April 7%2C 2017 (1) Save
April 7%2C 2017 (1) by Dr. Cush
Transcription
Hey now. It's the 04/07/2017. This is the room now we can review. I'm doctor Jack Cush, executive editor of roomnow.com. I'm coming to you live from the Cleveland Clinic where they're having their seventh biannual Biologics Summit.
This is a meeting that Lenny Calabrese hosts here at the clinic at, usually brings in some of the biggest and best of minds regarding biologics. It's a four day conference. We're two days in. It's been a great conference thus far. Some highlights of the meeting thus far, Chris Richland reviewed psoriatic arthritis, its pathogenesis, some of its therapies.
A few nice tidbits from him, thirty percent of patients with psoriasis will develop psoriatic arthritis. But yet if you go into the clinics of the dermatologists and have rheumatologists examine all their patients, as many as fifteen percent of patients in the clinics right now in the dermatology clinic at least will have psoriatic arthritis. Risk factors for psoriatic arthritis are numerous. High on the list is obesity, but there are others, smoking, nail dystrophy, severe psoriasis, trauma, fractures, family history of psoriasis, and rubella vaccination. When Chris was reviewing the genetics of psoriatic disease, he clearly showed that C0602 has a very high association with skin psoriasis, as much as sixty percent of patients will have that gene.
On the other hand, the same gene is seen less frequently in patients with psoriatic arthritis, only about twenty eight percent of patients with that same gene. An interesting lecture from a pediatric immunologist, Doctor. Torgerson, looked at a number of interesting factors around the immune system and immunodeficiency. One thing I liked that he said talked about the function of neutrophils and said that there's 100,000,000,000 neutrophils made every day. They live about six and a half hours, and that they're removed from our system by complement and phagocytes.
He used the quote that these cells were involved in scavenging and basically cleaning up the garbage. He says the neutrophils live fast and die hard. A real interesting lecture from Mike Hollers from Denver looked at the whole issue of preclinical RA, a number of important points. First, that first degree relatives of those who have seropositive RA have about a frequency of rheumatoid factor or CCP of around sixteen percent. If you look at first degree relatives who are rheumatoid factor or CCV positive, the risk of developing RA in that person goes up with the titer of the rheumatoid factor and can be as high as fifty percent.
So in those at risk individuals, lot of discussion was had about modifying lifestyle including smoking and weight and gingival care in an effort to minimize the risk, but that such advice is good overall health advice. He also pointed out that the data on smoking is a little discouraging but while we all would recommend stopping smoking so as to avoid arthritis, at least in women who have rheumatoid arthritis, the benefits of stopping smoking can take as long as twenty years according to the nurse's health study. And lastly, he showed a lot of very good evidence about the importance of mucosal immunity and we know that from studies involving the lung, involving the GI tract and whatnot, the evidence for important mucosal immunity leading to, the development of disease in those who may be at risk comes from several lines of evidence. Number one, that almost all of the autoantibodies that are present, the earliest of them are all IgA. There's evidence that he's done showing that airway disease is present in ACPA positive first degree relatives, that there's a high level IgA plasmablast and certainly the evidence from the altered gut microbiome, the dysbiosis seen there, that has been seen in at risk individuals, all points to the mucosal immunity as an important factor.
Interestingly, the studies that have thus far been lined up to test whether drug intervention in at risk individuals who don't yet have arthritis, who are first degree relatives, are CCP or rheumatoid factor positive, were using conventional drugs, Plaquenil, Abatacept, and the recently completed Prairie study with Rituximab. None of these are specifically targeting mucosal immunity so these are test cases. We're going to probably learn as much from the placebo population as we will in those that are actually on the drug. A great lecture from Doctor. Ian McGinnis from Glasgow.
Ian started out by saying one of the major lessons in the last decade is that we are bad at choosing the right target for rheumatoid arthritis. That's been pretty much by happenstance. We've learned more going from bedside to bench than we've learned by going bench to bedside and there's a lot of reasons for that. He pointed out that the issue of how we approach disease the same all along its course from the earliest stages to the later stages is a little bit nonsensical when you consider the fact that the immune system dynamics change continually over the life cycle of rheumatoid arthritis but yet our therapies remain the same and that he feels we need a different approach. And he ended with some important data and important suggestions suggesting that we need to focus on the synovium because the synovium tells us as much about inflammation but really the synovium in remission is likely to tell us more.
