The RheumNow Week In Review 31 March 2017 Save
The RheumNow Week In Review 31 March 2017 by Dr. Cush
Transcription
It's the 03/31/2017. This is the RheumNow we can review, and I'm Jack Cush, executive editor of rheumnow.com. This week, I'm tweeting and reporting from advances in targeted therapies, a meeting being held here in Mandalu, France. This week, a few of the tweets that I thought were interesting, included a great lecture by doctor Max Cooper on when did the immune system start, and he dates it all the way back to 450,000,000 years ago where the first evidence of adaptive immunity is being found in jawless hagfish and lampreys, which are sort of defend descendants of the catfish. In those species, they found, VLR receptors and antigen specific responses that indicated the evidence of the the start of an adaptive immune response much like what we have today.
A great lecture. Doctor. Ray Chowdhury, reviewed some of the genetics behind rheumatoid arthritis, and I thought a notable point was that position 13 in the, pocket of HLA Doctor beta one is probably responsible for as much as ninety percent of the risk of rheumatoid arthritis. Good information suggesting that you might be able to identify a putative antigen with that kind of power. A great lecture by Bernard Manger from Germany looked at paraneoplastic syndromes with rheumatic manifestations, and he had a number of them, including clubbing and associations with hypertrophic osteoarthropathy, a cancer associated polyarthritis, myocyte associated with cancer, palmar fasciitis, paniculitis, vasculitis, and something called oncogenic osteomalacia, all these being paraneoplastic syndromes.
A great lecture by Kevin Winthrop reviewed, what is a safe spot on steroid use? Is there a sweet spot? Is there a dose we should or shouldn't use? Interestingly, you showed a number of studies that showed well, first off, I've always thought that, any dose of steroid can increase risk. There are multiple studies showing the higher the dose you use, the greater the risk, and it's always been a dose dependent phenomenon.
And you do see a number of studies where the risk is present at five milligrams a day of prednisone. He showed a few studies where five milligrams a day of prednisone was not associated with a higher risk, and they were tended to be in relatively new and relatively simple patients, without complex therapies and whatnot. However, if you look at prednisone use in conjunction with complex therapies, often given to very sick patients, you don't see quite the same. You see now an increased risk. So he cited the CAPRA two study from Frank Bucharest, which showed that five milligrams of prednisone did not increase the risk of infection in RA patients on DMARDs, but then cited a number of other ones.
Another, I think, great take home from him was that, doses that are higher are clearly going to be, an increased risk, and he pointed out that fifteen milligrams above almost consistently gives you a higher and deleterious effect as far as infectious risk. You can get it at lower rates, but the bottom line is a simple patient, low dose steroids is probably not going to be harmful. But a complex patient, multiple comorbidities, very severe inflammation, it's the same story as that seen with the rabbit registry and TNF inhibitor use. The greatest risk for infection is in those who have the worst disease, the worst number of comorbidities, and worst prognostic factors. Those are people, when you add on more advanced therapies or even steroids, you get a higher risk of infection.
From the news this week, hepatitis B testing, an interesting report, looked at fifteen thousand, USRA patients and over forty six thousand Taiwanese patients and found surprisingly low rates of hepatitis B testing. Twenty percent in The US and twenty four percent in The Taiwanese, suggesting we are way, way under testing in high risk patients going on high risk drugs that could lead to hepatitis B reactivation. The FDA this week approved ocrelizumab. This is an anti c d twenty monoclonal antibody. It was in clinical trials for rheumatoid arthritis, was suspended for unclear reasons to me, and is now gonna be marketed for multiple sclerosis for both the relapsing form and the aggressive primary progressive form.
The approval is based on, OPRA one and OPRA two trials and something called the OPTAVIA study. It's gonna be priced at over $60,000 a year. It's felt to be a major advance in the treatment of multiple sclerosis. Another important news item this week was the approval of tofacitinib in the European Union by the EMA. As you know, this has been up for, consideration for a number of years, and finally is, has taken place.
In fact, baricitinib was approved earlier this year in EU, and now tofacitinib is approved at five milligrams twice a day. There's a nice review of psoriasis induced by TNF inhibitors in the derm, literature. This is the Journal of, American Academy of Dermatology. An interesting article looked at over, 88 articles and identified 216 patients to come up with basically a picture as to who gets this. It was mainly seen in Crohn's patients about forty percent, rheumatoid arthritis of a little bit less than thirty seven percent.
