MDedge Rheumatology

Editor in Chief of this news organization Eric Topol, MD, founder and director of the Scripps Research Translational Institute in La Jolla, Calif., and professor of molecular medicine, has been closely following COVID-19 data since the pandemic began. He spoke with writer Miriam E. Tucker about the latest on SARS-CoV-2 variants and their impact on vaccine efficacy. The conversation serves as a follow-up to his April 13, 2021, New York Times opinion piece, in which he advised readers that “all variants are innocent until proven guilty.”

You have expressed overall confidence in the efficacy of the vaccines thus far despite the emergence of variants, with some caveats. How do you see the current situation?

The Centers for Disease Control and Prevention has designated five “variants of concern,” but only three of them are real concerns – B.1.1.7, first detected in the United Kingdom; P.1, in Brazil and Japan; and B.1.351, in South Africa. Yet, all three are susceptible to our current vaccines.

The U.K. B.1.1.7 is the worst variant of all because it’s hypertransmissible, so I call it a “superspreader strain.” It also causes more severe illness independent of the spread, so it’s a double whammy. It’s clear that it also causes more deaths. The only arguable point is whether it’s 30% or 50% more deaths, but regardless, it’s more lethal and more transmissible.

The B.1.1.7 is going to be the dominant strain worldwide. It could develop new mutations within it that could come back to haunt us. We must keep watch.

But for now, it’s fully responsive to all the vaccines, which is great because if we didn’t have them, we wouldn’t have gotten through this U.S. pandemic like we have, and neither would Israel and the United Kingdom and other countries that have been able to get out of the crisis. We met the enemy and put it in check.

As for the South Africa variant of concern, B.1.351, we just got some encouraging news showing that it›s very responsive to the Pfizer/BioNTech mRNA vaccine in large numbers of people. The study was conducted in Qatar following that country’s mass immunization campaign in which a total of 385,853 people had received at least one vaccine dose and 265,410 had completed the two doses as of March 31, 2021.

At 2 weeks past the second dose, the vaccine was 75% effective at preventing any documented infection with the B.1.351 variant and 89.5% effective against B.1.1.7. The vaccine’s effectiveness against severe, critical, or fatal COVID-19 was greater than 97.4% for all circulating strains in Qatar, where B.1.1.7 and B.1.351 are most prominent.

We also know that B.1.351 is very responsive to the Johnson & Johnson vaccine and the Novavax [vaccine in development] to a lesser degree. It is the most immune-evading variant we’ve seen thus far, with the highest likelihood of providing some vaccine resistance, yet not enough to interfere with vaccination campaigns. So that’s great news.

The caveats here are that you definitely need two doses of the mRNA vaccines to combat the B.1.351 variant. Also, the AstraZeneca vaccine failed to prevent it in South Africa. However, that study was hard to judge because it was underpowered for number of people with mild infections. So, it didn’t look as if it had any efficacy, but maybe it would if tested in a real trial.

The P.1 (Brazil) variant is the second-highest concern after B.1.1.7 because it’s the only one in the United States that’s still headed up. It seems to be competing a bit with B.1.1.7 here. We know it was associated with the crisis in Brazil, in Chile, and some other South American countries. It has some immune escape, but not as bad as B.1.351. It also appears to have somewhat greater transmissibility but not as much as B.1.1.7.

With P.1, we just don’t know enough yet. It was difficult to assess in Brazil because they were in the midst of a catastrophe – like India is now – and you don’t know how much of it is dragged by the catastrophe vs driving it.

We have to respond to P.1 carefully. There are some good data that it does respond to the Chinese vaccine Sinovac and the AstraZeneca vaccine, and it appears to respond to the others as well, based on serum studies. So it doesn’t look like vaccines will be the worry with this variant. Rather, it could be competing with B.1.1.7 and could lead to breakthrough infections in vaccinated people or reinfections in unvaccinated people who had COVID-19. We need several more weeks to sort it out.

Although the B.1.427 and B.1.429 variants initially seen in California remain on the CDC’s concern list, I’m not worried about them.
 

You mentioned the current COVID-19 crisis in India, where a new variant has been described as a “double mutant,” but on Twitter you called it a “scariant.” Why?

First of all, the B.1.617 variant isn’t a double mutant. It has 15 mutations. It’s a stupid term, focusing on two mutations which largely have been put aside as to concern. One of them is the L452R, which is the same as one of the California variants, and that hasn’t proved to be particularly serious or concerning. The other is the 484Q, and it’s not clear whether that has any function.

The B.1.617 is not the driver of the catastrophe in India. It may be contributing a small amount, but it has been overhyped as the double mutant that’s causing it all. Adding to that are what I call “scariant” headlines here in the United States when a few cases of that variant have been seen.

I coined the term scariant in early February because it was a pretty clear trend. People don’t know what variants are. They know a little bit about mutations but not variants, and they’re scared. A few variants are concerning, but we keep learning more and more things to decrease the concern. That’s why I wrote the New York Times op-ed, to try to provide some reassurance, since there’s such paranoia.
 

Do you think booster vaccinations will be necessary? If so, will those be of the original vaccines or new ones that incorporate the variants?

As we go forward, there’s still potential for new variants that we haven’t seen yet that combine the worst of all features – transmissibility and immune evasion – especially since we have a world where COVID-19 is unchecked. So, we’re not out of it yet, but at least for the moment, we have vaccines that are capable of protecting against all variants.

In most people, the immune response against SARS-CoV-2 is very durable and strong and may well last for years. With the most closely related SARS-CoV-1, people still had immune responses up to 18 years later. However, some people will have less robust vaccine responses, including the elderly and the immunocompromised. If they don’t have great responses to the vaccine to start with, over time they’re likely to become more vulnerable, especially if they’re exposed to the variants with some degree of immune evasion.

I think we need to study these individuals post vaccination. A lot of people fit into those categories, including seniors, people being treated for cancer or autoimmune conditions, or post organ transplant. We could set up a prospective study to see whether they develop symptomatic COVID-19 and if so, from what – the original strain, B.1.1.7, or the newer variants.

That’s where I think booster shots may be needed. They may not be necessary across the board, but perhaps just in these special subgroups.

All of the current vaccines can be tweaked to include new variants, but the need for that is uncertain as of now. Moderna is working on a so-called bivalent vaccine that includes the original SARS-CoV-2 strain plus the B.1.351 variant, but it isn’t clear that that’s going to be necessary.

Currently, at least 200 COVID-19 vaccines are in development. There will be vaccines you can inhale, room temperature mRNA vaccines, and potentially even oral vaccines.

In the near future, Novavax is close, and there will likely be a two-dose Johnson & Johnson version that has the same potency as the mRNA vaccines. There are a lot of moving parts here.

There may be a step down in efficacy from mRNA to the others, though, and that shouldn’t be discounted. All of the available vaccines so far protect very well against severe disease and death, but some are less effective against mild to moderate infections, which may then lead to long COVID. We don’t yet know whether those who get mild infection post vaccination can still get long COVID.
 

What do you think it will take to achieve herd immunity?

I prefer the term “containment.” It’s quantitative. If you get to an infection rate of less than 1 in 100,000 people, as they’ve done in Israel, with 0.8 per 100,000, then you have the virus in check, and there will be very little spread when it’s at that controlled rate, with no outbreaks. The United States is currently at about 15 per 100,000. California is at 4. That still has to get lower.

It will be a challenge to get to President Biden’s goal of having 70% of U.S. adults given at least one dose by July 4. We’re now at about 57%. To get that next 13% of adults is going to take an all-out effort: mobile units, going to homes, making it ultraconvenient, education for people with safety concerns, incentivization, and days off.

We also need to get employers, universities, and health systems to get to the mandatory level. We haven’t done that yet. Some universities have mandated it for students, faculty, and staff. We need it in more health care systems. Right now, we only have a couple. We mandate flu shots, and flu is nothing, compared with COVID-19. And the COVID-19 vaccine is far more efficacious – flu shots are 40% efficacious, while these are 95%. COVID-19 is a tenfold more lethal and serious disease, and much more spreadable.

People are using the lack of full licensure by the Food and Drug Administration – as opposed to emergency use authorization – as an excuse not to get vaccinated. A biologics license application takes time to approve. Meanwhile, we have hundreds of millions of doses that have been well tolerated and incredibly effective.

Another aspect to consider regarding containment is that about 110 million Americans have already had COVID-19, even though only about 30 million cases have been confirmed. Most of these people have immune protection, although it’s not as good as if they have one vaccine dose. But they have enough protection to be part of the story here of the wall against COVID-19 and will help us get through this.

That’s a silver lining of having an unchecked epidemic for the entire year of 2020. The good part is that’s helping to get us to achieve an incredible level of containment when we haven’t even been close. Right now, we’re as good as the country has been in the pandemic, but we still have a long gap to get down to that 1 per 100,000. That’s what we should be working toward, and we can get there.

A version of this article first appeared on Medscape.com.

Editor in Chief of this news organization Eric Topol, MD, founder and director of the Scripps Research Translational Institute in La Jolla, Calif., and professor of molecular medicine, has been closely following COVID-19 data since the pandemic began. He spoke with writer Miriam E. Tucker about the latest on SARS-CoV-2 variants and their impact on vaccine efficacy. The conversation serves as a follow-up to his April 13, 2021, New York Times opinion piece, in which he advised readers that “all variants are innocent until proven guilty.”

You have expressed overall confidence in the efficacy of the vaccines thus far despite the emergence of variants, with some caveats. How do you see the current situation?

The Centers for Disease Control and Prevention has designated five “variants of concern,” but only three of them are real concerns – B.1.1.7, first detected in the United Kingdom; P.1, in Brazil and Japan; and B.1.351, in South Africa. Yet, all three are susceptible to our current vaccines.

The U.K. B.1.1.7 is the worst variant of all because it’s hypertransmissible, so I call it a “superspreader strain.” It also causes more severe illness independent of the spread, so it’s a double whammy. It’s clear that it also causes more deaths. The only arguable point is whether it’s 30% or 50% more deaths, but regardless, it’s more lethal and more transmissible.

The B.1.1.7 is going to be the dominant strain worldwide. It could develop new mutations within it that could come back to haunt us. We must keep watch.

But for now, it’s fully responsive to all the vaccines, which is great because if we didn’t have them, we wouldn’t have gotten through this U.S. pandemic like we have, and neither would Israel and the United Kingdom and other countries that have been able to get out of the crisis. We met the enemy and put it in check.

As for the South Africa variant of concern, B.1.351, we just got some encouraging news showing that it›s very responsive to the Pfizer/BioNTech mRNA vaccine in large numbers of people. The study was conducted in Qatar following that country’s mass immunization campaign in which a total of 385,853 people had received at least one vaccine dose and 265,410 had completed the two doses as of March 31, 2021.

At 2 weeks past the second dose, the vaccine was 75% effective at preventing any documented infection with the B.1.351 variant and 89.5% effective against B.1.1.7. The vaccine’s effectiveness against severe, critical, or fatal COVID-19 was greater than 97.4% for all circulating strains in Qatar, where B.1.1.7 and B.1.351 are most prominent.

We also know that B.1.351 is very responsive to the Johnson & Johnson vaccine and the Novavax [vaccine in development] to a lesser degree. It is the most immune-evading variant we’ve seen thus far, with the highest likelihood of providing some vaccine resistance, yet not enough to interfere with vaccination campaigns. So that’s great news.

The caveats here are that you definitely need two doses of the mRNA vaccines to combat the B.1.351 variant. Also, the AstraZeneca vaccine failed to prevent it in South Africa. However, that study was hard to judge because it was underpowered for number of people with mild infections. So, it didn’t look as if it had any efficacy, but maybe it would if tested in a real trial.

The P.1 (Brazil) variant is the second-highest concern after B.1.1.7 because it’s the only one in the United States that’s still headed up. It seems to be competing a bit with B.1.1.7 here. We know it was associated with the crisis in Brazil, in Chile, and some other South American countries. It has some immune escape, but not as bad as B.1.351. It also appears to have somewhat greater transmissibility but not as much as B.1.1.7.

With P.1, we just don’t know enough yet. It was difficult to assess in Brazil because they were in the midst of a catastrophe – like India is now – and you don’t know how much of it is dragged by the catastrophe vs driving it.

We have to respond to P.1 carefully. There are some good data that it does respond to the Chinese vaccine Sinovac and the AstraZeneca vaccine, and it appears to respond to the others as well, based on serum studies. So it doesn’t look like vaccines will be the worry with this variant. Rather, it could be competing with B.1.1.7 and could lead to breakthrough infections in vaccinated people or reinfections in unvaccinated people who had COVID-19. We need several more weeks to sort it out.

Although the B.1.427 and B.1.429 variants initially seen in California remain on the CDC’s concern list, I’m not worried about them.
 

You mentioned the current COVID-19 crisis in India, where a new variant has been described as a “double mutant,” but on Twitter you called it a “scariant.” Why?

First of all, the B.1.617 variant isn’t a double mutant. It has 15 mutations. It’s a stupid term, focusing on two mutations which largely have been put aside as to concern. One of them is the L452R, which is the same as one of the California variants, and that hasn’t proved to be particularly serious or concerning. The other is the 484Q, and it’s not clear whether that has any function.

The B.1.617 is not the driver of the catastrophe in India. It may be contributing a small amount, but it has been overhyped as the double mutant that’s causing it all. Adding to that are what I call “scariant” headlines here in the United States when a few cases of that variant have been seen.

I coined the term scariant in early February because it was a pretty clear trend. People don’t know what variants are. They know a little bit about mutations but not variants, and they’re scared. A few variants are concerning, but we keep learning more and more things to decrease the concern. That’s why I wrote the New York Times op-ed, to try to provide some reassurance, since there’s such paranoia.
 

Do you think booster vaccinations will be necessary? If so, will those be of the original vaccines or new ones that incorporate the variants?

As we go forward, there’s still potential for new variants that we haven’t seen yet that combine the worst of all features – transmissibility and immune evasion – especially since we have a world where COVID-19 is unchecked. So, we’re not out of it yet, but at least for the moment, we have vaccines that are capable of protecting against all variants.

In most people, the immune response against SARS-CoV-2 is very durable and strong and may well last for years. With the most closely related SARS-CoV-1, people still had immune responses up to 18 years later. However, some people will have less robust vaccine responses, including the elderly and the immunocompromised. If they don’t have great responses to the vaccine to start with, over time they’re likely to become more vulnerable, especially if they’re exposed to the variants with some degree of immune evasion.

I think we need to study these individuals post vaccination. A lot of people fit into those categories, including seniors, people being treated for cancer or autoimmune conditions, or post organ transplant. We could set up a prospective study to see whether they develop symptomatic COVID-19 and if so, from what – the original strain, B.1.1.7, or the newer variants.

That’s where I think booster shots may be needed. They may not be necessary across the board, but perhaps just in these special subgroups.

All of the current vaccines can be tweaked to include new variants, but the need for that is uncertain as of now. Moderna is working on a so-called bivalent vaccine that includes the original SARS-CoV-2 strain plus the B.1.351 variant, but it isn’t clear that that’s going to be necessary.

Currently, at least 200 COVID-19 vaccines are in development. There will be vaccines you can inhale, room temperature mRNA vaccines, and potentially even oral vaccines.

In the near future, Novavax is close, and there will likely be a two-dose Johnson & Johnson version that has the same potency as the mRNA vaccines. There are a lot of moving parts here.

There may be a step down in efficacy from mRNA to the others, though, and that shouldn’t be discounted. All of the available vaccines so far protect very well against severe disease and death, but some are less effective against mild to moderate infections, which may then lead to long COVID. We don’t yet know whether those who get mild infection post vaccination can still get long COVID.
 

What do you think it will take to achieve herd immunity?

I prefer the term “containment.” It’s quantitative. If you get to an infection rate of less than 1 in 100,000 people, as they’ve done in Israel, with 0.8 per 100,000, then you have the virus in check, and there will be very little spread when it’s at that controlled rate, with no outbreaks. The United States is currently at about 15 per 100,000. California is at 4. That still has to get lower.

It will be a challenge to get to President Biden’s goal of having 70% of U.S. adults given at least one dose by July 4. We’re now at about 57%. To get that next 13% of adults is going to take an all-out effort: mobile units, going to homes, making it ultraconvenient, education for people with safety concerns, incentivization, and days off.

We also need to get employers, universities, and health systems to get to the mandatory level. We haven’t done that yet. Some universities have mandated it for students, faculty, and staff. We need it in more health care systems. Right now, we only have a couple. We mandate flu shots, and flu is nothing, compared with COVID-19. And the COVID-19 vaccine is far more efficacious – flu shots are 40% efficacious, while these are 95%. COVID-19 is a tenfold more lethal and serious disease, and much more spreadable.

People are using the lack of full licensure by the Food and Drug Administration – as opposed to emergency use authorization – as an excuse not to get vaccinated. A biologics license application takes time to approve. Meanwhile, we have hundreds of millions of doses that have been well tolerated and incredibly effective.

Another aspect to consider regarding containment is that about 110 million Americans have already had COVID-19, even though only about 30 million cases have been confirmed. Most of these people have immune protection, although it’s not as good as if they have one vaccine dose. But they have enough protection to be part of the story here of the wall against COVID-19 and will help us get through this.

That’s a silver lining of having an unchecked epidemic for the entire year of 2020. The good part is that’s helping to get us to achieve an incredible level of containment when we haven’t even been close. Right now, we’re as good as the country has been in the pandemic, but we still have a long gap to get down to that 1 per 100,000. That’s what we should be working toward, and we can get there.

A version of this article first appeared on Medscape.com.

Editor in Chief of this news organization Eric Topol, MD, founder and director of the Scripps Research Translational Institute in La Jolla, Calif., and professor of molecular medicine, has been closely following COVID-19 data since the pandemic began. He spoke with writer Miriam E. Tucker about the latest on SARS-CoV-2 variants and their impact on vaccine efficacy. The conversation serves as a follow-up to his April 13, 2021, New York Times opinion piece, in which he advised readers that “all variants are innocent until proven guilty.”

You have expressed overall confidence in the efficacy of the vaccines thus far despite the emergence of variants, with some caveats. How do you see the current situation?

The Centers for Disease Control and Prevention has designated five “variants of concern,” but only three of them are real concerns – B.1.1.7, first detected in the United Kingdom; P.1, in Brazil and Japan; and B.1.351, in South Africa. Yet, all three are susceptible to our current vaccines.

