RheumNow Podcast Women Takeover Rheumatology (10.4.19) Save
RheumNow Podcast Women Takeover Rheumatology (10.4.19) by Dr. Cush
Transcription
10/04/2019. This is the RheumNow podcast. I'm doctor Jack Cush, executive editor of roomnow.com. This week in the news, the hazards of seropositivity. Which do you prefer in psoriatic arthritis?
Old versus new, Execizumab or adalimumab? And lastly, when do rheumatologists do MRIs in rheumatoid arthritis patients? Let's start with an oldie but goodie, and a total shocker, could Vioxx be making a comeback? As you know, Vioxx was taken off the market in 2003, but its patent has, actually worn out as of 2017. In a recent move, a small pharma company has petitioned the FDA for a new orphan drug indication for Rofocoxime, that's right, Vioxx, for its use in patients who have hemophilia arthropathy.
They make the claim that there's a large unmet need here. There are no effective therapies. There are some studies showing its efficacy and they hope to get approval. Now, of course, there's a big concern here about the safety of Vioxx in the open market. And if it does get approved for a small orphan drug indication, no doubt it's going to get widespread use.
The only thing that might prevent that would be a much higher cost because of the rarity of the indication. So that might prevent the use, but it's unclear as to why the FDA may take this application seriously. It does meet the standards for an orphan drug indication. We'll have to wait and see. Another study comes out of CMHA, that's a Canadian medical journal.
It's a study from British Columbia and some of the health data they have there. Haiyun Choi and colleagues looked specifically at severe skin reactions that occur with allopurinol. We know they're relatively rare. They're more common in certain Chinese groups, but they looked at the association with renal disease and heart disease. Specifically, found that if you have cardiac disease, you have up to about a one and a half fold higher risk or fifty percent, forty percent higher risk of developing these very severe cutaneous reactions.
However, if you have renal disease, it's eleven fold, that would be an eleven hundred percent increased risk. This sort of speaks strongly in favor of using low dose allopurinol for your first dose, especially in patients who either have heart disease or patients with renal disease. Mother to baby is an interesting prospective study. In this particular report, they, chronicle the results of five twenty eight RA patients who become pregnant. And specifically, they look at the risk of using steroids in these patients and developing preterm birth.
Now, preterm birth is not an uncommon outcome in patients with inflammatory or autoimmune disease, patients who are on either DMARDs or biologics. It seems to be higher than that seen in the general population. That's a significant problem for both the mother and for the baby. But nonetheless, this particular study looked at steroid use and showed that preterm birth was associated with steroid use, especially with higher doses, suggesting it may be that steroids are the risk factor here. If you were using very high dose steroids, you had up to a fivefold increased risk.
If you were using medium dose steroids, you had almost a two fold increased risk. The risks seem to get more substantial in the second half of pregnancy, but overall steroid use could be a risk factor for preterm birth, especially amongst rheumatoid arthritis patients. J. Rheum has an interesting study coming from Kaiser Health that again attempts to look at the really problematic issue of adherence to hydroxychloroquine amongst patients with lupus. This is a large study.
This is almost two thousand patients who have lupus within the Kaiser system in California and shows that only fifty eight percent of patients were adherent to hydroxychloroquine. Shocking. They define adherence as actually filling and using at least eighty percent or more of the prescription each month. Non adherence was not predicted by the rheumatologist, the hospital setting, the hospital, or the socioeconomic status of the patient. It seems that some of the maybe substantial risk factors that we can learn from is that it was more likely in older lupus patients, in Caucasian lupus patients, and those who have had more visits in the last year.
That doesn't make any sense. They're having more visits, presumably they're having more activity and need more drug. Well, obviously you're worried about the patient. The patient's worried about what you're giving them. This is a major issue, especially in the control of lupus, but we have this issue with all our drugs.
It just seems to be more important in that particular population. Arthritis Care and Research has done an interesting study on seropositivity and outcomes of rheumatoid arthritis. In the last year, I've had an increasing interest in this particular issue of seropositive versus seronegative patients. I will lecture on this. Now, seronegative patients is number one, an opportunity for you to constantly rethink the diagnosis and the need for ongoing DMARR therapy.
But it turns out that seronegative patients don't have milder disease. In many respects, they have to have more criteria to be called seronegative RA. They often have more disease activity measures than do seropositive patients. It's a very interesting subset and many of them do revert to other diagnoses if followed over time. In this particular study, they looked at the association between seropositivity and mortality.