He made the point that we now probably know better who to study, that is those who actually achieve remission and response on a specific drug, and now he's also suggesting where to study it and that being the Synovium. So that's it thus far from the meeting this week. There's other data that's actually on the website this week. The FDA approved the website 23andMe. This is a company that markets at home genetic testing.
The FDA has approved them to do direct marketing for a battery of tests that would look at the genes for Alzheimer's, Parkinson's, and celiac disease, but also some very rare diseases such as dystonia, Gaucher's disease, and hemochromatosis. It's not probably far in the future that they'll be doing other genetic tests that would look at the genes, for instance, associated with rheumatoid arthritis and trying to let people ascertain their possible risks. A nice review of statin myopathy was seen looking at one hundred patients, had a mean age of 65 years of age, mean CPK due to the statin of over six thousand eight hundred, but when tested, one hundred percent of these people had autoantibodies against HMG Co Reductase. So that's an important advance in our understanding of that pretty rare syndrome. A number of regulatory things happened this week.
The FDA granted approval to AbbVie for the use of adalimumab in severe fingernail psoriasis. That's right, fingernail psoriasis. So they now have I think nine indications for the use of that drug. The FDA Oncologic Advisory Committee, an advisory committee that hasn't, that obviously is the first step in getting a drug approved, has actually unanimously approved the use of subcutaneous rituximab in patients who have lymphoma and CLL. We can anticipate then that this will be approved.
The good news is that this can be given in minutes as opposed to the many hours we use when trying to use rituximab for either rheumatoid arthritis, lymphoma, or GPA. The FDA has also recently granted breakthrough status which means an expedited review for rituximab in the use on the treatment of pemphigus, a very difficult study largely based on a study that came out this week in Lancet. If you're interested in that, it's on the website. Discussion of Orafan came up recently and I reviewed some of the literature and surprisingly an Orafan, which none of us have used in probably over twenty five years, has become a more popular drug recently. It's an off label drug and it's being used in a number of cancers, and in resistant infections, specifically bacterial, fungal, and parasitic infections.
So Aranofin is still out there and being used, not helping arthritis, but it may be helping those other conditions. There's a nice report from the Journal of Bone and Mineral Research that looks at the activity of adolescents. They studied nearly 300 children and adolescents between the ages, I think, of 12 and 20 and looked at their activity levels and how that manifested as far as bone strength and they showed that vigorous physical activity was associated with greater bone strength and cortical porosity and that the converse was also seen, that those that were lazy actually had weaker bones. Since about 35% of your bone mass is being formed during these early formative years, exercise obviously should be vigorously promoted to children. There's an interesting article about abatacept during surgery, can you use drugs during surgery, should you stop, when should you stop?
This is a review from the Aura French Registry of over a thousand patients who are taking abatacept and they didn't have a control group but they did show a fairly low rate of serious infections, about seven point five percent in those that were having surgery while on abatacept. They did show that those who stopped their drug and then had different intervals, that the intervals had no effect on the rates of surgical infections. They also showed that the thing that predicted surgical infections the most was the use of steroids. And lastly, there's a blog that I wrote about the great masquerader. It's about In the past, we used to call TB and syphilis the great masquerader.
It's been replaced by lupus and vasculitis and sarcoidosis, but really the much more common, more undiagnosed and often masquerading as something else is fibromyalgia. There's up to four to seven million people affected with fibromyalgia making it highly prevalent. The problem is they never come in with a complaint of widespread pain, trigger points and a sleep disorder. They come in with elbow pain, my doctor thinks I have lupus, do I have multiple sclerosis? Again, their presentations are varied such that Doctor.
Cavanagh many years ago said that it should be called multi organ dysesthesia, and depending on what clinic you present to, it's really fibromyalgia. So in the allergy clinic, it's chronic sinusitis and allergic rhinitis. In the neurology clinic, it may be cognitive dysfunction or migraine, etc. So consider that fibromyalgia should be high on our list of diagnoses. That's it for this week, roomnow.com.
