A New RA Approval (8.1.2025) Save
Dr. Jack Cush reviews the news, journal reports and a new treatment for RA from the FDA.
Transcription
It's 08/01/2025. This is the RheumNow podcast. Hi. I'm doctor Jack Cush, executive editor of rheumnow.com. August 1.
I feel like the summer just got started, and it's half over. We got a lot of catching up to do. This week on the podcast, we're talking EGPA, seropositivity and the risk of gout, cognitive dysfunction in RA, what? And the FDA has been busy, and you should know about it. Let's begin with, how long women who are pregnant can take their biologic.
You do know that you can take a biologic during pregnancy. You could take a biologic to conceive, you know, and there is a lot of data. It is always not good clinical trial level data because no one can really study this. But, this particular study of, I guess, a meta analysis of 3,700 pregnancies in forty nine thousand women with IMiD, immune mediated inflammatory disease, RA, AS, PSA, PSO, IBD, they showed that those that were exposed to TNF inhibitors, sixty four percent of them took the TNF inhibitor throughout the pregnancy. They had full three trimester use.
Eighty nine percent were exposed prior to conception, and over two thirds continued the TNF inhibitor after the delivery. This has become the standard, you know, and more and more of you have actually can let your patients conceive on a TNF and stay on a TNF, because you know that the best way to make a baby is to not have any inflammation on board, to have the disease under control, especially in RA, PSA, AS, IBD, etc. Over a ten year span, 2011 to 2021, TNF inhibitor use associated with pregnancy grew from fifty five percent to seventy three percent. I think that this means that you're paying attention to the literature, and we're paying attention to the ACR reproductive guidelines authored by Lisa Samaritano et al. You should have that as a resource.
Kara had an interesting study this week that supports what I've been saying in the past, not with a lot of excitement or not well received by you. I've been saying that rheumatologists are amazing, that you can do amazing things in management, but yet you still have faults. One of the faults is that despite writing moderate or severe active disease in the chart, you're slow to change DMARDs, slower than you think. And this is a CARA registry, that's a Pediatric Rheumatology Registry of almost 3,000 JIA patients who were classified, seventy one percent as having minimal or no activity, twenty five percent with moderate to high activity, two percent flaring, two percent improving. Over a twelve month period, only ten percent, had DMARD escalation, and despite patients being classified as having moderate to high disease activity, only fifteen percent.
And and by the way, on two separate consecutive occasions, only fifteen percent had escalation of their DMAR therapy. Again, think we're not paying attention to the numbers, or we're not doing the numbers, or we're certainly not doing treat to target, which as you know, has been proven to benefit the patient greatly even when you're using the mildest of medicines. I like to study this week about mild cognitive impairment. This is something that was ascertained by something called the Montreal Cognitive Assessment Tool, and MCI was those people who had scores ranging from 20 to 26. This was a cohort study of older RA patients, three seventy eight, and looked at their Montreal Cognitive Assessment tools, and found that mild cognitive impairment, which is felt to be a precursor to dementia, was significantly associated with, the type of disease that you had, the course of disease, more importantly the -twenty eight odds ratio thirty one, percent higher, odds ratio 1.31, and high CRP and osteoporosis.
That these are all features associated with, cognitive impairment going forward. This is something you sort of need to know about, right? Especially people that you don't know first time, first few visits. If you've been seeing people over time, you can see changes in cognitive abilities, but this is something we might should be looking for or asking family members about. I like this, report about the safety of TNF inhibitors with melanoma.
This was a cohort study of RA patients, older RA patients, who were diagnosed with melanoma, and even if you were treated with methotrexate or TNF inhibitors, was no increase in mortality, in the year after they, were on a TNF inhibitor. This included the more benign melanoma in situ in half the patients, and others, you know, regional, and, there were a few invasive melanomas in there as well. So while methotrexate and TNF did any difference on melanoma and mortality outcomes, turns out that steroids did. People that were on steroids were more likely to have reduced survival and that's been shown in many, many studies. We've talked in the past about can RA patients get gout, can gout patients get RA, I like to teach that they're mutually exclusive.
