October 27 2017 - RheumNow Week In Review Save
October 27 2017 - RheumNow Week In Review by Dr. Cush
Transcription
It's October 2737. This is the RheumNow Weekend Review. I'm Doctor. Jack Cush, Executive Head of roomnow.com. A lot of interesting news this week.
At the top of the news, a meta analysis of multiple trials looking at urate lowering therapy in gout sought to disclose the amount of non adherence that's seen. And you know these patients, those patients with gout, are really quite non compliant. They often don't come back, they're often hard to treat, and you wonder whether compliance is an issue. This specific meta analysis looked at 16 studies and showed on average less than half the patients, forty six to forty eight percent of patients, were non adherent to urate lowering therapy. If you're looking for a ray of sunshine here, it might be that compliance is a little bit higher in patients who are older, those who have diabetes and hypertension, and those who have comorbidities.
Maybe such patients are more concerned or get the message for taking medicines otherwise that they're more likely to take their gout medicines too. But this remains, as in many of our disciplines in rheumatology, one of the harder areas to manage when it comes to patient compliance and the issue of prescription non adherence. As you know, one of the big issues in rheumatoid arthritis care these days is the secondary effects of inflammation on cardiovascular risk amongst rheumatoid arthritis patients, and many people have sought to look at this. And one of the more interesting, recent observations comes from a small study of patients on tofacitinib, specifically forty six patients. And they looked at them over a period of time and measured CIMT, which is Carotid Intima Media Thickness, a surrogate measure for atherosclerotic disease, a direct measure of carotid plaque.
And this is a often useful tool to assess cardiovascular disease and cardiovascular risk in patients. They showed that RA patients did have an elevated CIMT, but more importantly when patients went on tofacitinib they showed a reduction in CIMT suggesting improvement. And what's maybe even more important here is you know this therapy, tofacitinib along with tocilizumab, both have the unusual side effect of increasing the lipid profiles of the patients. And not just LDL, but all of them HDL, triglycerides, LDL, total cholesterol, etc, that they're all increased. And one wonders whether or not there may be an increased risk of cardiovascular disease when that happens even though the drug is working.
Well, this small study of 46 patients it showed that even while the lipid levels were going up in a subset of patients on tofacitinib that this did not affect the outcomes and there was improvement in atherosclerotic risk as measured by CIMT. So this is an encouraging data. It's actually somewhat like the data that was seen last year in a direct head to head three year study of tocilizumab versus etanercept. And we know that etanercept does not increase lipid levels, that tocilizumab may. But that the cardiovascular outcomes in a long study were the same between the two, suggesting that this effect of inflammation and control of inflammation on lipid profiles doesn't necessarily equate to a cardiovascular risk, especially when you're controlling disease activity.
A claims data study showed that RA patients who have been on a TNF inhibitor and then have to make a switch. They have to either, because of uncontrolled disease, to either be one who cycles between multiple TNFs or one who switches to another mechanism of action or MOA drug such as B cell inhibition, T cell inhibition, IL-six inhibition. And this observational claim study looked at 900 TNF cyclers versus five eighty one MOA switchers, and looked at the outcomes after a year. And what they showed was that those who were the MOA switchers had better persistence as a measure of drug success compared to the TNF cyclers. So persistence was seen in forty eight percent of the MOA switchers versus only forty percent in the TNF cyclers.
More importantly, or as important, is that there were lower healthcare costs in those who were MOA switchers. Often we're faced with whether it's worth going to a second TNF inhibitor or a third, or to choose another MOA. And my rule is number one, if you are a primary non responder, you should be moving on to another mechanism of action regardless of whatever your first biologic is. And we do know that people who go from the first to second to third TNF inhibitor, they have a stepwise decrease in efficacy over time, regardless of whether there was a loss of response or toxicity. So there's a growing amount of evidence that MOA switching may be the next best step after initial TNF failure.