The U.K. B.1.1.7 is the worst variant of all because it’s hypertransmissible, so I call it a “superspreader strain.” It also causes more severe illness independent of the spread, so it’s a double whammy. It’s clear that it also causes more deaths. The only arguable point is whether it’s 30% or 50% more deaths, but regardless, it’s more lethal and more transmissible.

The B.1.1.7 is going to be the dominant strain worldwide. It could develop new mutations within it that could come back to haunt us. We must keep watch.

But for now, it’s fully responsive to all the vaccines, which is great because if we didn’t have them, we wouldn’t have gotten through this U.S. pandemic like we have, and neither would Israel and the United Kingdom and other countries that have been able to get out of the crisis. We met the enemy and put it in check.

As for the South Africa variant of concern, B.1.351, we just got some encouraging news showing that it›s very responsive to the Pfizer/BioNTech mRNA vaccine in large numbers of people. The study was conducted in Qatar following that country’s mass immunization campaign in which a total of 385,853 people had received at least one vaccine dose and 265,410 had completed the two doses as of March 31, 2021.

At 2 weeks past the second dose, the vaccine was 75% effective at preventing any documented infection with the B.1.351 variant and 89.5% effective against B.1.1.7. The vaccine’s effectiveness against severe, critical, or fatal COVID-19 was greater than 97.4% for all circulating strains in Qatar, where B.1.1.7 and B.1.351 are most prominent.

We also know that B.1.351 is very responsive to the Johnson & Johnson vaccine and the Novavax [vaccine in development] to a lesser degree. It is the most immune-evading variant we’ve seen thus far, with the highest likelihood of providing some vaccine resistance, yet not enough to interfere with vaccination campaigns. So that’s great news.

The caveats here are that you definitely need two doses of the mRNA vaccines to combat the B.1.351 variant. Also, the AstraZeneca vaccine failed to prevent it in South Africa. However, that study was hard to judge because it was underpowered for number of people with mild infections. So, it didn’t look as if it had any efficacy, but maybe it would if tested in a real trial.

The P.1 (Brazil) variant is the second-highest concern after B.1.1.7 because it’s the only one in the United States that’s still headed up. It seems to be competing a bit with B.1.1.7 here. We know it was associated with the crisis in Brazil, in Chile, and some other South American countries. It has some immune escape, but not as bad as B.1.351. It also appears to have somewhat greater transmissibility but not as much as B.1.1.7.

With P.1, we just don’t know enough yet. It was difficult to assess in Brazil because they were in the midst of a catastrophe – like India is now – and you don’t know how much of it is dragged by the catastrophe vs driving it.

We have to respond to P.1 carefully. There are some good data that it does respond to the Chinese vaccine Sinovac and the AstraZeneca vaccine, and it appears to respond to the others as well, based on serum studies. So it doesn’t look like vaccines will be the worry with this variant. Rather, it could be competing with B.1.1.7 and could lead to breakthrough infections in vaccinated people or reinfections in unvaccinated people who had COVID-19. We need several more weeks to sort it out.

Although the B.1.427 and B.1.429 variants initially seen in California remain on the CDC’s concern list, I’m not worried about them.
 

You mentioned the current COVID-19 crisis in India, where a new variant has been described as a “double mutant,” but on Twitter you called it a “scariant.” Why?

First of all, the B.1.617 variant isn’t a double mutant. It has 15 mutations. It’s a stupid term, focusing on two mutations which largely have been put aside as to concern. One of them is the L452R, which is the same as one of the California variants, and that hasn’t proved to be particularly serious or concerning. The other is the 484Q, and it’s not clear whether that has any function.

The B.1.617 is not the driver of the catastrophe in India. It may be contributing a small amount, but it has been overhyped as the double mutant that’s causing it all. Adding to that are what I call “scariant” headlines here in the United States when a few cases of that variant have been seen.

I coined the term scariant in early February because it was a pretty clear trend. People don’t know what variants are. They know a little bit about mutations but not variants, and they’re scared. A few variants are concerning, but we keep learning more and more things to decrease the concern. That’s why I wrote the New York Times op-ed, to try to provide some reassurance, since there’s such paranoia.
 

Do you think booster vaccinations will be necessary? If so, will those be of the original vaccines or new ones that incorporate the variants?

As we go forward, there’s still potential for new variants that we haven’t seen yet that combine the worst of all features – transmissibility and immune evasion – especially since we have a world where COVID-19 is unchecked. So, we’re not out of it yet, but at least for the moment, we have vaccines that are capable of protecting against all variants.

In most people, the immune response against SARS-CoV-2 is very durable and strong and may well last for years. With the most closely related SARS-CoV-1, people still had immune responses up to 18 years later. However, some people will have less robust vaccine responses, including the elderly and the immunocompromised. If they don’t have great responses to the vaccine to start with, over time they’re likely to become more vulnerable, especially if they’re exposed to the variants with some degree of immune evasion.

I think we need to study these individuals post vaccination. A lot of people fit into those categories, including seniors, people being treated for cancer or autoimmune conditions, or post organ transplant. We could set up a prospective study to see whether they develop symptomatic COVID-19 and if so, from what – the original strain, B.1.1.7, or the newer variants.

That’s where I think booster shots may be needed. They may not be necessary across the board, but perhaps just in these special subgroups.

All of the current vaccines can be tweaked to include new variants, but the need for that is uncertain as of now. Moderna is working on a so-called bivalent vaccine that includes the original SARS-CoV-2 strain plus the B.1.351 variant, but it isn’t clear that that’s going to be necessary.

Currently, at least 200 COVID-19 vaccines are in development. There will be vaccines you can inhale, room temperature mRNA vaccines, and potentially even oral vaccines.

In the near future, Novavax is close, and there will likely be a two-dose Johnson & Johnson version that has the same potency as the mRNA vaccines. There are a lot of moving parts here.

There may be a step down in efficacy from mRNA to the others, though, and that shouldn’t be discounted. All of the available vaccines so far protect very well against severe disease and death, but some are less effective against mild to moderate infections, which may then lead to long COVID. We don’t yet know whether those who get mild infection post vaccination can still get long COVID.
 

What do you think it will take to achieve herd immunity?

I prefer the term “containment.” It’s quantitative. If you get to an infection rate of less than 1 in 100,000 people, as they’ve done in Israel, with 0.8 per 100,000, then you have the virus in check, and there will be very little spread when it’s at that controlled rate, with no outbreaks. The United States is currently at about 15 per 100,000. California is at 4. That still has to get lower.

It will be a challenge to get to President Biden’s goal of having 70% of U.S. adults given at least one dose by July 4. We’re now at about 57%. To get that next 13% of adults is going to take an all-out effort: mobile units, going to homes, making it ultraconvenient, education for people with safety concerns, incentivization, and days off.

We also need to get employers, universities, and health systems to get to the mandatory level. We haven’t done that yet. Some universities have mandated it for students, faculty, and staff. We need it in more health care systems. Right now, we only have a couple. We mandate flu shots, and flu is nothing, compared with COVID-19. And the COVID-19 vaccine is far more efficacious – flu shots are 40% efficacious, while these are 95%. COVID-19 is a tenfold more lethal and serious disease, and much more spreadable.

People are using the lack of full licensure by the Food and Drug Administration – as opposed to emergency use authorization – as an excuse not to get vaccinated. A biologics license application takes time to approve. Meanwhile, we have hundreds of millions of doses that have been well tolerated and incredibly effective.

Another aspect to consider regarding containment is that about 110 million Americans have already had COVID-19, even though only about 30 million cases have been confirmed. Most of these people have immune protection, although it’s not as good as if they have one vaccine dose. But they have enough protection to be part of the story here of the wall against COVID-19 and will help us get through this.

That’s a silver lining of having an unchecked epidemic for the entire year of 2020. The good part is that’s helping to get us to achieve an incredible level of containment when we haven’t even been close. Right now, we’re as good as the country has been in the pandemic, but we still have a long gap to get down to that 1 per 100,000. That’s what we should be working toward, and we can get there.

A version of this article first appeared on Medscape.com.

The first clinical trial of fecal microbiota transplantation in patients with psoriatic arthritis has found the procedure to be as safe as a sham procedure, but it didn’t show any effectiveness in decreasing PsA symptoms over 6 months, a team of researchers in Denmark reported in Annals of the Rheumatic Diseases (2021 Apr 29. 10.1136/annrheumdis-2020-219511).

ChrisChrisW/Getty Images

Nonetheless, the investigators said the trial indicates fecal microbiota transplantation (FMT) is worthy of further study.

“Overall, we think that the results are very interesting and that the feasibility and safety aspects as well as the clinical results of the trial may encourage more research into the potential of FMT in the treatment of inflammatory arthritis and may help guide the direction of future trials within the field,” lead author Maja S. Kragsnaes, MD, PhD, and principal investigator Torkell Ellingsen, MD, PhD, of Odense (Denmark) University Hospital said together in an interview.

“The most important findings from this trial is that FMT appears to be safe in patients with PsA and that the patients find the treatment acceptable, and it supports future research into the therapeutic potential of FMT in PsA,” they said.

The study evaluated 6-month outcomes of 31 patients randomized to the FMT and sham groups. FMT patients were three times more likely to experience treatment failure – defined by the need for treatment intensification – with failure rates of 60% versus 20% in the sham group.

As a secondary endpoint, the study used 6-month change in the Health Assessment Questionnaire Disability Index (HAQ-DI) and 20% improvement in American College of Rheumatology criteria (ACR20). The sham group demonstrated a greater decrease in HAQ-DI, indicating better physical function (–0.30 vs. –0.07; P = .031). The proportion of ACR20 responders was similar between both groups: 47% for the FMT patients (7 of 15) and 53% for sham (8 of 15).

The study included adults aged 18-75 years with active peripheral disease, defined as three or more swollen joints, who’d been taking at least15 mg methotrexate a week for at least 3 months before enrolling in the study, with a washout period of 12 weeks (26 weeks for those on biologic agents). Four healthy donors provided the stool transplants.

In the study, Dr. Kragsnaes and Dr. Ellingsen acknowledged that FMT has been shown to be safe for Clostridioides difficile infection or inflammatory bowel disease when “thoroughly screened stool” is used. “Hence,” they wrote, “our findings add to the growing body of evidence suggesting a gut-joint axis in the pathogenesis of PsA.”

Factors that may influence the effectiveness of FMT in PsA merit further investigation, Dr. Kragsnaes and Dr. Ellingsen said. “From FMT trials in patients with active ulcerative colitis, higher dose and repeated administration appear to be effective and safe in inducing remission,” they said in their joint statement, pointing to research from China.

“Moreover,” they added, “successes of FMT in inflammatory bowel disease appear to have been driven by ‘superdonors’ characterized by the presence or absence of specific bacteria species.”

They said will continue to investigate the effectiveness of FMT in immune-mediated diseases, including how to characterize superdonors.

“We will conduct new randomized trials using different FMT strategies – by changing the type of administration form, dose, and treatment frequency – to explore whether microbial dysbiosis or specific bacteria are common or decisive mediators of disease activity in inflammatory diseases and whether this proposed relation can be modified without exacerbating the disease,” Dr. Kragsnaes and Dr. Ellingsen said.

Dr. Kragsnaes and Dr. Ellingsen had no relevant financial relationships to disclose.

The first clinical trial of fecal microbiota transplantation in patients with psoriatic arthritis has found the procedure to be as safe as a sham procedure, but it didn’t show any effectiveness in decreasing PsA symptoms over 6 months, a team of researchers in Denmark reported in Annals of the Rheumatic Diseases (2021 Apr 29. 10.1136/annrheumdis-2020-219511).

ChrisChrisW/Getty Images

Nonetheless, the investigators said the trial indicates fecal microbiota transplantation (FMT) is worthy of further study.

“Overall, we think that the results are very interesting and that the feasibility and safety aspects as well as the clinical results of the trial may encourage more research into the potential of FMT in the treatment of inflammatory arthritis and may help guide the direction of future trials within the field,” lead author Maja S. Kragsnaes, MD, PhD, and principal investigator Torkell Ellingsen, MD, PhD, of Odense (Denmark) University Hospital said together in an interview.

“The most important findings from this trial is that FMT appears to be safe in patients with PsA and that the patients find the treatment acceptable, and it supports future research into the therapeutic potential of FMT in PsA,” they said.

The study evaluated 6-month outcomes of 31 patients randomized to the FMT and sham groups. FMT patients were three times more likely to experience treatment failure – defined by the need for treatment intensification – with failure rates of 60% versus 20% in the sham group.

As a secondary endpoint, the study used 6-month change in the Health Assessment Questionnaire Disability Index (HAQ-DI) and 20% improvement in American College of Rheumatology criteria (ACR20). The sham group demonstrated a greater decrease in HAQ-DI, indicating better physical function (–0.30 vs. –0.07; P = .031). The proportion of ACR20 responders was similar between both groups: 47% for the FMT patients (7 of 15) and 53% for sham (8 of 15).

The study included adults aged 18-75 years with active peripheral disease, defined as three or more swollen joints, who’d been taking at least15 mg methotrexate a week for at least 3 months before enrolling in the study, with a washout period of 12 weeks (26 weeks for those on biologic agents). Four healthy donors provided the stool transplants.

In the study, Dr. Kragsnaes and Dr. Ellingsen acknowledged that FMT has been shown to be safe for Clostridioides difficile infection or inflammatory bowel disease when “thoroughly screened stool” is used. “Hence,” they wrote, “our findings add to the growing body of evidence suggesting a gut-joint axis in the pathogenesis of PsA.”

Factors that may influence the effectiveness of FMT in PsA merit further investigation, Dr. Kragsnaes and Dr. Ellingsen said. “From FMT trials in patients with active ulcerative colitis, higher dose and repeated administration appear to be effective and safe in inducing remission,” they said in their joint statement, pointing to research from China.

“Moreover,” they added, “successes of FMT in inflammatory bowel disease appear to have been driven by ‘superdonors’ characterized by the presence or absence of specific bacteria species.”

They said will continue to investigate the effectiveness of FMT in immune-mediated diseases, including how to characterize superdonors.

“We will conduct new randomized trials using different FMT strategies – by changing the type of administration form, dose, and treatment frequency – to explore whether microbial dysbiosis or specific bacteria are common or decisive mediators of disease activity in inflammatory diseases and whether this proposed relation can be modified without exacerbating the disease,” Dr. Kragsnaes and Dr. Ellingsen said.

Dr. Kragsnaes and Dr. Ellingsen had no relevant financial relationships to disclose.

The first clinical trial of fecal microbiota transplantation in patients with psoriatic arthritis has found the procedure to be as safe as a sham procedure, but it didn’t show any effectiveness in decreasing PsA symptoms over 6 months, a team of researchers in Denmark reported in Annals of the Rheumatic Diseases (2021 Apr 29. 10.1136/annrheumdis-2020-219511).

ChrisChrisW/Getty Images

Nonetheless, the investigators said the trial indicates fecal microbiota transplantation (FMT) is worthy of further study.

“Overall, we think that the results are very interesting and that the feasibility and safety aspects as well as the clinical results of the trial may encourage more research into the potential of FMT in the treatment of inflammatory arthritis and may help guide the direction of future trials within the field,” lead author Maja S. Kragsnaes, MD, PhD, and principal investigator Torkell Ellingsen, MD, PhD, of Odense (Denmark) University Hospital said together in an interview.

“The most important findings from this trial is that FMT appears to be safe in patients with PsA and that the patients find the treatment acceptable, and it supports future research into the therapeutic potential of FMT in PsA,” they said.

The study evaluated 6-month outcomes of 31 patients randomized to the FMT and sham groups. FMT patients were three times more likely to experience treatment failure – defined by the need for treatment intensification – with failure rates of 60% versus 20% in the sham group.

As a secondary endpoint, the study used 6-month change in the Health Assessment Questionnaire Disability Index (HAQ-DI) and 20% improvement in American College of Rheumatology criteria (ACR20). The sham group demonstrated a greater decrease in HAQ-DI, indicating better physical function (–0.30 vs. –0.07; P = .031). The proportion of ACR20 responders was similar between both groups: 47% for the FMT patients (7 of 15) and 53% for sham (8 of 15).

The study included adults aged 18-75 years with active peripheral disease, defined as three or more swollen joints, who’d been taking at least15 mg methotrexate a week for at least 3 months before enrolling in the study, with a washout period of 12 weeks (26 weeks for those on biologic agents). Four healthy donors provided the stool transplants.

In the study, Dr. Kragsnaes and Dr. Ellingsen acknowledged that FMT has been shown to be safe for Clostridioides difficile infection or inflammatory bowel disease when “thoroughly screened stool” is used. “Hence,” they wrote, “our findings add to the growing body of evidence suggesting a gut-joint axis in the pathogenesis of PsA.”

Factors that may influence the effectiveness of FMT in PsA merit further investigation, Dr. Kragsnaes and Dr. Ellingsen said. “From FMT trials in patients with active ulcerative colitis, higher dose and repeated administration appear to be effective and safe in inducing remission,” they said in their joint statement, pointing to research from China.

“Moreover,” they added, “successes of FMT in inflammatory bowel disease appear to have been driven by ‘superdonors’ characterized by the presence or absence of specific bacteria species.”

They said will continue to investigate the effectiveness of FMT in immune-mediated diseases, including how to characterize superdonors.

“We will conduct new randomized trials using different FMT strategies – by changing the type of administration form, dose, and treatment frequency – to explore whether microbial dysbiosis or specific bacteria are common or decisive mediators of disease activity in inflammatory diseases and whether this proposed relation can be modified without exacerbating the disease,” Dr. Kragsnaes and Dr. Ellingsen said.

Dr. Kragsnaes and Dr. Ellingsen had no relevant financial relationships to disclose.

The serious infection risk associated with rituximab treatment for antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is high but can be offset by co-prescribing co-trimoxazole, data from a single-center, retrospective study reaffirm.

Over the course of a 3-year study period, 14 (28%) of 50 patients with AAV treated with rituximab experienced at latest one severe infection defined as a grade 3 or higher event. The incidence of severe infections was 15.4 per 100 person-years.

However, a lower rate of infections was seen in patients who had been co-prescribed co-trimoxazole (trimethoprim and sulfamethoxazole), Francesco Dernie, a fifth-year medical student at the University of Oxford (England), reported at the British Society for Rheumatology annual conference.

“In the case of rituximab, the depletion of B cells and associated immune suppression is a double-edged sword, allowing effective disease control, but also leaving the body vulnerable to opportunistic and severe infections,” Mr. Dernie said at the meeting.

Of the patients who developed a severe infection on rituximab, just 7% had been treated with co-trimoxazole. In comparison, 44% of those who did not get a severe infection had received co-trimoxazole. Multivariate analysis confirmed that co-trimoxazole use was an influencing factor, with an odds ratio (OR) of 0.096 (95% confidence interval, 0.009–0.996; P = .05).