You can't have RA and you can't have gout, but you know we do see these people. So this was an interesting study of 35,000 new RA patients and a 103,000 controls. RA patients had a two point seven fold, almost a three fold higher risk of getting gout, and it turns out that seropositivity didn't matter, that seronegatives, seropositives had an equally high risk, slightly higher maybe in seropositives by about seven percent. But interestingly, RA patients treated with either a biologic or a JAK inhibitor had a lower risk of developing gout. It dropped by from a hazard ratio of 2.8 to 1.9, and if you were treated.
If you were untreated, it was back up to two point eight. So there is this risk, I gotta wonder, you know, is a Korean, large data set, I gotta wonder are these accurate diagnoses or not? Cause I still think the adage of treating people, when you're teaching people, that you've got gout or RA not both, check the rheumatoid factor CCP and uric acid, and that'll help you figure it out if you're not experienced as we rheumatologists are. But again, I will admit in my forty year career I've got two or three really good cases that have both proven in multiple multiple ways. Another interesting study this week on plant extracts being useful in osteoarthritis.
We've talked about plant products in the past being helpful, statistically significant in clinical trials, that's with Boswellia, Curcumin, avocado, the unsatoxaponified oils, and this is another study of plant extract C. Longa B. Serrata studied in hand away for three months, double blind, randomized, placebo controlled trial, one hundred and sixty two patients, and if you were on a plant extract, significant decrease in patient global PASS score SF36 pain, SF36 health change. Plant based products do work in osteoarthritis, and I don't think we use enough of them. Speaking of the future, there is a study about machine learning to predict lupus flares.
A group of researchers came up with a machine learning model called FLAME, and they studied data on twenty eight thousand lupus patients over an eleven year period, looking at clinical variables and social determinants of health variables to predict FLAIR within three months. Clinical variables were better. In their model that they came up with, they had an area on the curve of 0.67, not bad, but it was better than, social determinants, which means social determinants can be useful in determining flare risk to some extent, alright? SHAP analysis basically said that predictors, and I find this a little bit of a head scratcher, predictors of flare within three months were pyuria, organic brain syndrome and headache. My goodness, don't go to the bingo hall, that might be everybody there.
So anyway, I think this is the future. I think these machine learning models will look at your large data sets and be able to apply to you what the risk of FLAIR for lupus or RA is in the future. That's going to be integrated into your electronic health records. There is another test, I like these, you know, neutrophil to lymphocyte ratio, platelet to lymphocyte ratio as markers of inflammation that can compete with, extra tests that you have to buy, the SED rate and the CRP, but most of you don't do it. There's another one here called the Systemic Immune Inflammation Index, the SII, another potential biomarker.
It's the platelet count times the neutrophil count divided by the lymphocyte count. Again, are all CBC variables that are at your disposal that you could program in to give you a number, and it turns out that these have been shown to be very helpful in predicting, disease activity, drug response in lupus PSA, RA, SPA and vasculitis. These values, like the SII, NLR, are complementary and can supplement that which you get with your set rate and CRP. The FDA has been looking at a new drug that has been approved for myasthenia gravis, that's efgartimod, also called Vivgart Hytrulo. They're a little concerned they've had reports, in, this worsening, patients with chronic inflammatory demyelinating polyradiculopathy, CDIP or CIDP, there's a clinical trial going on, and they've had flares of activity, so they're evaluating this.
These flares of CIDP were not noticed in patients taking this for myasthenia, not per the FDA reports, but they're looking at this yesterday. Haven't actually put out a formal warning letter or a change in prescribing label. This is, another one of these FcRn antibody blockers that are under study for Sjogren's syndrome, lupus, rheumatoid even, and right now they're only approved in myasthenia gravis. So this is a potential warning. Maybe the big surprise of the week was FDA approving a device for use in rheumatoid arthritis.
The company who makes the Setpoint system has, applied, and and you know, they we talked about the RESET study that was, talked about at both Barcelona and other meetings. The RESET study was a February RA trial of people who had failed, I think, TNF inhibitors, a double blind sham controlled trial showing that vagal nerve stimulation could significantly, yield ACR20 responses in RA patients with active disease. Based on that study and their application for this device, it's a neurostimulation device that basically again stimulates the vagus nerve once a day, it has an anti inflammatory effect, In those studies, they showed an X-ray benefit as well. So this is basically neuromodulation, neuroimmunomodulation of RA with a device. It's gonna be interesting to see how this is marketed and how this is used in rheumatoid arthritis going forward, but you'll be hearing more and more about that now that it's FDA approved.
