Dermatology News

Ideally, Americans receiving their Pfizer/BioNTech or Moderna COVID-19 vaccines will get both doses from the same manufacturer, said Gregory Poland, MD, a vaccinologist at the Mayo Clinic in Rochester, Minn.

After all, that’s how they were tested for efficacy and safety, and it was results from those studies that led to emergency use authorization (EUA) being granted by the Food and Drug Administration.

But states and countries have struggled to keep up with the demand for vaccine, and more flexible vaccination schedules could help.

So researchers are exploring whether it is safe and effective to get the first and second doses from different manufacturers. And they are even wondering whether mixing doses from different manufacturers could increase effectiveness, particularly in light of emerging variants.

It’s called the “interchangeability issue,” said Dr. Poland, who has gotten a steady stream of questions about it.

For example, a patient recently asked about options for his father, who had gotten his first dose of the AstraZeneca vaccine in Ecuador, but had since moved to the United States, where that product has not been approved for use.

Dr. Poland said in an interview that he prefaces each answer with: “I’ve got no science for what I’m about to tell you.”

In this particular case, he recommended that the man’s father talk with his doctor about his level of COVID-19 risk and consider whether he should gamble on the AstraZeneca vaccine getting approved in the United States soon, or whether he should ask for a second dose from one of the three vaccines currently approved.

On March 22, 2021, AstraZeneca released positive results from its phase 3 trial, which will likely speed its path toward use in the United States.

Although clinical trials have started to test combinations and boosters, there’s currently no definitive evidence from human trials on mixing COVID vaccines, Dr. Poland pointed out.

But a study of a mixed-vaccine regimen is currently underway in the United Kingdom.

Participants in that 13-month trial will be given the Oxford/AstraZeneca and Pfizer/BioNTech vaccines in different combinations and at different intervals. The first results from that trial are expected this summer.

And interim results from a trial combining Russia’s Sputnik V and the AstraZeneca vaccines are expected in 2 months, according to a Reuters report.
 

Mix only in ‘exceptional situations’

The Centers for Disease Control and Prevention has been hesitant to open the door to mixing Pfizer and Moderna vaccinations, noting that the two “are not interchangeable.” But CDC guidance has changed slightly. Now, instead of saying the two vaccines should not be mixed, CDC guidance says they can be mixed in “exceptional situations,” and that the second dose can be administered up to 6 weeks after the first dose.

It is reasonable to assume that mixing COVID-19 vaccines that use the same platform – such as the mRNA platform used by both the Pfizer and Moderna vaccines – will be acceptable, Dr. Poland said, although human trials have not proven that.

However, it is unclear whether vaccines that use different platforms can be mixed. Can the first dose of an mRNA vaccine be followed by an adenovirus-based vaccine, like the Johnson & Johnson product or Novavax, if that vaccine is granted an EUA?

Ross Kedl, PhD, a vaccine researcher and professor of immunology at the University of Colorado at Denver, Aurora, said matching vaccine platforms might not be the preferred vaccination strategy.

He disagreed that there’s a lack of science surrounding the issue, and said all signs point to mixing as not only a good option, but probably a better one.
 

Researcher says science backs mixing

A mix of two different vaccine platforms likely enhances immunity, Dr. Kedl said. The heterologous prime-boost strategy has been used in animal studies for decades, “and it is well known that this promotes a much better immune response than when immunizing with the same vaccine twice.

“If you think about it in a Venn diagram sort of way, it makes sense,” he said in an interview. “Each vaccine has a number of components in it that influence immunity in various ways, but between the two of them, they only have one component that is similar. In the case of the coronavirus vaccines, the one thing both have in common is the spike protein from SARS-CoV-2. In essence, this gives you two shots at generating immunity against the one thing in each vaccine you care most about, but only one shot for the other vaccine components in each platform, resulting in an amplified response against the common target.”

In fact, the heterologous prime-boost vaccination strategy has proven to be effective in humans in early studies.

For example, an Ebola regimen that consisted of an adenovirus vector, similar to the AstraZeneca COVID vaccine, and a modified vaccinia virus vector showed promise in a phase 1 study. And an HIV regimen that consisted of the combination of a DNA vaccine, similar to the Pfizer and Moderna mRNA vaccines, and another viral vector showed encouraging results in a proof-of-concept study.

In both these cases, the heterologous prime-boost strategy was far better than single-vaccine prime-boost regimens, Dr. Kedl pointed out. And neither study reported any safety issues with the combinations.

For now, it’s best to stick with the same manufacturer for both shots, as the CDC guidance suggests, he said, agreeing with Dr. Poland.

But “I would be very surprised if we didn’t move to a mixing of vaccine platforms for the population,” Dr. Kedl said.

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

Ideally, Americans receiving their Pfizer/BioNTech or Moderna COVID-19 vaccines will get both doses from the same manufacturer, said Gregory Poland, MD, a vaccinologist at the Mayo Clinic in Rochester, Minn.

After all, that’s how they were tested for efficacy and safety, and it was results from those studies that led to emergency use authorization (EUA) being granted by the Food and Drug Administration.

But states and countries have struggled to keep up with the demand for vaccine, and more flexible vaccination schedules could help.

So researchers are exploring whether it is safe and effective to get the first and second doses from different manufacturers. And they are even wondering whether mixing doses from different manufacturers could increase effectiveness, particularly in light of emerging variants.

It’s called the “interchangeability issue,” said Dr. Poland, who has gotten a steady stream of questions about it.

For example, a patient recently asked about options for his father, who had gotten his first dose of the AstraZeneca vaccine in Ecuador, but had since moved to the United States, where that product has not been approved for use.

Dr. Poland said in an interview that he prefaces each answer with: “I’ve got no science for what I’m about to tell you.”

In this particular case, he recommended that the man’s father talk with his doctor about his level of COVID-19 risk and consider whether he should gamble on the AstraZeneca vaccine getting approved in the United States soon, or whether he should ask for a second dose from one of the three vaccines currently approved.

On March 22, 2021, AstraZeneca released positive results from its phase 3 trial, which will likely speed its path toward use in the United States.

Although clinical trials have started to test combinations and boosters, there’s currently no definitive evidence from human trials on mixing COVID vaccines, Dr. Poland pointed out.

But a study of a mixed-vaccine regimen is currently underway in the United Kingdom.

Participants in that 13-month trial will be given the Oxford/AstraZeneca and Pfizer/BioNTech vaccines in different combinations and at different intervals. The first results from that trial are expected this summer.

And interim results from a trial combining Russia’s Sputnik V and the AstraZeneca vaccines are expected in 2 months, according to a Reuters report.
 