Another finding was that patients with low immunoglobulin G levels (less than 6 g/L) were more likely to develop a severe infection than were those with higher IgG levels. Indeed, the OR for hypogammaglobulinemia and the risk for infection was 8.782 (95% CI, 1.19–64.6; P = .033).

“Our results support the monitoring of IgG levels to identify patients who may be more susceptible to infection, as well as the prescription of prophylactic co-trimoxazole to reduce overall severe infection risk,” Mr. Dernie and associates concluded in their abstract.

It’s a “really important message around co-trimoxazole,” observed Neil Basu, MBChB, a clinical senior lecturer and honorary consultant at the Institute of Infection, Immunity & Inflammation, University of Glasgow (Scotland).

“It still frustrates me when I see that patients haven’t received that while receiving rituximab. Of course, co-trimoxazole can have its problems,” said Dr. Basu, who was not involved in the study. “It’s not uncommon for patients to develop reactions or be intolerant to the drug.”

Raashid Luqmani, DM, a senior coauthor of the work and professor of rheumatology at the Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Science, University of Oxford, said: “The tolerance of co-trimoxazole has been remarkably good in this cohort.” If there was a problem with using co-trimoxazole, then “our standard would be to go with trimethoprim alone as the next in line and follow that with inhaled pentamidine. So, it’s kind of following what we would all generally do,” Dr. Luqmani said.

Study details

To look at the characteristics of and risk factors for serious infections associated with rituximab use in AAV, Mr. Dernie and associates retrospectively examined the electronic records of patients who had been treated between August 2016 and August 2019. Follow-up was until August 2020.

Of the 50 patients identified, nearly half (48%) were men. The average age was 60 years, ranging from 25 to 90 years. Most (n = 36; 72%) patients had a diagnosis of granulomatosis with polyangiitis, while another 2 (4%) had microscopic polyangiitis, 1 (2%) had eosinophilic granulomatosis with polyangiitis, and 11 (22%) had an overlapping type of vasculitis or undefined AAV.

Of the 18 severe infection events recorded, most (56%) involved the respiratory tract. Less than one-third (28%) were sepsis or neutropenic sepsis events, and there was one case each (6%) of cellulitis, complicated urinary tract infection, and recurrent wound infection.

There were “small numbers of individual comorbidities that were not sufficient to enter into our regression analysis,” Mr. Dernie noted. “It’s likely that comorbid conditions such as COPD [chronic obstructive pulmonary disease] also contribute to an individual’s risk of developing severe infections, and thus should factor into their individualized management.”

Mr. Dernie acknowledged in discussion: “One of the limitations of the study was we just looked at patients in a time when they were receiving rituximab, so they may have historically been exposed to other treatment options.” However, he added, “they weren’t having any other major DMARDs or immunosuppressive treatments at the time.”

Dr. Luqmani observed: “If you look at Francesco’s data on the hypogammaglobulinemia at the start of rituximab, that probably gives you a good idea of just how immunosuppressed these patients were already before we got to this point.”

Dr. Luqmani added: “I suspect that’s in keeping with a lot of other centers that have started using rituximab an awful lot for patients who previously had episodes of vasculitis treated with other disease-modifying therapies, particularly cyclophosphamide.”

But for how long should co-trimoxazole be given after the last rituximab dose? asked the chair of the session, Richard Watts, DM, of Norwich (England) Medical School. These data are purely observational, so it’s not possible to say, Mr. Dernie noted: “The patients that we included as having co-trimoxazole seem to be on it more or less consistently, permanently,” he said.

What about the best dose? “It’s a tricky one,” Dr. Luqmani said, as “we not only use co-trimoxazole for prophylaxis, but we often also want to use it for treatment of the vasculitis itself.”

It’s very likely that there was a mix of patients in the analysis that had received co-trimoxazole as either a treatment or prophylaxis, which means different doses, he said.

“It might be interesting to know whether there was a difference” between doses used and the prevention of infection, added Dr. Luqmani, “but I suspect the numbers are too small to tell.”

Mr. Dernie, Dr. Luqmani, and the other coauthors had no disclosures.

The serious infection risk associated with rituximab treatment for antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is high but can be offset by co-prescribing co-trimoxazole, data from a single-center, retrospective study reaffirm.

Over the course of a 3-year study period, 14 (28%) of 50 patients with AAV treated with rituximab experienced at latest one severe infection defined as a grade 3 or higher event. The incidence of severe infections was 15.4 per 100 person-years.

However, a lower rate of infections was seen in patients who had been co-prescribed co-trimoxazole (trimethoprim and sulfamethoxazole), Francesco Dernie, a fifth-year medical student at the University of Oxford (England), reported at the British Society for Rheumatology annual conference.

“In the case of rituximab, the depletion of B cells and associated immune suppression is a double-edged sword, allowing effective disease control, but also leaving the body vulnerable to opportunistic and severe infections,” Mr. Dernie said at the meeting.

Of the patients who developed a severe infection on rituximab, just 7% had been treated with co-trimoxazole. In comparison, 44% of those who did not get a severe infection had received co-trimoxazole. Multivariate analysis confirmed that co-trimoxazole use was an influencing factor, with an odds ratio (OR) of 0.096 (95% confidence interval, 0.009–0.996; P = .05).

Another finding was that patients with low immunoglobulin G levels (less than 6 g/L) were more likely to develop a severe infection than were those with higher IgG levels. Indeed, the OR for hypogammaglobulinemia and the risk for infection was 8.782 (95% CI, 1.19–64.6; P = .033).

“Our results support the monitoring of IgG levels to identify patients who may be more susceptible to infection, as well as the prescription of prophylactic co-trimoxazole to reduce overall severe infection risk,” Mr. Dernie and associates concluded in their abstract.

It’s a “really important message around co-trimoxazole,” observed Neil Basu, MBChB, a clinical senior lecturer and honorary consultant at the Institute of Infection, Immunity & Inflammation, University of Glasgow (Scotland).

“It still frustrates me when I see that patients haven’t received that while receiving rituximab. Of course, co-trimoxazole can have its problems,” said Dr. Basu, who was not involved in the study. “It’s not uncommon for patients to develop reactions or be intolerant to the drug.”

Raashid Luqmani, DM, a senior coauthor of the work and professor of rheumatology at the Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Science, University of Oxford, said: “The tolerance of co-trimoxazole has been remarkably good in this cohort.” If there was a problem with using co-trimoxazole, then “our standard would be to go with trimethoprim alone as the next in line and follow that with inhaled pentamidine. So, it’s kind of following what we would all generally do,” Dr. Luqmani said.

Study details

To look at the characteristics of and risk factors for serious infections associated with rituximab use in AAV, Mr. Dernie and associates retrospectively examined the electronic records of patients who had been treated between August 2016 and August 2019. Follow-up was until August 2020.

Of the 50 patients identified, nearly half (48%) were men. The average age was 60 years, ranging from 25 to 90 years. Most (n = 36; 72%) patients had a diagnosis of granulomatosis with polyangiitis, while another 2 (4%) had microscopic polyangiitis, 1 (2%) had eosinophilic granulomatosis with polyangiitis, and 11 (22%) had an overlapping type of vasculitis or undefined AAV.

Of the 18 severe infection events recorded, most (56%) involved the respiratory tract. Less than one-third (28%) were sepsis or neutropenic sepsis events, and there was one case each (6%) of cellulitis, complicated urinary tract infection, and recurrent wound infection.

There were “small numbers of individual comorbidities that were not sufficient to enter into our regression analysis,” Mr. Dernie noted. “It’s likely that comorbid conditions such as COPD [chronic obstructive pulmonary disease] also contribute to an individual’s risk of developing severe infections, and thus should factor into their individualized management.”

Mr. Dernie acknowledged in discussion: “One of the limitations of the study was we just looked at patients in a time when they were receiving rituximab, so they may have historically been exposed to other treatment options.” However, he added, “they weren’t having any other major DMARDs or immunosuppressive treatments at the time.”

Dr. Luqmani observed: “If you look at Francesco’s data on the hypogammaglobulinemia at the start of rituximab, that probably gives you a good idea of just how immunosuppressed these patients were already before we got to this point.”

Dr. Luqmani added: “I suspect that’s in keeping with a lot of other centers that have started using rituximab an awful lot for patients who previously had episodes of vasculitis treated with other disease-modifying therapies, particularly cyclophosphamide.”

But for how long should co-trimoxazole be given after the last rituximab dose? asked the chair of the session, Richard Watts, DM, of Norwich (England) Medical School. These data are purely observational, so it’s not possible to say, Mr. Dernie noted: “The patients that we included as having co-trimoxazole seem to be on it more or less consistently, permanently,” he said.

What about the best dose? “It’s a tricky one,” Dr. Luqmani said, as “we not only use co-trimoxazole for prophylaxis, but we often also want to use it for treatment of the vasculitis itself.”

It’s very likely that there was a mix of patients in the analysis that had received co-trimoxazole as either a treatment or prophylaxis, which means different doses, he said.

“It might be interesting to know whether there was a difference” between doses used and the prevention of infection, added Dr. Luqmani, “but I suspect the numbers are too small to tell.”

Mr. Dernie, Dr. Luqmani, and the other coauthors had no disclosures.

The serious infection risk associated with rituximab treatment for antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is high but can be offset by co-prescribing co-trimoxazole, data from a single-center, retrospective study reaffirm.

Over the course of a 3-year study period, 14 (28%) of 50 patients with AAV treated with rituximab experienced at latest one severe infection defined as a grade 3 or higher event. The incidence of severe infections was 15.4 per 100 person-years.

However, a lower rate of infections was seen in patients who had been co-prescribed co-trimoxazole (trimethoprim and sulfamethoxazole), Francesco Dernie, a fifth-year medical student at the University of Oxford (England), reported at the British Society for Rheumatology annual conference.

“In the case of rituximab, the depletion of B cells and associated immune suppression is a double-edged sword, allowing effective disease control, but also leaving the body vulnerable to opportunistic and severe infections,” Mr. Dernie said at the meeting.

Of the patients who developed a severe infection on rituximab, just 7% had been treated with co-trimoxazole. In comparison, 44% of those who did not get a severe infection had received co-trimoxazole. Multivariate analysis confirmed that co-trimoxazole use was an influencing factor, with an odds ratio (OR) of 0.096 (95% confidence interval, 0.009–0.996; P = .05).

Another finding was that patients with low immunoglobulin G levels (less than 6 g/L) were more likely to develop a severe infection than were those with higher IgG levels. Indeed, the OR for hypogammaglobulinemia and the risk for infection was 8.782 (95% CI, 1.19–64.6; P = .033).

“Our results support the monitoring of IgG levels to identify patients who may be more susceptible to infection, as well as the prescription of prophylactic co-trimoxazole to reduce overall severe infection risk,” Mr. Dernie and associates concluded in their abstract.

It’s a “really important message around co-trimoxazole,” observed Neil Basu, MBChB, a clinical senior lecturer and honorary consultant at the Institute of Infection, Immunity & Inflammation, University of Glasgow (Scotland).

“It still frustrates me when I see that patients haven’t received that while receiving rituximab. Of course, co-trimoxazole can have its problems,” said Dr. Basu, who was not involved in the study. “It’s not uncommon for patients to develop reactions or be intolerant to the drug.”

Raashid Luqmani, DM, a senior coauthor of the work and professor of rheumatology at the Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Science, University of Oxford, said: “The tolerance of co-trimoxazole has been remarkably good in this cohort.” If there was a problem with using co-trimoxazole, then “our standard would be to go with trimethoprim alone as the next in line and follow that with inhaled pentamidine. So, it’s kind of following what we would all generally do,” Dr. Luqmani said.

Study details

To look at the characteristics of and risk factors for serious infections associated with rituximab use in AAV, Mr. Dernie and associates retrospectively examined the electronic records of patients who had been treated between August 2016 and August 2019. Follow-up was until August 2020.

Of the 50 patients identified, nearly half (48%) were men. The average age was 60 years, ranging from 25 to 90 years. Most (n = 36; 72%) patients had a diagnosis of granulomatosis with polyangiitis, while another 2 (4%) had microscopic polyangiitis, 1 (2%) had eosinophilic granulomatosis with polyangiitis, and 11 (22%) had an overlapping type of vasculitis or undefined AAV.

Of the 18 severe infection events recorded, most (56%) involved the respiratory tract. Less than one-third (28%) were sepsis or neutropenic sepsis events, and there was one case each (6%) of cellulitis, complicated urinary tract infection, and recurrent wound infection.

There were “small numbers of individual comorbidities that were not sufficient to enter into our regression analysis,” Mr. Dernie noted. “It’s likely that comorbid conditions such as COPD [chronic obstructive pulmonary disease] also contribute to an individual’s risk of developing severe infections, and thus should factor into their individualized management.”

Mr. Dernie acknowledged in discussion: “One of the limitations of the study was we just looked at patients in a time when they were receiving rituximab, so they may have historically been exposed to other treatment options.” However, he added, “they weren’t having any other major DMARDs or immunosuppressive treatments at the time.”

Dr. Luqmani observed: “If you look at Francesco’s data on the hypogammaglobulinemia at the start of rituximab, that probably gives you a good idea of just how immunosuppressed these patients were already before we got to this point.”

Dr. Luqmani added: “I suspect that’s in keeping with a lot of other centers that have started using rituximab an awful lot for patients who previously had episodes of vasculitis treated with other disease-modifying therapies, particularly cyclophosphamide.”

But for how long should co-trimoxazole be given after the last rituximab dose? asked the chair of the session, Richard Watts, DM, of Norwich (England) Medical School. These data are purely observational, so it’s not possible to say, Mr. Dernie noted: “The patients that we included as having co-trimoxazole seem to be on it more or less consistently, permanently,” he said.

What about the best dose? “It’s a tricky one,” Dr. Luqmani said, as “we not only use co-trimoxazole for prophylaxis, but we often also want to use it for treatment of the vasculitis itself.”

It’s very likely that there was a mix of patients in the analysis that had received co-trimoxazole as either a treatment or prophylaxis, which means different doses, he said.

“It might be interesting to know whether there was a difference” between doses used and the prevention of infection, added Dr. Luqmani, “but I suspect the numbers are too small to tell.”

Mr. Dernie, Dr. Luqmani, and the other coauthors had no disclosures.

Intramuscular injections of glucocorticoids have efficacy similar to that of intra-articular injections in reducing pain in knee osteoarthritis but without the concerns about joint infection and the challenges of administration, according to results from a randomized, controlled trial reported at the OARSI 2021 World Congress.

Intra-articular injections of glucocorticoids are commonly used to relieve OA pain, but some general practitioners have difficulty administering them to patients, said Qiuke Wang, a PhD candidate at Erasmus University Medical Center in Rotterdam, the Netherlands. There are also concerns about whether intra-articular injections may cause damage to knee cartilage, Mr. Wang said at the conference, which is sponsored by the Osteoarthritis Research Society International.

Mr. Wang and colleagues conducted a randomized, controlled trial in which 145 patients with symptomatic knee OA received either an intramuscular or intra-articular injection of 40 mg triamcinolone acetonide, and then followed up at regular intervals for 24 weeks.

The study showed that Knee Injury and Osteoarthritis Outcome Scores for pain improved in both the intra-articular and intramuscular groups. Improvements in pain scores peaked in the intra-articular injection group at the 4-week mark, when the difference with intramuscular injections was statistically significant. However, the two groups showed no significant differences in pain improvement at the 8-, 12-, and 24-week follow-up points.

“Intra-articular injection can act immediately on inhibiting joint inflammation after injection,” Mr. Wang said in an interview. “In contrast, for intramuscular injection, glucocorticoid needs firstly to be absorbed by muscle into blood and then travel into the knee via the circulatory system.”

The study also showed no significant differences between the two groups in the secondary outcomes of patient symptoms, stiffness, function, and sport and quality of life scores. There were more adverse events in the intra-articular injection group: 42% of patients reported an adverse event, compared to 33% in the intramuscular group, and the adverse events reported in the intramuscular group were nonserious events, such as headache and flushing.

Mr. Wang told the conference that while the intramuscular injection was inferior to intra-articular injections at 4 weeks, it was noninferior at 8 and 24 weeks and should be considered an effective way to reduce pain in patients with knee OA.

“This trial provides evidence for shared decision making because in some cases a patient may have a preference for specific injection and the GP may feel incompetent to administer the intra-articular injection,” he said.

An audience member pointed out that there was now a growing body of evidence suggesting that intra-articular injections may contribute to faster progression of knee OA because of effects on knee cartilage.

Mr. Wang acknowledged that their own research had shown these side effects of intra-articular injections, which was why the trial was intended to examine whether intramuscular injections might achieve the same pain relief.

“In the real practice, I would say that both injections are effective, but the intra-articular injection may provide a slightly [better] effect in the short term,” he said.

Commenting on the findings, Martin van der Esch, PhD, of Amsterdam University of Applied Sciences, said there were no guidelines as to whether intra-articular or intramuscular injections were the best option, so it really came down to the clinician’s decision.

“Therefore this is really an interesting study, because it gives some light – not the answer – but some light in what direction it could go for specific groups of patients,” Dr. van der Esch said in an interview.

Dr. van der Esch suggested that intramuscular injections might be more appropriate for patients with more systemic disease affecting multiple joints, but intra-articular injections might offer greater benefits in a patient with severe and long-lasting disease in a single joint.

No conflicts of interest were declared.

Intramuscular injections of glucocorticoids have efficacy similar to that of intra-articular injections in reducing pain in knee osteoarthritis but without the concerns about joint infection and the challenges of administration, according to results from a randomized, controlled trial reported at the OARSI 2021 World Congress.

Intra-articular injections of glucocorticoids are commonly used to relieve OA pain, but some general practitioners have difficulty administering them to patients, said Qiuke Wang, a PhD candidate at Erasmus University Medical Center in Rotterdam, the Netherlands. There are also concerns about whether intra-articular injections may cause damage to knee cartilage, Mr. Wang said at the conference, which is sponsored by the Osteoarthritis Research Society International.

Mr. Wang and colleagues conducted a randomized, controlled trial in which 145 patients with symptomatic knee OA received either an intramuscular or intra-articular injection of 40 mg triamcinolone acetonide, and then followed up at regular intervals for 24 weeks.

The study showed that Knee Injury and Osteoarthritis Outcome Scores for pain improved in both the intra-articular and intramuscular groups. Improvements in pain scores peaked in the intra-articular injection group at the 4-week mark, when the difference with intramuscular injections was statistically significant. However, the two groups showed no significant differences in pain improvement at the 8-, 12-, and 24-week follow-up points.