A British registry of psoriasis patients called BadBir, B A D B I R, BadBir, sorry. We're not talking about the beer in Britain, don't think, but we're talking about psoriasis in Great Britain, And this specifically looked at three drugs used in treating psoriasis: adalimumab, etanercept, and ustekinumab, and compared them to those who were not taking a biologic. And all told they had between eight thousand 9,000 patients, and they were able to show in this study that there was not an increased risk of serious infectious events when you were taking either etanercept adalimumab or ustekinumab with SIE rates ranging from about one point four to one point five per 100 patient years. That's really low compared to RA for certain. And compared to even the non biologic cohort that was seen in this study, was used in the study, where the same rate was seen, one point four per 100 patient years.
So again, you don't have as much SIEs in patients with psoriasis than compared to rheumatoid arthritis, and that may be because there's less overall systemic inflammation, less it's really hard to say why that number is lower. As you know, the background rate in the pre biologic era for a serious infectious event for RA is three-nine SIEs per one hundred patient years. So one hundred patients fall for a year, three-nine might end up in the hospital with a pneumonia or septic arthritis or sepsis, etc. We know that in the clinical trials the numbers are not much higher, they're about the same, they're often four, five, two, three per one hundred patient years. And when you look at psoriasis and psoriatic arthritis trials, that their numbers are even lower, ranging one, two, three, and that's what we've seen in this British Bad Beer Biologics registry.
A study of ANCA associated vasculitis has shown that over time there's been a decreased malignancy risk presumably with better therapies, but it's also been shown that this may very well be due to less cytotoxin use as well. An interesting bit of news for those of us who treat ANCA associated vasculitis. And a nice effort was made to look at the utility or the impact of weight loss in patients with gout. Gout patients often have the metabolic syndrome, frequently are overweight, and weight loss is one of the non medical interventions we can do. It's hard to estimate the effects of that or even, the compliance with that, but in this particular review of multiple studies showed that there were 10 weight loss trials, there was a tremendous amount of heterogeneity in finding trials to include in this meta analysis, but they did show that six out of eight trials showed that weight loss could reduce the number and frequency of gout attacks.
And we're talking about weight loss in these studies that was seen somewhere around eight-sixty pounds, and that when you had such weight loss you had a variable decrease in serum uric acid levels as I'm showing you here, a significantly reduced amount of gout attacks. So that's good news, one that we should spend some time on because it's not a medicine patients like not taking medicines and I think that lifestyle is often what they're looking for. As you may have read this week, the FDA has been active and has approved the drug Symphony Aria, that's the intravenous administration of golimumab, for use in patients with psoriatic arthritis and ankylosing spondylitis. This is, good news and it adds to our arsenal of therapies. I was impressed by the Go Vibrant study, Arti Kavanaugh was the lead author on that, and the ACR20 responses in that were seventy five percent with galimumab IV versus twenty two percent in placebo.
That's a really large therapeutic effect, a large margin that I wouldn't have anticipated based on many other trials and certainly in this era when it's harder to get really good results in low placebo responses in clinical trials, that's an impressive number. So it'll be interesting to see whether or not these kind of results and this approval will change our use of golimumab. Biosimilars were written about this week by the RAND Corporation. They keep track of this and ten years ago came up with projections that they modified just this past week. They're now saying that in the next decade we are estimated to save $54,000,000,000, just by the use of biologics.
And I think that's an impressive number. What we do know is that biologic use account is less used by less than 1%, maybe 2% the most of the general population, yet these drugs, the biologic drugs account for more than a third of total expenditures in drug cost expenditures. It's estimated that this is going to overall that biologics may account for up to 70% of the growth in prescription drug spending. So there's a great worry about these drugs which start these days at around, $45,000 to $80,000 a year that maybe we should be getting into the biosimilars. But we're going to need to get into it full scale.