Mix only in ‘exceptional situations’

The Centers for Disease Control and Prevention has been hesitant to open the door to mixing Pfizer and Moderna vaccinations, noting that the two “are not interchangeable.” But CDC guidance has changed slightly. Now, instead of saying the two vaccines should not be mixed, CDC guidance says they can be mixed in “exceptional situations,” and that the second dose can be administered up to 6 weeks after the first dose.

It is reasonable to assume that mixing COVID-19 vaccines that use the same platform – such as the mRNA platform used by both the Pfizer and Moderna vaccines – will be acceptable, Dr. Poland said, although human trials have not proven that.

However, it is unclear whether vaccines that use different platforms can be mixed. Can the first dose of an mRNA vaccine be followed by an adenovirus-based vaccine, like the Johnson & Johnson product or Novavax, if that vaccine is granted an EUA?

Ross Kedl, PhD, a vaccine researcher and professor of immunology at the University of Colorado at Denver, Aurora, said matching vaccine platforms might not be the preferred vaccination strategy.

He disagreed that there’s a lack of science surrounding the issue, and said all signs point to mixing as not only a good option, but probably a better one.
 

Researcher says science backs mixing

A mix of two different vaccine platforms likely enhances immunity, Dr. Kedl said. The heterologous prime-boost strategy has been used in animal studies for decades, “and it is well known that this promotes a much better immune response than when immunizing with the same vaccine twice.

“If you think about it in a Venn diagram sort of way, it makes sense,” he said in an interview. “Each vaccine has a number of components in it that influence immunity in various ways, but between the two of them, they only have one component that is similar. In the case of the coronavirus vaccines, the one thing both have in common is the spike protein from SARS-CoV-2. In essence, this gives you two shots at generating immunity against the one thing in each vaccine you care most about, but only one shot for the other vaccine components in each platform, resulting in an amplified response against the common target.”

In fact, the heterologous prime-boost vaccination strategy has proven to be effective in humans in early studies.

For example, an Ebola regimen that consisted of an adenovirus vector, similar to the AstraZeneca COVID vaccine, and a modified vaccinia virus vector showed promise in a phase 1 study. And an HIV regimen that consisted of the combination of a DNA vaccine, similar to the Pfizer and Moderna mRNA vaccines, and another viral vector showed encouraging results in a proof-of-concept study.

In both these cases, the heterologous prime-boost strategy was far better than single-vaccine prime-boost regimens, Dr. Kedl pointed out. And neither study reported any safety issues with the combinations.

For now, it’s best to stick with the same manufacturer for both shots, as the CDC guidance suggests, he said, agreeing with Dr. Poland.

But “I would be very surprised if we didn’t move to a mixing of vaccine platforms for the population,” Dr. Kedl said.

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

Ideally, Americans receiving their Pfizer/BioNTech or Moderna COVID-19 vaccines will get both doses from the same manufacturer, said Gregory Poland, MD, a vaccinologist at the Mayo Clinic in Rochester, Minn.

After all, that’s how they were tested for efficacy and safety, and it was results from those studies that led to emergency use authorization (EUA) being granted by the Food and Drug Administration.

But states and countries have struggled to keep up with the demand for vaccine, and more flexible vaccination schedules could help.

So researchers are exploring whether it is safe and effective to get the first and second doses from different manufacturers. And they are even wondering whether mixing doses from different manufacturers could increase effectiveness, particularly in light of emerging variants.

It’s called the “interchangeability issue,” said Dr. Poland, who has gotten a steady stream of questions about it.

For example, a patient recently asked about options for his father, who had gotten his first dose of the AstraZeneca vaccine in Ecuador, but had since moved to the United States, where that product has not been approved for use.

Dr. Poland said in an interview that he prefaces each answer with: “I’ve got no science for what I’m about to tell you.”

In this particular case, he recommended that the man’s father talk with his doctor about his level of COVID-19 risk and consider whether he should gamble on the AstraZeneca vaccine getting approved in the United States soon, or whether he should ask for a second dose from one of the three vaccines currently approved.

On March 22, 2021, AstraZeneca released positive results from its phase 3 trial, which will likely speed its path toward use in the United States.

Although clinical trials have started to test combinations and boosters, there’s currently no definitive evidence from human trials on mixing COVID vaccines, Dr. Poland pointed out.

But a study of a mixed-vaccine regimen is currently underway in the United Kingdom.

Participants in that 13-month trial will be given the Oxford/AstraZeneca and Pfizer/BioNTech vaccines in different combinations and at different intervals. The first results from that trial are expected this summer.

And interim results from a trial combining Russia’s Sputnik V and the AstraZeneca vaccines are expected in 2 months, according to a Reuters report.
 

Mix only in ‘exceptional situations’

The Centers for Disease Control and Prevention has been hesitant to open the door to mixing Pfizer and Moderna vaccinations, noting that the two “are not interchangeable.” But CDC guidance has changed slightly. Now, instead of saying the two vaccines should not be mixed, CDC guidance says they can be mixed in “exceptional situations,” and that the second dose can be administered up to 6 weeks after the first dose.

It is reasonable to assume that mixing COVID-19 vaccines that use the same platform – such as the mRNA platform used by both the Pfizer and Moderna vaccines – will be acceptable, Dr. Poland said, although human trials have not proven that.

However, it is unclear whether vaccines that use different platforms can be mixed. Can the first dose of an mRNA vaccine be followed by an adenovirus-based vaccine, like the Johnson & Johnson product or Novavax, if that vaccine is granted an EUA?

Ross Kedl, PhD, a vaccine researcher and professor of immunology at the University of Colorado at Denver, Aurora, said matching vaccine platforms might not be the preferred vaccination strategy.

He disagreed that there’s a lack of science surrounding the issue, and said all signs point to mixing as not only a good option, but probably a better one.
 

Researcher says science backs mixing

A mix of two different vaccine platforms likely enhances immunity, Dr. Kedl said. The heterologous prime-boost strategy has been used in animal studies for decades, “and it is well known that this promotes a much better immune response than when immunizing with the same vaccine twice.

“If you think about it in a Venn diagram sort of way, it makes sense,” he said in an interview. “Each vaccine has a number of components in it that influence immunity in various ways, but between the two of them, they only have one component that is similar. In the case of the coronavirus vaccines, the one thing both have in common is the spike protein from SARS-CoV-2. In essence, this gives you two shots at generating immunity against the one thing in each vaccine you care most about, but only one shot for the other vaccine components in each platform, resulting in an amplified response against the common target.”

In fact, the heterologous prime-boost vaccination strategy has proven to be effective in humans in early studies.

For example, an Ebola regimen that consisted of an adenovirus vector, similar to the AstraZeneca COVID vaccine, and a modified vaccinia virus vector showed promise in a phase 1 study. And an HIV regimen that consisted of the combination of a DNA vaccine, similar to the Pfizer and Moderna mRNA vaccines, and another viral vector showed encouraging results in a proof-of-concept study.

