The RheumNow Week In Review Life Savers For Rheumatologists %286.29.18%29 Save
The RheumNow Week In Review Life Savers For Rheumatologists %286.29.18%29 by Dr. Cush
Transcription
It's the 06/29/2018. Hi, I'm doctor Jack Cush, executive editor of roomnow.com. This week, there's a lifesaving vaccine. There's a lifesaving prophylaxis, and maybe there's a drug you shouldn't take if you'd like to save a life. First, we should talk about next week.
Next week is a holiday week here in The United States, the July 4, and RheumNow will be on vacation. What you'll find on the website next week is sort of a best of, We'll publish every day, and you can follow us every day. But, it's not going to be fresh material. It's gonna be the best of our old material. So look for that.
Let's start out with new approvals. The EMA, the EMA, used to be the EMA. The agency in the European Commission has approved the use of tofacitinib or Zeljans for use in patients with active psoriatic arthritis who've had an inadequate response to DMARD therapy. That includes, the starting dose there is gonna be five milligrams twice daily. I assume that they'll later later come along with eleven milligram once a day dose.
But right now, it's gonna be available in the European Union at five milligrams twice a day for PSA patients. Good news for those of you treating PSA. A lot of good information this week about vasculitis is kind of novel. I think that there was a novel study that looked at the EGPA, Church Strauss vasculitis, in children, and that is what made this group unique. In fact, they had 14 children, that was carried over, that was found over a long period of time to accrue 14 patients, but their series is useful in that the average age of their patients was 12.
And again, is usually an adult disorder, or young adult disorder, all of them had lung involvement almost by definition, Upper airway involvement in 85%, skin involvement in 71%, GI tract in two thirds, heart in 50%, and CNS disease and renal disease were actually quite rare. And other interesting aspect of this is that only thirty one percent of their patients were ANCA positive. So compared to adults, kids who have EGPA are more likely to have ENT, cardiovascular, and GI involvement, same amount of respiratory involvement, but obviously not as much in the way of CNS or renal. In seeing patients this week in clinic, I came across a number actually who had MPO antibodies and did not have ANCA associated vasculitis, and that led me to do some research on who gets MPO or myeloperoxidase antibodies, the constituent that underlies a positive P ANCA. And there's a wide variety.
We certainly know that C ANCA and PR3 antibodies are much more specific for, patients with Wegener's granulomatosis or GPA, but that also GPA may have patients who have just MPO and not PR3 antibody positivity. But unlike PR3 and C ANCAs, P ANCAs and MPOs are much wider differential diagnosis and that includes not just GPA and EGPA, but also microscopic polyangiitis, Goodpasture's, polyarteritis nodosa, patients with acute or chronically progressive glomerulonephritis, lupus patients with or without nephritis. Interestingly, a number of lung diseases, interstitial lung disease, patients with bronchiectasis, alveolar hemorrhage have all been reported in association with NPO antibodies as has been rheumatoid arthritis, IBD, and patients with autoimmune liver disease. Quite a list for those of us who take care of patients and sometimes see those results. A very interesting paper came from a study of a fairly large cohort, almost 200 patients with ANCA associated vasculitis who were treated with rituximab and looked at what happened to patients who receive Bactrim prophylaxis after being treated.
That is the drug trimethoprim sulfamethoxazole given three times a week to patients with in this case vasculitis and what they saw was a seventy percent reduction in infections. The hazard ratio of infection was zero point three zero that was highly significant. They had a total of forty nine patients with infections, ninety two infections, only one of them was due to Pneumocystis, urovecchii, and that's sort of interesting because it's one of the main reasons why you give that prophylaxis. But what they saw was, again, a seventy percent reduction in a whole host of infections, not just PJP. So it sort of really is strong data.
Lenny Calabrese made a comment on Twitter that this has become his new standard of care. I think if you're looking for who should be getting Bactrim, it should certainly be patients with vasculitis who go on rituximab. We recently did, it's not published yet, but Kevin Winthrop and myself and a group of his trainees and residents and a few of our rheumatology fellows including Cassie Calabrese did an interesting study where we surveyed you rheumatologists. We got a number of reports back about how you use and when you see PJP. Interestingly, almost all the reports were in patients who had been treated with rituximab.
