The RheumNow Week in Review - 16 February 2018 Save
The RheumNow Week in Review - 16 February 2018 by Dr. Cush
Transcription
It's the 02/16/2018. This is the RheumNow we can review. I'm doctor Jack Cush, executive editor of roomnow.com. This week in the news, DMARDs is brain savers. What about cherry picking for responses in lupus with B cell monoclonal antibodies?
And which is the safer joint replacement, the rheumatoid or osteoarthritic patient? These and more on this episode of the week in review. An interesting study comes out of Cambridge and of all places, the American Journal of Anthropology, talking about, muscle mass and fat mass and thermal regulation. It was an interesting study. It actually looked at, hands being immersed in cold water and to look at how heat is dissipated and try to correlate that with skeletal mass, fat mass, and total body mass.
They did this in over 200 patients of European descent, and basically they showed that the loss of heat and the thermal regulation that goes on is more dependent upon muscle mass than on fat mass. They found that skeletal muscle mass relative to body mass was a highly significant predictor of heat loss, while body mass and fat mass and stature body size were not. So basically what this means is now we have an explanation as to why women have much greater, much more frequent complaints about hands being cold than women. It's really a matter of muscle mass and not fat mass. There's an interesting study about drug safety and the use of social media to track drug safety.
This study was actually done, in a UK cohort that looked at Twitter as a tool for tracking adverse events due to glucocorticoid therapy. So they tracked Twitter for a three year period and during the same period, they looked at the MHRA, that's the equivalent of our FDA and the adverse event reporting system, they have a yellow card system there and they specifically looked at the number of reports on adverse events for glucocorticoids. Glucocorticoids. They found over twenty thousand such reports after a lot of combing and sort of paring down the data, over 20,000 reports on glucocorticoids and adverse events, whereas during the same timeframe, only about 3,000 in The UK regulatory system suggesting that there's a lot of signal to be had in social media that is very similar to that being seen with the usual tools by the regulatory agencies and that in this study they found the most common side effects were that of insomnia and weight gain. This week FDA granted a priority review to rituximab for its use in pemphigus vulgaris.
There's actually a few studies that are out there on this subject. There's a large one that was published in 2017 in Lancet about the use of rituximab in patients with very severe pemphigus vulgaris showing its efficacy. That may well be another indication in the future for this B cell directed therapy. A study comes from CHEST looking at the risk of fracture in COPD patients who happen to take corticosteroid inhalers. What they did was they looked at over two hundred and forty thousand patients with COPD who were over the age of 55, and they basically showed that those who had been on steroids, inhaled steroids that is, for more than four years and had received more than a thousand milligrams of steroid had basically a significantly higher, albeit only a ten percent higher rate of fractures, and this was equally seen in men and women.
This is not necessarily surprising because we know steroids are associated with fracture risk, but it is nonetheless interesting that it happens in those who are just receiving it for COPD. Another review takes the form of a systematic review of deck scanning and gout and what its utility could be. They actually looked at 32 articles and over 1,500 patients and surmised that DECT and that's dual energy CT scanning, which you know are great ways of imaging total body urate load. Can find where there is no disease or symptomatology tissue deposition of large urate stores that are problematic for patients with gout. These deck scans basically take little time.
They have low radiation exposure. The biggest problem is that they're not generally available. They're also not as generally cheap. They do have fairly good sensitivity and specificity of greater than 80% and their performance was certainly better than that of x-ray CT and maybe equal to or slightly better than ultrasound. I think in the future we'll see more deck scanning.
We're just starting to use it here in Dallas, and I think it may be useful in several ways. One, making a difficult diagnosis. Two, estimating for the patient the total body urate deposition. If patients knew the amount of urate deposition that was in their body, maybe they would be a little more driven to either take therapy, seek therapy, or advice and maybe be more compliant with therapy. An interesting study comes from the Dan Bio registry, that's the Danish Biologics Registry, specifically it looked at RA patients who are undergoing either total knee or total hip joint replacement, and they compared their four thousand patients to over one hundred and twenty thousand who had osteoarthritis.