It was mainly seen in the first year or fourteen months on average. Infliximab was the most frequent offender, but that's probably because of the Crohn's association with sixty two percent of the cases that they identified being associated with infliximab and about twenty one percent with adalimumab, only fourteen percent were with etanercept. The skin manifestations were about forty percent plaque psoriasis, thirty six percent pustular psoriasis, and a few with psoriasis psoriasiform dermatitis. It's a little bit different than some of the other reviews that suggest there was a higher rate of pomopustular disease in patients with this, TNF inhibitor induced form of psoriasis. The authors recommended topical therapy.
It seems to work while continuing the TNF inhibitor in a number of patients, but the most often, therapeutic maneuver was cessation of the TNF inhibitor in nearly half the patients and that led to improvement or resolution ninety four percent. But they did also show that thirty two percent, thirty three percent continued therapy and thirty three percent improved and fifty seven percent, actually resolved. So, again, you could switch, you could continue. I think it depends on the severity. I think, I would also recommend that palmar pustular psoriasis is more difficult to treat, less likely to go away on its own, probably should merit, consideration of drug cessation rather than continuation, and or switching.
A report has come in in ARD this week about biologics not increasing the risk of invasive melanoma. I think the data is pretty clear that TNF inhibitors don't really cause cancers above that seen in RA patients sick enough to get a TNF inhibitor, meaning RA and inflammation promotes a higher risk of lymphoma, lung cancer, skin cancers, leukemia, maybe melanoma. When you look at patients who had a prior cancer, and you give them a TNF inhibitor, what happens? Well, studies have shown that actually the rates of recurrence are low except for one, and that's been, seen for a while with just and mainly with one citation, the British Biologics Registry showing an eighteen percent recurrence rate when you gave a TNF inhibitor to those who had previously had melanoma. They didn't specify whether it was invasive or in situ melanoma, so it's a little confused, but it's led a lot of patients and a lot of doctors to believe don't use TNF inhibitors with melanoma.
So because of the, controversy, nine countries pooled the data of 11 registries, 11 RA registries to look at several 100,000 patients and basically came up with the fact that, there is no higher rate of melanoma when you use a biologic, specifically a TNF inhibitor, but also rituximab, and tocilizumab, and abatacib were shown to not increase the risk of, first
A great lecture. Doctor. Ray Chowdhury, reviewed some of the genetics behind rheumatoid arthritis, and I thought a notable point was that position 13 in the, pocket of HLA Doctor beta one is probably responsible for as much as ninety percent of the risk of rheumatoid arthritis. Good information suggesting that you might be able to identify a putative antigen with that kind of power. A great lecture by Bernard Manger from Germany looked at paraneoplastic syndromes with rheumatic manifestations, and he had a number of them, including clubbing and associations with hypertrophic osteoarthropathy, a cancer associated polyarthritis, myocyte associated with cancer, palmar fasciitis, paniculitis, vasculitis, and something called oncogenic osteomalacia, all these being paraneoplastic syndromes.
A great lecture by Kevin Winthrop reviewed, what is a safe spot on steroid use? Is there a sweet spot? Is there a dose we should or shouldn't use? Interestingly, you showed a number of studies that showed well, first off, I've always thought that, any dose of steroid can increase risk. There are multiple studies showing the higher the dose you use, the greater the risk, and it's always been a dose dependent phenomenon.
And you do see a number of studies where the risk is present at five milligrams a day of prednisone. He showed a few studies where five milligrams a day of prednisone was not associated with a higher risk, and they were tended to be in relatively new and relatively simple patients, without complex therapies and whatnot. However, if you look at prednisone use in conjunction with complex therapies, often given to very sick patients, you don't see quite the same. You see now an increased risk. So he cited the CAPRA two study from Frank Bucharest, which showed that five milligrams of prednisone did not increase the risk of infection in RA patients on DMARDs, but then cited a number of other ones.