“Intra-articular injection can act immediately on inhibiting joint inflammation after injection,” Mr. Wang said in an interview. “In contrast, for intramuscular injection, glucocorticoid needs firstly to be absorbed by muscle into blood and then travel into the knee via the circulatory system.”

The study also showed no significant differences between the two groups in the secondary outcomes of patient symptoms, stiffness, function, and sport and quality of life scores. There were more adverse events in the intra-articular injection group: 42% of patients reported an adverse event, compared to 33% in the intramuscular group, and the adverse events reported in the intramuscular group were nonserious events, such as headache and flushing.

Mr. Wang told the conference that while the intramuscular injection was inferior to intra-articular injections at 4 weeks, it was noninferior at 8 and 24 weeks and should be considered an effective way to reduce pain in patients with knee OA.

“This trial provides evidence for shared decision making because in some cases a patient may have a preference for specific injection and the GP may feel incompetent to administer the intra-articular injection,” he said.

An audience member pointed out that there was now a growing body of evidence suggesting that intra-articular injections may contribute to faster progression of knee OA because of effects on knee cartilage.

Mr. Wang acknowledged that their own research had shown these side effects of intra-articular injections, which was why the trial was intended to examine whether intramuscular injections might achieve the same pain relief.

“In the real practice, I would say that both injections are effective, but the intra-articular injection may provide a slightly [better] effect in the short term,” he said.

Commenting on the findings, Martin van der Esch, PhD, of Amsterdam University of Applied Sciences, said there were no guidelines as to whether intra-articular or intramuscular injections were the best option, so it really came down to the clinician’s decision.

“Therefore this is really an interesting study, because it gives some light – not the answer – but some light in what direction it could go for specific groups of patients,” Dr. van der Esch said in an interview.

Dr. van der Esch suggested that intramuscular injections might be more appropriate for patients with more systemic disease affecting multiple joints, but intra-articular injections might offer greater benefits in a patient with severe and long-lasting disease in a single joint.

No conflicts of interest were declared.

Intramuscular injections of glucocorticoids have efficacy similar to that of intra-articular injections in reducing pain in knee osteoarthritis but without the concerns about joint infection and the challenges of administration, according to results from a randomized, controlled trial reported at the OARSI 2021 World Congress.

Intra-articular injections of glucocorticoids are commonly used to relieve OA pain, but some general practitioners have difficulty administering them to patients, said Qiuke Wang, a PhD candidate at Erasmus University Medical Center in Rotterdam, the Netherlands. There are also concerns about whether intra-articular injections may cause damage to knee cartilage, Mr. Wang said at the conference, which is sponsored by the Osteoarthritis Research Society International.

Mr. Wang and colleagues conducted a randomized, controlled trial in which 145 patients with symptomatic knee OA received either an intramuscular or intra-articular injection of 40 mg triamcinolone acetonide, and then followed up at regular intervals for 24 weeks.

The study showed that Knee Injury and Osteoarthritis Outcome Scores for pain improved in both the intra-articular and intramuscular groups. Improvements in pain scores peaked in the intra-articular injection group at the 4-week mark, when the difference with intramuscular injections was statistically significant. However, the two groups showed no significant differences in pain improvement at the 8-, 12-, and 24-week follow-up points.

“Intra-articular injection can act immediately on inhibiting joint inflammation after injection,” Mr. Wang said in an interview. “In contrast, for intramuscular injection, glucocorticoid needs firstly to be absorbed by muscle into blood and then travel into the knee via the circulatory system.”

The study also showed no significant differences between the two groups in the secondary outcomes of patient symptoms, stiffness, function, and sport and quality of life scores. There were more adverse events in the intra-articular injection group: 42% of patients reported an adverse event, compared to 33% in the intramuscular group, and the adverse events reported in the intramuscular group were nonserious events, such as headache and flushing.

Mr. Wang told the conference that while the intramuscular injection was inferior to intra-articular injections at 4 weeks, it was noninferior at 8 and 24 weeks and should be considered an effective way to reduce pain in patients with knee OA.

“This trial provides evidence for shared decision making because in some cases a patient may have a preference for specific injection and the GP may feel incompetent to administer the intra-articular injection,” he said.

An audience member pointed out that there was now a growing body of evidence suggesting that intra-articular injections may contribute to faster progression of knee OA because of effects on knee cartilage.

Mr. Wang acknowledged that their own research had shown these side effects of intra-articular injections, which was why the trial was intended to examine whether intramuscular injections might achieve the same pain relief.

“In the real practice, I would say that both injections are effective, but the intra-articular injection may provide a slightly [better] effect in the short term,” he said.

Commenting on the findings, Martin van der Esch, PhD, of Amsterdam University of Applied Sciences, said there were no guidelines as to whether intra-articular or intramuscular injections were the best option, so it really came down to the clinician’s decision.

“Therefore this is really an interesting study, because it gives some light – not the answer – but some light in what direction it could go for specific groups of patients,” Dr. van der Esch said in an interview.

Dr. van der Esch suggested that intramuscular injections might be more appropriate for patients with more systemic disease affecting multiple joints, but intra-articular injections might offer greater benefits in a patient with severe and long-lasting disease in a single joint.

No conflicts of interest were declared.

A panel of federal advisers on May 6 lent support to the ChemoCentryx bid for approval of avacopan for a rare and serious autoimmune condition. But they also flagged concerns about both the evidence supporting claims of a benefit for this experimental drug and its safety.

At a meeting of the Food and Drug Administration’s Arthritis Advisory Committee, panelists voted 10-8 on a question of whether the risk-benefit profile of avacopan is adequate to support approval.

ChemoCentryx is seeking approval of avacopan for antineutrophil cytoplasmic autoantibody (ANCA)–associated vasculitis in the subtypes of granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA).

Regardless of their vote on this approval question, the panelists shared an interest in avacopan’s potential to reduce glucocorticoid use among some patients with ANCA-associated vasculitis, also called AAV. Mara L. Becker, MD, MSCE, the chair of the FDA’s panel, was among the panelists who said they reluctantly voted no.

“It pains me because I really want more steroid-sparing” medicines, said Dr. Becker of Duke University, Durham, N.C., who cited a need to gather more data on avacopan.

Margrit Wiesendanger, MD, PhD, of the Icahn School of Medicine at Mount Sinai, New York, who was among the panelists voting yes, spoke of a need for caution if the FDA approves avacopan.

“Judicious use of this new medication will be warranted and perhaps additional guidance could be given to rheumatologists to help them decide for whom this medication is best,” she said.

Panelists had spoken earlier of avacopan as a possible alternative medicine for people with AAV who have conditions that make glucocorticoids riskier for them, such as those who have diabetes.
 

Close votes on safety profile, efficacy

The panel also voted 10-8 on a question about whether the safety profile of avacopan is adequate to support approval of avacopan for the treatment of adult patients with AAV.

In addition, the panel voted 9-9 on a question about whether efficacy data support approval of avacopan for the treatment of adult patients with AAV.

The FDA considers the recommendations of its advisory panels, but is not bound by them.

The FDA staff clearly expressed the view that ChemoCentryx fell short with the evidence presented for avacopan approval. Shares of San Carlos, Calif.–based ChemoCentryx dropped sharply from a May 3 closing price of $48.82 to a May 4 closing price of $26.63 after the FDA released the staff’s review of avacopan.

In a briefing prepared for the meeting, FDA staff detailed concerns about the evidence ChemoCentryx is using to seek approval. While acknowledging a need for new treatments for AAV as a rare condition, FDA staff honed in on what they described flaws in the testing of this experimental medicine, which is a small-molecule antagonist of the receptor of C5a, an end product of the complement cascade that acts as a potent neutrophil chemoattractant and agonist.

The FDA usually requires two phase 3 studies for approval of a new medicine but will do so with a single trial in cases of exceptional need, the agency staff said. But in these cases, the bar rises for the evidence provided from that single trial.
 

Difficulties in interpretation of complex study design

In the case of avacopan, though, the data from the key avacopan trial, Study CL010_168, known as ADVOCATE, there were substantial uncertainties around the phase 3 study design and results, raising questions about the adequacy of this single trial to inform the benefit-risk assessment.

In the briefing document, the FDA staff noted that it had “communicated many of the concerns” about ChemoCentryx’s research earlier to the company.

“Complexities of the study design, as detailed in the briefing document, raise questions about the interpretability of the data to define a clinically meaningful benefit of avacopan and its role in the management of AAV,” the FDA staff wrote.

“We acknowledge that AAV is a rare and serious disease associated with high morbidity and increased mortality. It is also a disease with high unmet need for new therapies. However, FDA wants to ensure that new products have a defined context of use, i.e., how a product would be used, and a favorable benefit-risk assessment for patients,” the staff added.

In addition, there were differences in the assessments performed by investigators and the adjudication committee, most frequently related to the attribution of persistent vasculitis, the FDA staff noted.

Statistical analyses of the primary endpoint using investigators’ estimates “resulted in more conservative estimates of treatment effect, e.g., statistical significance for superiority would no longer be demonstrated,” the FDA staff noted. “While the prespecified analysis used the Adjudicator assessments, the assessment based on the Investigators, experienced in management of vasculitis, may better reflect real-world use.”
 

Imbalances in use of glucocorticoids and maintenance therapy

Also among the complications in assessing the ADVOCATE trial data were the glucocorticoids taken by patients in the study, the FDA staff said.

In the avacopan arm of the trial, 86% of patients received non–study-supplied glucocorticoids. In addition, more avacopan‐treated patients experienced adverse events and serious adverse events within the hepatobiliary system leading to discontinuation.

Subgroups given different treatments represented another challenge in interpreting ADVOCATE results for the FDA staff.

At week 26, the proportion of patients in disease remission in the avacopan group (72.3%) was noninferior to the prednisone group (70.1%), the FDA staff said in the briefing document.

But at week 52, a disparity was observed between subgroups that had received rituximab and cyclophosphamide (intravenous and oral) induction treatment. The estimated risk difference for disease remission at week 52 was 15.0% (95% CI, 2.2%-27.7%) in the subgroup receiving induction with rituximab and 3.3% (95% CI, –14.8% to 21.4%) in the cyclophosphamide plus maintenance azathioprine subgroup, the agency’s staff said.

“Based on the data, there is no evidence of clinically meaningful treatment effect in the cyclophosphamide induction subgroup,” the FDA staff wrote. “Further, the treatment comparison in the complementary rituximab induction subgroup may not be considered meaningful because these patients did not receive maintenance therapy, i.e., due to undertreating of patients, the effect observed in the rituximab subgroup may not represent a clinically meaningful treatment effect, compared to standard of care.”

Bruce Jancin/MDedge News

Rachel L. Glaser, MD, clinical team leader in FDA’s division of rheumatology and transplant medicine, reiterated these concerns to the advisory committee at the May 6 meeting.

“Throughout the development program, FDA advised the applicant that a noninferiority comparison would not be sufficient to show that avacopan can replaced glucocorticoids as it would be difficult to establish whether avacopan is effective or whether an effect was due to the rituximab or cyclophosphamide administered to both treatment arms,” she said.

In its briefing for the meeting, ChemoCentryx noted the limits of treatments now available for AAV. It also emphasized the toll of the condition, ranging from skin manifestations to glomerulonephritis to life-threatening pulmonary hemorrhage. If untreated, 80% of patients with GPA or MPA die within 2 years of disease onset, ChemoCentryx said in its briefing materials for the meeting.

The side effects of glucocorticoids were well known to the FDA panelists and the ChemoCentryx presenters. Witnesses at an open public hearing told their own stories of depression, anxiety, and irritability caused by these medicines.

Bruce Jancin/MDedge News

During the ChemoCentryx presentation, a presenter for the company, Peter Merkel, MD, MPH, of the University of Pennsylvania, Philadelphia, said avacopan would provide patients with AAV with an alternative allowing them “to go on a much lower glucocorticoids regimen.”

A similar view was presented in a February 2021 editorial in the New England Journal of Medicine, titled “Avacopan – Time to Replace Glucocorticoids?” Written by Kenneth J. Warrington, MD, of the Mayo Clinic, Rochester, Minn., the opinion article called the ADVOCATE trial “a milestone in the treatment of ANCA-associated vasculitis; complement inhibition with avacopan has glucocorticoid-sparing effects and results in superior disease control.”

Dr. Warrington reported no conflicts in connection with his editorial nor payments from ChemoCentryx. He did report grants from other firms such as Eli Lilly.

Julia Lewis, MD, of Vanderbilt University, Nashville, Tenn., was among the more skeptical members of the FDA panel. She was among the “nays” in all three voting questions put to the panel. Still, she said there were signs of “clinically meaningful benefit” in the data presented, but noted that the nonstudy use of glucocorticoids made it difficult to interpret the ADVOCATE results.

Dr. Lewis noted that the FDA usually requires two studies for a drug approval, particularly with a compound not yet cleared for any use. While ANCA-associated vasculitis is rare, it would be possible to recruit patients for another trial of avacopan, adding to the results reported already for avacopan from ADVOCATE, she said.

“Were there to be another study, this would certainly be a supportive study and maybe qualify as two studies,” she said.

A panel of federal advisers on May 6 lent support to the ChemoCentryx bid for approval of avacopan for a rare and serious autoimmune condition. But they also flagged concerns about both the evidence supporting claims of a benefit for this experimental drug and its safety.

At a meeting of the Food and Drug Administration’s Arthritis Advisory Committee, panelists voted 10-8 on a question of whether the risk-benefit profile of avacopan is adequate to support approval.

ChemoCentryx is seeking approval of avacopan for antineutrophil cytoplasmic autoantibody (ANCA)–associated vasculitis in the subtypes of granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA).

Regardless of their vote on this approval question, the panelists shared an interest in avacopan’s potential to reduce glucocorticoid use among some patients with ANCA-associated vasculitis, also called AAV. Mara L. Becker, MD, MSCE, the chair of the FDA’s panel, was among the panelists who said they reluctantly voted no.

“It pains me because I really want more steroid-sparing” medicines, said Dr. Becker of Duke University, Durham, N.C., who cited a need to gather more data on avacopan.

Margrit Wiesendanger, MD, PhD, of the Icahn School of Medicine at Mount Sinai, New York, who was among the panelists voting yes, spoke of a need for caution if the FDA approves avacopan.

“Judicious use of this new medication will be warranted and perhaps additional guidance could be given to rheumatologists to help them decide for whom this medication is best,” she said.

Panelists had spoken earlier of avacopan as a possible alternative medicine for people with AAV who have conditions that make glucocorticoids riskier for them, such as those who have diabetes.
 

Close votes on safety profile, efficacy

The panel also voted 10-8 on a question about whether the safety profile of avacopan is adequate to support approval of avacopan for the treatment of adult patients with AAV.

In addition, the panel voted 9-9 on a question about whether efficacy data support approval of avacopan for the treatment of adult patients with AAV.

The FDA considers the recommendations of its advisory panels, but is not bound by them.

The FDA staff clearly expressed the view that ChemoCentryx fell short with the evidence presented for avacopan approval. Shares of San Carlos, Calif.–based ChemoCentryx dropped sharply from a May 3 closing price of $48.82 to a May 4 closing price of $26.63 after the FDA released the staff’s review of avacopan.

In a briefing prepared for the meeting, FDA staff detailed concerns about the evidence ChemoCentryx is using to seek approval. While acknowledging a need for new treatments for AAV as a rare condition, FDA staff honed in on what they described flaws in the testing of this experimental medicine, which is a small-molecule antagonist of the receptor of C5a, an end product of the complement cascade that acts as a potent neutrophil chemoattractant and agonist.

The FDA usually requires two phase 3 studies for approval of a new medicine but will do so with a single trial in cases of exceptional need, the agency staff said. But in these cases, the bar rises for the evidence provided from that single trial.
 

Difficulties in interpretation of complex study design

In the case of avacopan, though, the data from the key avacopan trial, Study CL010_168, known as ADVOCATE, there were substantial uncertainties around the phase 3 study design and results, raising questions about the adequacy of this single trial to inform the benefit-risk assessment.

In the briefing document, the FDA staff noted that it had “communicated many of the concerns” about ChemoCentryx’s research earlier to the company.

“Complexities of the study design, as detailed in the briefing document, raise questions about the interpretability of the data to define a clinically meaningful benefit of avacopan and its role in the management of AAV,” the FDA staff wrote.

“We acknowledge that AAV is a rare and serious disease associated with high morbidity and increased mortality. It is also a disease with high unmet need for new therapies. However, FDA wants to ensure that new products have a defined context of use, i.e., how a product would be used, and a favorable benefit-risk assessment for patients,” the staff added.

In addition, there were differences in the assessments performed by investigators and the adjudication committee, most frequently related to the attribution of persistent vasculitis, the FDA staff noted.

Statistical analyses of the primary endpoint using investigators’ estimates “resulted in more conservative estimates of treatment effect, e.g., statistical significance for superiority would no longer be demonstrated,” the FDA staff noted. “While the prespecified analysis used the Adjudicator assessments, the assessment based on the Investigators, experienced in management of vasculitis, may better reflect real-world use.”
 

Imbalances in use of glucocorticoids and maintenance therapy

Also among the complications in assessing the ADVOCATE trial data were the glucocorticoids taken by patients in the study, the FDA staff said.

In the avacopan arm of the trial, 86% of patients received non–study-supplied glucocorticoids. In addition, more avacopan‐treated patients experienced adverse events and serious adverse events within the hepatobiliary system leading to discontinuation.

Subgroups given different treatments represented another challenge in interpreting ADVOCATE results for the FDA staff.

At week 26, the proportion of patients in disease remission in the avacopan group (72.3%) was noninferior to the prednisone group (70.1%), the FDA staff said in the briefing document.

But at week 52, a disparity was observed between subgroups that had received rituximab and cyclophosphamide (intravenous and oral) induction treatment. The estimated risk difference for disease remission at week 52 was 15.0% (95% CI, 2.2%-27.7%) in the subgroup receiving induction with rituximab and 3.3% (95% CI, –14.8% to 21.4%) in the cyclophosphamide plus maintenance azathioprine subgroup, the agency’s staff said.

“Based on the data, there is no evidence of clinically meaningful treatment effect in the cyclophosphamide induction subgroup,” the FDA staff wrote. “Further, the treatment comparison in the complementary rituximab induction subgroup may not be considered meaningful because these patients did not receive maintenance therapy, i.e., due to undertreating of patients, the effect observed in the rituximab subgroup may not represent a clinically meaningful treatment effect, compared to standard of care.”