In both these cases, the heterologous prime-boost strategy was far better than single-vaccine prime-boost regimens, Dr. Kedl pointed out. And neither study reported any safety issues with the combinations.

For now, it’s best to stick with the same manufacturer for both shots, as the CDC guidance suggests, he said, agreeing with Dr. Poland.

But “I would be very surprised if we didn’t move to a mixing of vaccine platforms for the population,” Dr. Kedl said.

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

Two-thirds of epidemiologists from leading academic institutions say the world will need new or modified vaccines for COVID-19 within a year, new research shows.

South_agency/Getty Images

In a survey of 77 epidemiologists from 28 countries by the People’s Vaccine Alliance, 66.2% predicted that the world has a year or less before variants make current vaccines ineffective. The People’s Vaccine Alliance is a coalition of more than 50 organizations, including the African Alliance, Oxfam, Public Citizen, and UNAIDS (the Joint United Nations Programme on HIV/AIDS).

Almost a third (32.5%) of those surveyed said ineffectiveness would happen in 9 months or less; 18.2% said 6 months or less.

Paul A. Offit, MD, director of the Vaccine Education Center at the Children’s Hospital of Philadelphia, said in an interview that, while it’s hard to say whether vaccines could become ineffective in that time frame, “It’s perfectly reasonable to think it could happen.”

The good news, said Dr. Offit, who was not involved with the survey, is that SARS-CoV-2 mutates slowly, compared with other viruses such as influenza.

“To date,” he said, “the mutations that have occurred are not far enough away from the immunity induced by your natural infection or immunization such that one isn’t protected at least against severe and critical disease.”

That’s the goal of vaccines, he noted: “to keep people from suffering mightily.”
 

A line may be crossed

“And so far that’s happening, even with the variants,” Dr. Offit said. “That line has not been crossed. But I think we should assume that it might be.”

Dr. Offit said it will be critical to monitor anyone who gets hospitalized who is known to have been infected or fully vaccinated. Then countries need to get really good at sequencing those viruses.

The great majority of those surveyed (88%) said that persistently low vaccine coverage in many countries would make it more likely that vaccine-resistant mutations will appear.

Coverage comparisons between countries are stark.
 

Many countries haven’t given a single vaccine dose

While rich countries are giving COVID-19 vaccinations at the rate of a person a second, many of the poorest countries have given hardly any vaccines, the People’s Vaccine Alliance says.

Additionally, according to researchers at the Global Health Innovation Center at Duke University, Durham, N.C., high- and upper-middle–income countries, which represent one-fifth of the world’s population, have bought about 6 billion doses. But low- and lower-middle–income countries, which make up four-fifths of the population, have bought only about 2.6 billion, an article in Nature reports.

“You’re only as strong as your weakest country,” Dr. Offit said. “If we haven’t learned that what happens in other countries can [affect the global population], we haven’t been paying attention.”

Gregg Gonsalves, PhD, associate professor of epidemiology at Yale University, New Haven, Conn., one of the academic centers surveyed, didn’t specify a timeline for when vaccines would become ineffective, but said in a press release that the urgency for widespread global vaccination is real.

“Unless we vaccinate the world,” he said, “we leave the playing field open to more and more mutations, which could churn out variants that could evade our current vaccines and require booster shots to deal with them.”
 

“Dire, but not surprising”

Panagis Galiatsatos, MD, MHS, a pulmonologist at John Hopkins University, Baltimore, whose research focuses on health care disparities, said the survey findings were “dire, but not surprising.”

Johns Hopkins was another of the centers surveyed, but Dr. Galiatsatos wasn’t personally involved with the survey.

COVID-19, Dr. Galiatsatos pointed out, has laid bare disparities, both in who gets the vaccine and who’s involved in trials to develop the vaccines.

“It’s morally concerning and an ethical reckoning,” he said in an interview.

Recognition of the borderless swath of destruction the virus is exacting is critical, he said.

The United States “has to realize this can’t be a U.S.-centric issue,” he said. “We’re going to be back to the beginning if we don’t make sure that every country is doing well. We haven’t seen that level of uniform approach.”

He noted that scientists have always known that viruses mutate, but now the race is on to find the parts of SARS-CoV-2 that don’t mutate as much.

“My suspicion is we’ll probably need boosters instead of a whole different vaccine,” Dr. Galiatsatos said.

Among the strategies sought by the People’s Vaccine Alliance is for all pharmaceutical companies working on COVID-19 vaccines to openly share technology and intellectual property through the World Health Organization COVID-19 Technology Access Pool, to speed production and rollout of vaccines to all countries.

In the survey, 74% said that open sharing of technology and intellectual property could boost global vaccine coverage; 23% said maybe and 3% said it wouldn’t help.

The survey was carried out between Feb. 17 and March 25, 2021. Respondents included epidemiologists, virologists, and infection disease specialists from the following countries: Algeria, Argentina, Australia, Belgium, Bolivia, Canada, Denmark, Ethiopia, France, Guatemala, India, Italy, Kenya, Lebanon, Norway, Philippines, Senegal, Somalia, South Africa, South Sudan, Spain, United Arab Emirates, Uganda, United Kingdom, United States, Vietnam, Zambia, and Zimbabwe.

Dr. Offit and Dr. Galiatsatos reported no relevant financial relationships.

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

Two-thirds of epidemiologists from leading academic institutions say the world will need new or modified vaccines for COVID-19 within a year, new research shows.

South_agency/Getty Images

In a survey of 77 epidemiologists from 28 countries by the People’s Vaccine Alliance, 66.2% predicted that the world has a year or less before variants make current vaccines ineffective. The People’s Vaccine Alliance is a coalition of more than 50 organizations, including the African Alliance, Oxfam, Public Citizen, and UNAIDS (the Joint United Nations Programme on HIV/AIDS).

Almost a third (32.5%) of those surveyed said ineffectiveness would happen in 9 months or less; 18.2% said 6 months or less.

Paul A. Offit, MD, director of the Vaccine Education Center at the Children’s Hospital of Philadelphia, said in an interview that, while it’s hard to say whether vaccines could become ineffective in that time frame, “It’s perfectly reasonable to think it could happen.”

The good news, said Dr. Offit, who was not involved with the survey, is that SARS-CoV-2 mutates slowly, compared with other viruses such as influenza.

“To date,” he said, “the mutations that have occurred are not far enough away from the immunity induced by your natural infection or immunization such that one isn’t protected at least against severe and critical disease.”

That’s the goal of vaccines, he noted: “to keep people from suffering mightily.”
 

A line may be crossed

“And so far that’s happening, even with the variants,” Dr. Offit said. “That line has not been crossed. But I think we should assume that it might be.”

Dr. Offit said it will be critical to monitor anyone who gets hospitalized who is known to have been infected or fully vaccinated. Then countries need to get really good at sequencing those viruses.

