus, one seventy one percent higher if you're on one to two milligrams a day of tacrolimus, and 2.3 fold higher if you're on three milligrams a day. Unfortunately, this impressive clinical efficacy comes with a toxicity risk, mainly that in the way of renal risk. So the odds of bumping your creatinine are twofold higher at one to two milligrams a high a day and almost fourfold higher at three milligrams per day. So, again, a good drug, you gotta monitor. It's a lot like cyclosporine.
Head drop is a symptom of myopathy. I thought this was interesting because I heard a foot drop. I've even heard a hand drop. Never heard a head drop. Thinking maybe I've seen a few people that are looking like this and, you know, don't know why.
Well, a hundred and seven patients were reviewed, and fifty three percent had a specific diagnosis. That's somewhat encouraging, guess. Inflammatory myositis made up sixteen, or that's about fifteen percent of the overall group. Myopathy with Rheum vacuoles ten, radiation myositis myopathy eight, enemeline, nemeline, myositis seven, myofibrilar myositis four, fascioscapulohumeral, something that looks like polymyositis three, and two each with inclusion body myositis or a mitochondrial myopathy and even myopathy associated with scleroderma. So we have a few conditions on that list that can lead to a present would lead to a presentation of head drop as someone who has myopathy.
So I teased with the idea of urticaria in your patients and what to do with this. This came up this week in clinic where I overheard the fellow and consult attending talking about a consult they're seeing someone who has chronic urticaria now is in the hospital with an ANA and an FUO. ANA positivity with urticaria is not that uncommon, may not indicate an autoimmune process like lupus or myositis or etc. Anyway, a Danish registry of almost 12,000 patients with chronic urticaria looked at what their disease associations were. And as you might imagine, there was a fairly high overrepresentation of anaphylaxis patients and those with mastocytosis.
But also in the in the list with healthy representations were atopic dermatitis, rheumatoid arthritis, lupus, thyroiditis, and vitiligo, all autoimmune disease. I don't know what that means for the consult with a fever and doesn't seem to have lupus, but nonetheless, it's out there for them to consider. A nice report compared the utility of MRA and FDG PET scanning in patients with newly diagnosed either Takayasu's arteritis or giant cell arteritis and tried to show the differences as far as their presentations and what was found on imaging. The takeaway messages were that keratodynia and arm claudication were way more common with Takayasu's arteritis and that vascular inflammation was easily picked up on by PET scan in Takayasu's arteritis. Much better than maybe what you would see with MRA, magnetic resonance angiography.
GCA lesions were largely found by MRA and showed the evidence of damage more so than evidence of inflammation. This report sort of parallels a tweet from last week where I said, based on a lecture I list was listening to, that MRA, much more affordable, much more accessible, is really good at defining the extent of disease and damage. On the other hand, PET scanning, very expensive, not affordable, often not covered, is really quite good at picking up on inflammatory lesions and generalized inflammation. And it's also good in FUO cases if you can get it paid for. Had a nice report that we just put out about from JAMA Dermatology about which biologics are best in psoriasis.
Not psoriatic arthritis, but psoriasis. And specifically, they looked at 60 trials with basically all the biologics. And it didn't matter whether you were looking at sixteen week short term outcomes or sixty week one year outcomes, long term outcomes, that the drugs that fared the best were rizanquizumab, an IL twenty three drug, guselkumab, an IL twenty three drug, brodalumab, an IL twenty three drug, and exakis I'm sorry. That's brodalumab is an IL seventeen inhibitor, and execizumab, an IL seventeen inhibitor. With the ace with the PASI 90 results in the trials ranging from 74 to seventy nine percent between those four.
You know, the other IL seventeen inhibitors, Cosentyx, secukinumab, are just behind that. Nifliximab is pretty high on the list. Middle of the pack are things like ustekinumab and adalimumab. Bottom of the bucket includes tildrakizumab, another IL twenty three inhibitor. I'm not sure why that is.
Eitanercept never did very well in skin compared to joints. And Eprimulast, we know has a low level of response in psoriasis and psoriatic arthritis. But it's really safe. Congratulations. Our last report is on bariatric surgery as a means of avoiding rheumatoid arthritis.
Well, you know, obesity is a risk factor for developing rheumatoid arthritis. And obesity is also a factor in disease severity because patients who are obese are less likely to respond to a lot of DMARDs and a number of biologics. And it's not just volume and distribution. So even when you dose them according to weight, like with infliximab, obese patients just don't do as well. So this study in Scandinavia, it's a a cohort called the Swedish Obese Subject Study or the SOS study, studies two thousand patients with obesity and their disease associations over time.
They compared that cohort to another two patient two thousand patients who were not obese, and overall, amongst the four thousand patients, they found ninety two incident cases of rheumatoid arthritis. Guess what? Getting bariatric surgery did not prevent the risk of rheumatoid arthritis. That RA risk was the same whether you had bariatric surgery and lost a lot of weight, or you didn't have surgery, and so that's sort of disappointing. What they did find was that CRP and smoking were associated with an increased risk of incident rheumatoid arthritis.
