RheumNow Podcast - Rheumatic Patients With COVID (5.29.20) Save
Dr. Jack Cush reviews the news and journal articles from the past week on RheumNow.com.
Transcription
This is the RheumNow podcast. It's the 05/29/2020. Hi, I'm doctor Jack Cush, executive editor of roomnow.com. This week, should you worry about the skin or the other stuff with ANCA associated vasculitis? Also, does your therapies have any impact on diabetes in your RA patients?
You know, they kind of coexist. Maybe your therapies make a difference. And lastly, I'm going to tell you about the one thing that is truly unique to our rheumatic disease patients when they become infected with the coronavirus. Stay tuned for this and more. So I want to remind you about this past Tuesday night rheumatology grand rounds presentation by Doctor.
Randy Kron from UAB where he gave a great presentation on the cytokine storm syndrome. Check it out, it'll, I think I have a better understanding of what the telltale signs are, what the risk factors are, what the biology is behind the syndrome. It's important for us as consultants to know how to manage MAS and cytokine storm. The UPI came out with a very important quote from Doctor. Fauci.
You know, get the email sometimes from David Mandel in Ohio, and David ends his emails with me with LTF, listen to Fauci. And that's way better than WTF. So yes, I listened to Fauci, and this week, UPI reported Doctor. Fauci stating that the scientific data is really quite evident now about the lack of efficacy, and of course, he's talking about hydroxychloroquine. So take it from the source, LTF.
As you know, this also comes at a time when the WHO suspended its very big solidarity trial. It enrolled 3,500 patients. It's still gonna continue observing those 3,500 patients, but no more patients are being enrolled in this very large WHO trial. And as such, other countries have now stepped up and said no more hydroxychloroquine. That includes France, Italy, Belgium and I'm sure there'll be others to follow.
Again, think that our country where we're doing trials, they should continue, for instance, a HERO trial where healthcare workers are being treated prophylactically with hydroxychlorine to see what that effect is. I think we should follow that out and see where it's going to go. You know, there's this other new therapy that's in development for rheumatoid arthritis called fenbrutinib. This is a BTK inhibitor. Its mechanisms are maybe not quite as direct as some of the other ones, but there's a rationale for its use.
And some of the early data didn't look all that great. But this week in ANR, Doctor. Stan Cohen, a good friend and colleague of mine here in Dallas, who's lead author on a very large trial of four eighty methotrexate incomplete responders who were randomized to either receive placebo. Again, these are people stayed on their methotrexate and then they get additional therapy, either placebo fifty milligrams of fenbutrinib once a day or one hundred and fifty once a day. And later on the trial, some patients got 200 BID.
The primary endpoint in this trial was at twelve weeks and an ACR 50 response, very aggressive, and the placebo response was fifteen percent. The fenbutrin of fifty milligrams didn't work, it was eighteen percent. There was an adalimumab arm in there where they had a thirty six percent response, ACR 50 response, which is pretty good at week twelve. And then the, 100 and 50 was 28 respond twenty eight percent and the 200 BID was thirty five percent suggesting there's probably good evidence to proceed in further development for this con this compound. The ACR 20 numbers were, like, thirty percent for placebo and about sixty percent for the higher dose fembryutinib.
There was no, effects on myeloid or B cell biomarkers in the study. Side effects were pretty pretty mild, mainly nonserious infections like UTI. So this is gonna go forward as another potential therapy in RA. Speaking of RA, you know, the age old question. Does, triple DMAR therapy, methotrexate sulfasalazine, hydroxychlorine, does it work?
You know, does it work outside of the middle of the country in the RAIN network where their data is astounding and their data is undeniably great? Most of you don't use triple DMAR therapy because you're not forced to use triple DMARD therapy. But if you did, you might see RAIN like numbers. Well, the corona network, has, like, almost forty thousand RA patients, did an analysis of patients going on triple DMARD versus those going on TNF inhibitors with methotrexate. And what they could say was that first off, triple DMARD is not used very often.