The great majority of those surveyed (88%) said that persistently low vaccine coverage in many countries would make it more likely that vaccine-resistant mutations will appear.

Coverage comparisons between countries are stark.
 

Many countries haven’t given a single vaccine dose

While rich countries are giving COVID-19 vaccinations at the rate of a person a second, many of the poorest countries have given hardly any vaccines, the People’s Vaccine Alliance says.

Additionally, according to researchers at the Global Health Innovation Center at Duke University, Durham, N.C., high- and upper-middle–income countries, which represent one-fifth of the world’s population, have bought about 6 billion doses. But low- and lower-middle–income countries, which make up four-fifths of the population, have bought only about 2.6 billion, an article in Nature reports.

“You’re only as strong as your weakest country,” Dr. Offit said. “If we haven’t learned that what happens in other countries can [affect the global population], we haven’t been paying attention.”

Gregg Gonsalves, PhD, associate professor of epidemiology at Yale University, New Haven, Conn., one of the academic centers surveyed, didn’t specify a timeline for when vaccines would become ineffective, but said in a press release that the urgency for widespread global vaccination is real.

“Unless we vaccinate the world,” he said, “we leave the playing field open to more and more mutations, which could churn out variants that could evade our current vaccines and require booster shots to deal with them.”
 

“Dire, but not surprising”

Panagis Galiatsatos, MD, MHS, a pulmonologist at John Hopkins University, Baltimore, whose research focuses on health care disparities, said the survey findings were “dire, but not surprising.”

Johns Hopkins was another of the centers surveyed, but Dr. Galiatsatos wasn’t personally involved with the survey.

COVID-19, Dr. Galiatsatos pointed out, has laid bare disparities, both in who gets the vaccine and who’s involved in trials to develop the vaccines.

“It’s morally concerning and an ethical reckoning,” he said in an interview.

Recognition of the borderless swath of destruction the virus is exacting is critical, he said.

The United States “has to realize this can’t be a U.S.-centric issue,” he said. “We’re going to be back to the beginning if we don’t make sure that every country is doing well. We haven’t seen that level of uniform approach.”

He noted that scientists have always known that viruses mutate, but now the race is on to find the parts of SARS-CoV-2 that don’t mutate as much.

“My suspicion is we’ll probably need boosters instead of a whole different vaccine,” Dr. Galiatsatos said.

Among the strategies sought by the People’s Vaccine Alliance is for all pharmaceutical companies working on COVID-19 vaccines to openly share technology and intellectual property through the World Health Organization COVID-19 Technology Access Pool, to speed production and rollout of vaccines to all countries.

In the survey, 74% said that open sharing of technology and intellectual property could boost global vaccine coverage; 23% said maybe and 3% said it wouldn’t help.

The survey was carried out between Feb. 17 and March 25, 2021. Respondents included epidemiologists, virologists, and infection disease specialists from the following countries: Algeria, Argentina, Australia, Belgium, Bolivia, Canada, Denmark, Ethiopia, France, Guatemala, India, Italy, Kenya, Lebanon, Norway, Philippines, Senegal, Somalia, South Africa, South Sudan, Spain, United Arab Emirates, Uganda, United Kingdom, United States, Vietnam, Zambia, and Zimbabwe.

Dr. Offit and Dr. Galiatsatos reported no relevant financial relationships.

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

Two-thirds of epidemiologists from leading academic institutions say the world will need new or modified vaccines for COVID-19 within a year, new research shows.

South_agency/Getty Images

In a survey of 77 epidemiologists from 28 countries by the People’s Vaccine Alliance, 66.2% predicted that the world has a year or less before variants make current vaccines ineffective. The People’s Vaccine Alliance is a coalition of more than 50 organizations, including the African Alliance, Oxfam, Public Citizen, and UNAIDS (the Joint United Nations Programme on HIV/AIDS).

Almost a third (32.5%) of those surveyed said ineffectiveness would happen in 9 months or less; 18.2% said 6 months or less.

Paul A. Offit, MD, director of the Vaccine Education Center at the Children’s Hospital of Philadelphia, said in an interview that, while it’s hard to say whether vaccines could become ineffective in that time frame, “It’s perfectly reasonable to think it could happen.”

The good news, said Dr. Offit, who was not involved with the survey, is that SARS-CoV-2 mutates slowly, compared with other viruses such as influenza.

“To date,” he said, “the mutations that have occurred are not far enough away from the immunity induced by your natural infection or immunization such that one isn’t protected at least against severe and critical disease.”

That’s the goal of vaccines, he noted: “to keep people from suffering mightily.”
 

A line may be crossed

“And so far that’s happening, even with the variants,” Dr. Offit said. “That line has not been crossed. But I think we should assume that it might be.”

Dr. Offit said it will be critical to monitor anyone who gets hospitalized who is known to have been infected or fully vaccinated. Then countries need to get really good at sequencing those viruses.

The great majority of those surveyed (88%) said that persistently low vaccine coverage in many countries would make it more likely that vaccine-resistant mutations will appear.

Coverage comparisons between countries are stark.
 

Many countries haven’t given a single vaccine dose

While rich countries are giving COVID-19 vaccinations at the rate of a person a second, many of the poorest countries have given hardly any vaccines, the People’s Vaccine Alliance says.

Additionally, according to researchers at the Global Health Innovation Center at Duke University, Durham, N.C., high- and upper-middle–income countries, which represent one-fifth of the world’s population, have bought about 6 billion doses. But low- and lower-middle–income countries, which make up four-fifths of the population, have bought only about 2.6 billion, an article in Nature reports.

“You’re only as strong as your weakest country,” Dr. Offit said. “If we haven’t learned that what happens in other countries can [affect the global population], we haven’t been paying attention.”

Gregg Gonsalves, PhD, associate professor of epidemiology at Yale University, New Haven, Conn., one of the academic centers surveyed, didn’t specify a timeline for when vaccines would become ineffective, but said in a press release that the urgency for widespread global vaccination is real.

“Unless we vaccinate the world,” he said, “we leave the playing field open to more and more mutations, which could churn out variants that could evade our current vaccines and require booster shots to deal with them.”
 

“Dire, but not surprising”

Panagis Galiatsatos, MD, MHS, a pulmonologist at John Hopkins University, Baltimore, whose research focuses on health care disparities, said the survey findings were “dire, but not surprising.”

Johns Hopkins was another of the centers surveyed, but Dr. Galiatsatos wasn’t personally involved with the survey.

COVID-19, Dr. Galiatsatos pointed out, has laid bare disparities, both in who gets the vaccine and who’s involved in trials to develop the vaccines.

“It’s morally concerning and an ethical reckoning,” he said in an interview.

Recognition of the borderless swath of destruction the virus is exacting is critical, he said.