Go to the website for these links and more. Watch the Cleveland Clinic and you can actually get some of this education online, some truly wonderful lectures that are worth reviewing. See you next week.
This is a meeting that Lenny Calabrese hosts here at the clinic at, usually brings in some of the biggest and best of minds regarding biologics. It's a four day conference. We're two days in. It's been a great conference thus far. Some highlights of the meeting thus far, Chris Richland reviewed psoriatic arthritis, its pathogenesis, some of its therapies.
A few nice tidbits from him, thirty percent of patients with psoriasis will develop psoriatic arthritis. But yet if you go into the clinics of the dermatologists and have rheumatologists examine all their patients, as many as fifteen percent of patients in the clinics right now in the dermatology clinic at least will have psoriatic arthritis. Risk factors for psoriatic arthritis are numerous. High on the list is obesity, but there are others, smoking, nail dystrophy, severe psoriasis, trauma, fractures, family history of psoriasis, and rubella vaccination. When Chris was reviewing the genetics of psoriatic disease, he clearly showed that C0602 has a very high association with skin psoriasis, as much as sixty percent of patients will have that gene.
On the other hand, the same gene is seen less frequently in patients with psoriatic arthritis, only about twenty eight percent of patients with that same gene. An interesting lecture from a pediatric immunologist, Doctor. Torgerson, looked at a number of interesting factors around the immune system and immunodeficiency. One thing I liked that he said talked about the function of neutrophils and said that there's 100,000,000,000 neutrophils made every day. They live about six and a half hours, and that they're removed from our system by complement and phagocytes.
He used the quote that these cells were involved in scavenging and basically cleaning up the garbage. He says the neutrophils live fast and die hard. A real interesting lecture from Mike Hollers from Denver looked at the whole issue of preclinical RA, a number of important points. First, that first degree relatives of those who have seropositive RA have about a frequency of rheumatoid factor or CCP of around sixteen percent. If you look at first degree relatives who are rheumatoid factor or CCV positive, the risk of developing RA in that person goes up with the titer of the rheumatoid factor and can be as high as fifty percent.
So in those at risk individuals, lot of discussion was had about modifying lifestyle including smoking and weight and gingival care in an effort to minimize the risk, but that such advice is good overall health advice. He also pointed out that the data on smoking is a little discouraging but while we all would recommend stopping smoking so as to avoid arthritis, at least in women who have rheumatoid arthritis, the benefits of stopping smoking can take as long as twenty years according to the nurse's health study. And lastly, he showed a lot of very good evidence about the importance of mucosal immunity and we know that from studies involving the lung, involving the GI tract and whatnot, the evidence for important mucosal immunity leading to, the development of disease in those who may be at risk comes from several lines of evidence. Number one, that almost all of the autoantibodies that are present, the earliest of them are all IgA. There's evidence that he's done showing that airway disease is present in ACPA positive first degree relatives, that there's a high level IgA plasmablast and certainly the evidence from the altered gut microbiome, the dysbiosis seen there, that has been seen in at risk individuals, all points to the mucosal immunity as an important factor.
Interestingly, the studies that have thus far been lined up to test whether drug intervention in at risk individuals who don't yet have arthritis, who are first degree relatives, are CCP or rheumatoid factor positive, were using conventional drugs, Plaquenil, Abatacept, and the recently completed Prairie study with Rituximab. None of these are specifically targeting mucosal immunity so these are test cases. We're going to probably learn as much from the placebo population as we will in those that are actually on the drug. A great lecture from Doctor. Ian McGinnis from Glasgow.
Ian started out by saying one of the major lessons in the last decade is that we are bad at choosing the right target for rheumatoid arthritis. That's been pretty much by happenstance. We've learned more going from bedside to bench than we've learned by going bench to bedside and there's a lot of reasons for that. He pointed out that the issue of how we approach disease the same all along its course from the earliest stages to the later stages is a little bit nonsensical when you consider the fact that the immune system dynamics change continually over the life cycle of rheumatoid arthritis but yet our therapies remain the same and that he feels we need a different approach. And he ended with some important data and important suggestions suggesting that we need to focus on the synovium because the synovium tells us as much about inflammation but really the synovium in remission is likely to tell us more.