And that reflects the bias against it by most of us, most of you, including me. But and that shows up in the profile of the patients compared to those who got more aggressive TNF, more expensive TNF methotrexate therapy. Triple DMARC patients were older, had longer disease durations, had less activity, had more cancer as a background, and had more comorbidities. Not an ideal population. And not surprisingly, it didn't do well by comparison.
They were less likely to get to low disease activity state and had a higher rate of discontinuations. I think this is a negative report about triple DMARD, but it really reflects the selection bias that we all have. It's not fair. I think if you really wanna be able to say it doesn't work, then you should use it in your next 10 or 15 patients who you're considering starting on a TNF inhibitor. Put them on triple DMARD, watch them closely, see how they do, or do your own trial, one on one off, one on aggressive, expensive therapy, one on cheaper, triple DMARD therapy, tell me what you see.
There's an interesting report in arthritis and rheumatism about skin involvement with ANCA associated vasculitis that includes MPO and PR3 associated vasculitis, MPAs and GPA patients. Eleven eighty four patients, this is a worldwide registry, think of 13 centers, and they showed that skin involvement is seen in over a third of patients, especially with GPA. It was a little less with MPA patients and a little more with EGPA patients or Church Strauss patients. The common skin manifestations were petechiae or purpuric lesions, urticarial lesions and maculopapular rashes. The interesting thing about this study was if you had skin involvement with an ANCA associated vasculitis, guess what?
You are more likely to have systemic disease that was worse. And that includes glomerulonephritis and, alveolar hemorrhage and other serious manifestations associated with ANCA associated vasculitis. So look for skin involvement, worry about skin involvement when you see it. A meta analysis of 15 studies looked at the potential of therapy on the risk of getting diabetes if you have rheumatoid arthritis. A lot of patients, almost a half million patients in this study, and they showed quite convincingly, a lot of studies show that hydroxychloroquine lowers the risk by thirty nine percent.
Methotrexate lowers the risk by nineteen percent. TNF inhibitors lowers the risk by thirty seven percent. These are all significant reductions in the risk of diabetes. You know what increased the risk of diabetes? That's right.
Glucocorticoids where there was at least a 50% increase for all doses. And if you're taking ten milligrams or more, it was like a hundred and twenty five percent increased risk of getting diabetes. Speaking of RA, new drugs in development includes filgotinib. You know, the data looks fairly good on filgotinib. They might get a an FDA hearing a decision about its approval or not the sometime this year.
But in addition to developing this selective JAK one inhibitor for rheumatoid arthritis, filgotinib is being studied in other diseases. This week, we report on the results in ulcerative colitis, plus minus here, meaning that compared to placebo, the two hundred milligram dose, looked good at ten week responses. I'm sorry. Yeah. Ten week responses.
So it worked fast as you would expect the JAK inhibitor to work. However, the hundred milligram dose did not was not significant. But if you lasted out worked out to, like, six months, both the hundred and two hundred milligram dose, was both significant. That's really the big issue with this drug. They have a hundred milligram dose and a two hundred milligram dose.
Will they get both doses approved by the FDA? We have to wait and see. They're gonna it looks like they probably are gonna go for both doses, but remains to be seen. Both look good, but we need to see what happens in RA. Speaking of JAK inhibitors, baricitinib, some data came out this week about the risk of developing hepatitis B reactivation with baricitinib.
The data comes from the phase three RA trials of almost 3,000 patients where they've had two hundred and fifteen patients who had evidence of occult or resolve hepatitis B, meaning they were B surface antigen negative but hepatitis B core antibody positive. When they looked at two hundred and fifteen patients, there were eight who had an elevated hepatitis B, viral load by DNA, PCR, showing that they could have therefore reactivation. Half of those met the definition of reactivation, and, a total of five out of the eight actually required or three out of the eight required antiviral therapy. So, you know, this has been seen with other drugs, including abatacept and certainly with TNF inhibitors. The risk with TNF inhibitors for hep b reactivation is about two percent if you pool all the data on all the observational trials.