So further evidence I think that that's the population who should receive, prophylaxis. Interesting claims data comes out of Taiwan and the use of the influenza vaccine where although the penetration of influenza vaccination seasonally was very low, less than thirty percent, What they did show was a dramatic lowering of the rate of death and hospitalizations due to sepsis, bacteremia and viremia. So some of those were influenza deaths that were prevented by this, but it was all other infections as well, suggesting that again, that's a good practice that should be instituted in all practices. Plaquenil use, certainly it's a miracle drug, especially in lupus and it's got lots of great indications. Acclaims data from Taiwan also showed that in the first year of use, use of Plaquenil in lupus was associated with a thirty two percent overall reduction in all cause mortality.
Further evidence that hydroxychloroquine is vitamin H for your patients with lupus, there's got to be a good reason for a lupus patient to not be on it for it to not be in play. You know, there's often a concern about psoriasis and the risk of psoriatic arthritis. You know, you looked at a lot of that early data, it said anywhere is from like five percent to forty percent of psoriasis patients would develop psoriatic arthritis. More recent important studies, well done studies by Dafna Gladman and others suggest it's probably around a thirty percent risk for those who have psoriasis who will go on to develop psoriatic arthritis, and we know that may take up to ten years. A recent study looked at this as well utilizing CASPER criteria, they found in a large cohort, I'm sorry, in a systematic review of all papers.
This was published in the JAAD, this is the dermatology journal, JAAD, I think that's the Journal of the Academy of something dermatologists. And their overall incidence of psoriatic arthritis among psoriasis patients range from point two seven to two point seven per one 100 patient years. But the number you wanna remember is that there looks to be a twenty four percent, twenty three point eight percent risk of developing psoriatic arthritis in a large population or many populations of psoriasis. Another large population study looking at twenty thousand patients or ten thousand each with RA or OA undergoing hip or knee replacements looked at the outcomes and found that RA patients not surprisingly are at a higher risk of developing myocardial infarction, a three and a half fold increased risk of post op myocardial infarction, and actually the RA patients were higher risk of developing, of having the need for major revision surgeries. This is in a cohort that actually was followed out for ten years.
And there the hazard ratio was a sixty one percent increase risk or a hazard ratio of 1.61. The public citizen, as you know, that led by Sidney Wolf has called for a removal of febuxostat from the marketplace, citing recent publications, citing a recent warning by the FDA that came out earlier this year. Earlier this year was a paper from the New England Journal looking at a higher risk of cardiovascular deaths in patients on febuxostat compared to allopurinol. Again, there seems to be a mounting evidence for a slight hazard risk, for febuxostat compared to allopurinol. As you know, though, such patients, gout patients requiring therapy like this, urate lowering therapy are a horrible group to study.
They have a lot of adverse events. You know, they have the metabolic syndrome, have renal disease, hypertension, etc. And therefore there's a lot of deaths and there's a lot of cardiac deaths when you're doing these studies. In the original development trials of febuxostat, they couldn't get the drug by the FDA. The FDA denied them because it was an imbalance of cardiovascular events in the fabuxtat treated patients compared to those on allopurinol.
So they made the company go back and do a large two thousand plus several year study of high risk patients who got either fabuxtat or allopurinol. Allopurinol and in the new study, the sort of confirmatory safety study, they showed a flip. Now it wasn't febuxostat, there were actually more cardiovascular events. This was the confirmed study, and this led to febuxostat being approved but now we know in real world use, seems like there still is this signal and concern. I would say look for the FDA to come down with a hearing on this and possibly even drug withdrawal.
What do you do until then? Use it in the patients in whom you need to do it. If your patients are on this drug and benefiting this drug, I don't think that this news constitutes a reason to stop the use of the drug, especially if it's working as someone who needs it. Lastly, there's a report from a phase two trial from, on the use of ixekizumab or Taltz in patients with ankylosing spondylitis. They have a drug development program called the COAST program, C O A S T, and there's a COAST V in DMARR naive individuals, then there's a COAST W and which is I believe in, TNF, in non responders or experienced individuals, and then as a COAST X study which is going to be in non radiographic axial SpA patients.
Well, they're reporting the results of their phase two COAST W study, and again without giving too much detail they showed that execizumab was superior in producing ASAS 40 outcomes compared to those who were treated with placebo. This is good news. This will proceed through and it's possible that execizumab will in addition to its current approvals for psoriasis, psoriatic arthritis, may obtain approval for ankylosing spondylitis in the future, but they have to go finish with these other phase two and phase three trials. That's it for this week at roomnow.com. Go to the website to find these citations, and to read on.