An interesting phase three study was published this week, only one hundred and five patients, and they compared but it was a double blind, randomized, placebo controlled, double blind study, of EGPA patients who were either treated with Rituximab, two infusions two weeks apart, with steroids compared to either high dose steroids alone, or they included patients with steroids and cyclophosphamide. And this was for induction of remission in people who are starting therapy. In this phase three trial, at six months, the response was, they had to have active disease with a British, Birmingham Vascolyzed Activity Score greater than three. They had to be in remission. Rituximab achieved this in sixty three percent, conventional therapy sixty percent.
Time to remission forty nine weeks versus forty nine weeks. This says that rituximab isn't necessarily more effective than what you might have otherwise used in the past. And you know prior to the, you know, the other new drugs that are available for EGPA, right, that are much better, A lot of literature extolled the value of rituximab in treating EGPA and this data sort of suggests maybe not so. So that was at a six month end point, the results were the same at one year. I got two more reports I think here, one more report on hydroxychloroquine preserving renal function.
More than 200 patients with lupus nephritis looked at what happened to their renal function over time. This is a retrospective chart review looking at ten years of data, and it basically showed that, in lupus patients with CKD grade three or higher, being on hydroxychloroquine protected seventy seven percent of patients from having a significant decline in their eGFR as determined by a greater than 30% increase. So if you increase your eGFR that was a worsening of renal function, if you were on hydroxychloroquine it presented it in more than three quarters of patients. Again, there's data out there that says that there's less flares of lupus on hydroxychloroquine. Hydroxychloroquine has tons of benefits, in hydroxychloroquine, both antithrombotic, pregnancy, diabetes, arthritis, flares, but now, this is another bit of evidence saying, yes, everybody should be on vitamin HCQ if you have lupus.
So I hope that you've enjoyed that. That's it for this week's podcast. I want to let you know that we have the Room IQ quiz that's out there and, and being used. I I think that you'll find it really useful. I wanna say that not everyone's getting the questions right.
We had a Room IQ question that, asked whether, true or false, Asians have the lowest risk of uveitis, and that was true, but only half of you got it right. Turns out that the right answer, the highest risk is basically Northern European, right, and Caucasian populations, for a risk of uveitis, just based on population. So look for Room IQ, it'll be in your inbox on Saturdays. Take it, see how high you can score on this week's quiz. Take care.
I feel like the summer just got started, and it's half over. We got a lot of catching up to do. This week on the podcast, we're talking EGPA, seropositivity and the risk of gout, cognitive dysfunction in RA, what? And the FDA has been busy, and you should know about it. Let's begin with, how long women who are pregnant can take their biologic.
You do know that you can take a biologic during pregnancy. You could take a biologic to conceive, you know, and there is a lot of data. It is always not good clinical trial level data because no one can really study this. But, this particular study of, I guess, a meta analysis of 3,700 pregnancies in forty nine thousand women with IMiD, immune mediated inflammatory disease, RA, AS, PSA, PSO, IBD, they showed that those that were exposed to TNF inhibitors, sixty four percent of them took the TNF inhibitor throughout the pregnancy. They had full three trimester use.
Eighty nine percent were exposed prior to conception, and over two thirds continued the TNF inhibitor after the delivery. This has become the standard, you know, and more and more of you have actually can let your patients conceive on a TNF and stay on a TNF, because you know that the best way to make a baby is to not have any inflammation on board, to have the disease under control, especially in RA, PSA, AS, IBD, etc. Over a ten year span, 2011 to 2021, TNF inhibitor use associated with pregnancy grew from fifty five percent to seventy three percent. I think that this means that you're paying attention to the literature, and we're paying attention to the ACR reproductive guidelines authored by Lisa Samaritano et al. You should have that as a resource.
Kara had an interesting study this week that supports what I've been saying in the past, not with a lot of excitement or not well received by you. I've been saying that rheumatologists are amazing, that you can do amazing things in management, but yet you still have faults. One of the faults is that despite writing moderate or severe active disease in the chart, you're slow to change DMARDs, slower than you think. And this is a CARA registry, that's a Pediatric Rheumatology Registry of almost 3,000 JIA patients who were classified, seventy one percent as having minimal or no activity, twenty five percent with moderate to high activity, two percent flaring, two percent improving. Over a twelve month period, only ten percent, had DMARD escalation, and despite patients being classified as having moderate to high disease activity, only fifteen percent.