The rate here looks like it's about two to three point seven percent. So the risk could be constitutive to RA alone, or it could be related to the therapies we use, remains to be seen. I think the most important report this week was when I combined two different reports on COVID and rheumatic disease patients. One coming from Wuhan, China, where they had twenty one patients with rheumatic disease who are COVID positive and who are hospitalized with, with the condition. Of their twenty one patients, you know what?
They looked like all the other COVID patients had the same symptoms, same risk of hospitalization, same, mortality rate. But the one thing that was different was, the presence of pulmonary complications, mainly that of respiratory failure. In in their rheumatic disease patients, thirty eight percent of them actually developed respiratory failure compared to ten percent who did not have rheumatic disease, clearly distinguishing, what may happen in rheumatic disease patients. This was mirrored by Jeff Sparks' group in Boston where they had reported on fifty two fifty two patients, not necessarily hospitalized, but amongst their fifty two patients with rheumatic disease, the thing that was distinguishing them from the non rheumatic patients was that the rate of ICU hospitalization and the need for mechanical ventilation was higher in the rheum the rheumatic patients, forty eight percent versus eighteen percent in the non rheumatic patients. That's really kind of striking.
Now why our patients would have more pulmonary involvement? It might well be because a lot of our patients most of these patients we're talking about, by the way, are female, and most of them are RA, but there's some lupus in there. You know, it's not surprising that they would have a background risk of occult or, symptomatic, pulmonary conditions. So it that might be the reason. We really don't know, but it is something that's unique to our rheumatic disease population.
Yet, we also had a report this week saying that there's a low risk of COVID pneumonia in rheumatic patients. This actually so the former two studies were looking at patients who had severe disease and rheumatic disease and COVID. This particular study I'm reporting is actually collective experience of survey of 859 patients from Siena, Italy, they and surveyed their patients by telephone to find out, you know, who got COVID, what kind of problems they had. Turns out there were only two cases. And one had pneumonia but was not hospitalized, was treated with antiviral therapy and basically resolved.
The other one was a nursing home patient who upon nasal swab testing for COVID was positive, but was asymptomatic. The point of their paper was that our patients do very well in this Corona era and that the risk of them getting the virus seems to be really low, and that's been said by other patients. Now, turns out if they do get it, and you know this has happened, the patient's on hydroxychloroquine or not, or on other biologics or not, that our patients may be at higher risk for pulmonary complications, again, the report from Jess Barks Group in Wuhan, China as well. Lastly, a very important report, meta analysis, actually I'm sorry, meta analysis, this is actually a case, a nested case control study from Vancouver, British Columbia showing that, hydroxychloroquine improves survival in lupus patients. I think that's the important point.
With all the hydroxychloroquine in the news right now, I worry our patient's gonna get the inappropriate message that it it's dangerous, that it causes more heart problems or more death when they should know that that's only in COVID patients who have a risk of heart problems and death because they have a lot of comorbidities. Plus, those trials are using higher doses than what they usually do. So that data does not apply to our patients. In this particular study of just hydroxychloroquine and lupus, it's nothing to with COVID, they showed that using hydroxychloroquine reduced mortality by fifty percent in their large cohort. They also showed that stopping hydroxychloroquine was associated with an increase in mortality, with a odds ratio of two point five.
And why would that be? Well, it's probably because a sick stopper, meaning patients were sick and had to stop therapy and therefore mortality risk was going to be higher, or that stopping hydroxychloroquine could in fact lead to a loss of the protective effect of hydroxychloroquine as regards mortality. So, again, really important inter interesting papers this week on the website. You can go to the website to to get these links and read more about these particular reports. I wanna remind you next week on June 2, Tuesday, 8PM, doctor John Kay, Tuesday night rheumatology.