That's it for this edition of the podcast. Go to the website. You can find the links to these reports. You can read more on these exciting articles. Check out rheumnow.live and our program.
It looks really, really good. Let me give you one session. How about the session on spondyloarthritis? Advances in spondyloarthritis by Atul Dayadar. The gut joint access, IBD arthritis by Arti Kavanaugh, and imaging in spondylitis by Walter Maximovich from the University of Edmonton.
That's just one of, like, you know, hours of great programming at RheumNow Live. We'll talk to you next week.
How long has it been there? Oh my goodness. Is it still good? Let's start off with that report, which is an interesting analysis of 30 synovial fluid samples, 18 with CPPD, 12 with MSU gout. And they took the samples and stored them in either EDTA or heparinized tubes, and then they left them in either the refrigerator or at room temperature and assessed their viability of those crystals at days one, three, and seven.
Guess what? MSU crystals are hard to kill. I mean, they were basically ninety two percent viable for out to seven was it seven seven days when they were at room temperature and a 100% viable when they were refrigerated. Again, they're really durable. CPB CPPD or the calcium pyrophosphate crystals are less durable.
They do pretty well, but they don't do well at room temperature compared to the refrigerator. They do better in in the refrigerator, And they don't do well in EDTA. So optimal CPB CPPD results are seen when they're in heparinized tubes and refrigerated. At room temperature, the viability goes down by 33%. Only 67% were able to identify the crystal at seven days.
Still's disease and how do you assess when they're gonna have a flare? Most of us would point to ferritin. I You have to stop doing that by the way. Ferritin is really nice and dramatic, but only in a small number of Still's patients. Fifty percent of Still's patients will have an elevated ferritin.
Ninety five percent will have an elevated CRP and sed rate. Which one you're gonna look at? Hyperferonemia is fabulous, but it's not that frequently seen and it's got other causes for that too. Anyway, Tom Takeuchi's group in Japan studied seventy five patients with Still's disease over a time period and they looked at FLAIR biomarkers. Of the seventy five patients, twenty five were not taking so tocilizumab than they previously had been.
Six were on others were on other drugs. They looked at AOSD flares and what happened to Sedrate, CRP, and ferritin. Guess what? When you flared with Still's disease, Sedrate, CRP, and ferritin were significantly elevated and were dynamic in patients who, were not on tocilizumab. But when they were on tocilizumab, guess what?
Not quite so good. Tocilizumab blunted the response of SED rate, CRP, and ferritin. On the other hand, white blood cell count and LDH levels rose whether you're on tocilizumab or not, and they were both quite dynamic. So they put forward that if you're following patients with Still's, white blood cell count, LDH in everyone, CRP and ferritin are helpful, but recognize they may drop or may not be as impactful in patients who are on the IL six inhibitor tocilizumab. A nice Canadian study comes out of Calgary, and I had put this up because I it's the kind of stuff we see all the time, and it's what do you do with ANA positive individuals?
It's a study from I think 2015, and they basically have this triage system at the university there, and they identified over a three year period six hundred and forty three patients who were referred because of a positive ANA. About half the patients were seen by a rheumatologist, and this is what they came up with. Twenty five percent, twenty four percent had the ANA that was due to an ANA associated rheumatic condition, you know, lupus, myositis, etcetera. Next, twenty six percent had no disease, no nothing, no known cause. Third, thirty nine percent had another rheumatic condition and they were quite vague about that.
Eleven percent failed to meet these autoimmune rheumatic disease criteria. I'm not sure what that was. What they didn't put in there was the number of people that had an ANA due to other disease associations that are not autoimmune or rheumatic. That would include, obviously, the number one, which is thyroid disease, cancer, hepatitis, chronic renal disease, chronic lung disease, some drugs, etcetera, pregnancy, there are a number of things obviously, renal failure. But nonetheless, I think it's an interesting interesting study.
And it actually says that not all ANA consults are gonna be nonsense. Maybe as many twenty five percent will have a real disease. Difficult RA and its management comes up quite often. We're often at a loss for what is left in choices. Timely comes a report on the utility of tacrolimus in patients with rheumatoid arthritis.
And meta analyses of five different studies shows that the odds of achieving an ACR twenty response were significantly higher with tacrolimus, one seventy one percent higher if you're on one to two milligrams a day of tacrolimus, and 2.3 fold higher if you're on three milligrams a day. Unfortunately, this impressive clinical efficacy comes with a toxicity risk, mainly that in the way of renal risk. So the odds of bumping your creatinine are twofold higher at one to two milligrams a high a day and almost fourfold higher at three milligrams per day. So, again, a good drug, you gotta monitor. It's a lot like cyclosporine.
Head drop is a symptom of myopathy. I thought this was interesting because I heard a foot drop. I've even heard a hand drop. Never heard a head drop. Thinking maybe I've seen a few people that are looking like this and, you know, don't know why.