Another, I think, great take home from him was that, doses that are higher are clearly going to be, an increased risk, and he pointed out that fifteen milligrams above almost consistently gives you a higher and deleterious effect as far as infectious risk. You can get it at lower rates, but the bottom line is a simple patient, low dose steroids is probably not going to be harmful. But a complex patient, multiple comorbidities, very severe inflammation, it's the same story as that seen with the rabbit registry and TNF inhibitor use. The greatest risk for infection is in those who have the worst disease, the worst number of comorbidities, and worst prognostic factors. Those are people, when you add on more advanced therapies or even steroids, you get a higher risk of infection.
From the news this week, hepatitis B testing, an interesting report, looked at fifteen thousand, USRA patients and over forty six thousand Taiwanese patients and found surprisingly low rates of hepatitis B testing. Twenty percent in The US and twenty four percent in The Taiwanese, suggesting we are way, way under testing in high risk patients going on high risk drugs that could lead to hepatitis B reactivation. The FDA this week approved ocrelizumab. This is an anti c d twenty monoclonal antibody. It was in clinical trials for rheumatoid arthritis, was suspended for unclear reasons to me, and is now gonna be marketed for multiple sclerosis for both the relapsing form and the aggressive primary progressive form.
The approval is based on, OPRA one and OPRA two trials and something called the OPTAVIA study. It's gonna be priced at over $60,000 a year. It's felt to be a major advance in the treatment of multiple sclerosis. Another important news item this week was the approval of tofacitinib in the European Union by the EMA. As you know, this has been up for, consideration for a number of years, and finally is, has taken place.
In fact, baricitinib was approved earlier this year in EU, and now tofacitinib is approved at five milligrams twice a day. There's a nice review of psoriasis induced by TNF inhibitors in the derm, literature. This is the Journal of, American Academy of Dermatology. An interesting article looked at over, 88 articles and identified 216 patients to come up with basically a picture as to who gets this. It was mainly seen in Crohn's patients about forty percent, rheumatoid arthritis of a little bit less than thirty seven percent.
It was mainly seen in the first year or fourteen months on average. Infliximab was the most frequent offender, but that's probably because of the Crohn's association with sixty two percent of the cases that they identified being associated with infliximab and about twenty one percent with adalimumab, only fourteen percent were with etanercept. The skin manifestations were about forty percent plaque psoriasis, thirty six percent pustular psoriasis, and a few with psoriasis psoriasiform dermatitis. It's a little bit different than some of the other reviews that suggest there was a higher rate of pomopustular disease in patients with this, TNF inhibitor induced form of psoriasis. The authors recommended topical therapy.
It seems to work while continuing the TNF inhibitor in a number of patients, but the most often, therapeutic maneuver was cessation of the TNF inhibitor in nearly half the patients and that led to improvement or resolution ninety four percent. But they did also show that thirty two percent, thirty three percent continued therapy and thirty three percent improved and fifty seven percent, actually resolved. So, again, you could switch, you could continue. I think it depends on the severity. I think, I would also recommend that palmar pustular psoriasis is more difficult to treat, less likely to go away on its own, probably should merit, consideration of drug cessation rather than continuation, and or switching.
A report has come in in ARD this week about biologics not increasing the risk of invasive melanoma. I think the data is pretty clear that TNF inhibitors don't really cause cancers above that seen in RA patients sick enough to get a TNF inhibitor, meaning RA and inflammation promotes a higher risk of lymphoma, lung cancer, skin cancers, leukemia, maybe melanoma. When you look at patients who had a prior cancer, and you give them a TNF inhibitor, what happens? Well, studies have shown that actually the rates of recurrence are low except for one, and that's been, seen for a while with just and mainly with one citation, the British Biologics Registry showing an eighteen percent recurrence rate when you gave a TNF inhibitor to those who had previously had melanoma. They didn't specify whether it was invasive or in situ melanoma, so it's a little confused, but it's led a lot of patients and a lot of doctors to believe don't use TNF inhibitors with melanoma.
So because of the, controversy, nine countries pooled the data of 11 registries, 11 RA registries to look at several 100,000 patients and basically came up with the fact that, there is no higher rate of melanoma when you use a biologic, specifically a TNF inhibitor, but also rituximab, and tocilizumab, and abatacib were shown to not increase the risk of, first
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