Bruce Jancin/MDedge News

Rachel L. Glaser, MD, clinical team leader in FDA’s division of rheumatology and transplant medicine, reiterated these concerns to the advisory committee at the May 6 meeting.

“Throughout the development program, FDA advised the applicant that a noninferiority comparison would not be sufficient to show that avacopan can replaced glucocorticoids as it would be difficult to establish whether avacopan is effective or whether an effect was due to the rituximab or cyclophosphamide administered to both treatment arms,” she said.

In its briefing for the meeting, ChemoCentryx noted the limits of treatments now available for AAV. It also emphasized the toll of the condition, ranging from skin manifestations to glomerulonephritis to life-threatening pulmonary hemorrhage. If untreated, 80% of patients with GPA or MPA die within 2 years of disease onset, ChemoCentryx said in its briefing materials for the meeting.

The side effects of glucocorticoids were well known to the FDA panelists and the ChemoCentryx presenters. Witnesses at an open public hearing told their own stories of depression, anxiety, and irritability caused by these medicines.

Bruce Jancin/MDedge News

During the ChemoCentryx presentation, a presenter for the company, Peter Merkel, MD, MPH, of the University of Pennsylvania, Philadelphia, said avacopan would provide patients with AAV with an alternative allowing them “to go on a much lower glucocorticoids regimen.”

A similar view was presented in a February 2021 editorial in the New England Journal of Medicine, titled “Avacopan – Time to Replace Glucocorticoids?” Written by Kenneth J. Warrington, MD, of the Mayo Clinic, Rochester, Minn., the opinion article called the ADVOCATE trial “a milestone in the treatment of ANCA-associated vasculitis; complement inhibition with avacopan has glucocorticoid-sparing effects and results in superior disease control.”

Dr. Warrington reported no conflicts in connection with his editorial nor payments from ChemoCentryx. He did report grants from other firms such as Eli Lilly.

Julia Lewis, MD, of Vanderbilt University, Nashville, Tenn., was among the more skeptical members of the FDA panel. She was among the “nays” in all three voting questions put to the panel. Still, she said there were signs of “clinically meaningful benefit” in the data presented, but noted that the nonstudy use of glucocorticoids made it difficult to interpret the ADVOCATE results.

Dr. Lewis noted that the FDA usually requires two studies for a drug approval, particularly with a compound not yet cleared for any use. While ANCA-associated vasculitis is rare, it would be possible to recruit patients for another trial of avacopan, adding to the results reported already for avacopan from ADVOCATE, she said.

“Were there to be another study, this would certainly be a supportive study and maybe qualify as two studies,” she said.

A panel of federal advisers on May 6 lent support to the ChemoCentryx bid for approval of avacopan for a rare and serious autoimmune condition. But they also flagged concerns about both the evidence supporting claims of a benefit for this experimental drug and its safety.

At a meeting of the Food and Drug Administration’s Arthritis Advisory Committee, panelists voted 10-8 on a question of whether the risk-benefit profile of avacopan is adequate to support approval.

ChemoCentryx is seeking approval of avacopan for antineutrophil cytoplasmic autoantibody (ANCA)–associated vasculitis in the subtypes of granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA).

Regardless of their vote on this approval question, the panelists shared an interest in avacopan’s potential to reduce glucocorticoid use among some patients with ANCA-associated vasculitis, also called AAV. Mara L. Becker, MD, MSCE, the chair of the FDA’s panel, was among the panelists who said they reluctantly voted no.

“It pains me because I really want more steroid-sparing” medicines, said Dr. Becker of Duke University, Durham, N.C., who cited a need to gather more data on avacopan.

Margrit Wiesendanger, MD, PhD, of the Icahn School of Medicine at Mount Sinai, New York, who was among the panelists voting yes, spoke of a need for caution if the FDA approves avacopan.

“Judicious use of this new medication will be warranted and perhaps additional guidance could be given to rheumatologists to help them decide for whom this medication is best,” she said.

Panelists had spoken earlier of avacopan as a possible alternative medicine for people with AAV who have conditions that make glucocorticoids riskier for them, such as those who have diabetes.
 

Close votes on safety profile, efficacy

The panel also voted 10-8 on a question about whether the safety profile of avacopan is adequate to support approval of avacopan for the treatment of adult patients with AAV.

In addition, the panel voted 9-9 on a question about whether efficacy data support approval of avacopan for the treatment of adult patients with AAV.

The FDA considers the recommendations of its advisory panels, but is not bound by them.

The FDA staff clearly expressed the view that ChemoCentryx fell short with the evidence presented for avacopan approval. Shares of San Carlos, Calif.–based ChemoCentryx dropped sharply from a May 3 closing price of $48.82 to a May 4 closing price of $26.63 after the FDA released the staff’s review of avacopan.

In a briefing prepared for the meeting, FDA staff detailed concerns about the evidence ChemoCentryx is using to seek approval. While acknowledging a need for new treatments for AAV as a rare condition, FDA staff honed in on what they described flaws in the testing of this experimental medicine, which is a small-molecule antagonist of the receptor of C5a, an end product of the complement cascade that acts as a potent neutrophil chemoattractant and agonist.

The FDA usually requires two phase 3 studies for approval of a new medicine but will do so with a single trial in cases of exceptional need, the agency staff said. But in these cases, the bar rises for the evidence provided from that single trial.
 

Difficulties in interpretation of complex study design

In the case of avacopan, though, the data from the key avacopan trial, Study CL010_168, known as ADVOCATE, there were substantial uncertainties around the phase 3 study design and results, raising questions about the adequacy of this single trial to inform the benefit-risk assessment.

In the briefing document, the FDA staff noted that it had “communicated many of the concerns” about ChemoCentryx’s research earlier to the company.

“Complexities of the study design, as detailed in the briefing document, raise questions about the interpretability of the data to define a clinically meaningful benefit of avacopan and its role in the management of AAV,” the FDA staff wrote.

“We acknowledge that AAV is a rare and serious disease associated with high morbidity and increased mortality. It is also a disease with high unmet need for new therapies. However, FDA wants to ensure that new products have a defined context of use, i.e., how a product would be used, and a favorable benefit-risk assessment for patients,” the staff added.

In addition, there were differences in the assessments performed by investigators and the adjudication committee, most frequently related to the attribution of persistent vasculitis, the FDA staff noted.

Statistical analyses of the primary endpoint using investigators’ estimates “resulted in more conservative estimates of treatment effect, e.g., statistical significance for superiority would no longer be demonstrated,” the FDA staff noted. “While the prespecified analysis used the Adjudicator assessments, the assessment based on the Investigators, experienced in management of vasculitis, may better reflect real-world use.”
 

Imbalances in use of glucocorticoids and maintenance therapy

Also among the complications in assessing the ADVOCATE trial data were the glucocorticoids taken by patients in the study, the FDA staff said.

In the avacopan arm of the trial, 86% of patients received non–study-supplied glucocorticoids. In addition, more avacopan‐treated patients experienced adverse events and serious adverse events within the hepatobiliary system leading to discontinuation.

Subgroups given different treatments represented another challenge in interpreting ADVOCATE results for the FDA staff.

At week 26, the proportion of patients in disease remission in the avacopan group (72.3%) was noninferior to the prednisone group (70.1%), the FDA staff said in the briefing document.

But at week 52, a disparity was observed between subgroups that had received rituximab and cyclophosphamide (intravenous and oral) induction treatment. The estimated risk difference for disease remission at week 52 was 15.0% (95% CI, 2.2%-27.7%) in the subgroup receiving induction with rituximab and 3.3% (95% CI, –14.8% to 21.4%) in the cyclophosphamide plus maintenance azathioprine subgroup, the agency’s staff said.

“Based on the data, there is no evidence of clinically meaningful treatment effect in the cyclophosphamide induction subgroup,” the FDA staff wrote. “Further, the treatment comparison in the complementary rituximab induction subgroup may not be considered meaningful because these patients did not receive maintenance therapy, i.e., due to undertreating of patients, the effect observed in the rituximab subgroup may not represent a clinically meaningful treatment effect, compared to standard of care.”

Bruce Jancin/MDedge News

Rachel L. Glaser, MD, clinical team leader in FDA’s division of rheumatology and transplant medicine, reiterated these concerns to the advisory committee at the May 6 meeting.

“Throughout the development program, FDA advised the applicant that a noninferiority comparison would not be sufficient to show that avacopan can replaced glucocorticoids as it would be difficult to establish whether avacopan is effective or whether an effect was due to the rituximab or cyclophosphamide administered to both treatment arms,” she said.

In its briefing for the meeting, ChemoCentryx noted the limits of treatments now available for AAV. It also emphasized the toll of the condition, ranging from skin manifestations to glomerulonephritis to life-threatening pulmonary hemorrhage. If untreated, 80% of patients with GPA or MPA die within 2 years of disease onset, ChemoCentryx said in its briefing materials for the meeting.

The side effects of glucocorticoids were well known to the FDA panelists and the ChemoCentryx presenters. Witnesses at an open public hearing told their own stories of depression, anxiety, and irritability caused by these medicines.

Bruce Jancin/MDedge News

During the ChemoCentryx presentation, a presenter for the company, Peter Merkel, MD, MPH, of the University of Pennsylvania, Philadelphia, said avacopan would provide patients with AAV with an alternative allowing them “to go on a much lower glucocorticoids regimen.”

A similar view was presented in a February 2021 editorial in the New England Journal of Medicine, titled “Avacopan – Time to Replace Glucocorticoids?” Written by Kenneth J. Warrington, MD, of the Mayo Clinic, Rochester, Minn., the opinion article called the ADVOCATE trial “a milestone in the treatment of ANCA-associated vasculitis; complement inhibition with avacopan has glucocorticoid-sparing effects and results in superior disease control.”

Dr. Warrington reported no conflicts in connection with his editorial nor payments from ChemoCentryx. He did report grants from other firms such as Eli Lilly.

Julia Lewis, MD, of Vanderbilt University, Nashville, Tenn., was among the more skeptical members of the FDA panel. She was among the “nays” in all three voting questions put to the panel. Still, she said there were signs of “clinically meaningful benefit” in the data presented, but noted that the nonstudy use of glucocorticoids made it difficult to interpret the ADVOCATE results.

Dr. Lewis noted that the FDA usually requires two studies for a drug approval, particularly with a compound not yet cleared for any use. While ANCA-associated vasculitis is rare, it would be possible to recruit patients for another trial of avacopan, adding to the results reported already for avacopan from ADVOCATE, she said.

“Were there to be another study, this would certainly be a supportive study and maybe qualify as two studies,” she said.

Physicians and nonphysicians clearly differ in whether or not a PhD or EdD should be able to call themselves ‘doctor,’ a new Medscape poll Who Should Get to Be Called ‘Doctor’? shows. The topic has clearly struck a nerve, since a record number of respondents – over 12,000 – voted in the poll.

Most physicians think it’s appropriate for people with other doctorate degrees such as a PhD or EdD to call themselves ‘doctor,’ although slightly more than half said it depends on the context.

The controversy over who gets to be called a doctor was reignited when a Wall Street Journal opinion piece criticized First Lady Jill Biden, EdD, for wanting to be called “Dr Biden.” The piece also challenged the idea that having a PhD is worth the honorific of ‘doctor.’

Medical ethicist Arthur Caplan, PhD, disagreed with that viewpoint, saying the context matters. For example, he prefers to be called “professor” when he’s introduced to the public rather than “doctor” to avoid any confusion about his professional status.

More than 12,000 clinicians including physicians, medical students, nurses, pharmacists, and other health care professionals responded to the poll. The non-MD clinicians were the most likely to say it was always appropriate to be called “doctor” while physicians were the least likely.
 

Context matters

Large percentages of clinicians – 54% of doctors, 62% of medical students, and 41% of nurses – said that the context matters for being called “doctor.’’

“I earned my PhD in 1995 and my MD in 2000. I think it is contextual. In a research or University setting, “Dr.” seems appropriate for a PhD. That same person in public should probably not hold themselves out as “Dr.” So, maybe MDs and DOs can choose, while others maintain the title in their specific setting.” 

Some readers proposed that people with MDs call themselves physicians rather than doctors. Said one: “Anyone with a terminal doctorate degree has the right to use the word doctor.  As a physician when someone asks what I do, I say: ‘I am a physician.’ Problem solved. There can only be one physician but there are many types of doctors.”

Physicians and nurses differed most in their views. Just 24% of physicians said it was always appropriate for people with other doctorate degrees to call themselves doctor whereas about an equal number (22%) thought it was never appropriate.

In contrast, 43% of nurses (including advance practice nurses) said it was always appropriate for people with non-MD doctorates to be called doctor. Only 16% said it’s never appropriate. 

This difference may reflect the growing number of nurses with doctorate degrees, either a DNP or PhD, who want to be called doctor in clinical settings.

Age made a difference too. Only 16% of physicians younger than age 45 said it was always appropriate for people with non-MD doctorate degrees to be called doctor, compared with 27% of physicians aged 45 and up.

Medical students (31%) were also more likely than physicians to say it was always appropriate for non-MD doctorates to use the title “doctor” and 64% said it depends on the context. This was noteworthy because twice as many medical students as physicians (16% vs. 8%) said they work in academia, research, or military government settings.
 

Too many ‘doctors’ confuse the public

Physicians (70%) were also more likely to say it was always or often confusing for the public to hear someone without a medical degree addressed as “doctor.” Only 6% of physicians thought it was never or rarely confusing.

Nurses disagreed. Just 45% said that it was always or often confusing while 16% said it was never or rarely confusing.

Medical students were more aligned with physicians on this issue – 60% said it was always or often confusing to the public and just 10% said it was never or rarely confusing.  

One reader commented, “The problem is the confusion the ‘doctor’ title causes for patients, especially in a hospital setting. Is the ‘doctor’ a physician, a pharmacist, a psychologist, a nurse, etc., etc.? We need to think not of our own egos but if and how  the confusion about this plethora of titles may be hindering good patient care.”

These concerns are not unfounded. The American Medical Association reported in its Truth in Advertising campaign that “patients mistake physicians with nonphysician providers” based on an online survey of 802 adults in 2018. The participants thought these specialists were MDs: dentists (61%), podiatrists (67%), optometrists (47%), psychologists (43%), doctors of nursing (39%), and chiropractors (27%).

The AMA has advocated that states pass the “Health Care Professional Transparency Act,” which New Jersey has enacted. The law requires all health care professionals dealing with patients to wear a name tag that clearly identifies their licensure. Health care professionals must also display their education, training, and licensure in their office.

A version of this article first appeared on Medscape.com.

Physicians and nonphysicians clearly differ in whether or not a PhD or EdD should be able to call themselves ‘doctor,’ a new Medscape poll Who Should Get to Be Called ‘Doctor’? shows. The topic has clearly struck a nerve, since a record number of respondents – over 12,000 – voted in the poll.

Most physicians think it’s appropriate for people with other doctorate degrees such as a PhD or EdD to call themselves ‘doctor,’ although slightly more than half said it depends on the context.

The controversy over who gets to be called a doctor was reignited when a Wall Street Journal opinion piece criticized First Lady Jill Biden, EdD, for wanting to be called “Dr Biden.” The piece also challenged the idea that having a PhD is worth the honorific of ‘doctor.’

Medical ethicist Arthur Caplan, PhD, disagreed with that viewpoint, saying the context matters. For example, he prefers to be called “professor” when he’s introduced to the public rather than “doctor” to avoid any confusion about his professional status.

More than 12,000 clinicians including physicians, medical students, nurses, pharmacists, and other health care professionals responded to the poll. The non-MD clinicians were the most likely to say it was always appropriate to be called “doctor” while physicians were the least likely.
 

Context matters

Large percentages of clinicians – 54% of doctors, 62% of medical students, and 41% of nurses – said that the context matters for being called “doctor.’’

“I earned my PhD in 1995 and my MD in 2000. I think it is contextual. In a research or University setting, “Dr.” seems appropriate for a PhD. That same person in public should probably not hold themselves out as “Dr.” So, maybe MDs and DOs can choose, while others maintain the title in their specific setting.” 

Some readers proposed that people with MDs call themselves physicians rather than doctors. Said one: “Anyone with a terminal doctorate degree has the right to use the word doctor.  As a physician when someone asks what I do, I say: ‘I am a physician.’ Problem solved. There can only be one physician but there are many types of doctors.”

Physicians and nurses differed most in their views. Just 24% of physicians said it was always appropriate for people with other doctorate degrees to call themselves doctor whereas about an equal number (22%) thought it was never appropriate.

In contrast, 43% of nurses (including advance practice nurses) said it was always appropriate for people with non-MD doctorates to be called doctor. Only 16% said it’s never appropriate. 

This difference may reflect the growing number of nurses with doctorate degrees, either a DNP or PhD, who want to be called doctor in clinical settings.

Age made a difference too. Only 16% of physicians younger than age 45 said it was always appropriate for people with non-MD doctorate degrees to be called doctor, compared with 27% of physicians aged 45 and up.

Medical students (31%) were also more likely than physicians to say it was always appropriate for non-MD doctorates to use the title “doctor” and 64% said it depends on the context. This was noteworthy because twice as many medical students as physicians (16% vs. 8%) said they work in academia, research, or military government settings.
 

Too many ‘doctors’ confuse the public

Physicians (70%) were also more likely to say it was always or often confusing for the public to hear someone without a medical degree addressed as “doctor.” Only 6% of physicians thought it was never or rarely confusing.

Nurses disagreed. Just 45% said that it was always or often confusing while 16% said it was never or rarely confusing.

Medical students were more aligned with physicians on this issue – 60% said it was always or often confusing to the public and just 10% said it was never or rarely confusing.  

One reader commented, “The problem is the confusion the ‘doctor’ title causes for patients, especially in a hospital setting. Is the ‘doctor’ a physician, a pharmacist, a psychologist, a nurse, etc., etc.? We need to think not of our own egos but if and how  the confusion about this plethora of titles may be hindering good patient care.”

These concerns are not unfounded. The American Medical Association reported in its Truth in Advertising campaign that “patients mistake physicians with nonphysician providers” based on an online survey of 802 adults in 2018. The participants thought these specialists were MDs: dentists (61%), podiatrists (67%), optometrists (47%), psychologists (43%), doctors of nursing (39%), and chiropractors (27%).

The AMA has advocated that states pass the “Health Care Professional Transparency Act,” which New Jersey has enacted. The law requires all health care professionals dealing with patients to wear a name tag that clearly identifies their licensure. Health care professionals must also display their education, training, and licensure in their office.