He's going to lecture on an update in biosimilars. This is gonna be the last of our Tuesday night rheumatology series for before we start the summer, before we start reporting on, EULAR, which begins next week. That's it for this week in our room now. We hope to talk to you next week. Goodbye.
You know, they kind of coexist. Maybe your therapies make a difference. And lastly, I'm going to tell you about the one thing that is truly unique to our rheumatic disease patients when they become infected with the coronavirus. Stay tuned for this and more. So I want to remind you about this past Tuesday night rheumatology grand rounds presentation by Doctor.
Randy Kron from UAB where he gave a great presentation on the cytokine storm syndrome. Check it out, it'll, I think I have a better understanding of what the telltale signs are, what the risk factors are, what the biology is behind the syndrome. It's important for us as consultants to know how to manage MAS and cytokine storm. The UPI came out with a very important quote from Doctor. Fauci.
You know, get the email sometimes from David Mandel in Ohio, and David ends his emails with me with LTF, listen to Fauci. And that's way better than WTF. So yes, I listened to Fauci, and this week, UPI reported Doctor. Fauci stating that the scientific data is really quite evident now about the lack of efficacy, and of course, he's talking about hydroxychloroquine. So take it from the source, LTF.
As you know, this also comes at a time when the WHO suspended its very big solidarity trial. It enrolled 3,500 patients. It's still gonna continue observing those 3,500 patients, but no more patients are being enrolled in this very large WHO trial. And as such, other countries have now stepped up and said no more hydroxychloroquine. That includes France, Italy, Belgium and I'm sure there'll be others to follow.
Again, think that our country where we're doing trials, they should continue, for instance, a HERO trial where healthcare workers are being treated prophylactically with hydroxychlorine to see what that effect is. I think we should follow that out and see where it's going to go. You know, there's this other new therapy that's in development for rheumatoid arthritis called fenbrutinib. This is a BTK inhibitor. Its mechanisms are maybe not quite as direct as some of the other ones, but there's a rationale for its use.
And some of the early data didn't look all that great. But this week in ANR, Doctor. Stan Cohen, a good friend and colleague of mine here in Dallas, who's lead author on a very large trial of four eighty methotrexate incomplete responders who were randomized to either receive placebo. Again, these are people stayed on their methotrexate and then they get additional therapy, either placebo fifty milligrams of fenbutrinib once a day or one hundred and fifty once a day. And later on the trial, some patients got 200 BID.
The primary endpoint in this trial was at twelve weeks and an ACR 50 response, very aggressive, and the placebo response was fifteen percent. The fenbutrin of fifty milligrams didn't work, it was eighteen percent. There was an adalimumab arm in there where they had a thirty six percent response, ACR 50 response, which is pretty good at week twelve. And then the, 100 and 50 was 28 respond twenty eight percent and the 200 BID was thirty five percent suggesting there's probably good evidence to proceed in further development for this con this compound. The ACR 20 numbers were, like, thirty percent for placebo and about sixty percent for the higher dose fembryutinib.
There was no, effects on myeloid or B cell biomarkers in the study. Side effects were pretty pretty mild, mainly nonserious infections like UTI. So this is gonna go forward as another potential therapy in RA. Speaking of RA, you know, the age old question. Does, triple DMAR therapy, methotrexate sulfasalazine, hydroxychlorine, does it work?
You know, does it work outside of the middle of the country in the RAIN network where their data is astounding and their data is undeniably great? Most of you don't use triple DMAR therapy because you're not forced to use triple DMARD therapy. But if you did, you might see RAIN like numbers. Well, the corona network, has, like, almost forty thousand RA patients, did an analysis of patients going on triple DMARD versus those going on TNF inhibitors with methotrexate. And what they could say was that first off, triple DMARD is not used very often.