So, they looked at patients who were ACPA positive or rheumatoid factor positive, and they showed that higher titers of ACPA or CCP and or rheumatoid factor were independently associated with a sixty to eighty percent increased mortality risk compared to patients who were seronegative. That's substantial. And while we think a lot of that mortality risk may be related to inflammation, I just told you that a lot of patients with seronegative disease often have a lot of disease activity may not actually have the degree of inflammation as measured by maybe synovitis or sed rate CRP. But nonetheless, this is a curious issue. It turns out that if you look at patients, RA patients who are on DMARDs, seropositivity has the same effect, a significant increase in mortality.
If you look at patients who are on biologics or biologic DMARDs, as some call them, actually that difference is now gone, suggesting that biologic control may be of inflammation. While it may not control or lessen rheumatoid factor or CCD positivity, it certainly may affect inflammation to a point that may lower, the risk of death. So that's a very interesting study. We'll see more data on this going forward. Also talking about RA and death, we know that one of the main reasons for death in RA patients is cardiac disease.
Another Arthritis Care and Research article looked at one hundred and one RA patients followed prospectively, looking at cardiac CTs. And these patients were followed for up to, looks like seven years, eighty three months. Half the patients, forty eight percent, had progression of plaque by these cardiac CTs. It looks like if you're looking at those who had high calcium, CT scores, the progressors were more likely to be older, obese, hypertensive, and have more cumulative inflammation. This is something rheumatologists are paying attention to and need to pay more attention to in counseling their patients and assessing their patients for cardiovascular risk early on in the disease.
And these are studies of patients with established disease. I think we need to be paying close attention to this. We reported this particular study last week, but didn't include it in the podcast. It's about TIF1 gamma antibodies. It comes from the September issue of Rheumatology, wherein they had a supplement devoted to reports from the British Society of Rheumatology meeting.
It's a nice short report that gives you an overview of TIF1 gamma. As you know, this has been seen associated with cancer, but specifically it may be seen in dermatomyositis patients in up to thirty one percent of adults and up to twenty nine percent of kids. It turns out the association with cancer is only seen in adults over the age of 39. So it's a nice teaching point. TIF-one gamma is one of several new autoantibodies that are seen in patients with dermatomyositis that you should be looking for.
I'm looking for TIF-one gamma, NXP-two, and also MDA5. NXP2 also has association with cancer, has an association seen in kids and adults, has an association with calcinosis, as we reported before. And the MDA5 is seen in patients who don't have much in the way of myositis, but may have really ugly ulcerative skin lesions and a strong propensity for lung disease. So we also included some nice news articles this week about women going into subspecialty fellowships. This particular report comes from JAMA Internal Medicine, where they compared the percentage of women from 1991 to 2017.
In 1991, the number of women in internal medicine residency was thirty percent. By 2016, this had risen to forty three percent. There was a similar increase in the number of women in fellowships, and it turns out that the greatest increase was seen in endocrinology, rheumatology, and geriatrics, such that by 2017, 60% of those in rheumatology fellowships were women, only to be outdone by endocrinology where it was 71% and geriatric medicine where it was 77% who were women. The question is, why are all these women going into it? Number one, there's more women going into medicine these days than ever before.
Two, these are specialties where there's more personal, interpersonal contact. These are specialties where only the brightest and smartest of doctors go into these fellowships, rheumatology, endocrinology, even geriatrics, very challenging. And it could also be a lifestyle issue that may suit women as well. I think it's a trend we'll see more of. There's another nice report that comes from the Alzheimer's Rheumatic Disease.
It's a direct head to head study of ixekizumab versus adalimumab in patients who are biologic naive, who had previously seen DMARR prior to starting this particular study. They had that active disease going in. And here, the interesting point of this study was that a co primary endpoint of an ACR 50 response along with a PASI 100 response. That's total clearing of their psoriasis. So they enrolled 500, they enrolled a whole bunch, but they actually randomized five sixty patients to either execizumab or adalimumab in standard doses.
It's a fifty two week study. The primary endpoint was at twenty four weeks and at twenty four weeks, the primary endpoint favored ixekizumab thirty six percent over adalimumab. And that was significant. This difference between these two was really driven by skin responses. So if you're looking at PASI 100s, takes a sixty percent PASI 100 rate versus forty seven percent in adalimumab, and that was significant.