A version of this article first appeared on Medscape.com.

Physicians and nonphysicians clearly differ in whether or not a PhD or EdD should be able to call themselves ‘doctor,’ a new Medscape poll Who Should Get to Be Called ‘Doctor’? shows. The topic has clearly struck a nerve, since a record number of respondents – over 12,000 – voted in the poll.

Most physicians think it’s appropriate for people with other doctorate degrees such as a PhD or EdD to call themselves ‘doctor,’ although slightly more than half said it depends on the context.

The controversy over who gets to be called a doctor was reignited when a Wall Street Journal opinion piece criticized First Lady Jill Biden, EdD, for wanting to be called “Dr Biden.” The piece also challenged the idea that having a PhD is worth the honorific of ‘doctor.’

Medical ethicist Arthur Caplan, PhD, disagreed with that viewpoint, saying the context matters. For example, he prefers to be called “professor” when he’s introduced to the public rather than “doctor” to avoid any confusion about his professional status.

More than 12,000 clinicians including physicians, medical students, nurses, pharmacists, and other health care professionals responded to the poll. The non-MD clinicians were the most likely to say it was always appropriate to be called “doctor” while physicians were the least likely.
 

Context matters

Large percentages of clinicians – 54% of doctors, 62% of medical students, and 41% of nurses – said that the context matters for being called “doctor.’’

“I earned my PhD in 1995 and my MD in 2000. I think it is contextual. In a research or University setting, “Dr.” seems appropriate for a PhD. That same person in public should probably not hold themselves out as “Dr.” So, maybe MDs and DOs can choose, while others maintain the title in their specific setting.” 

Some readers proposed that people with MDs call themselves physicians rather than doctors. Said one: “Anyone with a terminal doctorate degree has the right to use the word doctor.  As a physician when someone asks what I do, I say: ‘I am a physician.’ Problem solved. There can only be one physician but there are many types of doctors.”

Physicians and nurses differed most in their views. Just 24% of physicians said it was always appropriate for people with other doctorate degrees to call themselves doctor whereas about an equal number (22%) thought it was never appropriate.

In contrast, 43% of nurses (including advance practice nurses) said it was always appropriate for people with non-MD doctorates to be called doctor. Only 16% said it’s never appropriate. 

This difference may reflect the growing number of nurses with doctorate degrees, either a DNP or PhD, who want to be called doctor in clinical settings.

Age made a difference too. Only 16% of physicians younger than age 45 said it was always appropriate for people with non-MD doctorate degrees to be called doctor, compared with 27% of physicians aged 45 and up.

Medical students (31%) were also more likely than physicians to say it was always appropriate for non-MD doctorates to use the title “doctor” and 64% said it depends on the context. This was noteworthy because twice as many medical students as physicians (16% vs. 8%) said they work in academia, research, or military government settings.
 

Too many ‘doctors’ confuse the public

Physicians (70%) were also more likely to say it was always or often confusing for the public to hear someone without a medical degree addressed as “doctor.” Only 6% of physicians thought it was never or rarely confusing.

Nurses disagreed. Just 45% said that it was always or often confusing while 16% said it was never or rarely confusing.

Medical students were more aligned with physicians on this issue – 60% said it was always or often confusing to the public and just 10% said it was never or rarely confusing.  

One reader commented, “The problem is the confusion the ‘doctor’ title causes for patients, especially in a hospital setting. Is the ‘doctor’ a physician, a pharmacist, a psychologist, a nurse, etc., etc.? We need to think not of our own egos but if and how  the confusion about this plethora of titles may be hindering good patient care.”

These concerns are not unfounded. The American Medical Association reported in its Truth in Advertising campaign that “patients mistake physicians with nonphysician providers” based on an online survey of 802 adults in 2018. The participants thought these specialists were MDs: dentists (61%), podiatrists (67%), optometrists (47%), psychologists (43%), doctors of nursing (39%), and chiropractors (27%).

The AMA has advocated that states pass the “Health Care Professional Transparency Act,” which New Jersey has enacted. The law requires all health care professionals dealing with patients to wear a name tag that clearly identifies their licensure. Health care professionals must also display their education, training, and licensure in their office.

A version of this article first appeared on Medscape.com.

The Moderna SARS-CoV-2 vaccine booster developed specifically with variant B.1.351 in mind shows efficacy against that strain and the P1 variant among people already vaccinated for COVID-19, according to first results released May 5.
 

Furthermore, data from the company’s ongoing phase 2 study show the variant-specific booster, known as mRNA-1273.351, achieved higher antibody titers against the B.1.351 variant than did a booster with the original Moderna vaccine.

“We are encouraged by these new data, which reinforce our confidence that our booster strategy should be protective against these newly detected variants. The strong and rapid boost in titers to levels above primary vaccination also clearly demonstrates the ability of mRNA-1273 to induce immune memory,” Stéphane Bancel, chief executive officer of Moderna, said in a statement.

The phase 2 study researchers also are evaluating a multivariant booster that is a 50/50 mix of mRNA-1273.351 and mRNA-1273, the initial vaccine given Food and Drug Administration emergency use authorization, in a single vial.

Unlike the two-dose regimen with the original vaccine, the boosters are administered as a single dose immunization.

The trial participants received a booster 6-8 months after primary vaccination. Titers to the wild-type SARS-CoV-2 virus remained high and detectable in 37 out of 40 participants. However, prior to the booster, titers against the two variants of concern, B.1.351 and P.1, were lower, with about half of participants showing undetectable levels.

In contrast, 2 weeks after a booster with the original vaccine or the B.1.351 strain-specific product, pseudovirus neutralizing titers were boosted in all participants and all variants tested.

“Following [the] boost, geometric mean titers against the wild-type, B.1.351, and P.1 variants increased to levels similar to or higher than the previously reported peak titers against the ancestral (D614G) strain following primary vaccination,” the company stated.

Both mRNA-1273.351 and mRNA-1273 booster doses were generally well tolerated, the company reported. Safety and tolerability were generally comparable to those reported after the second dose of the original vaccine. Most adverse events were mild to moderate, with injection site pain most common in both groups. Participants also reported fatigue, headache, myalgia, and arthralgia.

The company plans to release data shortly on the booster efficacy at additional time points beyond 2 weeks for mRNA-1273.351, a lower-dose booster with mRNA-1272/351, as well as data on the multivariant mRNA vaccine booster.

In addition to the company’s phase 2 study, the National Institute of Allergy and Infectious Diseases is conducting a separate phase 1 study of mRNA-1273.351.

A version of this article first appeared on Medscape.com.

The Moderna SARS-CoV-2 vaccine booster developed specifically with variant B.1.351 in mind shows efficacy against that strain and the P1 variant among people already vaccinated for COVID-19, according to first results released May 5.
 

Furthermore, data from the company’s ongoing phase 2 study show the variant-specific booster, known as mRNA-1273.351, achieved higher antibody titers against the B.1.351 variant than did a booster with the original Moderna vaccine.

“We are encouraged by these new data, which reinforce our confidence that our booster strategy should be protective against these newly detected variants. The strong and rapid boost in titers to levels above primary vaccination also clearly demonstrates the ability of mRNA-1273 to induce immune memory,” Stéphane Bancel, chief executive officer of Moderna, said in a statement.

The phase 2 study researchers also are evaluating a multivariant booster that is a 50/50 mix of mRNA-1273.351 and mRNA-1273, the initial vaccine given Food and Drug Administration emergency use authorization, in a single vial.

Unlike the two-dose regimen with the original vaccine, the boosters are administered as a single dose immunization.

The trial participants received a booster 6-8 months after primary vaccination. Titers to the wild-type SARS-CoV-2 virus remained high and detectable in 37 out of 40 participants. However, prior to the booster, titers against the two variants of concern, B.1.351 and P.1, were lower, with about half of participants showing undetectable levels.

In contrast, 2 weeks after a booster with the original vaccine or the B.1.351 strain-specific product, pseudovirus neutralizing titers were boosted in all participants and all variants tested.

“Following [the] boost, geometric mean titers against the wild-type, B.1.351, and P.1 variants increased to levels similar to or higher than the previously reported peak titers against the ancestral (D614G) strain following primary vaccination,” the company stated.

Both mRNA-1273.351 and mRNA-1273 booster doses were generally well tolerated, the company reported. Safety and tolerability were generally comparable to those reported after the second dose of the original vaccine. Most adverse events were mild to moderate, with injection site pain most common in both groups. Participants also reported fatigue, headache, myalgia, and arthralgia.

The company plans to release data shortly on the booster efficacy at additional time points beyond 2 weeks for mRNA-1273.351, a lower-dose booster with mRNA-1272/351, as well as data on the multivariant mRNA vaccine booster.

In addition to the company’s phase 2 study, the National Institute of Allergy and Infectious Diseases is conducting a separate phase 1 study of mRNA-1273.351.

A version of this article first appeared on Medscape.com.

The Moderna SARS-CoV-2 vaccine booster developed specifically with variant B.1.351 in mind shows efficacy against that strain and the P1 variant among people already vaccinated for COVID-19, according to first results released May 5.
 

Furthermore, data from the company’s ongoing phase 2 study show the variant-specific booster, known as mRNA-1273.351, achieved higher antibody titers against the B.1.351 variant than did a booster with the original Moderna vaccine.

“We are encouraged by these new data, which reinforce our confidence that our booster strategy should be protective against these newly detected variants. The strong and rapid boost in titers to levels above primary vaccination also clearly demonstrates the ability of mRNA-1273 to induce immune memory,” Stéphane Bancel, chief executive officer of Moderna, said in a statement.

The phase 2 study researchers also are evaluating a multivariant booster that is a 50/50 mix of mRNA-1273.351 and mRNA-1273, the initial vaccine given Food and Drug Administration emergency use authorization, in a single vial.

Unlike the two-dose regimen with the original vaccine, the boosters are administered as a single dose immunization.

The trial participants received a booster 6-8 months after primary vaccination. Titers to the wild-type SARS-CoV-2 virus remained high and detectable in 37 out of 40 participants. However, prior to the booster, titers against the two variants of concern, B.1.351 and P.1, were lower, with about half of participants showing undetectable levels.

In contrast, 2 weeks after a booster with the original vaccine or the B.1.351 strain-specific product, pseudovirus neutralizing titers were boosted in all participants and all variants tested.

“Following [the] boost, geometric mean titers against the wild-type, B.1.351, and P.1 variants increased to levels similar to or higher than the previously reported peak titers against the ancestral (D614G) strain following primary vaccination,” the company stated.

Both mRNA-1273.351 and mRNA-1273 booster doses were generally well tolerated, the company reported. Safety and tolerability were generally comparable to those reported after the second dose of the original vaccine. Most adverse events were mild to moderate, with injection site pain most common in both groups. Participants also reported fatigue, headache, myalgia, and arthralgia.

The company plans to release data shortly on the booster efficacy at additional time points beyond 2 weeks for mRNA-1273.351, a lower-dose booster with mRNA-1272/351, as well as data on the multivariant mRNA vaccine booster.

In addition to the company’s phase 2 study, the National Institute of Allergy and Infectious Diseases is conducting a separate phase 1 study of mRNA-1273.351.

A version of this article first appeared on Medscape.com.

Nearly one out of five American adults with hypertension is on a prescription drug known to raise blood pressure, based on analysis of more than 27,000 people included in recent reports from the recurring National Health and Nutrition Examination Survey (NHANES).

Nearly half of these American adults had hypertension, and in this subgroup, 18.5% reported using a prescription drug known to increase blood pressure. The most widely used class of agents with this effect was antidepressants, used by 8.7%; followed by nonsteroidal anti-inflammatory drugs (NSAIDs), used by 6.5%; steroids, 1.9%; estrogens, 1.7%; and several other agents each used by fewer than 1% of the study cohort, John Vitarello, MD, said during a press briefing on reports from the upcoming annual scientific sessions of the American College of Cardiology.

He and his associates estimated that this use of prescription drugs known to raise blood pressure could be what stands in the way of some 560,000-2.2 million Americans from having their hypertension under control, depending on the exact blood pressure impact that various pressure-increasing drugs have and presuming that half of those on blood pressure increasing agents could stop them and switch to alternative agents, said Dr. Vitarello, a researcher at Beth Israel Deaconess Medical Center in Boston.

He also highlighted that the study assessed only prescription drugs and did not examine OTC drug use, which may be especially relevant for the many people who regularly take NSAIDs.

“Clinicians should review the prescription and OTC drug use of patients with hypertension and consider stopping drugs that increase blood pressure or switching the patient to alternatives” that are blood pressure neutral, Dr. Vitarello said during the briefing. He cautioned that maintaining hypertensive patients on agents that raise their blood pressure can result in “prescribing cascades” where taking drugs that boost blood pressure results in need for intensified antihypertensive treatment.
 

An opportunity for NSAID alternatives

“This study hopefully raises awareness that there is a very high use of medications that increase blood pressure, and use of OTC agents could increase the rate even higher” said Eugene Yang, MD, a cardiologist and codirector of the Cardiovascular Wellness and Prevention Program of the University of Washington, Seattle. Substituting for certain antidepressant agents may often not be realistic, but an opportunity exists for reducing NSAID use, a class also linked with an increased risk for bleeding and other adverse effects, Dr. Yang said during the briefing. Minimizing use of NSAIDs including ibuprofen and naproxen use “is something to think about,” he suggested.

“The effect of NSAIDs on blood pressure is not well studied and can vary from person to person” noted Dr. Vitarello, who added that higher NSAID dosages and more prolonged use likely increase the risk for an adverse effect on blood pressure. One reasonable option is to encourage patients to use an alternative class of pain reliever such as acetaminophen.

It remains “a challenge” to discern differences in adverse blood pressure effects, and in all adverse cardiovascular effects among different NSAIDs, said Dr. Yang. Results from “some studies show that certain NSAIDs may be safer, but other studies did not. We need to be very careful using NSAIDs because, on average, they increase blood pressure by about 3 mm Hg. We need to be mindful to try to prescribe alternative agents, like acetaminophen.”
 

A decade of data from NHANES

The analysis run by Dr. Vitarello and associates used data from 27,599 American adults included in the NHANES during 2009-2018, and focused on the 44% who either had an average blood pressure measurement of at least 130/80 mm Hg or reported having ever been told by a clinician that they had hypertension. The NHANES assessments included the prescription medications taken by each participant. The prevalence of using at least one prescription drug known to raise blood pressure was 24% among women and 14% among men, and 4% of those with hypertension were on two or more pressure-increasing agents.

The researchers based their identification of pressure-increasing prescription drugs on the list included in the 2017 guideline for managing high blood pressure from the American College of Cardiology and American Heart Association. This list specifies that the antidepressants that raise blood pressure are the monoamine oxidase inhibitors, serotonin norepinephrine reuptake inhibitors, and tricyclic antidepressants.

Dr. Vitarello and Dr. Yang had no disclosures.

[email protected]

Nearly one out of five American adults with hypertension is on a prescription drug known to raise blood pressure, based on analysis of more than 27,000 people included in recent reports from the recurring National Health and Nutrition Examination Survey (NHANES).

Nearly half of these American adults had hypertension, and in this subgroup, 18.5% reported using a prescription drug known to increase blood pressure. The most widely used class of agents with this effect was antidepressants, used by 8.7%; followed by nonsteroidal anti-inflammatory drugs (NSAIDs), used by 6.5%; steroids, 1.9%; estrogens, 1.7%; and several other agents each used by fewer than 1% of the study cohort, John Vitarello, MD, said during a press briefing on reports from the upcoming annual scientific sessions of the American College of Cardiology.

He and his associates estimated that this use of prescription drugs known to raise blood pressure could be what stands in the way of some 560,000-2.2 million Americans from having their hypertension under control, depending on the exact blood pressure impact that various pressure-increasing drugs have and presuming that half of those on blood pressure increasing agents could stop them and switch to alternative agents, said Dr. Vitarello, a researcher at Beth Israel Deaconess Medical Center in Boston.

He also highlighted that the study assessed only prescription drugs and did not examine OTC drug use, which may be especially relevant for the many people who regularly take NSAIDs.

“Clinicians should review the prescription and OTC drug use of patients with hypertension and consider stopping drugs that increase blood pressure or switching the patient to alternatives” that are blood pressure neutral, Dr. Vitarello said during the briefing. He cautioned that maintaining hypertensive patients on agents that raise their blood pressure can result in “prescribing cascades” where taking drugs that boost blood pressure results in need for intensified antihypertensive treatment.
 

An opportunity for NSAID alternatives

“This study hopefully raises awareness that there is a very high use of medications that increase blood pressure, and use of OTC agents could increase the rate even higher” said Eugene Yang, MD, a cardiologist and codirector of the Cardiovascular Wellness and Prevention Program of the University of Washington, Seattle. Substituting for certain antidepressant agents may often not be realistic, but an opportunity exists for reducing NSAID use, a class also linked with an increased risk for bleeding and other adverse effects, Dr. Yang said during the briefing. Minimizing use of NSAIDs including ibuprofen and naproxen use “is something to think about,” he suggested.

“The effect of NSAIDs on blood pressure is not well studied and can vary from person to person” noted Dr. Vitarello, who added that higher NSAID dosages and more prolonged use likely increase the risk for an adverse effect on blood pressure. One reasonable option is to encourage patients to use an alternative class of pain reliever such as acetaminophen.

It remains “a challenge” to discern differences in adverse blood pressure effects, and in all adverse cardiovascular effects among different NSAIDs, said Dr. Yang. Results from “some studies show that certain NSAIDs may be safer, but other studies did not. We need to be very careful using NSAIDs because, on average, they increase blood pressure by about 3 mm Hg. We need to be mindful to try to prescribe alternative agents, like acetaminophen.”
 

A decade of data from NHANES

The analysis run by Dr. Vitarello and associates used data from 27,599 American adults included in the NHANES during 2009-2018, and focused on the 44% who either had an average blood pressure measurement of at least 130/80 mm Hg or reported having ever been told by a clinician that they had hypertension. The NHANES assessments included the prescription medications taken by each participant. The prevalence of using at least one prescription drug known to raise blood pressure was 24% among women and 14% among men, and 4% of those with hypertension were on two or more pressure-increasing agents.

The researchers based their identification of pressure-increasing prescription drugs on the list included in the 2017 guideline for managing high blood pressure from the American College of Cardiology and American Heart Association. This list specifies that the antidepressants that raise blood pressure are the monoamine oxidase inhibitors, serotonin norepinephrine reuptake inhibitors, and tricyclic antidepressants.

Dr. Vitarello and Dr. Yang had no disclosures.