Basically what they showed that RA patients had a decreased risk of joint revision, about thirty percent decreased risk, although they did have a higher rate of prosthetic joint infections, about a forty six percent higher rate of infection. Turns out that this was not affected by biologic therapy in RA patients. What was affecting these outcomes were this use of steroids and the amount of disease activity as measured by DAS. Research from a large UK database called The UK Clinical Practice Research Database showed that amongst over six thousand seven hundred patients with psoriatic arthritis, they look for disease associations and they found that not surprisingly that psoriatic arthritis was associated with a higher risk of developing uveitis, almost a three and a half fold increased risk and a higher risk of developing Crohn's disease, threefold increased risk, but not necessarily a higher rate of ulcerative colitis that I found to be surprising. And hence why I reported it.
Now, you may be familiar with lupus trials and that, there's a lot of problems in doing lupus trials and that rituximab failed in lupus, trials. There was a more recent study that was done by UCB with eprituzumab, e mab, an anti c d 22 monoclonal antibody. Two phase three trials showed it did not work and failed to meet its primary endpoint. However, a sub analysis of their large data set shows of those patients who had lupus and secondary Sjogren's, a total of seven percent of the population, that such patients were more likely to have a significant bickler response and significant decreases in B cell numbers and IgM. Now, this real?
Does this mean anything? Are we cherry picking here to find something that might justify what seems to be the rational approach to problematic lupus by inhibiting B cell activity? Give it up. It hasn't been shown to work. Everything that's been shown to work is uncontrolled, observational, skewed by bias.
Again, the trials show that it doesn't work in lupus. You might need to look better at patients who are responders to such therapy to find out who it may in fact work in. So yes, I'm not in favor of B cell monoclonal antibodies in lupus until we have better data supporting such use. Otherwise, it's off label experimental. Good luck, Charlie.
There is an interesting study that happened in primary care and gout showing that guess what? You can teach how to manage gout in this. I think this is the Geisinger Medical System in Danville, Pennsylvania. They look at two large internal medicine clinics or primary care clinics. One was the intervention clinic, the other one was not.
Basically they showed that when you did the intervention, which was give them education, showing that if you show them when to use your rate lowering therapy, how to monitor your rate lowering therapy and treat the target in treating patients with gout, guess what? They do better. So the endpoints in this study were that rate lowering therapy was more likely to be used, ten percent more likely to be used in the intervention group, sixty one versus fifty four percent. Monitoring was more likely to be used eighty percent versus fifty six percent and achieving achieving a treat to target goal with a urate of less than six was more likely at forty three percent versus twenty seven percent in the intervention versus non intervention groups. Now these are small increases, they are significant increases and these were over a short period of time, but nonetheless this is encouraging and this is the kind of stuff we need to do because frankly everyone's bad at managing gout, just primary care, but even rheumatologists and having rules and living by the rules can only benefit patients.
There's an interesting study that comes also from a large data set that looked at, over 4,000 patients or nearly four thousand patients with rheumatoid arthritis that were treated with DMARDs and compared that to, those that were not 2,000 or so patients. And basically they showed that DMAR therapy was associated with a forty percent reduced risk of developing dementia over time. And if you were on methotrexate, you had a fifty percent reduced risk of developing dementia. Says a lot about the power of DMARD, says a lot about maybe the pathogenesis of dementia that it might be inflammatory mediated or that maybe you need long term therapy with DMARDs to have such benefits. I think you'll see more about this in the future.
And lastly, we just reported today about the NHANES study, which you know is another one of those, NIH driven epidemiologic studies, and it shows that the frequency and prevalence of osteoarthritis has increased. It's gone up from two thousand and nine to twenty fourteen from six to fourteen percent and rheumatoid arthritis has decreased from five point nine to three point eight percent. Not surprising that first off, the overall numbers of arthritis is about twenty five percent prevalence of arthritis in The United States in 2014 and that number hasn't changed over time. But the rising numbers of OA and decreasing numbers of RA could get some attention. OA not surprising with the aging of our society, the obesification of our society, especially United States, and that RA may be decreasing just like what we saw with, streptococcal diseases and, rheumatic fever with better, more widespread therapy, you can change the natural history of the disease.
I know that we've went from when we first started out studying rheumatoid arthritis in late 1980s, were talking about the prevalence of RA being over two million people. And now the number, the most recent number, the best done number is one point three million people and this number says it may be still declining. So congratulations to all of you for doing such a good job at managing RA and you know what, You got to get on the horse and start working on osteoarthritis. There's a lot of work to be done there where the therapies ain't so great, the patients are hard to manage, it can be really frustrating and there's really not enough research and development in the osteoarthritis arena. That's it for this week on rheumnow.com.