Be sure to follow us on podcasts or on YouTube, and, make sure that you tune in next week and watch The Best of RheumNow. We'll be back the week after. That means next Friday, there will not be a webcast or a podcast or a videocast in our Friday edition. Have a great holiday and a great weekend. Bye now.
Next week is a holiday week here in The United States, the July 4, and RheumNow will be on vacation. What you'll find on the website next week is sort of a best of, We'll publish every day, and you can follow us every day. But, it's not going to be fresh material. It's gonna be the best of our old material. So look for that.
Let's start out with new approvals. The EMA, the EMA, used to be the EMA. The agency in the European Commission has approved the use of tofacitinib or Zeljans for use in patients with active psoriatic arthritis who've had an inadequate response to DMARD therapy. That includes, the starting dose there is gonna be five milligrams twice daily. I assume that they'll later later come along with eleven milligram once a day dose.
But right now, it's gonna be available in the European Union at five milligrams twice a day for PSA patients. Good news for those of you treating PSA. A lot of good information this week about vasculitis is kind of novel. I think that there was a novel study that looked at the EGPA, Church Strauss vasculitis, in children, and that is what made this group unique. In fact, they had 14 children, that was carried over, that was found over a long period of time to accrue 14 patients, but their series is useful in that the average age of their patients was 12.
And again, is usually an adult disorder, or young adult disorder, all of them had lung involvement almost by definition, Upper airway involvement in 85%, skin involvement in 71%, GI tract in two thirds, heart in 50%, and CNS disease and renal disease were actually quite rare. And other interesting aspect of this is that only thirty one percent of their patients were ANCA positive. So compared to adults, kids who have EGPA are more likely to have ENT, cardiovascular, and GI involvement, same amount of respiratory involvement, but obviously not as much in the way of CNS or renal. In seeing patients this week in clinic, I came across a number actually who had MPO antibodies and did not have ANCA associated vasculitis, and that led me to do some research on who gets MPO or myeloperoxidase antibodies, the constituent that underlies a positive P ANCA. And there's a wide variety.
We certainly know that C ANCA and PR3 antibodies are much more specific for, patients with Wegener's granulomatosis or GPA, but that also GPA may have patients who have just MPO and not PR3 antibody positivity. But unlike PR3 and C ANCAs, P ANCAs and MPOs are much wider differential diagnosis and that includes not just GPA and EGPA, but also microscopic polyangiitis, Goodpasture's, polyarteritis nodosa, patients with acute or chronically progressive glomerulonephritis, lupus patients with or without nephritis. Interestingly, a number of lung diseases, interstitial lung disease, patients with bronchiectasis, alveolar hemorrhage have all been reported in association with NPO antibodies as has been rheumatoid arthritis, IBD, and patients with autoimmune liver disease. Quite a list for those of us who take care of patients and sometimes see those results. A very interesting paper came from a study of a fairly large cohort, almost 200 patients with ANCA associated vasculitis who were treated with rituximab and looked at what happened to patients who receive Bactrim prophylaxis after being treated.
That is the drug trimethoprim sulfamethoxazole given three times a week to patients with in this case vasculitis and what they saw was a seventy percent reduction in infections. The hazard ratio of infection was zero point three zero that was highly significant. They had a total of forty nine patients with infections, ninety two infections, only one of them was due to Pneumocystis, urovecchii, and that's sort of interesting because it's one of the main reasons why you give that prophylaxis. But what they saw was, again, a seventy percent reduction in a whole host of infections, not just PJP. So it sort of really is strong data.
Lenny Calabrese made a comment on Twitter that this has become his new standard of care. I think if you're looking for who should be getting Bactrim, it should certainly be patients with vasculitis who go on rituximab. We recently did, it's not published yet, but Kevin Winthrop and myself and a group of his trainees and residents and a few of our rheumatology fellows including Cassie Calabrese did an interesting study where we surveyed you rheumatologists. We got a number of reports back about how you use and when you see PJP. Interestingly, almost all the reports were in patients who had been treated with rituximab.
So further evidence I think that that's the population who should receive, prophylaxis. Interesting claims data comes out of Taiwan and the use of the influenza vaccine where although the penetration of influenza vaccination seasonally was very low, less than thirty percent, What they did show was a dramatic lowering of the rate of death and hospitalizations due to sepsis, bacteremia and viremia. So some of those were influenza deaths that were prevented by this, but it was all other infections as well, suggesting that again, that's a good practice that should be instituted in all practices. Plaquenil use, certainly it's a miracle drug, especially in lupus and it's got lots of great indications. Acclaims data from Taiwan also showed that in the first year of use, use of Plaquenil in lupus was associated with a thirty two percent overall reduction in all cause mortality.