And that reflects the bias against it by most of us, most of you, including me. But and that shows up in the profile of the patients compared to those who got more aggressive TNF, more expensive TNF methotrexate therapy. Triple DMARC patients were older, had longer disease durations, had less activity, had more cancer as a background, and had more comorbidities. Not an ideal population. And not surprisingly, it didn't do well by comparison.
They were less likely to get to low disease activity state and had a higher rate of discontinuations. I think this is a negative report about triple DMARD, but it really reflects the selection bias that we all have. It's not fair. I think if you really wanna be able to say it doesn't work, then you should use it in your next 10 or 15 patients who you're considering starting on a TNF inhibitor. Put them on triple DMARD, watch them closely, see how they do, or do your own trial, one on one off, one on aggressive, expensive therapy, one on cheaper, triple DMARD therapy, tell me what you see.
There's an interesting report in arthritis and rheumatism about skin involvement with ANCA associated vasculitis that includes MPO and PR3 associated vasculitis, MPAs and GPA patients. Eleven eighty four patients, this is a worldwide registry, think of 13 centers, and they showed that skin involvement is seen in over a third of patients, especially with GPA. It was a little less with MPA patients and a little more with EGPA patients or Church Strauss patients. The common skin manifestations were petechiae or purpuric lesions, urticarial lesions and maculopapular rashes. The interesting thing about this study was if you had skin involvement with an ANCA associated vasculitis, guess what?
You are more likely to have systemic disease that was worse. And that includes glomerulonephritis and, alveolar hemorrhage and other serious manifestations associated with ANCA associated vasculitis. So look for skin involvement, worry about skin involvement when you see it. A meta analysis of 15 studies looked at the potential of therapy on the risk of getting diabetes if you have rheumatoid arthritis. A lot of patients, almost a half million patients in this study, and they showed quite convincingly, a lot of studies show that hydroxychloroquine lowers the risk by thirty nine percent.
Methotrexate lowers the risk by nineteen percent. TNF inhibitors lowers the risk by thirty seven percent. These are all significant reductions in the risk of diabetes. You know what increased the risk of diabetes? That's right.
Glucocorticoids where there was at least a 50% increase for all doses. And if you're taking ten milligrams or more, it was like a hundred and twenty five percent increased risk of getting diabetes. Speaking of RA, new drugs in development includes filgotinib. You know, the data looks fairly good on filgotinib. They might get a an FDA hearing a decision about its approval or not the sometime this year.
But in addition to developing this selective JAK one inhibitor for rheumatoid arthritis, filgotinib is being studied in other diseases. This week, we report on the results in ulcerative colitis, plus minus here, meaning that compared to placebo, the two hundred milligram dose, looked good at ten week responses. I'm sorry. Yeah. Ten week responses.
So it worked fast as you would expect the JAK inhibitor to work. However, the hundred milligram dose did not was not significant. But if you lasted out worked out to, like, six months, both the hundred and two hundred milligram dose, was both significant. That's really the big issue with this drug. They have a hundred milligram dose and a two hundred milligram dose.
Will they get both doses approved by the FDA? We have to wait and see. They're gonna it looks like they probably are gonna go for both doses, but remains to be seen. Both look good, but we need to see what happens in RA. Speaking of JAK inhibitors, baricitinib, some data came out this week about the risk of developing hepatitis B reactivation with baricitinib.
The data comes from the phase three RA trials of almost 3,000 patients where they've had two hundred and fifteen patients who had evidence of occult or resolve hepatitis B, meaning they were B surface antigen negative but hepatitis B core antibody positive. When they looked at two hundred and fifteen patients, there were eight who had an elevated hepatitis B, viral load by DNA, PCR, showing that they could have therefore reactivation. Half of those met the definition of reactivation, and, a total of five out of the eight actually required or three out of the eight required antiviral therapy. So, you know, this has been seen with other drugs, including abatacept and certainly with TNF inhibitors. The risk with TNF inhibitors for hep b reactivation is about two percent if you pool all the data on all the observational trials.