What we're seeing from the payers is that the cost savings that we're going to get from biosimilars are not going to be realized until there's an across the board agreement we're going to use biosimilars in all new prescriptions and in switchovers. If we want to maintain our prescriptive authority and the option to keep people on their existing biologic, the total health care savings will not be realized because there will be the biologic, the originator drug in play with its discounted program, and then there's a variable use of the biosimilar. So it's going to take a while and it's going to take probably some forced prescribing before we can actually realize some of these savings in rheumatology where we have four TNF inhibitors approved in the last year or so. A nice report on something I was interested in called the Rabbit risk score. Rabbit is a German biologics registry.
They came up with risk score that you can calculate the patient's risk for a serious infectious event in the next year based on the biologic you use. They based that calculation on the patient's age, use of steroids, the use of how many DMARDs you failed in the past, the presence of a comorbidity, and then which particular biologic you want to use. You can plug that in and get a calculation of one percent risk in the next year versus a fifty percent risk in the next year. When they looked at the rabbit risk scores of RA patients who are hospitalized into an ICU, presumably usually for infection, they showed that those patients had much higher rabbit risk scores. Such patients, compared to those who are patients not hospitalized, patients hospitalized into the ICU had higher risk scores.
They were fifty-one hundred percent more likely to be on DMARDs, biologics and steroids. Conversely, you could say that if you had been on steroids or you're elderly or you had COPD, you had a two to three fold risk of getting an ICU admission compared to those who did not. And if you had CKD, chronic kidney disease, you had up to a 16 fold increased risk. So there is a validity to this rabbit risk score if you're having a hard time making a decision about whether a patient should get a biologic therapy. You could go to biologica.de and find it there, on the website, you can find the link with the URL and you can use this in your daily calculation.
That's it for this week on roomnow.com we can review. Make sure you tune in next week, we will do the preview for ACR twenty seventeen in San Diego. RheumNow will be having extensive coverage that you can follow us on Twitter at RheumNow or using the hashtag ACR17 or you can just go to the RheumNow micro site that we have developed, acr17.roomnow.com and you'll be seeing a whirlwind of information, new videos, great news reports, quotes, pictures, etc. And we'll give you the real world experience of being in San Diego with all of us. Take care, have a great week, we'll see you next weekend right before the ACR.
At the top of the news, a meta analysis of multiple trials looking at urate lowering therapy in gout sought to disclose the amount of non adherence that's seen. And you know these patients, those patients with gout, are really quite non compliant. They often don't come back, they're often hard to treat, and you wonder whether compliance is an issue. This specific meta analysis looked at 16 studies and showed on average less than half the patients, forty six to forty eight percent of patients, were non adherent to urate lowering therapy. If you're looking for a ray of sunshine here, it might be that compliance is a little bit higher in patients who are older, those who have diabetes and hypertension, and those who have comorbidities.
Maybe such patients are more concerned or get the message for taking medicines otherwise that they're more likely to take their gout medicines too. But this remains, as in many of our disciplines in rheumatology, one of the harder areas to manage when it comes to patient compliance and the issue of prescription non adherence. As you know, one of the big issues in rheumatoid arthritis care these days is the secondary effects of inflammation on cardiovascular risk amongst rheumatoid arthritis patients, and many people have sought to look at this. And one of the more interesting, recent observations comes from a small study of patients on tofacitinib, specifically forty six patients. And they looked at them over a period of time and measured CIMT, which is Carotid Intima Media Thickness, a surrogate measure for atherosclerotic disease, a direct measure of carotid plaque.
And this is a often useful tool to assess cardiovascular disease and cardiovascular risk in patients. They showed that RA patients did have an elevated CIMT, but more importantly when patients went on tofacitinib they showed a reduction in CIMT suggesting improvement. And what's maybe even more important here is you know this therapy, tofacitinib along with tocilizumab, both have the unusual side effect of increasing the lipid profiles of the patients. And not just LDL, but all of them HDL, triglycerides, LDL, total cholesterol, etc, that they're all increased. And one wonders whether or not there may be an increased risk of cardiovascular disease when that happens even though the drug is working.