Further evidence that hydroxychloroquine is vitamin H for your patients with lupus, there's got to be a good reason for a lupus patient to not be on it for it to not be in play. You know, there's often a concern about psoriasis and the risk of psoriatic arthritis. You know, you looked at a lot of that early data, it said anywhere is from like five percent to forty percent of psoriasis patients would develop psoriatic arthritis. More recent important studies, well done studies by Dafna Gladman and others suggest it's probably around a thirty percent risk for those who have psoriasis who will go on to develop psoriatic arthritis, and we know that may take up to ten years. A recent study looked at this as well utilizing CASPER criteria, they found in a large cohort, I'm sorry, in a systematic review of all papers.
This was published in the JAAD, this is the dermatology journal, JAAD, I think that's the Journal of the Academy of something dermatologists. And their overall incidence of psoriatic arthritis among psoriasis patients range from point two seven to two point seven per one 100 patient years. But the number you wanna remember is that there looks to be a twenty four percent, twenty three point eight percent risk of developing psoriatic arthritis in a large population or many populations of psoriasis. Another large population study looking at twenty thousand patients or ten thousand each with RA or OA undergoing hip or knee replacements looked at the outcomes and found that RA patients not surprisingly are at a higher risk of developing myocardial infarction, a three and a half fold increased risk of post op myocardial infarction, and actually the RA patients were higher risk of developing, of having the need for major revision surgeries. This is in a cohort that actually was followed out for ten years.
And there the hazard ratio was a sixty one percent increase risk or a hazard ratio of 1.61. The public citizen, as you know, that led by Sidney Wolf has called for a removal of febuxostat from the marketplace, citing recent publications, citing a recent warning by the FDA that came out earlier this year. Earlier this year was a paper from the New England Journal looking at a higher risk of cardiovascular deaths in patients on febuxostat compared to allopurinol. Again, there seems to be a mounting evidence for a slight hazard risk, for febuxostat compared to allopurinol. As you know, though, such patients, gout patients requiring therapy like this, urate lowering therapy are a horrible group to study.
They have a lot of adverse events. You know, they have the metabolic syndrome, have renal disease, hypertension, etc. And therefore there's a lot of deaths and there's a lot of cardiac deaths when you're doing these studies. In the original development trials of febuxostat, they couldn't get the drug by the FDA. The FDA denied them because it was an imbalance of cardiovascular events in the fabuxtat treated patients compared to those on allopurinol.
So they made the company go back and do a large two thousand plus several year study of high risk patients who got either fabuxtat or allopurinol. Allopurinol and in the new study, the sort of confirmatory safety study, they showed a flip. Now it wasn't febuxostat, there were actually more cardiovascular events. This was the confirmed study, and this led to febuxostat being approved but now we know in real world use, seems like there still is this signal and concern. I would say look for the FDA to come down with a hearing on this and possibly even drug withdrawal.
What do you do until then? Use it in the patients in whom you need to do it. If your patients are on this drug and benefiting this drug, I don't think that this news constitutes a reason to stop the use of the drug, especially if it's working as someone who needs it. Lastly, there's a report from a phase two trial from, on the use of ixekizumab or Taltz in patients with ankylosing spondylitis. They have a drug development program called the COAST program, C O A S T, and there's a COAST V in DMARR naive individuals, then there's a COAST W and which is I believe in, TNF, in non responders or experienced individuals, and then as a COAST X study which is going to be in non radiographic axial SpA patients.
Well, they're reporting the results of their phase two COAST W study, and again without giving too much detail they showed that execizumab was superior in producing ASAS 40 outcomes compared to those who were treated with placebo. This is good news. This will proceed through and it's possible that execizumab will in addition to its current approvals for psoriasis, psoriatic arthritis, may obtain approval for ankylosing spondylitis in the future, but they have to go finish with these other phase two and phase three trials. That's it for this week at roomnow.com. Go to the website to find these citations, and to read on.
Be sure to follow us on podcasts or on YouTube, and, make sure that you tune in next week and watch The Best of RheumNow. We'll be back the week after. That means next Friday, there will not be a webcast or a podcast or a videocast in our Friday edition. Have a great holiday and a great weekend. Bye now.
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