And and by the way, on two separate consecutive occasions, only fifteen percent had escalation of their DMAR therapy. Again, think we're not paying attention to the numbers, or we're not doing the numbers, or we're certainly not doing treat to target, which as you know, has been proven to benefit the patient greatly even when you're using the mildest of medicines. I like to study this week about mild cognitive impairment. This is something that was ascertained by something called the Montreal Cognitive Assessment Tool, and MCI was those people who had scores ranging from 20 to 26. This was a cohort study of older RA patients, three seventy eight, and looked at their Montreal Cognitive Assessment tools, and found that mild cognitive impairment, which is felt to be a precursor to dementia, was significantly associated with, the type of disease that you had, the course of disease, more importantly the -twenty eight odds ratio thirty one, percent higher, odds ratio 1.31, and high CRP and osteoporosis.
That these are all features associated with, cognitive impairment going forward. This is something you sort of need to know about, right? Especially people that you don't know first time, first few visits. If you've been seeing people over time, you can see changes in cognitive abilities, but this is something we might should be looking for or asking family members about. I like this, report about the safety of TNF inhibitors with melanoma.
This was a cohort study of RA patients, older RA patients, who were diagnosed with melanoma, and even if you were treated with methotrexate or TNF inhibitors, was no increase in mortality, in the year after they, were on a TNF inhibitor. This included the more benign melanoma in situ in half the patients, and others, you know, regional, and, there were a few invasive melanomas in there as well. So while methotrexate and TNF did any difference on melanoma and mortality outcomes, turns out that steroids did. People that were on steroids were more likely to have reduced survival and that's been shown in many, many studies. We've talked in the past about can RA patients get gout, can gout patients get RA, I like to teach that they're mutually exclusive.
You can't have RA and you can't have gout, but you know we do see these people. So this was an interesting study of 35,000 new RA patients and a 103,000 controls. RA patients had a two point seven fold, almost a three fold higher risk of getting gout, and it turns out that seropositivity didn't matter, that seronegatives, seropositives had an equally high risk, slightly higher maybe in seropositives by about seven percent. But interestingly, RA patients treated with either a biologic or a JAK inhibitor had a lower risk of developing gout. It dropped by from a hazard ratio of 2.8 to 1.9, and if you were treated.
If you were untreated, it was back up to two point eight. So there is this risk, I gotta wonder, you know, is a Korean, large data set, I gotta wonder are these accurate diagnoses or not? Cause I still think the adage of treating people, when you're teaching people, that you've got gout or RA not both, check the rheumatoid factor CCP and uric acid, and that'll help you figure it out if you're not experienced as we rheumatologists are. But again, I will admit in my forty year career I've got two or three really good cases that have both proven in multiple multiple ways. Another interesting study this week on plant extracts being useful in osteoarthritis.
We've talked about plant products in the past being helpful, statistically significant in clinical trials, that's with Boswellia, Curcumin, avocado, the unsatoxaponified oils, and this is another study of plant extract C. Longa B. Serrata studied in hand away for three months, double blind, randomized, placebo controlled trial, one hundred and sixty two patients, and if you were on a plant extract, significant decrease in patient global PASS score SF36 pain, SF36 health change. Plant based products do work in osteoarthritis, and I don't think we use enough of them. Speaking of the future, there is a study about machine learning to predict lupus flares.
A group of researchers came up with a machine learning model called FLAME, and they studied data on twenty eight thousand lupus patients over an eleven year period, looking at clinical variables and social determinants of health variables to predict FLAIR within three months. Clinical variables were better. In their model that they came up with, they had an area on the curve of 0.67, not bad, but it was better than, social determinants, which means social determinants can be useful in determining flare risk to some extent, alright? SHAP analysis basically said that predictors, and I find this a little bit of a head scratcher, predictors of flare within three months were pyuria, organic brain syndrome and headache. My goodness, don't go to the bingo hall, that might be everybody there.
So anyway, I think this is the future. I think these machine learning models will look at your large data sets and be able to apply to you what the risk of FLAIR for lupus or RA is in the future. That's going to be integrated into your electronic health records. There is another test, I like these, you know, neutrophil to lymphocyte ratio, platelet to lymphocyte ratio as markers of inflammation that can compete with, extra tests that you have to buy, the SED rate and the CRP, but most of you don't do it. There's another one here called the Systemic Immune Inflammation Index, the SII, another potential biomarker.