What was not significant was the ACR 50s. They were similar between both drugs achieving either 51 or 57% ACR50 responses, suggesting that IL-seventeen inhibition may be equal to TNF inhibition in patients with psoriatic arthritis. But if the skin is a big issue, well, the IL-17s win hands down and may make the better choice. Our last report comes from G Rheum, and it's interesting because it's the use of anakinra in hospitalized patients who have gout or pseudo gout. This is a 100 patient prospective, actually retrospective study that had a total of 115 episodes of inflammatory arthritis, most of which were gout, some of which were pseudo gout.
These were mostly men. The average age was 60 years of age. And they looked at these events between 2014 and 2017. They identified the patients really because they received Anakinra. This wasn't a randomized study.
This is open label retrospective report of their experience. Nonetheless, older males, and they saw really dramatic responses. These people in general have been tried on other therapies, and when they used anakinra, they had a partial or complete response to anakinra within four days and seventy five percent of patients. Of those who did respond, seventy five percent of them responded within one day. There was no unusual or untoward outcomes here.
So we know that IL-one inhibition does work in gout. We know it's not going to get approved for management of acute gout in the outpatient setting, although you could choose to use it on your own if the patient wants to pay for it. In a hospitalized setting where patients are more complex, may have renal transplant, may have multiple comorbidities or steroids or whatever, this may be a very vital and useful option for patients who are otherwise difficult to control. I'll end with, I think, an interesting survey I did this week on Twitter. The survey question was when would you use an MRI in your RA patients and maybe what to assess.
The answers were treatment response, uncertain clinical status, response to therapy. I said, Oh, if they have erosions, uncertain status, or I don't do MRI. The answers were, think about that, what would you do? Two percent said they would do it for treatment response. Eleven percent said they would do it to assess erosions.
Thirty eight percent said they would do it to assess a patient's uncertain status, meaning maybe they don't understand the clinical situation, maybe it was for diagnostic purposes, maybe it was to discern whether it's mechanical versus periarticular versus inflammatory activity. Again, I left uncertain status up to the person answering the question. But the half of you, forty nine percent said they nearly never do an MRI, in RA patients. That's where I am. I nearly never do it.
Occasionally I've done it if I'm looking at uncertain status, but boy, I could count on two fingers the number of MRIs I've done in RA in the last ten years. It'll be interesting to see again how your responses are compared to your peers. That's it for this week on RheumNow. Go to the website, check out these citations, learn more, tune into RheumNow. Take care.
Old versus new, Execizumab or adalimumab? And lastly, when do rheumatologists do MRIs in rheumatoid arthritis patients? Let's start with an oldie but goodie, and a total shocker, could Vioxx be making a comeback? As you know, Vioxx was taken off the market in 2003, but its patent has, actually worn out as of 2017. In a recent move, a small pharma company has petitioned the FDA for a new orphan drug indication for Rofocoxime, that's right, Vioxx, for its use in patients who have hemophilia arthropathy.
They make the claim that there's a large unmet need here. There are no effective therapies. There are some studies showing its efficacy and they hope to get approval. Now, of course, there's a big concern here about the safety of Vioxx in the open market. And if it does get approved for a small orphan drug indication, no doubt it's going to get widespread use.
The only thing that might prevent that would be a much higher cost because of the rarity of the indication. So that might prevent the use, but it's unclear as to why the FDA may take this application seriously. It does meet the standards for an orphan drug indication. We'll have to wait and see. Another study comes out of CMHA, that's a Canadian medical journal.
It's a study from British Columbia and some of the health data they have there. Haiyun Choi and colleagues looked specifically at severe skin reactions that occur with allopurinol. We know they're relatively rare. They're more common in certain Chinese groups, but they looked at the association with renal disease and heart disease. Specifically, found that if you have cardiac disease, you have up to about a one and a half fold higher risk or fifty percent, forty percent higher risk of developing these very severe cutaneous reactions.
However, if you have renal disease, it's eleven fold, that would be an eleven hundred percent increased risk. This sort of speaks strongly in favor of using low dose allopurinol for your first dose, especially in patients who either have heart disease or patients with renal disease. Mother to baby is an interesting prospective study. In this particular report, they, chronicle the results of five twenty eight RA patients who become pregnant. And specifically, they look at the risk of using steroids in these patients and developing preterm birth.