The United States “has to realize this can’t be a U.S.-centric issue,” he said. “We’re going to be back to the beginning if we don’t make sure that every country is doing well. We haven’t seen that level of uniform approach.”

He noted that scientists have always known that viruses mutate, but now the race is on to find the parts of SARS-CoV-2 that don’t mutate as much.

“My suspicion is we’ll probably need boosters instead of a whole different vaccine,” Dr. Galiatsatos said.

Among the strategies sought by the People’s Vaccine Alliance is for all pharmaceutical companies working on COVID-19 vaccines to openly share technology and intellectual property through the World Health Organization COVID-19 Technology Access Pool, to speed production and rollout of vaccines to all countries.

In the survey, 74% said that open sharing of technology and intellectual property could boost global vaccine coverage; 23% said maybe and 3% said it wouldn’t help.

The survey was carried out between Feb. 17 and March 25, 2021. Respondents included epidemiologists, virologists, and infection disease specialists from the following countries: Algeria, Argentina, Australia, Belgium, Bolivia, Canada, Denmark, Ethiopia, France, Guatemala, India, Italy, Kenya, Lebanon, Norway, Philippines, Senegal, Somalia, South Africa, South Sudan, Spain, United Arab Emirates, Uganda, United Kingdom, United States, Vietnam, Zambia, and Zimbabwe.

Dr. Offit and Dr. Galiatsatos reported no relevant financial relationships.

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

Oral sarecycline proved rapidly effective for the treatment of moderate to severe papulopustular rosacea in a proof-of-concept pilot study, Linda Stein Gold, MD, said at Innovations in Dermatology: Virtual Spring Conference 2021.

Patrick McNamara Photography

The oral broad-spectrum second-generation tetracyclines doxycycline and minocycline have long been considered first-line therapy for papulopustular rosacea that isn’t cleared using topical agents. But the widespread use of these oral tetracyclines has encouraged the development of antimicrobial resistance. In contrast, sarecycline (Seysara) is a third-generation, narrow-spectrum tetracycline designed to minimize antibiotic resistance. The Food and Drug Administration approved the drug for treatment of moderate to severe acne vulgaris in 2018.

At the meeting, Dr. Stein Gold, director of dermatology clinical research at the Henry Ford Health System in Detroit, highlighted a recent pilot study of oral sarecycline for papulopustular rosacea carried out by James Q. Del Rosso, DO, of Las Vegas and coinvestigators. Although she wasn’t involved in the study, she is a veteran clinical trialist with vast experience leading studies of new therapies for rosacea, acne, and other major dermatologic disorders.

The 12-week, prospective, investigator-blinded study included 97 adults with moderate to severe papulopustular rosacea; 72 were randomized to weight-based dosing of once-daily sarecycline, while the 25 controls took a daily oral vitamin.

One coprimary endpoint was achievement of an Investigator Global Assessment score of 0 or 1, meaning clear or almost clear skin, at week 12. The rates were 75% in the sarecycline group and 16% in controls. The other coprimary endpoint was the percent reduction from baseline to week 12 in inflammatory lesion count. Here again, there was a statistically significant difference in favor of the third-generation tetracycline derivative, which achieved an 80% reduction, compared with 50% in the control group.

Of note, the difference was already significant at the first evaluation at week 4, with a 58% reduction in inflammatory lesions in the sarecycline group versus 31% decrease in controls, Dr. Stein Gold observed at the conference, sponsored by MedscapeLIVE! and the producers of the Hawaii Dermatology Seminar and Caribbean Dermatology Symposium.

Also at week 12, 96% of patients on sarecycline reported having no or only trace symptoms of facial burning, 63% had no or only trace facial erythema, and 94% had no or trace facial itch, compared with 76%, 12%, and 76% of controls, respectively. The sarecycline group was also significantly more likely to report no or trace skin dryness and oiliness.

The side-effect profile was favorable and the same as encountered with the use of sarecycline for acne: no major photosensitivity issues, no serious adverse events, and only 2 of the original 75 patients in the active-treatment arm discontinued sarecycline for treatment-emergent headache or gastroenteritis considered “probably” related to the study drug. The investigators deemed further studies of sarecycline for rosacea to be warranted as a potential expanded indication.

Aiming for clear skin rather than ‘almost clear’

Dr. Stein Gold shared her mantra for rosacea therapy: “Always aim for clear skin.”

She cited a study led by Guy Webster, MD, professor of dermatology, Thomas Jefferson University, Philadelphia, in which he and his coinvestigators looked at the durability of treatment response in a pooled analysis of 1,366 rosacea patients in four clinical trials. If patients improved to “almost clear” after treatment, their median time to relapse was 3 months; if they reached “clear,” it was more than 8 months. Also, more clear patients rated their outcomes as excellent and reported that their skin disease no longer had any effect on their quality of life.

“That’s more than a 5-month difference,” Dr. Stein Gold noted. “It shows the importance of really striving to get that skin completely clear.”

The sarecycline study was funded by Almirall, which markets the antibiotic. Dr. Stein Gold, who has no financial relationship with Almirall, has received research funding from and/or served as a consultant to roughly a dozen other pharmaceutical companies. MedscapeLIVE! and this news organization are owned by the same parent company.
 

[email protected]

Oral sarecycline proved rapidly effective for the treatment of moderate to severe papulopustular rosacea in a proof-of-concept pilot study, Linda Stein Gold, MD, said at Innovations in Dermatology: Virtual Spring Conference 2021.

Patrick McNamara Photography

The oral broad-spectrum second-generation tetracyclines doxycycline and minocycline have long been considered first-line therapy for papulopustular rosacea that isn’t cleared using topical agents. But the widespread use of these oral tetracyclines has encouraged the development of antimicrobial resistance. In contrast, sarecycline (Seysara) is a third-generation, narrow-spectrum tetracycline designed to minimize antibiotic resistance. The Food and Drug Administration approved the drug for treatment of moderate to severe acne vulgaris in 2018.

At the meeting, Dr. Stein Gold, director of dermatology clinical research at the Henry Ford Health System in Detroit, highlighted a recent pilot study of oral sarecycline for papulopustular rosacea carried out by James Q. Del Rosso, DO, of Las Vegas and coinvestigators. Although she wasn’t involved in the study, she is a veteran clinical trialist with vast experience leading studies of new therapies for rosacea, acne, and other major dermatologic disorders.

The 12-week, prospective, investigator-blinded study included 97 adults with moderate to severe papulopustular rosacea; 72 were randomized to weight-based dosing of once-daily sarecycline, while the 25 controls took a daily oral vitamin.