[email protected]

Nearly one out of five American adults with hypertension is on a prescription drug known to raise blood pressure, based on analysis of more than 27,000 people included in recent reports from the recurring National Health and Nutrition Examination Survey (NHANES).

Nearly half of these American adults had hypertension, and in this subgroup, 18.5% reported using a prescription drug known to increase blood pressure. The most widely used class of agents with this effect was antidepressants, used by 8.7%; followed by nonsteroidal anti-inflammatory drugs (NSAIDs), used by 6.5%; steroids, 1.9%; estrogens, 1.7%; and several other agents each used by fewer than 1% of the study cohort, John Vitarello, MD, said during a press briefing on reports from the upcoming annual scientific sessions of the American College of Cardiology.

He and his associates estimated that this use of prescription drugs known to raise blood pressure could be what stands in the way of some 560,000-2.2 million Americans from having their hypertension under control, depending on the exact blood pressure impact that various pressure-increasing drugs have and presuming that half of those on blood pressure increasing agents could stop them and switch to alternative agents, said Dr. Vitarello, a researcher at Beth Israel Deaconess Medical Center in Boston.

He also highlighted that the study assessed only prescription drugs and did not examine OTC drug use, which may be especially relevant for the many people who regularly take NSAIDs.

“Clinicians should review the prescription and OTC drug use of patients with hypertension and consider stopping drugs that increase blood pressure or switching the patient to alternatives” that are blood pressure neutral, Dr. Vitarello said during the briefing. He cautioned that maintaining hypertensive patients on agents that raise their blood pressure can result in “prescribing cascades” where taking drugs that boost blood pressure results in need for intensified antihypertensive treatment.
 

An opportunity for NSAID alternatives

“This study hopefully raises awareness that there is a very high use of medications that increase blood pressure, and use of OTC agents could increase the rate even higher” said Eugene Yang, MD, a cardiologist and codirector of the Cardiovascular Wellness and Prevention Program of the University of Washington, Seattle. Substituting for certain antidepressant agents may often not be realistic, but an opportunity exists for reducing NSAID use, a class also linked with an increased risk for bleeding and other adverse effects, Dr. Yang said during the briefing. Minimizing use of NSAIDs including ibuprofen and naproxen use “is something to think about,” he suggested.

“The effect of NSAIDs on blood pressure is not well studied and can vary from person to person” noted Dr. Vitarello, who added that higher NSAID dosages and more prolonged use likely increase the risk for an adverse effect on blood pressure. One reasonable option is to encourage patients to use an alternative class of pain reliever such as acetaminophen.

It remains “a challenge” to discern differences in adverse blood pressure effects, and in all adverse cardiovascular effects among different NSAIDs, said Dr. Yang. Results from “some studies show that certain NSAIDs may be safer, but other studies did not. We need to be very careful using NSAIDs because, on average, they increase blood pressure by about 3 mm Hg. We need to be mindful to try to prescribe alternative agents, like acetaminophen.”
 

A decade of data from NHANES

The analysis run by Dr. Vitarello and associates used data from 27,599 American adults included in the NHANES during 2009-2018, and focused on the 44% who either had an average blood pressure measurement of at least 130/80 mm Hg or reported having ever been told by a clinician that they had hypertension. The NHANES assessments included the prescription medications taken by each participant. The prevalence of using at least one prescription drug known to raise blood pressure was 24% among women and 14% among men, and 4% of those with hypertension were on two or more pressure-increasing agents.

The researchers based their identification of pressure-increasing prescription drugs on the list included in the 2017 guideline for managing high blood pressure from the American College of Cardiology and American Heart Association. This list specifies that the antidepressants that raise blood pressure are the monoamine oxidase inhibitors, serotonin norepinephrine reuptake inhibitors, and tricyclic antidepressants.

Dr. Vitarello and Dr. Yang had no disclosures.

[email protected]

When caring for older adults with multiple chronic conditions, prioritizing patient goals is more effective and efficient than trying to address each condition in isolation, said Mary Tinetti, MD, Gladys Phillips Crofoot Professor of Medicine and Public Health and chief of geriatrics at Yale University, New Haven, Conn.

During a virtual presentation at the American College of Physicians annual Internal Medicine meeting, the gerontologist noted that primary care providers face a number of challenges when managing elderly patients with multimorbidity. These challenges include a lack of representative data in clinical trials, conflicting guideline recommendations, patient nonadherence, and decreased benefit from therapies due to competing conditions, she said.

“Trying to follow multiple guidelines can result in unintentional harms to these people with multiple conditions,” Dr. Tinetti said. She gave examples of the wide-ranging goals patients can have.

“Some [patients] will maximize the focus on function, regardless of how long they are likely to live,” Dr. Tinetti said. “Others will say symptom burden management is most important to them. And others will say they want to live as long as possible, and survival is most important, even if that means a reduction in their function. These individuals also vary in the care they are willing and able to receive to achieve the outcomes that matter most to them.”

For these reasons, Dr. Tinetti recommended patient priorities care, which she and her colleagues have been developing and implementing over the past 5-6 years.

“If the benefits and harms of addressing each condition in isolation is of uncertain benefit and potentially burdensome to both clinician and patient, and we know that patients vary in their health priorities ... then what else would you want to focus on in your 20-minute visit ... except each patient’s priorities?” Dr. Tinetti asked. “This is one solution to the challenge.”


 

What is patient priorities care?

Patient priorities care is a multidisciplinary, cyclical approach to clinical decision-making composed of three steps, Dr. Tinetti explained. First, a clinician identifies the patient’s health priorities. Second, this information is transmitted to comanaging providers, who decide which of their respective treatments are consistent with the patient’s priorities. And third, those decisions are disseminated to everyone involved in the patient’s care, both within and outside of the health care system, allowing all care providers to align with the patient’s priorities, she noted.

“Each person does that from their own expertise,” Dr. Tinetti said. “The social worker will do something different than the cardiologist, the physical therapist, the endocrinologist – but everybody is aiming at the same outcome – the patient’s priorities.”

In 2019, Dr. Tinetti led a nonrandomized clinical trial to test the feasibility of patient priorities care. The study involved 366 older adults with multimorbidity, among whom 203 received usual care, while 163 received this type of care. Patients in the latter group were twice as likely to have medications stopped, and significantly less likely to have self-management tasks added and diagnostic tests ordered.
 

How electronic health records can help

In an interview, Dr. Tinetti suggested that comanaging physicians communicate through electronic health records (EHRs), first to ensure that all care providers understand a patient’s goals, then to determine if recommended therapies align with those goals.

“It would be a little bit of a culture change to do that,” Dr. Tinetti said, “but the technology is there and it isn’t too terribly time consuming.”

She went on to suggest that primary care providers are typically best suited to coordinate this process; however, if a patient receives the majority of their care from a particular specialist, then that clinician may be the most suitable coordinator.
 

Systemic obstacles and solutions

According to Cynthia Boyd, MD, interim director of the division of geriatric medicine and gerontology, Johns Hopkins University, Baltimore, clinicians may encounter obstacles when implementing patient priorities care.

When caring for older adults with multiple chronic conditions, prioritizing patient goals is more effective and efficient than trying to address each condition in isolation, said Mary Tinetti, MD, Gladys Phillips Crofoot Professor of Medicine and Public Health and chief of geriatrics at Yale University, New Haven, Conn.

During a virtual presentation at the American College of Physicians annual Internal Medicine meeting, the gerontologist noted that primary care providers face a number of challenges when managing elderly patients with multimorbidity. These challenges include a lack of representative data in clinical trials, conflicting guideline recommendations, patient nonadherence, and decreased benefit from therapies due to competing conditions, she said.

“Trying to follow multiple guidelines can result in unintentional harms to these people with multiple conditions,” Dr. Tinetti said. She gave examples of the wide-ranging goals patients can have.

“Some [patients] will maximize the focus on function, regardless of how long they are likely to live,” Dr. Tinetti said. “Others will say symptom burden management is most important to them. And others will say they want to live as long as possible, and survival is most important, even if that means a reduction in their function. These individuals also vary in the care they are willing and able to receive to achieve the outcomes that matter most to them.”

For these reasons, Dr. Tinetti recommended patient priorities care, which she and her colleagues have been developing and implementing over the past 5-6 years.

“If the benefits and harms of addressing each condition in isolation is of uncertain benefit and potentially burdensome to both clinician and patient, and we know that patients vary in their health priorities ... then what else would you want to focus on in your 20-minute visit ... except each patient’s priorities?” Dr. Tinetti asked. “This is one solution to the challenge.”


 

What is patient priorities care?

Patient priorities care is a multidisciplinary, cyclical approach to clinical decision-making composed of three steps, Dr. Tinetti explained. First, a clinician identifies the patient’s health priorities. Second, this information is transmitted to comanaging providers, who decide which of their respective treatments are consistent with the patient’s priorities. And third, those decisions are disseminated to everyone involved in the patient’s care, both within and outside of the health care system, allowing all care providers to align with the patient’s priorities, she noted.

“Each person does that from their own expertise,” Dr. Tinetti said. “The social worker will do something different than the cardiologist, the physical therapist, the endocrinologist – but everybody is aiming at the same outcome – the patient’s priorities.”

In 2019, Dr. Tinetti led a nonrandomized clinical trial to test the feasibility of patient priorities care. The study involved 366 older adults with multimorbidity, among whom 203 received usual care, while 163 received this type of care. Patients in the latter group were twice as likely to have medications stopped, and significantly less likely to have self-management tasks added and diagnostic tests ordered.
 

How electronic health records can help

In an interview, Dr. Tinetti suggested that comanaging physicians communicate through electronic health records (EHRs), first to ensure that all care providers understand a patient’s goals, then to determine if recommended therapies align with those goals.

“It would be a little bit of a culture change to do that,” Dr. Tinetti said, “but the technology is there and it isn’t too terribly time consuming.”

She went on to suggest that primary care providers are typically best suited to coordinate this process; however, if a patient receives the majority of their care from a particular specialist, then that clinician may be the most suitable coordinator.
 

Systemic obstacles and solutions

According to Cynthia Boyd, MD, interim director of the division of geriatric medicine and gerontology, Johns Hopkins University, Baltimore, clinicians may encounter obstacles when implementing patient priorities care.

When caring for older adults with multiple chronic conditions, prioritizing patient goals is more effective and efficient than trying to address each condition in isolation, said Mary Tinetti, MD, Gladys Phillips Crofoot Professor of Medicine and Public Health and chief of geriatrics at Yale University, New Haven, Conn.

During a virtual presentation at the American College of Physicians annual Internal Medicine meeting, the gerontologist noted that primary care providers face a number of challenges when managing elderly patients with multimorbidity. These challenges include a lack of representative data in clinical trials, conflicting guideline recommendations, patient nonadherence, and decreased benefit from therapies due to competing conditions, she said.

“Trying to follow multiple guidelines can result in unintentional harms to these people with multiple conditions,” Dr. Tinetti said. She gave examples of the wide-ranging goals patients can have.

“Some [patients] will maximize the focus on function, regardless of how long they are likely to live,” Dr. Tinetti said. “Others will say symptom burden management is most important to them. And others will say they want to live as long as possible, and survival is most important, even if that means a reduction in their function. These individuals also vary in the care they are willing and able to receive to achieve the outcomes that matter most to them.”

For these reasons, Dr. Tinetti recommended patient priorities care, which she and her colleagues have been developing and implementing over the past 5-6 years.

“If the benefits and harms of addressing each condition in isolation is of uncertain benefit and potentially burdensome to both clinician and patient, and we know that patients vary in their health priorities ... then what else would you want to focus on in your 20-minute visit ... except each patient’s priorities?” Dr. Tinetti asked. “This is one solution to the challenge.”


 

What is patient priorities care?

Patient priorities care is a multidisciplinary, cyclical approach to clinical decision-making composed of three steps, Dr. Tinetti explained. First, a clinician identifies the patient’s health priorities. Second, this information is transmitted to comanaging providers, who decide which of their respective treatments are consistent with the patient’s priorities. And third, those decisions are disseminated to everyone involved in the patient’s care, both within and outside of the health care system, allowing all care providers to align with the patient’s priorities, she noted.

“Each person does that from their own expertise,” Dr. Tinetti said. “The social worker will do something different than the cardiologist, the physical therapist, the endocrinologist – but everybody is aiming at the same outcome – the patient’s priorities.”

In 2019, Dr. Tinetti led a nonrandomized clinical trial to test the feasibility of patient priorities care. The study involved 366 older adults with multimorbidity, among whom 203 received usual care, while 163 received this type of care. Patients in the latter group were twice as likely to have medications stopped, and significantly less likely to have self-management tasks added and diagnostic tests ordered.
 

How electronic health records can help

In an interview, Dr. Tinetti suggested that comanaging physicians communicate through electronic health records (EHRs), first to ensure that all care providers understand a patient’s goals, then to determine if recommended therapies align with those goals.

“It would be a little bit of a culture change to do that,” Dr. Tinetti said, “but the technology is there and it isn’t too terribly time consuming.”

She went on to suggest that primary care providers are typically best suited to coordinate this process; however, if a patient receives the majority of their care from a particular specialist, then that clinician may be the most suitable coordinator.
 

Systemic obstacles and solutions

According to Cynthia Boyd, MD, interim director of the division of geriatric medicine and gerontology, Johns Hopkins University, Baltimore, clinicians may encounter obstacles when implementing patient priorities care.

Reduced access to medical care, increased mental health issues, poor lifestyle habits, and concern over future care are just some of the patient-reported problems associated with the early phases of the COVID-19 pandemic, according to the results of multiple studies.

Data from the Europe-based REUMAVID study, which surveyed more 1,800 patients between April and July last year, have revealed that 58% of patients with rheumatic and musculoskeletal diseases (RMDs) had their appointments with their rheumatologists canceled, 42% could not get in touch with their primary care physicians, and 52% experienced interrupted visits to mental health specialists.

Not surprisingly, this took a toll on patients’ self-perceived health, with nearly two-thirds stating that they had fair to very poor health, and 47% reporting that their health had worsened. Furthermore, 57% of respondents reported high levels of anxiety, almost 46% were at risk for depression, and 49% reported having poor well-being overall.

“The COVID-19 pandemic has had tremendous impact,” Marco Garrido-Cumbrera, PhD, of the University of Seville, Spain, said at the British Society for Rheumatology annual conference.

Dr. Garrido-Cumbrera, who is key player in the REUMAVID initiative, explained that the project was conceived to respond to concerns raised by the president of the Spanish Federation of Spondyloarthritis Associations (CEADE) about providing the right information to their members.

“First in Italy and then in Spain, it was really difficult to deal with the pandemic and there was a lot of uncertainty from a patient perspective,” Dr. Garrido-Cumbrera said.

Victoria Navarro-Compán, MD, PhD, of La Paz University Hospital, Madrid, who was not involved in the study, observed: “I think this reflects how important collaboration between patient organizations is in order to gather relevant data, and to do it in record time.”

The REUMAVID project was the result of initial collaboration between the Health and Territory Research Group at the University of Seville and CEADE but also involved patient organizations from six other European countries: the National Axial Spondyloarthritis Society, National Rheumatoid Arthritis Society, and Arthritis Action in the United Kingdom; the French Association for the Fight against Rheumatism (AFLAR; L’Association Française de Lutte Anti-Rhumatismale); the National Association of People with Rheumatological and Rare Diseases (APMARR; Associazione Nazionale Persone con Malattie Reumatologiche e Rare) in Italy; Portuguese League Against Rheumatic Diseases (LPCDR; Liga Portuguesa contra as Doenças Reumáticas) in Portugal; the Hellenic League Against Rheumatism (ELEANA) in Greece; and the Cyprus League Against Rheumatism.
 

Pandemic presented ‘perfect storm’

“We’ve never been so well-communicated as we are now,” said Helena Marzo-Ortega, MD, PhD, a consultant rheumatologist at Leeds Teaching Hospitals NHS Trust in England who participated the REUMAVID project. The beginning of the pandemic was “the perfect storm” in that everybody jumped in to try to do something. This resulted in a myriad of research publications, surveys, and attempts to try to understand and make sense of what was happening.

“Research is being conducted in a more structured manner, and it’s given us a lot of very insightful information,” Dr. Marzo-Ortega added. Obviously, patients are important stakeholders to consult when conducting research into how the pandemic has affected them, she added, as they are the ones who had their lives turned upside down.

“A pandemic knows no boundaries, has no limits, everybody can be affected equally. But patients with rheumatic conditions were at particular risk because of the treatments,” she said. “You can remember how worried we all were initially, and thinking about the potential impact of immunosuppressants and many other aspects of these conditions.”

One of the many positives to come out of the pandemic is the “possibility of doing collaborative research at a worldwide level, not just European,” Dr. Marzo-Ortega said, referring to how the EULAR COVID-19 registries are part of the COVID-19 Global Rheumatology Alliance.

Furthermore, Dr. Marzo-Ortega believes the rheumatology community is now better prepared for any upsurges in COVID-19 or any new potentially pandemic-causing viruses.

“What we know now is that we have to be alert, and we know how to respond. We also know how to communicate effectively in order to be able to improve outcomes, not only for the health of the whole population, but also to protect patients such as ours,” she said.
 

Rheumatology practice changed practically overnight

The REUMAVID study is not alone in looking at the impact that the COVID-19 pandemic has had on RMD patients’ health and well-being, particularly during periods of lockdown or where patients were advised to “shield.”

There were “near overnight changes to rheumatology practice,” said Chris Wincup, MBBS, a clinical research fellow at University College London (UCL), who presented the findings of another large-scale survey that looked at the early effects of the pandemic nationally in the United Kingdom.

“The recovery of those services has taken time and, speaking with patients, this varies between different locations,” Dr. Wincup noted. “Unfortunately, access to care does remain a major area of unmet need [and] is something that we’re going to need to think about when planning services in the future,” he added.

Between September and October last year, Dr. Wincup and fellow UCL researchers conducted an online survey among 2,054 patients attending U.K. rheumatology clinics. As in the REUMAVID study, accessing care was difficult or very difficult for a substantial proportion of patients. However, getting medication and monitoring “were generally well maintained” despite lockdown measures.

Many patients (57%) had “extremely high levels of worry about their future care being negatively impacted as a result of the pandemic,” Dr. Wincup said, with 44% saying that their current care was worse than before the pandemic and 41% being dissatisfied with the services they were able to access.

While 48% of patients welcomed a more hybrid approach to their care, 69% thought face-to-face appointments with their rheumatologists were important and 49% wanted only face-to-face appointments. “A possible more hybrid approach, compared with pure face-to-face, is going to be something that may be required,” he said.
 