Well, this small study of 46 patients it showed that even while the lipid levels were going up in a subset of patients on tofacitinib that this did not affect the outcomes and there was improvement in atherosclerotic risk as measured by CIMT. So this is an encouraging data. It's actually somewhat like the data that was seen last year in a direct head to head three year study of tocilizumab versus etanercept. And we know that etanercept does not increase lipid levels, that tocilizumab may. But that the cardiovascular outcomes in a long study were the same between the two, suggesting that this effect of inflammation and control of inflammation on lipid profiles doesn't necessarily equate to a cardiovascular risk, especially when you're controlling disease activity.
A claims data study showed that RA patients who have been on a TNF inhibitor and then have to make a switch. They have to either, because of uncontrolled disease, to either be one who cycles between multiple TNFs or one who switches to another mechanism of action or MOA drug such as B cell inhibition, T cell inhibition, IL-six inhibition. And this observational claim study looked at 900 TNF cyclers versus five eighty one MOA switchers, and looked at the outcomes after a year. And what they showed was that those who were the MOA switchers had better persistence as a measure of drug success compared to the TNF cyclers. So persistence was seen in forty eight percent of the MOA switchers versus only forty percent in the TNF cyclers.
More importantly, or as important, is that there were lower healthcare costs in those who were MOA switchers. Often we're faced with whether it's worth going to a second TNF inhibitor or a third, or to choose another MOA. And my rule is number one, if you are a primary non responder, you should be moving on to another mechanism of action regardless of whatever your first biologic is. And we do know that people who go from the first to second to third TNF inhibitor, they have a stepwise decrease in efficacy over time, regardless of whether there was a loss of response or toxicity. So there's a growing amount of evidence that MOA switching may be the next best step after initial TNF failure.
A British registry of psoriasis patients called BadBir, B A D B I R, BadBir, sorry. We're not talking about the beer in Britain, don't think, but we're talking about psoriasis in Great Britain, And this specifically looked at three drugs used in treating psoriasis: adalimumab, etanercept, and ustekinumab, and compared them to those who were not taking a biologic. And all told they had between eight thousand 9,000 patients, and they were able to show in this study that there was not an increased risk of serious infectious events when you were taking either etanercept adalimumab or ustekinumab with SIE rates ranging from about one point four to one point five per 100 patient years. That's really low compared to RA for certain. And compared to even the non biologic cohort that was seen in this study, was used in the study, where the same rate was seen, one point four per 100 patient years.
So again, you don't have as much SIEs in patients with psoriasis than compared to rheumatoid arthritis, and that may be because there's less overall systemic inflammation, less it's really hard to say why that number is lower. As you know, the background rate in the pre biologic era for a serious infectious event for RA is three-nine SIEs per one hundred patient years. So one hundred patients fall for a year, three-nine might end up in the hospital with a pneumonia or septic arthritis or sepsis, etc. We know that in the clinical trials the numbers are not much higher, they're about the same, they're often four, five, two, three per one hundred patient years. And when you look at psoriasis and psoriatic arthritis trials, that their numbers are even lower, ranging one, two, three, and that's what we've seen in this British Bad Beer Biologics registry.
A study of ANCA associated vasculitis has shown that over time there's been a decreased malignancy risk presumably with better therapies, but it's also been shown that this may very well be due to less cytotoxin use as well. An interesting bit of news for those of us who treat ANCA associated vasculitis. And a nice effort was made to look at the utility or the impact of weight loss in patients with gout. Gout patients often have the metabolic syndrome, frequently are overweight, and weight loss is one of the non medical interventions we can do. It's hard to estimate the effects of that or even, the compliance with that, but in this particular review of multiple studies showed that there were 10 weight loss trials, there was a tremendous amount of heterogeneity in finding trials to include in this meta analysis, but they did show that six out of eight trials showed that weight loss could reduce the number and frequency of gout attacks.