Be sure to go to the website to check out these links, read more about these articles. Be sure to subscribe to our podcast on iTunes and Stitcher, Outcast, Google Play Music. There's a whole bunch of places you can listen to it. We'll see you next week. Goodbye.
And which is the safer joint replacement, the rheumatoid or osteoarthritic patient? These and more on this episode of the week in review. An interesting study comes out of Cambridge and of all places, the American Journal of Anthropology, talking about, muscle mass and fat mass and thermal regulation. It was an interesting study. It actually looked at, hands being immersed in cold water and to look at how heat is dissipated and try to correlate that with skeletal mass, fat mass, and total body mass.
They did this in over 200 patients of European descent, and basically they showed that the loss of heat and the thermal regulation that goes on is more dependent upon muscle mass than on fat mass. They found that skeletal muscle mass relative to body mass was a highly significant predictor of heat loss, while body mass and fat mass and stature body size were not. So basically what this means is now we have an explanation as to why women have much greater, much more frequent complaints about hands being cold than women. It's really a matter of muscle mass and not fat mass. There's an interesting study about drug safety and the use of social media to track drug safety.
This study was actually done, in a UK cohort that looked at Twitter as a tool for tracking adverse events due to glucocorticoid therapy. So they tracked Twitter for a three year period and during the same period, they looked at the MHRA, that's the equivalent of our FDA and the adverse event reporting system, they have a yellow card system there and they specifically looked at the number of reports on adverse events for glucocorticoids. Glucocorticoids. They found over twenty thousand such reports after a lot of combing and sort of paring down the data, over 20,000 reports on glucocorticoids and adverse events, whereas during the same timeframe, only about 3,000 in The UK regulatory system suggesting that there's a lot of signal to be had in social media that is very similar to that being seen with the usual tools by the regulatory agencies and that in this study they found the most common side effects were that of insomnia and weight gain. This week FDA granted a priority review to rituximab for its use in pemphigus vulgaris.
There's actually a few studies that are out there on this subject. There's a large one that was published in 2017 in Lancet about the use of rituximab in patients with very severe pemphigus vulgaris showing its efficacy. That may well be another indication in the future for this B cell directed therapy. A study comes from CHEST looking at the risk of fracture in COPD patients who happen to take corticosteroid inhalers. What they did was they looked at over two hundred and forty thousand patients with COPD who were over the age of 55, and they basically showed that those who had been on steroids, inhaled steroids that is, for more than four years and had received more than a thousand milligrams of steroid had basically a significantly higher, albeit only a ten percent higher rate of fractures, and this was equally seen in men and women.
This is not necessarily surprising because we know steroids are associated with fracture risk, but it is nonetheless interesting that it happens in those who are just receiving it for COPD. Another review takes the form of a systematic review of deck scanning and gout and what its utility could be. They actually looked at 32 articles and over 1,500 patients and surmised that DECT and that's dual energy CT scanning, which you know are great ways of imaging total body urate load. Can find where there is no disease or symptomatology tissue deposition of large urate stores that are problematic for patients with gout. These deck scans basically take little time.
They have low radiation exposure. The biggest problem is that they're not generally available. They're also not as generally cheap. They do have fairly good sensitivity and specificity of greater than 80% and their performance was certainly better than that of x-ray CT and maybe equal to or slightly better than ultrasound. I think in the future we'll see more deck scanning.
We're just starting to use it here in Dallas, and I think it may be useful in several ways. One, making a difficult diagnosis. Two, estimating for the patient the total body urate deposition. If patients knew the amount of urate deposition that was in their body, maybe they would be a little more driven to either take therapy, seek therapy, or advice and maybe be more compliant with therapy. An interesting study comes from the Dan Bio registry, that's the Danish Biologics Registry, specifically it looked at RA patients who are undergoing either total knee or total hip joint replacement, and they compared their four thousand patients to over one hundred and twenty thousand who had osteoarthritis.
Basically what they showed that RA patients had a decreased risk of joint revision, about thirty percent decreased risk, although they did have a higher rate of prosthetic joint infections, about a forty six percent higher rate of infection. Turns out that this was not affected by biologic therapy in RA patients. What was affecting these outcomes were this use of steroids and the amount of disease activity as measured by DAS. Research from a large UK database called The UK Clinical Practice Research Database showed that amongst over six thousand seven hundred patients with psoriatic arthritis, they look for disease associations and they found that not surprisingly that psoriatic arthritis was associated with a higher risk of developing uveitis, almost a three and a half fold increased risk and a higher risk of developing Crohn's disease, threefold increased risk, but not necessarily a higher rate of ulcerative colitis that I found to be surprising. And hence why I reported it.