One coprimary endpoint was achievement of an Investigator Global Assessment score of 0 or 1, meaning clear or almost clear skin, at week 12. The rates were 75% in the sarecycline group and 16% in controls. The other coprimary endpoint was the percent reduction from baseline to week 12 in inflammatory lesion count. Here again, there was a statistically significant difference in favor of the third-generation tetracycline derivative, which achieved an 80% reduction, compared with 50% in the control group.

Of note, the difference was already significant at the first evaluation at week 4, with a 58% reduction in inflammatory lesions in the sarecycline group versus 31% decrease in controls, Dr. Stein Gold observed at the conference, sponsored by MedscapeLIVE! and the producers of the Hawaii Dermatology Seminar and Caribbean Dermatology Symposium.

Also at week 12, 96% of patients on sarecycline reported having no or only trace symptoms of facial burning, 63% had no or only trace facial erythema, and 94% had no or trace facial itch, compared with 76%, 12%, and 76% of controls, respectively. The sarecycline group was also significantly more likely to report no or trace skin dryness and oiliness.

The side-effect profile was favorable and the same as encountered with the use of sarecycline for acne: no major photosensitivity issues, no serious adverse events, and only 2 of the original 75 patients in the active-treatment arm discontinued sarecycline for treatment-emergent headache or gastroenteritis considered “probably” related to the study drug. The investigators deemed further studies of sarecycline for rosacea to be warranted as a potential expanded indication.

Aiming for clear skin rather than ‘almost clear’

Dr. Stein Gold shared her mantra for rosacea therapy: “Always aim for clear skin.”

She cited a study led by Guy Webster, MD, professor of dermatology, Thomas Jefferson University, Philadelphia, in which he and his coinvestigators looked at the durability of treatment response in a pooled analysis of 1,366 rosacea patients in four clinical trials. If patients improved to “almost clear” after treatment, their median time to relapse was 3 months; if they reached “clear,” it was more than 8 months. Also, more clear patients rated their outcomes as excellent and reported that their skin disease no longer had any effect on their quality of life.

“That’s more than a 5-month difference,” Dr. Stein Gold noted. “It shows the importance of really striving to get that skin completely clear.”

The sarecycline study was funded by Almirall, which markets the antibiotic. Dr. Stein Gold, who has no financial relationship with Almirall, has received research funding from and/or served as a consultant to roughly a dozen other pharmaceutical companies. MedscapeLIVE! and this news organization are owned by the same parent company.
 

[email protected]

Oral sarecycline proved rapidly effective for the treatment of moderate to severe papulopustular rosacea in a proof-of-concept pilot study, Linda Stein Gold, MD, said at Innovations in Dermatology: Virtual Spring Conference 2021.

Patrick McNamara Photography

The oral broad-spectrum second-generation tetracyclines doxycycline and minocycline have long been considered first-line therapy for papulopustular rosacea that isn’t cleared using topical agents. But the widespread use of these oral tetracyclines has encouraged the development of antimicrobial resistance. In contrast, sarecycline (Seysara) is a third-generation, narrow-spectrum tetracycline designed to minimize antibiotic resistance. The Food and Drug Administration approved the drug for treatment of moderate to severe acne vulgaris in 2018.

At the meeting, Dr. Stein Gold, director of dermatology clinical research at the Henry Ford Health System in Detroit, highlighted a recent pilot study of oral sarecycline for papulopustular rosacea carried out by James Q. Del Rosso, DO, of Las Vegas and coinvestigators. Although she wasn’t involved in the study, she is a veteran clinical trialist with vast experience leading studies of new therapies for rosacea, acne, and other major dermatologic disorders.

The 12-week, prospective, investigator-blinded study included 97 adults with moderate to severe papulopustular rosacea; 72 were randomized to weight-based dosing of once-daily sarecycline, while the 25 controls took a daily oral vitamin.

One coprimary endpoint was achievement of an Investigator Global Assessment score of 0 or 1, meaning clear or almost clear skin, at week 12. The rates were 75% in the sarecycline group and 16% in controls. The other coprimary endpoint was the percent reduction from baseline to week 12 in inflammatory lesion count. Here again, there was a statistically significant difference in favor of the third-generation tetracycline derivative, which achieved an 80% reduction, compared with 50% in the control group.

Of note, the difference was already significant at the first evaluation at week 4, with a 58% reduction in inflammatory lesions in the sarecycline group versus 31% decrease in controls, Dr. Stein Gold observed at the conference, sponsored by MedscapeLIVE! and the producers of the Hawaii Dermatology Seminar and Caribbean Dermatology Symposium.

Also at week 12, 96% of patients on sarecycline reported having no or only trace symptoms of facial burning, 63% had no or only trace facial erythema, and 94% had no or trace facial itch, compared with 76%, 12%, and 76% of controls, respectively. The sarecycline group was also significantly more likely to report no or trace skin dryness and oiliness.

The side-effect profile was favorable and the same as encountered with the use of sarecycline for acne: no major photosensitivity issues, no serious adverse events, and only 2 of the original 75 patients in the active-treatment arm discontinued sarecycline for treatment-emergent headache or gastroenteritis considered “probably” related to the study drug. The investigators deemed further studies of sarecycline for rosacea to be warranted as a potential expanded indication.

Aiming for clear skin rather than ‘almost clear’

Dr. Stein Gold shared her mantra for rosacea therapy: “Always aim for clear skin.”

She cited a study led by Guy Webster, MD, professor of dermatology, Thomas Jefferson University, Philadelphia, in which he and his coinvestigators looked at the durability of treatment response in a pooled analysis of 1,366 rosacea patients in four clinical trials. If patients improved to “almost clear” after treatment, their median time to relapse was 3 months; if they reached “clear,” it was more than 8 months. Also, more clear patients rated their outcomes as excellent and reported that their skin disease no longer had any effect on their quality of life.

“That’s more than a 5-month difference,” Dr. Stein Gold noted. “It shows the importance of really striving to get that skin completely clear.”

The sarecycline study was funded by Almirall, which markets the antibiotic. Dr. Stein Gold, who has no financial relationship with Almirall, has received research funding from and/or served as a consultant to roughly a dozen other pharmaceutical companies. MedscapeLIVE! and this news organization are owned by the same parent company.
 

[email protected]

The National Psoriasis Foundation COVID-19 Task Force now recommends that certain patients on methotrexate consider stopping the drug for 2 weeks after receiving the Johnson & Johnson COVID-19 vaccine, Joel M. Gelfand, MD, said at Innovations in Dermatology: Virtual Spring Conference 2021.

Courtesy Dr. Joel M. Gelfand

The new guidance states: “Patients 60 or older who have at least one comorbidity associated with an increased risk for poor COVID-19 outcomes, and who are taking methotrexate with well-controlled psoriatic disease, may, in consultation with their prescriber, consider holding it for 2 weeks after receiving the Ad26.COV2.S [Johnson & Johnson] vaccine in order to potentially improve vaccine response.”