Well, a hundred and seven patients were reviewed, and fifty three percent had a specific diagnosis. That's somewhat encouraging, guess. Inflammatory myositis made up sixteen, or that's about fifteen percent of the overall group. Myopathy with Rheum vacuoles ten, radiation myositis myopathy eight, enemeline, nemeline, myositis seven, myofibrilar myositis four, fascioscapulohumeral, something that looks like polymyositis three, and two each with inclusion body myositis or a mitochondrial myopathy and even myopathy associated with scleroderma. So we have a few conditions on that list that can lead to a present would lead to a presentation of head drop as someone who has myopathy.
So I teased with the idea of urticaria in your patients and what to do with this. This came up this week in clinic where I overheard the fellow and consult attending talking about a consult they're seeing someone who has chronic urticaria now is in the hospital with an ANA and an FUO. ANA positivity with urticaria is not that uncommon, may not indicate an autoimmune process like lupus or myositis or etc. Anyway, a Danish registry of almost 12,000 patients with chronic urticaria looked at what their disease associations were. And as you might imagine, there was a fairly high overrepresentation of anaphylaxis patients and those with mastocytosis.
But also in the in the list with healthy representations were atopic dermatitis, rheumatoid arthritis, lupus, thyroiditis, and vitiligo, all autoimmune disease. I don't know what that means for the consult with a fever and doesn't seem to have lupus, but nonetheless, it's out there for them to consider. A nice report compared the utility of MRA and FDG PET scanning in patients with newly diagnosed either Takayasu's arteritis or giant cell arteritis and tried to show the differences as far as their presentations and what was found on imaging. The takeaway messages were that keratodynia and arm claudication were way more common with Takayasu's arteritis and that vascular inflammation was easily picked up on by PET scan in Takayasu's arteritis. Much better than maybe what you would see with MRA, magnetic resonance angiography.
GCA lesions were largely found by MRA and showed the evidence of damage more so than evidence of inflammation. This report sort of parallels a tweet from last week where I said, based on a lecture I list was listening to, that MRA, much more affordable, much more accessible, is really good at defining the extent of disease and damage. On the other hand, PET scanning, very expensive, not affordable, often not covered, is really quite good at picking up on inflammatory lesions and generalized inflammation. And it's also good in FUO cases if you can get it paid for. Had a nice report that we just put out about from JAMA Dermatology about which biologics are best in psoriasis.
Not psoriatic arthritis, but psoriasis. And specifically, they looked at 60 trials with basically all the biologics. And it didn't matter whether you were looking at sixteen week short term outcomes or sixty week one year outcomes, long term outcomes, that the drugs that fared the best were rizanquizumab, an IL twenty three drug, guselkumab, an IL twenty three drug, brodalumab, an IL twenty three drug, and exakis I'm sorry. That's brodalumab is an IL seventeen inhibitor, and execizumab, an IL seventeen inhibitor. With the ace with the PASI 90 results in the trials ranging from 74 to seventy nine percent between those four.
You know, the other IL seventeen inhibitors, Cosentyx, secukinumab, are just behind that. Nifliximab is pretty high on the list. Middle of the pack are things like ustekinumab and adalimumab. Bottom of the bucket includes tildrakizumab, another IL twenty three inhibitor. I'm not sure why that is.
Eitanercept never did very well in skin compared to joints. And Eprimulast, we know has a low level of response in psoriasis and psoriatic arthritis. But it's really safe. Congratulations. Our last report is on bariatric surgery as a means of avoiding rheumatoid arthritis.
Well, you know, obesity is a risk factor for developing rheumatoid arthritis. And obesity is also a factor in disease severity because patients who are obese are less likely to respond to a lot of DMARDs and a number of biologics. And it's not just volume and distribution. So even when you dose them according to weight, like with infliximab, obese patients just don't do as well. So this study in Scandinavia, it's a a cohort called the Swedish Obese Subject Study or the SOS study, studies two thousand patients with obesity and their disease associations over time.
They compared that cohort to another two patient two thousand patients who were not obese, and overall, amongst the four thousand patients, they found ninety two incident cases of rheumatoid arthritis. Guess what? Getting bariatric surgery did not prevent the risk of rheumatoid arthritis. That RA risk was the same whether you had bariatric surgery and lost a lot of weight, or you didn't have surgery, and so that's sort of disappointing. What they did find was that CRP and smoking were associated with an increased risk of incident rheumatoid arthritis.
That's it for this edition of the podcast. Go to the website. You can find the links to these reports. You can read more on these exciting articles. Check out rheumnow.live and our program.
It looks really, really good. Let me give you one session. How about the session on spondyloarthritis? Advances in spondyloarthritis by Atul Dayadar. The gut joint access, IBD arthritis by Arti Kavanaugh, and imaging in spondylitis by Walter Maximovich from the University of Edmonton.
That's just one of, like, you know, hours of great programming at RheumNow Live. We'll talk to you next week.
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