Different approach taken in CONTAIN Study

A different approach to assessing the impact of the COVID pandemic was taken by researchers at the University of Aberdeen in Scotland, observed Gary Macfarlane, MBChB, PhD.

In the COVID-19 and Musculoskeletal Heath During Lockdown (CONTAIN) study, three well-defined populations of patients from existing cohort studies were looked at prospectively. This included patients with ankylosing spondylitis (AS) and psoriatic arthritis (PsA) participating in two separate British Society for Rheumatology registries, and patients at high risk for developing chronic widespread pain who had been part of the MAmMOTH (Maintaining Musculoskeletal Health) study.

“Our aim was to quantify the changes from the previous prepandemic assessment, focusing on quality of life, changes in lifestyle, and recording what has happened to their musculoskeletal health, including symptoms and disease-specific measures,” Dr. Macfarlane said.

Patients had been invited to participate in June 2020 and were reminded in October 2020 and could respond online or via a postal questionnaire. Some patients were invited to participate in in-depth interviews.

Although the participation rate was low, at 29%, this was typical of studies being conducted at this time due to “survey fatigue,” Dr. Macfarlane said. The CONTAIN study population still included a good number of patients, however, with 596 having AS, 162 PsA, and 296 at risk for chronic widespread pain.

According to Dr. Macfarlane, the CONTAIN study results were “generally reassuring.” Although there was a significant decrease in quality of life as measured by the five-level EQ-5D instrument overall, and in every subgroup population studied, “the magnitude of the decrease was small.” There was no change in disease-specific quality of life in patients with AS, for example.

Levels of pain, anxiety, or depression did increase somewhat, he reported, but the factors that influenced quality of life remained the same before and during the pandemic, such as high levels of deprivation, living in an urban location, low levels of physical activity, and sleep problems.

“Rather surprisingly, sleep problems significantly decreased overall,” Dr. Macfarlane reported. Again, it was only a small change, but “the benefit in terms of the improvement in sleep strengthened with later periods in the follow-up.”

There was also some evidence of increased low-level and high-level physical activity in patients with psoriatic arthritis.

“Mental health is a key issue not just in maintaining musculoskeletal health but also, in terms of the likelihood responding to therapy,” Dr. Macfarlane acknowledged. “Focusing on addressing anxiety is important,” he added.

“Providing enhanced support for self-management, including in relation to pain, is likely to be a priority in the absence of normal health care being available,” he suggested. Importantly, regardless of circumstances, “all patients can be affected.”

The REUMAVID study is conducted by the Health & Territory Research of the University of Seville, with the support of Novartis Pharma AG. The CONTAIN study is supported by the British Society for Rheumatology and Versus Arthritis.

No other relevant conflicts of interested were declared.
 

Reduced access to medical care, increased mental health issues, poor lifestyle habits, and concern over future care are just some of the patient-reported problems associated with the early phases of the COVID-19 pandemic, according to the results of multiple studies.

Data from the Europe-based REUMAVID study, which surveyed more 1,800 patients between April and July last year, have revealed that 58% of patients with rheumatic and musculoskeletal diseases (RMDs) had their appointments with their rheumatologists canceled, 42% could not get in touch with their primary care physicians, and 52% experienced interrupted visits to mental health specialists.

Not surprisingly, this took a toll on patients’ self-perceived health, with nearly two-thirds stating that they had fair to very poor health, and 47% reporting that their health had worsened. Furthermore, 57% of respondents reported high levels of anxiety, almost 46% were at risk for depression, and 49% reported having poor well-being overall.

“The COVID-19 pandemic has had tremendous impact,” Marco Garrido-Cumbrera, PhD, of the University of Seville, Spain, said at the British Society for Rheumatology annual conference.

Dr. Garrido-Cumbrera, who is key player in the REUMAVID initiative, explained that the project was conceived to respond to concerns raised by the president of the Spanish Federation of Spondyloarthritis Associations (CEADE) about providing the right information to their members.

“First in Italy and then in Spain, it was really difficult to deal with the pandemic and there was a lot of uncertainty from a patient perspective,” Dr. Garrido-Cumbrera said.

Victoria Navarro-Compán, MD, PhD, of La Paz University Hospital, Madrid, who was not involved in the study, observed: “I think this reflects how important collaboration between patient organizations is in order to gather relevant data, and to do it in record time.”

The REUMAVID project was the result of initial collaboration between the Health and Territory Research Group at the University of Seville and CEADE but also involved patient organizations from six other European countries: the National Axial Spondyloarthritis Society, National Rheumatoid Arthritis Society, and Arthritis Action in the United Kingdom; the French Association for the Fight against Rheumatism (AFLAR; L’Association Française de Lutte Anti-Rhumatismale); the National Association of People with Rheumatological and Rare Diseases (APMARR; Associazione Nazionale Persone con Malattie Reumatologiche e Rare) in Italy; Portuguese League Against Rheumatic Diseases (LPCDR; Liga Portuguesa contra as Doenças Reumáticas) in Portugal; the Hellenic League Against Rheumatism (ELEANA) in Greece; and the Cyprus League Against Rheumatism.
 

Pandemic presented ‘perfect storm’

“We’ve never been so well-communicated as we are now,” said Helena Marzo-Ortega, MD, PhD, a consultant rheumatologist at Leeds Teaching Hospitals NHS Trust in England who participated the REUMAVID project. The beginning of the pandemic was “the perfect storm” in that everybody jumped in to try to do something. This resulted in a myriad of research publications, surveys, and attempts to try to understand and make sense of what was happening.

“Research is being conducted in a more structured manner, and it’s given us a lot of very insightful information,” Dr. Marzo-Ortega added. Obviously, patients are important stakeholders to consult when conducting research into how the pandemic has affected them, she added, as they are the ones who had their lives turned upside down.

“A pandemic knows no boundaries, has no limits, everybody can be affected equally. But patients with rheumatic conditions were at particular risk because of the treatments,” she said. “You can remember how worried we all were initially, and thinking about the potential impact of immunosuppressants and many other aspects of these conditions.”

One of the many positives to come out of the pandemic is the “possibility of doing collaborative research at a worldwide level, not just European,” Dr. Marzo-Ortega said, referring to how the EULAR COVID-19 registries are part of the COVID-19 Global Rheumatology Alliance.

Furthermore, Dr. Marzo-Ortega believes the rheumatology community is now better prepared for any upsurges in COVID-19 or any new potentially pandemic-causing viruses.

“What we know now is that we have to be alert, and we know how to respond. We also know how to communicate effectively in order to be able to improve outcomes, not only for the health of the whole population, but also to protect patients such as ours,” she said.
 

Rheumatology practice changed practically overnight

The REUMAVID study is not alone in looking at the impact that the COVID-19 pandemic has had on RMD patients’ health and well-being, particularly during periods of lockdown or where patients were advised to “shield.”

There were “near overnight changes to rheumatology practice,” said Chris Wincup, MBBS, a clinical research fellow at University College London (UCL), who presented the findings of another large-scale survey that looked at the early effects of the pandemic nationally in the United Kingdom.

“The recovery of those services has taken time and, speaking with patients, this varies between different locations,” Dr. Wincup noted. “Unfortunately, access to care does remain a major area of unmet need [and] is something that we’re going to need to think about when planning services in the future,” he added.

Between September and October last year, Dr. Wincup and fellow UCL researchers conducted an online survey among 2,054 patients attending U.K. rheumatology clinics. As in the REUMAVID study, accessing care was difficult or very difficult for a substantial proportion of patients. However, getting medication and monitoring “were generally well maintained” despite lockdown measures.

Many patients (57%) had “extremely high levels of worry about their future care being negatively impacted as a result of the pandemic,” Dr. Wincup said, with 44% saying that their current care was worse than before the pandemic and 41% being dissatisfied with the services they were able to access.

While 48% of patients welcomed a more hybrid approach to their care, 69% thought face-to-face appointments with their rheumatologists were important and 49% wanted only face-to-face appointments. “A possible more hybrid approach, compared with pure face-to-face, is going to be something that may be required,” he said.
 

Different approach taken in CONTAIN Study

A different approach to assessing the impact of the COVID pandemic was taken by researchers at the University of Aberdeen in Scotland, observed Gary Macfarlane, MBChB, PhD.

In the COVID-19 and Musculoskeletal Heath During Lockdown (CONTAIN) study, three well-defined populations of patients from existing cohort studies were looked at prospectively. This included patients with ankylosing spondylitis (AS) and psoriatic arthritis (PsA) participating in two separate British Society for Rheumatology registries, and patients at high risk for developing chronic widespread pain who had been part of the MAmMOTH (Maintaining Musculoskeletal Health) study.

“Our aim was to quantify the changes from the previous prepandemic assessment, focusing on quality of life, changes in lifestyle, and recording what has happened to their musculoskeletal health, including symptoms and disease-specific measures,” Dr. Macfarlane said.

Patients had been invited to participate in June 2020 and were reminded in October 2020 and could respond online or via a postal questionnaire. Some patients were invited to participate in in-depth interviews.

Although the participation rate was low, at 29%, this was typical of studies being conducted at this time due to “survey fatigue,” Dr. Macfarlane said. The CONTAIN study population still included a good number of patients, however, with 596 having AS, 162 PsA, and 296 at risk for chronic widespread pain.

According to Dr. Macfarlane, the CONTAIN study results were “generally reassuring.” Although there was a significant decrease in quality of life as measured by the five-level EQ-5D instrument overall, and in every subgroup population studied, “the magnitude of the decrease was small.” There was no change in disease-specific quality of life in patients with AS, for example.

Levels of pain, anxiety, or depression did increase somewhat, he reported, but the factors that influenced quality of life remained the same before and during the pandemic, such as high levels of deprivation, living in an urban location, low levels of physical activity, and sleep problems.

“Rather surprisingly, sleep problems significantly decreased overall,” Dr. Macfarlane reported. Again, it was only a small change, but “the benefit in terms of the improvement in sleep strengthened with later periods in the follow-up.”

There was also some evidence of increased low-level and high-level physical activity in patients with psoriatic arthritis.

“Mental health is a key issue not just in maintaining musculoskeletal health but also, in terms of the likelihood responding to therapy,” Dr. Macfarlane acknowledged. “Focusing on addressing anxiety is important,” he added.

“Providing enhanced support for self-management, including in relation to pain, is likely to be a priority in the absence of normal health care being available,” he suggested. Importantly, regardless of circumstances, “all patients can be affected.”

The REUMAVID study is conducted by the Health & Territory Research of the University of Seville, with the support of Novartis Pharma AG. The CONTAIN study is supported by the British Society for Rheumatology and Versus Arthritis.

No other relevant conflicts of interested were declared.
 

Reduced access to medical care, increased mental health issues, poor lifestyle habits, and concern over future care are just some of the patient-reported problems associated with the early phases of the COVID-19 pandemic, according to the results of multiple studies.

Data from the Europe-based REUMAVID study, which surveyed more 1,800 patients between April and July last year, have revealed that 58% of patients with rheumatic and musculoskeletal diseases (RMDs) had their appointments with their rheumatologists canceled, 42% could not get in touch with their primary care physicians, and 52% experienced interrupted visits to mental health specialists.

Not surprisingly, this took a toll on patients’ self-perceived health, with nearly two-thirds stating that they had fair to very poor health, and 47% reporting that their health had worsened. Furthermore, 57% of respondents reported high levels of anxiety, almost 46% were at risk for depression, and 49% reported having poor well-being overall.

“The COVID-19 pandemic has had tremendous impact,” Marco Garrido-Cumbrera, PhD, of the University of Seville, Spain, said at the British Society for Rheumatology annual conference.

Dr. Garrido-Cumbrera, who is key player in the REUMAVID initiative, explained that the project was conceived to respond to concerns raised by the president of the Spanish Federation of Spondyloarthritis Associations (CEADE) about providing the right information to their members.

“First in Italy and then in Spain, it was really difficult to deal with the pandemic and there was a lot of uncertainty from a patient perspective,” Dr. Garrido-Cumbrera said.

Victoria Navarro-Compán, MD, PhD, of La Paz University Hospital, Madrid, who was not involved in the study, observed: “I think this reflects how important collaboration between patient organizations is in order to gather relevant data, and to do it in record time.”

The REUMAVID project was the result of initial collaboration between the Health and Territory Research Group at the University of Seville and CEADE but also involved patient organizations from six other European countries: the National Axial Spondyloarthritis Society, National Rheumatoid Arthritis Society, and Arthritis Action in the United Kingdom; the French Association for the Fight against Rheumatism (AFLAR; L’Association Française de Lutte Anti-Rhumatismale); the National Association of People with Rheumatological and Rare Diseases (APMARR; Associazione Nazionale Persone con Malattie Reumatologiche e Rare) in Italy; Portuguese League Against Rheumatic Diseases (LPCDR; Liga Portuguesa contra as Doenças Reumáticas) in Portugal; the Hellenic League Against Rheumatism (ELEANA) in Greece; and the Cyprus League Against Rheumatism.
 

Pandemic presented ‘perfect storm’

“We’ve never been so well-communicated as we are now,” said Helena Marzo-Ortega, MD, PhD, a consultant rheumatologist at Leeds Teaching Hospitals NHS Trust in England who participated the REUMAVID project. The beginning of the pandemic was “the perfect storm” in that everybody jumped in to try to do something. This resulted in a myriad of research publications, surveys, and attempts to try to understand and make sense of what was happening.

“Research is being conducted in a more structured manner, and it’s given us a lot of very insightful information,” Dr. Marzo-Ortega added. Obviously, patients are important stakeholders to consult when conducting research into how the pandemic has affected them, she added, as they are the ones who had their lives turned upside down.

“A pandemic knows no boundaries, has no limits, everybody can be affected equally. But patients with rheumatic conditions were at particular risk because of the treatments,” she said. “You can remember how worried we all were initially, and thinking about the potential impact of immunosuppressants and many other aspects of these conditions.”

One of the many positives to come out of the pandemic is the “possibility of doing collaborative research at a worldwide level, not just European,” Dr. Marzo-Ortega said, referring to how the EULAR COVID-19 registries are part of the COVID-19 Global Rheumatology Alliance.

Furthermore, Dr. Marzo-Ortega believes the rheumatology community is now better prepared for any upsurges in COVID-19 or any new potentially pandemic-causing viruses.

“What we know now is that we have to be alert, and we know how to respond. We also know how to communicate effectively in order to be able to improve outcomes, not only for the health of the whole population, but also to protect patients such as ours,” she said.
 

Rheumatology practice changed practically overnight

The REUMAVID study is not alone in looking at the impact that the COVID-19 pandemic has had on RMD patients’ health and well-being, particularly during periods of lockdown or where patients were advised to “shield.”

There were “near overnight changes to rheumatology practice,” said Chris Wincup, MBBS, a clinical research fellow at University College London (UCL), who presented the findings of another large-scale survey that looked at the early effects of the pandemic nationally in the United Kingdom.

“The recovery of those services has taken time and, speaking with patients, this varies between different locations,” Dr. Wincup noted. “Unfortunately, access to care does remain a major area of unmet need [and] is something that we’re going to need to think about when planning services in the future,” he added.

Between September and October last year, Dr. Wincup and fellow UCL researchers conducted an online survey among 2,054 patients attending U.K. rheumatology clinics. As in the REUMAVID study, accessing care was difficult or very difficult for a substantial proportion of patients. However, getting medication and monitoring “were generally well maintained” despite lockdown measures.

Many patients (57%) had “extremely high levels of worry about their future care being negatively impacted as a result of the pandemic,” Dr. Wincup said, with 44% saying that their current care was worse than before the pandemic and 41% being dissatisfied with the services they were able to access.

While 48% of patients welcomed a more hybrid approach to their care, 69% thought face-to-face appointments with their rheumatologists were important and 49% wanted only face-to-face appointments. “A possible more hybrid approach, compared with pure face-to-face, is going to be something that may be required,” he said.
 

Different approach taken in CONTAIN Study

A different approach to assessing the impact of the COVID pandemic was taken by researchers at the University of Aberdeen in Scotland, observed Gary Macfarlane, MBChB, PhD.

In the COVID-19 and Musculoskeletal Heath During Lockdown (CONTAIN) study, three well-defined populations of patients from existing cohort studies were looked at prospectively. This included patients with ankylosing spondylitis (AS) and psoriatic arthritis (PsA) participating in two separate British Society for Rheumatology registries, and patients at high risk for developing chronic widespread pain who had been part of the MAmMOTH (Maintaining Musculoskeletal Health) study.

“Our aim was to quantify the changes from the previous prepandemic assessment, focusing on quality of life, changes in lifestyle, and recording what has happened to their musculoskeletal health, including symptoms and disease-specific measures,” Dr. Macfarlane said.

Patients had been invited to participate in June 2020 and were reminded in October 2020 and could respond online or via a postal questionnaire. Some patients were invited to participate in in-depth interviews.

Although the participation rate was low, at 29%, this was typical of studies being conducted at this time due to “survey fatigue,” Dr. Macfarlane said. The CONTAIN study population still included a good number of patients, however, with 596 having AS, 162 PsA, and 296 at risk for chronic widespread pain.

According to Dr. Macfarlane, the CONTAIN study results were “generally reassuring.” Although there was a significant decrease in quality of life as measured by the five-level EQ-5D instrument overall, and in every subgroup population studied, “the magnitude of the decrease was small.” There was no change in disease-specific quality of life in patients with AS, for example.

Levels of pain, anxiety, or depression did increase somewhat, he reported, but the factors that influenced quality of life remained the same before and during the pandemic, such as high levels of deprivation, living in an urban location, low levels of physical activity, and sleep problems.

“Rather surprisingly, sleep problems significantly decreased overall,” Dr. Macfarlane reported. Again, it was only a small change, but “the benefit in terms of the improvement in sleep strengthened with later periods in the follow-up.”

There was also some evidence of increased low-level and high-level physical activity in patients with psoriatic arthritis.

“Mental health is a key issue not just in maintaining musculoskeletal health but also, in terms of the likelihood responding to therapy,” Dr. Macfarlane acknowledged. “Focusing on addressing anxiety is important,” he added.

“Providing enhanced support for self-management, including in relation to pain, is likely to be a priority in the absence of normal health care being available,” he suggested. Importantly, regardless of circumstances, “all patients can be affected.”

The REUMAVID study is conducted by the Health & Territory Research of the University of Seville, with the support of Novartis Pharma AG. The CONTAIN study is supported by the British Society for Rheumatology and Versus Arthritis.

No other relevant conflicts of interested were declared.