The key word here is “potentially.” There is no hard evidence that a 2-week hold on methotrexate after receiving the killed adenovirus vaccine will actually provide a clinically meaningful benefit. But it’s a hypothetical possibility. The rationale stems from a small randomized trial conducted in South Korea several years ago in which patients with rheumatoid arthritis were assigned to hold or continue their methotrexate for the first 2 weeks after receiving an inactivated-virus influenza vaccine. The antibody response to the vaccine was better in those who temporarily halted their methotrexate, explained Dr. Gelfand, cochair of the NPF COVID-19 Task Force and professor of dermatology and of epidemiology at the University of Pennsylvania, Philadelphia.

“If you have a patient on methotrexate who’s 60 or older and whose psoriasis is completely controlled and quiescent and the patient is concerned about how well the vaccine is going to work, this is a reasonable thing to consider in someone who’s at higher risk for poor outcomes if they get infected,” he said.

If the informed patient wants to continue on methotrexate without interruption, that’s fine, too, in light of the lack of compelling evidence on this issue, the dermatologist added at the conference, sponsored by MedscapeLIVE! and the producers of the Hawaii Dermatology Seminar and Caribbean Dermatology Symposium.

The NPF task force does not extend the recommendation to consider holding methotrexate in recipients of the mRNA-based Moderna and Pfizer vaccines because of their very different mechanisms of action. Nor is it recommended to hold biologic agents after receiving any of the available COVID-19 vaccines. Studies have shown no altered immunologic response to influenza or pneumococcal vaccines in patients who continued on tumor necrosis factor inhibitors or interleukin-17 inhibitors. The interleukin-23 inhibitors haven’t been studied in this regard.

The task force recommends that most psoriasis patients should continue on treatment throughout the pandemic, and newly diagnosed patients should commence appropriate therapy as if there was no pandemic.

“We’ve learned that many patients who stopped their treatment for psoriatic disease early in the pandemic came to regret that decision because their psoriasis flared and got worse and required reinstitution of therapy,” Dr. Gelfand said. “The current data is largely reassuring that if there is an effect of our therapies on the risk of COVID, it must be rather small and therefore unlikely to be clinically meaningful for our patients.”

Dr. Gelfand reported serving as a consultant to and recipient of institutional research grants from Pfizer and numerous other pharmaceutical companies.

MedscapeLIVE and this news organization are owned by the same parent company.

[email protected]

The National Psoriasis Foundation COVID-19 Task Force now recommends that certain patients on methotrexate consider stopping the drug for 2 weeks after receiving the Johnson & Johnson COVID-19 vaccine, Joel M. Gelfand, MD, said at Innovations in Dermatology: Virtual Spring Conference 2021.

Courtesy Dr. Joel M. Gelfand

The new guidance states: “Patients 60 or older who have at least one comorbidity associated with an increased risk for poor COVID-19 outcomes, and who are taking methotrexate with well-controlled psoriatic disease, may, in consultation with their prescriber, consider holding it for 2 weeks after receiving the Ad26.COV2.S [Johnson & Johnson] vaccine in order to potentially improve vaccine response.”

The key word here is “potentially.” There is no hard evidence that a 2-week hold on methotrexate after receiving the killed adenovirus vaccine will actually provide a clinically meaningful benefit. But it’s a hypothetical possibility. The rationale stems from a small randomized trial conducted in South Korea several years ago in which patients with rheumatoid arthritis were assigned to hold or continue their methotrexate for the first 2 weeks after receiving an inactivated-virus influenza vaccine. The antibody response to the vaccine was better in those who temporarily halted their methotrexate, explained Dr. Gelfand, cochair of the NPF COVID-19 Task Force and professor of dermatology and of epidemiology at the University of Pennsylvania, Philadelphia.

“If you have a patient on methotrexate who’s 60 or older and whose psoriasis is completely controlled and quiescent and the patient is concerned about how well the vaccine is going to work, this is a reasonable thing to consider in someone who’s at higher risk for poor outcomes if they get infected,” he said.

If the informed patient wants to continue on methotrexate without interruption, that’s fine, too, in light of the lack of compelling evidence on this issue, the dermatologist added at the conference, sponsored by MedscapeLIVE! and the producers of the Hawaii Dermatology Seminar and Caribbean Dermatology Symposium.

The NPF task force does not extend the recommendation to consider holding methotrexate in recipients of the mRNA-based Moderna and Pfizer vaccines because of their very different mechanisms of action. Nor is it recommended to hold biologic agents after receiving any of the available COVID-19 vaccines. Studies have shown no altered immunologic response to influenza or pneumococcal vaccines in patients who continued on tumor necrosis factor inhibitors or interleukin-17 inhibitors. The interleukin-23 inhibitors haven’t been studied in this regard.

The task force recommends that most psoriasis patients should continue on treatment throughout the pandemic, and newly diagnosed patients should commence appropriate therapy as if there was no pandemic.

“We’ve learned that many patients who stopped their treatment for psoriatic disease early in the pandemic came to regret that decision because their psoriasis flared and got worse and required reinstitution of therapy,” Dr. Gelfand said. “The current data is largely reassuring that if there is an effect of our therapies on the risk of COVID, it must be rather small and therefore unlikely to be clinically meaningful for our patients.”

Dr. Gelfand reported serving as a consultant to and recipient of institutional research grants from Pfizer and numerous other pharmaceutical companies.

MedscapeLIVE and this news organization are owned by the same parent company.

[email protected]

The National Psoriasis Foundation COVID-19 Task Force now recommends that certain patients on methotrexate consider stopping the drug for 2 weeks after receiving the Johnson & Johnson COVID-19 vaccine, Joel M. Gelfand, MD, said at Innovations in Dermatology: Virtual Spring Conference 2021.

Courtesy Dr. Joel M. Gelfand

The new guidance states: “Patients 60 or older who have at least one comorbidity associated with an increased risk for poor COVID-19 outcomes, and who are taking methotrexate with well-controlled psoriatic disease, may, in consultation with their prescriber, consider holding it for 2 weeks after receiving the Ad26.COV2.S [Johnson & Johnson] vaccine in order to potentially improve vaccine response.”

The key word here is “potentially.” There is no hard evidence that a 2-week hold on methotrexate after receiving the killed adenovirus vaccine will actually provide a clinically meaningful benefit. But it’s a hypothetical possibility. The rationale stems from a small randomized trial conducted in South Korea several years ago in which patients with rheumatoid arthritis were assigned to hold or continue their methotrexate for the first 2 weeks after receiving an inactivated-virus influenza vaccine. The antibody response to the vaccine was better in those who temporarily halted their methotrexate, explained Dr. Gelfand, cochair of the NPF COVID-19 Task Force and professor of dermatology and of epidemiology at the University of Pennsylvania, Philadelphia.