Now, preterm birth is not an uncommon outcome in patients with inflammatory or autoimmune disease, patients who are on either DMARDs or biologics. It seems to be higher than that seen in the general population. That's a significant problem for both the mother and for the baby. But nonetheless, this particular study looked at steroid use and showed that preterm birth was associated with steroid use, especially with higher doses, suggesting it may be that steroids are the risk factor here. If you were using very high dose steroids, you had up to a fivefold increased risk.
If you were using medium dose steroids, you had almost a two fold increased risk. The risks seem to get more substantial in the second half of pregnancy, but overall steroid use could be a risk factor for preterm birth, especially amongst rheumatoid arthritis patients. J. Rheum has an interesting study coming from Kaiser Health that again attempts to look at the really problematic issue of adherence to hydroxychloroquine amongst patients with lupus. This is a large study.
This is almost two thousand patients who have lupus within the Kaiser system in California and shows that only fifty eight percent of patients were adherent to hydroxychloroquine. Shocking. They define adherence as actually filling and using at least eighty percent or more of the prescription each month. Non adherence was not predicted by the rheumatologist, the hospital setting, the hospital, or the socioeconomic status of the patient. It seems that some of the maybe substantial risk factors that we can learn from is that it was more likely in older lupus patients, in Caucasian lupus patients, and those who have had more visits in the last year.
That doesn't make any sense. They're having more visits, presumably they're having more activity and need more drug. Well, obviously you're worried about the patient. The patient's worried about what you're giving them. This is a major issue, especially in the control of lupus, but we have this issue with all our drugs.
It just seems to be more important in that particular population. Arthritis Care and Research has done an interesting study on seropositivity and outcomes of rheumatoid arthritis. In the last year, I've had an increasing interest in this particular issue of seropositive versus seronegative patients. I will lecture on this. Now, seronegative patients is number one, an opportunity for you to constantly rethink the diagnosis and the need for ongoing DMARR therapy.
But it turns out that seronegative patients don't have milder disease. In many respects, they have to have more criteria to be called seronegative RA. They often have more disease activity measures than do seropositive patients. It's a very interesting subset and many of them do revert to other diagnoses if followed over time. In this particular study, they looked at the association between seropositivity and mortality.
So, they looked at patients who were ACPA positive or rheumatoid factor positive, and they showed that higher titers of ACPA or CCP and or rheumatoid factor were independently associated with a sixty to eighty percent increased mortality risk compared to patients who were seronegative. That's substantial. And while we think a lot of that mortality risk may be related to inflammation, I just told you that a lot of patients with seronegative disease often have a lot of disease activity may not actually have the degree of inflammation as measured by maybe synovitis or sed rate CRP. But nonetheless, this is a curious issue. It turns out that if you look at patients, RA patients who are on DMARDs, seropositivity has the same effect, a significant increase in mortality.
If you look at patients who are on biologics or biologic DMARDs, as some call them, actually that difference is now gone, suggesting that biologic control may be of inflammation. While it may not control or lessen rheumatoid factor or CCD positivity, it certainly may affect inflammation to a point that may lower, the risk of death. So that's a very interesting study. We'll see more data on this going forward. Also talking about RA and death, we know that one of the main reasons for death in RA patients is cardiac disease.
Another Arthritis Care and Research article looked at one hundred and one RA patients followed prospectively, looking at cardiac CTs. And these patients were followed for up to, looks like seven years, eighty three months. Half the patients, forty eight percent, had progression of plaque by these cardiac CTs. It looks like if you're looking at those who had high calcium, CT scores, the progressors were more likely to be older, obese, hypertensive, and have more cumulative inflammation. This is something rheumatologists are paying attention to and need to pay more attention to in counseling their patients and assessing their patients for cardiovascular risk early on in the disease.
And these are studies of patients with established disease. I think we need to be paying close attention to this. We reported this particular study last week, but didn't include it in the podcast. It's about TIF1 gamma antibodies. It comes from the September issue of Rheumatology, wherein they had a supplement devoted to reports from the British Society of Rheumatology meeting.
It's a nice short report that gives you an overview of TIF1 gamma. As you know, this has been seen associated with cancer, but specifically it may be seen in dermatomyositis patients in up to thirty one percent of adults and up to twenty nine percent of kids. It turns out the association with cancer is only seen in adults over the age of 39. So it's a nice teaching point. TIF-one gamma is one of several new autoantibodies that are seen in patients with dermatomyositis that you should be looking for.