The rate here looks like it's about two to three point seven percent. So the risk could be constitutive to RA alone, or it could be related to the therapies we use, remains to be seen. I think the most important report this week was when I combined two different reports on COVID and rheumatic disease patients. One coming from Wuhan, China, where they had twenty one patients with rheumatic disease who are COVID positive and who are hospitalized with, with the condition. Of their twenty one patients, you know what?
They looked like all the other COVID patients had the same symptoms, same risk of hospitalization, same, mortality rate. But the one thing that was different was, the presence of pulmonary complications, mainly that of respiratory failure. In in their rheumatic disease patients, thirty eight percent of them actually developed respiratory failure compared to ten percent who did not have rheumatic disease, clearly distinguishing, what may happen in rheumatic disease patients. This was mirrored by Jeff Sparks' group in Boston where they had reported on fifty two fifty two patients, not necessarily hospitalized, but amongst their fifty two patients with rheumatic disease, the thing that was distinguishing them from the non rheumatic patients was that the rate of ICU hospitalization and the need for mechanical ventilation was higher in the rheum the rheumatic patients, forty eight percent versus eighteen percent in the non rheumatic patients. That's really kind of striking.
Now why our patients would have more pulmonary involvement? It might well be because a lot of our patients most of these patients we're talking about, by the way, are female, and most of them are RA, but there's some lupus in there. You know, it's not surprising that they would have a background risk of occult or, symptomatic, pulmonary conditions. So it that might be the reason. We really don't know, but it is something that's unique to our rheumatic disease population.
Yet, we also had a report this week saying that there's a low risk of COVID pneumonia in rheumatic patients. This actually so the former two studies were looking at patients who had severe disease and rheumatic disease and COVID. This particular study I'm reporting is actually collective experience of survey of 859 patients from Siena, Italy, they and surveyed their patients by telephone to find out, you know, who got COVID, what kind of problems they had. Turns out there were only two cases. And one had pneumonia but was not hospitalized, was treated with antiviral therapy and basically resolved.
The other one was a nursing home patient who upon nasal swab testing for COVID was positive, but was asymptomatic. The point of their paper was that our patients do very well in this Corona era and that the risk of them getting the virus seems to be really low, and that's been said by other patients. Now, turns out if they do get it, and you know this has happened, the patient's on hydroxychloroquine or not, or on other biologics or not, that our patients may be at higher risk for pulmonary complications, again, the report from Jess Barks Group in Wuhan, China as well. Lastly, a very important report, meta analysis, actually I'm sorry, meta analysis, this is actually a case, a nested case control study from Vancouver, British Columbia showing that, hydroxychloroquine improves survival in lupus patients. I think that's the important point.
With all the hydroxychloroquine in the news right now, I worry our patient's gonna get the inappropriate message that it it's dangerous, that it causes more heart problems or more death when they should know that that's only in COVID patients who have a risk of heart problems and death because they have a lot of comorbidities. Plus, those trials are using higher doses than what they usually do. So that data does not apply to our patients. In this particular study of just hydroxychloroquine and lupus, it's nothing to with COVID, they showed that using hydroxychloroquine reduced mortality by fifty percent in their large cohort. They also showed that stopping hydroxychloroquine was associated with an increase in mortality, with a odds ratio of two point five.
And why would that be? Well, it's probably because a sick stopper, meaning patients were sick and had to stop therapy and therefore mortality risk was going to be higher, or that stopping hydroxychloroquine could in fact lead to a loss of the protective effect of hydroxychloroquine as regards mortality. So, again, really important inter interesting papers this week on the website. You can go to the website to to get these links and read more about these particular reports. I wanna remind you next week on June 2, Tuesday, 8PM, doctor John Kay, Tuesday night rheumatology.
He's going to lecture on an update in biosimilars. This is gonna be the last of our Tuesday night rheumatology series for before we start the summer, before we start reporting on, EULAR, which begins next week. That's it for this week in our room now. We hope to talk to you next week. Goodbye.
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