He made the point that we now probably know better who to study, that is those who actually achieve remission and response on a specific drug, and now he's also suggesting where to study it and that being the Synovium. So that's it thus far from the meeting this week. There's other data that's actually on the website this week. The FDA approved the website 23andMe. This is a company that markets at home genetic testing.
The FDA has approved them to do direct marketing for a battery of tests that would look at the genes for Alzheimer's, Parkinson's, and celiac disease, but also some very rare diseases such as dystonia, Gaucher's disease, and hemochromatosis. It's not probably far in the future that they'll be doing other genetic tests that would look at the genes, for instance, associated with rheumatoid arthritis and trying to let people ascertain their possible risks. A nice review of statin myopathy was seen looking at one hundred patients, had a mean age of 65 years of age, mean CPK due to the statin of over six thousand eight hundred, but when tested, one hundred percent of these people had autoantibodies against HMG Co Reductase. So that's an important advance in our understanding of that pretty rare syndrome. A number of regulatory things happened this week.
The FDA granted approval to AbbVie for the use of adalimumab in severe fingernail psoriasis. That's right, fingernail psoriasis. So they now have I think nine indications for the use of that drug. The FDA Oncologic Advisory Committee, an advisory committee that hasn't, that obviously is the first step in getting a drug approved, has actually unanimously approved the use of subcutaneous rituximab in patients who have lymphoma and CLL. We can anticipate then that this will be approved.
The good news is that this can be given in minutes as opposed to the many hours we use when trying to use rituximab for either rheumatoid arthritis, lymphoma, or GPA. The FDA has also recently granted breakthrough status which means an expedited review for rituximab in the use on the treatment of pemphigus, a very difficult study largely based on a study that came out this week in Lancet. If you're interested in that, it's on the website. Discussion of Orafan came up recently and I reviewed some of the literature and surprisingly an Orafan, which none of us have used in probably over twenty five years, has become a more popular drug recently. It's an off label drug and it's being used in a number of cancers, and in resistant infections, specifically bacterial, fungal, and parasitic infections.
So Aranofin is still out there and being used, not helping arthritis, but it may be helping those other conditions. There's a nice report from the Journal of Bone and Mineral Research that looks at the activity of adolescents. They studied nearly 300 children and adolescents between the ages, I think, of 12 and 20 and looked at their activity levels and how that manifested as far as bone strength and they showed that vigorous physical activity was associated with greater bone strength and cortical porosity and that the converse was also seen, that those that were lazy actually had weaker bones. Since about 35% of your bone mass is being formed during these early formative years, exercise obviously should be vigorously promoted to children. There's an interesting article about abatacept during surgery, can you use drugs during surgery, should you stop, when should you stop?
This is a review from the Aura French Registry of over a thousand patients who are taking abatacept and they didn't have a control group but they did show a fairly low rate of serious infections, about seven point five percent in those that were having surgery while on abatacept. They did show that those who stopped their drug and then had different intervals, that the intervals had no effect on the rates of surgical infections. They also showed that the thing that predicted surgical infections the most was the use of steroids. And lastly, there's a blog that I wrote about the great masquerader. It's about In the past, we used to call TB and syphilis the great masquerader.
It's been replaced by lupus and vasculitis and sarcoidosis, but really the much more common, more undiagnosed and often masquerading as something else is fibromyalgia. There's up to four to seven million people affected with fibromyalgia making it highly prevalent. The problem is they never come in with a complaint of widespread pain, trigger points and a sleep disorder. They come in with elbow pain, my doctor thinks I have lupus, do I have multiple sclerosis? Again, their presentations are varied such that Doctor.
Cavanagh many years ago said that it should be called multi organ dysesthesia, and depending on what clinic you present to, it's really fibromyalgia. So in the allergy clinic, it's chronic sinusitis and allergic rhinitis. In the neurology clinic, it may be cognitive dysfunction or migraine, etc. So consider that fibromyalgia should be high on our list of diagnoses. That's it for this week, roomnow.com.
Go to the website for these links and more. Watch the Cleveland Clinic and you can actually get some of this education online, some truly wonderful lectures that are worth reviewing. See you next week.
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