And we're talking about weight loss in these studies that was seen somewhere around eight-sixty pounds, and that when you had such weight loss you had a variable decrease in serum uric acid levels as I'm showing you here, a significantly reduced amount of gout attacks. So that's good news, one that we should spend some time on because it's not a medicine patients like not taking medicines and I think that lifestyle is often what they're looking for. As you may have read this week, the FDA has been active and has approved the drug Symphony Aria, that's the intravenous administration of golimumab, for use in patients with psoriatic arthritis and ankylosing spondylitis. This is, good news and it adds to our arsenal of therapies. I was impressed by the Go Vibrant study, Arti Kavanaugh was the lead author on that, and the ACR20 responses in that were seventy five percent with galimumab IV versus twenty two percent in placebo.
That's a really large therapeutic effect, a large margin that I wouldn't have anticipated based on many other trials and certainly in this era when it's harder to get really good results in low placebo responses in clinical trials, that's an impressive number. So it'll be interesting to see whether or not these kind of results and this approval will change our use of golimumab. Biosimilars were written about this week by the RAND Corporation. They keep track of this and ten years ago came up with projections that they modified just this past week. They're now saying that in the next decade we are estimated to save $54,000,000,000, just by the use of biologics.
And I think that's an impressive number. What we do know is that biologic use account is less used by less than 1%, maybe 2% the most of the general population, yet these drugs, the biologic drugs account for more than a third of total expenditures in drug cost expenditures. It's estimated that this is going to overall that biologics may account for up to 70% of the growth in prescription drug spending. So there's a great worry about these drugs which start these days at around, $45,000 to $80,000 a year that maybe we should be getting into the biosimilars. But we're going to need to get into it full scale.
What we're seeing from the payers is that the cost savings that we're going to get from biosimilars are not going to be realized until there's an across the board agreement we're going to use biosimilars in all new prescriptions and in switchovers. If we want to maintain our prescriptive authority and the option to keep people on their existing biologic, the total health care savings will not be realized because there will be the biologic, the originator drug in play with its discounted program, and then there's a variable use of the biosimilar. So it's going to take a while and it's going to take probably some forced prescribing before we can actually realize some of these savings in rheumatology where we have four TNF inhibitors approved in the last year or so. A nice report on something I was interested in called the Rabbit risk score. Rabbit is a German biologics registry.
They came up with risk score that you can calculate the patient's risk for a serious infectious event in the next year based on the biologic you use. They based that calculation on the patient's age, use of steroids, the use of how many DMARDs you failed in the past, the presence of a comorbidity, and then which particular biologic you want to use. You can plug that in and get a calculation of one percent risk in the next year versus a fifty percent risk in the next year. When they looked at the rabbit risk scores of RA patients who are hospitalized into an ICU, presumably usually for infection, they showed that those patients had much higher rabbit risk scores. Such patients, compared to those who are patients not hospitalized, patients hospitalized into the ICU had higher risk scores.
They were fifty-one hundred percent more likely to be on DMARDs, biologics and steroids. Conversely, you could say that if you had been on steroids or you're elderly or you had COPD, you had a two to three fold risk of getting an ICU admission compared to those who did not. And if you had CKD, chronic kidney disease, you had up to a 16 fold increased risk. So there is a validity to this rabbit risk score if you're having a hard time making a decision about whether a patient should get a biologic therapy. You could go to biologica.de and find it there, on the website, you can find the link with the URL and you can use this in your daily calculation.
That's it for this week on roomnow.com we can review. Make sure you tune in next week, we will do the preview for ACR twenty seventeen in San Diego. RheumNow will be having extensive coverage that you can follow us on Twitter at RheumNow or using the hashtag ACR17 or you can just go to the RheumNow micro site that we have developed, acr17.roomnow.com and you'll be seeing a whirlwind of information, new videos, great news reports, quotes, pictures, etc. And we'll give you the real world experience of being in San Diego with all of us. Take care, have a great week, we'll see you next weekend right before the ACR.
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