I'm looking for TIF-one gamma, NXP-two, and also MDA5. NXP2 also has association with cancer, has an association seen in kids and adults, has an association with calcinosis, as we reported before. And the MDA5 is seen in patients who don't have much in the way of myositis, but may have really ugly ulcerative skin lesions and a strong propensity for lung disease. So we also included some nice news articles this week about women going into subspecialty fellowships. This particular report comes from JAMA Internal Medicine, where they compared the percentage of women from 1991 to 2017.
In 1991, the number of women in internal medicine residency was thirty percent. By 2016, this had risen to forty three percent. There was a similar increase in the number of women in fellowships, and it turns out that the greatest increase was seen in endocrinology, rheumatology, and geriatrics, such that by 2017, 60% of those in rheumatology fellowships were women, only to be outdone by endocrinology where it was 71% and geriatric medicine where it was 77% who were women. The question is, why are all these women going into it? Number one, there's more women going into medicine these days than ever before.
Two, these are specialties where there's more personal, interpersonal contact. These are specialties where only the brightest and smartest of doctors go into these fellowships, rheumatology, endocrinology, even geriatrics, very challenging. And it could also be a lifestyle issue that may suit women as well. I think it's a trend we'll see more of. There's another nice report that comes from the Alzheimer's Rheumatic Disease.
It's a direct head to head study of ixekizumab versus adalimumab in patients who are biologic naive, who had previously seen DMARR prior to starting this particular study. They had that active disease going in. And here, the interesting point of this study was that a co primary endpoint of an ACR 50 response along with a PASI 100 response. That's total clearing of their psoriasis. So they enrolled 500, they enrolled a whole bunch, but they actually randomized five sixty patients to either execizumab or adalimumab in standard doses.
It's a fifty two week study. The primary endpoint was at twenty four weeks and at twenty four weeks, the primary endpoint favored ixekizumab thirty six percent over adalimumab. And that was significant. This difference between these two was really driven by skin responses. So if you're looking at PASI 100s, takes a sixty percent PASI 100 rate versus forty seven percent in adalimumab, and that was significant.
What was not significant was the ACR 50s. They were similar between both drugs achieving either 51 or 57% ACR50 responses, suggesting that IL-seventeen inhibition may be equal to TNF inhibition in patients with psoriatic arthritis. But if the skin is a big issue, well, the IL-17s win hands down and may make the better choice. Our last report comes from G Rheum, and it's interesting because it's the use of anakinra in hospitalized patients who have gout or pseudo gout. This is a 100 patient prospective, actually retrospective study that had a total of 115 episodes of inflammatory arthritis, most of which were gout, some of which were pseudo gout.
These were mostly men. The average age was 60 years of age. And they looked at these events between 2014 and 2017. They identified the patients really because they received Anakinra. This wasn't a randomized study.
This is open label retrospective report of their experience. Nonetheless, older males, and they saw really dramatic responses. These people in general have been tried on other therapies, and when they used anakinra, they had a partial or complete response to anakinra within four days and seventy five percent of patients. Of those who did respond, seventy five percent of them responded within one day. There was no unusual or untoward outcomes here.
So we know that IL-one inhibition does work in gout. We know it's not going to get approved for management of acute gout in the outpatient setting, although you could choose to use it on your own if the patient wants to pay for it. In a hospitalized setting where patients are more complex, may have renal transplant, may have multiple comorbidities or steroids or whatever, this may be a very vital and useful option for patients who are otherwise difficult to control. I'll end with, I think, an interesting survey I did this week on Twitter. The survey question was when would you use an MRI in your RA patients and maybe what to assess.
The answers were treatment response, uncertain clinical status, response to therapy. I said, Oh, if they have erosions, uncertain status, or I don't do MRI. The answers were, think about that, what would you do? Two percent said they would do it for treatment response. Eleven percent said they would do it to assess erosions.
Thirty eight percent said they would do it to assess a patient's uncertain status, meaning maybe they don't understand the clinical situation, maybe it was for diagnostic purposes, maybe it was to discern whether it's mechanical versus periarticular versus inflammatory activity. Again, I left uncertain status up to the person answering the question. But the half of you, forty nine percent said they nearly never do an MRI, in RA patients. That's where I am. I nearly never do it.
Occasionally I've done it if I'm looking at uncertain status, but boy, I could count on two fingers the number of MRIs I've done in RA in the last ten years. It'll be interesting to see again how your responses are compared to your peers. That's it for this week on RheumNow. Go to the website, check out these citations, learn more, tune into RheumNow. Take care.
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