It's the platelet count times the neutrophil count divided by the lymphocyte count. Again, are all CBC variables that are at your disposal that you could program in to give you a number, and it turns out that these have been shown to be very helpful in predicting, disease activity, drug response in lupus PSA, RA, SPA and vasculitis. These values, like the SII, NLR, are complementary and can supplement that which you get with your set rate and CRP. The FDA has been looking at a new drug that has been approved for myasthenia gravis, that's efgartimod, also called Vivgart Hytrulo. They're a little concerned they've had reports, in, this worsening, patients with chronic inflammatory demyelinating polyradiculopathy, CDIP or CIDP, there's a clinical trial going on, and they've had flares of activity, so they're evaluating this.
These flares of CIDP were not noticed in patients taking this for myasthenia, not per the FDA reports, but they're looking at this yesterday. Haven't actually put out a formal warning letter or a change in prescribing label. This is, another one of these FcRn antibody blockers that are under study for Sjogren's syndrome, lupus, rheumatoid even, and right now they're only approved in myasthenia gravis. So this is a potential warning. Maybe the big surprise of the week was FDA approving a device for use in rheumatoid arthritis.
The company who makes the Setpoint system has, applied, and and you know, they we talked about the RESET study that was, talked about at both Barcelona and other meetings. The RESET study was a February RA trial of people who had failed, I think, TNF inhibitors, a double blind sham controlled trial showing that vagal nerve stimulation could significantly, yield ACR20 responses in RA patients with active disease. Based on that study and their application for this device, it's a neurostimulation device that basically again stimulates the vagus nerve once a day, it has an anti inflammatory effect, In those studies, they showed an X-ray benefit as well. So this is basically neuromodulation, neuroimmunomodulation of RA with a device. It's gonna be interesting to see how this is marketed and how this is used in rheumatoid arthritis going forward, but you'll be hearing more and more about that now that it's FDA approved.
An interesting phase three study was published this week, only one hundred and five patients, and they compared but it was a double blind, randomized, placebo controlled, double blind study, of EGPA patients who were either treated with Rituximab, two infusions two weeks apart, with steroids compared to either high dose steroids alone, or they included patients with steroids and cyclophosphamide. And this was for induction of remission in people who are starting therapy. In this phase three trial, at six months, the response was, they had to have active disease with a British, Birmingham Vascolyzed Activity Score greater than three. They had to be in remission. Rituximab achieved this in sixty three percent, conventional therapy sixty percent.
Time to remission forty nine weeks versus forty nine weeks. This says that rituximab isn't necessarily more effective than what you might have otherwise used in the past. And you know prior to the, you know, the other new drugs that are available for EGPA, right, that are much better, A lot of literature extolled the value of rituximab in treating EGPA and this data sort of suggests maybe not so. So that was at a six month end point, the results were the same at one year. I got two more reports I think here, one more report on hydroxychloroquine preserving renal function.
More than 200 patients with lupus nephritis looked at what happened to their renal function over time. This is a retrospective chart review looking at ten years of data, and it basically showed that, in lupus patients with CKD grade three or higher, being on hydroxychloroquine protected seventy seven percent of patients from having a significant decline in their eGFR as determined by a greater than 30% increase. So if you increase your eGFR that was a worsening of renal function, if you were on hydroxychloroquine it presented it in more than three quarters of patients. Again, there's data out there that says that there's less flares of lupus on hydroxychloroquine. Hydroxychloroquine has tons of benefits, in hydroxychloroquine, both antithrombotic, pregnancy, diabetes, arthritis, flares, but now, this is another bit of evidence saying, yes, everybody should be on vitamin HCQ if you have lupus.
So I hope that you've enjoyed that. That's it for this week's podcast. I want to let you know that we have the Room IQ quiz that's out there and, and being used. I I think that you'll find it really useful. I wanna say that not everyone's getting the questions right.
We had a Room IQ question that, asked whether, true or false, Asians have the lowest risk of uveitis, and that was true, but only half of you got it right. Turns out that the right answer, the highest risk is basically Northern European, right, and Caucasian populations, for a risk of uveitis, just based on population. So look for Room IQ, it'll be in your inbox on Saturdays. Take it, see how high you can score on this week's quiz. Take care.
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