Now, you may be familiar with lupus trials and that, there's a lot of problems in doing lupus trials and that rituximab failed in lupus, trials. There was a more recent study that was done by UCB with eprituzumab, e mab, an anti c d 22 monoclonal antibody. Two phase three trials showed it did not work and failed to meet its primary endpoint. However, a sub analysis of their large data set shows of those patients who had lupus and secondary Sjogren's, a total of seven percent of the population, that such patients were more likely to have a significant bickler response and significant decreases in B cell numbers and IgM. Now, this real?
Does this mean anything? Are we cherry picking here to find something that might justify what seems to be the rational approach to problematic lupus by inhibiting B cell activity? Give it up. It hasn't been shown to work. Everything that's been shown to work is uncontrolled, observational, skewed by bias.
Again, the trials show that it doesn't work in lupus. You might need to look better at patients who are responders to such therapy to find out who it may in fact work in. So yes, I'm not in favor of B cell monoclonal antibodies in lupus until we have better data supporting such use. Otherwise, it's off label experimental. Good luck, Charlie.
There is an interesting study that happened in primary care and gout showing that guess what? You can teach how to manage gout in this. I think this is the Geisinger Medical System in Danville, Pennsylvania. They look at two large internal medicine clinics or primary care clinics. One was the intervention clinic, the other one was not.
Basically they showed that when you did the intervention, which was give them education, showing that if you show them when to use your rate lowering therapy, how to monitor your rate lowering therapy and treat the target in treating patients with gout, guess what? They do better. So the endpoints in this study were that rate lowering therapy was more likely to be used, ten percent more likely to be used in the intervention group, sixty one versus fifty four percent. Monitoring was more likely to be used eighty percent versus fifty six percent and achieving achieving a treat to target goal with a urate of less than six was more likely at forty three percent versus twenty seven percent in the intervention versus non intervention groups. Now these are small increases, they are significant increases and these were over a short period of time, but nonetheless this is encouraging and this is the kind of stuff we need to do because frankly everyone's bad at managing gout, just primary care, but even rheumatologists and having rules and living by the rules can only benefit patients.
There's an interesting study that comes also from a large data set that looked at, over 4,000 patients or nearly four thousand patients with rheumatoid arthritis that were treated with DMARDs and compared that to, those that were not 2,000 or so patients. And basically they showed that DMAR therapy was associated with a forty percent reduced risk of developing dementia over time. And if you were on methotrexate, you had a fifty percent reduced risk of developing dementia. Says a lot about the power of DMARD, says a lot about maybe the pathogenesis of dementia that it might be inflammatory mediated or that maybe you need long term therapy with DMARDs to have such benefits. I think you'll see more about this in the future.
And lastly, we just reported today about the NHANES study, which you know is another one of those, NIH driven epidemiologic studies, and it shows that the frequency and prevalence of osteoarthritis has increased. It's gone up from two thousand and nine to twenty fourteen from six to fourteen percent and rheumatoid arthritis has decreased from five point nine to three point eight percent. Not surprising that first off, the overall numbers of arthritis is about twenty five percent prevalence of arthritis in The United States in 2014 and that number hasn't changed over time. But the rising numbers of OA and decreasing numbers of RA could get some attention. OA not surprising with the aging of our society, the obesification of our society, especially United States, and that RA may be decreasing just like what we saw with, streptococcal diseases and, rheumatic fever with better, more widespread therapy, you can change the natural history of the disease.
I know that we've went from when we first started out studying rheumatoid arthritis in late 1980s, were talking about the prevalence of RA being over two million people. And now the number, the most recent number, the best done number is one point three million people and this number says it may be still declining. So congratulations to all of you for doing such a good job at managing RA and you know what, You got to get on the horse and start working on osteoarthritis. There's a lot of work to be done there where the therapies ain't so great, the patients are hard to manage, it can be really frustrating and there's really not enough research and development in the osteoarthritis arena. That's it for this week on rheumnow.com.
Be sure to go to the website to check out these links, read more about these articles. Be sure to subscribe to our podcast on iTunes and Stitcher, Outcast, Google Play Music. There's a whole bunch of places you can listen to it. We'll see you next week. Goodbye.
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