“If you have a patient on methotrexate who’s 60 or older and whose psoriasis is completely controlled and quiescent and the patient is concerned about how well the vaccine is going to work, this is a reasonable thing to consider in someone who’s at higher risk for poor outcomes if they get infected,” he said.

If the informed patient wants to continue on methotrexate without interruption, that’s fine, too, in light of the lack of compelling evidence on this issue, the dermatologist added at the conference, sponsored by MedscapeLIVE! and the producers of the Hawaii Dermatology Seminar and Caribbean Dermatology Symposium.

The NPF task force does not extend the recommendation to consider holding methotrexate in recipients of the mRNA-based Moderna and Pfizer vaccines because of their very different mechanisms of action. Nor is it recommended to hold biologic agents after receiving any of the available COVID-19 vaccines. Studies have shown no altered immunologic response to influenza or pneumococcal vaccines in patients who continued on tumor necrosis factor inhibitors or interleukin-17 inhibitors. The interleukin-23 inhibitors haven’t been studied in this regard.

The task force recommends that most psoriasis patients should continue on treatment throughout the pandemic, and newly diagnosed patients should commence appropriate therapy as if there was no pandemic.

“We’ve learned that many patients who stopped their treatment for psoriatic disease early in the pandemic came to regret that decision because their psoriasis flared and got worse and required reinstitution of therapy,” Dr. Gelfand said. “The current data is largely reassuring that if there is an effect of our therapies on the risk of COVID, it must be rather small and therefore unlikely to be clinically meaningful for our patients.”

Dr. Gelfand reported serving as a consultant to and recipient of institutional research grants from Pfizer and numerous other pharmaceutical companies.

MedscapeLIVE and this news organization are owned by the same parent company.

[email protected]

Physicians are active on social media with contact dermatitis content, but they can take more advantage of this opportunity to educate patients, according to a review of posts on YouTube, Facebook, Instagram, Google, Twitter, and Reddit.

Data on social media use suggest that approximately 65% of U.S. adults regularly use social media, and 40% of individuals use it in making medical decisions, Morgan Nguyen, a medical student at Northwestern University, Chicago, said at the annual meeting of the American Contact Dermatitis Society, held virtually this year.

“Dermatologists’ awareness of social media discussions can further their understanding of where patients go for information and what they might encounter,” she said. In particular, “contact dermatitis practitioners can tailor their counseling by knowing what their patients are seeing online.”

To characterize the social media landscape for content related to allergic contact dermatitis (ACD), Ms. Nguyen and colleagues assessed metrics on content and authorship on six different platforms.

For YouTube, the authors reviewed 15 videos related to ACD with views ranging from 24,262 to 232,300. Of these videos, two were produced as medical education, four were produced by patients, and nine were produced by physicians. The content of many videos was poor quality, with an average QUEST score of 7.4/28 overall and 8.7 for physician videos. Video quality was not associated with increased views. Video titles included “What to do if you have a rash on your face,” and “Contact dermatitis on lips!”

Overall, Instagram was more popular than Twitter, particularly among patients. The investigators searched using the hashtags #ContactDermatitis, #AllergicContactDermatitis, and #ContactDerm and reviewed the 100 most recent posts for authorship. The most recent 100 posts occurred over 16 days; physicians, patients, and companies each contributed approximately one-third of the content, but patient content was more focused on symptoms, treatment progress, and advice.

For Instagram, the hashtag search phrase made a notable difference in authorship, Ms. Nguyen said. Physicians were disproportionately more likely to use #AllergicContactDermatitis (43%) compared with patients (22%).

On Twitter, the most recent 100 posts were spread over 152 days, and professional organizations and companies generated approximately two-thirds of the posts. The #ContactDermatitis hashtag was the most common, and accounted for 94% of tweets.

Although patient support groups specific to ACD exist on Facebook, the researchers found none on Reddit. These two venues are designed for creating online communities, rather than simply providing information, and the researchers searched for support groups related to contact dermatitis. One of the main differences between the two is that Facebook allows for the creation of private groups, while Reddit is an open forum.

The largest contact dermatitis Facebook group, the “Eczema, Contact Dermatitis and Patch Testing Alliance,” had 4,665 members at the time of the study, and most groups were private. Although no support groups existed on Reddit, titles of Reddit forums discussing ACD included allergies, askdoctors, fragrance, haircarescience, legaladvice, skincareaddicts, beauty, dermatologyquestions, medical_advice, skincare_addiction, tretinoin, and vulvodynia.

For Google, the researchers used terms similar to “contact dermatitis” as generated by the Google Keyword Planner tool, and used Google Adwords data to estimate monthly searches. The top estimated term was “contact dermatitis,” with 8,322 searches, followed by “contact dermatitis pictures,” with 1,666 searches, and “contact dermatitis treatment” with 595 searches. By contrast, “allergic dermatitis” had an estimated 346 monthly searches, and “allergic contact dermatitis” had 194.

Overall, approximately 9,000 searches each month involve “contact dermatitis,” “allergic contact dermatitis,” or “allergic dermatitis,” said Ms. Nguyen. However, these estimated searches seemed comparatively low, given the high burden of ACD, she said. Although ACD ranks eighth among skin diseases based on health care costs, psoriasis (fourteenth based on health care costs) shows an estimated monthly Google search volume of 600,462, she pointed out.

The study findings were limited by several factors including the potential impact of the COVID-19 pandemic on social media use, and by the lack of specificity associated with the search term “contact dermatitis,” which is not unique to ACD, Ms. Nguyen said.

Although more research on quality assessment is needed, the results suggest that social media is a popular venue for ACD patients to seek and share information, Ms. Nguyen emphasized. There is an opportunity for patch testing physicians to create and disperse educational content for patients using these sites, she concluded.
 

Study highlights education opportunities

“Due to the pandemic, patients have been increasingly interacting with online resources in lieu of coming to a physician’s office,” corresponding author Walter J. Liszewski, MD, of the department of dermatology, Northwestern University, Chicago, said in an interview. “As social media is increasingly used by patients and physicians, it is important to get a sense of its footprint,” he said.

He and Ms. Nguyen were surprised by several of their findings: First, searches for ACD on Google were not particularly common given its relatively high prevalence and economic cost to society. In addition, they found that physicians often used different language than that of patients to describe ACD on Twitter and Instagram. They were also surprised at how often ACD appeared in Reddit posts, which they noted highlights that ACD impacts multiple sections of society.

The greatest challenge in studying social media and medicine is the quality of material available, Dr. Liszewski and Ms. Nguyen observed, emphasizing that while there are numerous videos on ACD on YouTube, the quality is highly variable, and there is a need for more patient-centered, educational materials. However, the results of their study highlight the opportunity for physicians and industry to create medically-accurate educational materials, they added.

Ms. Nguyen and Dr. Liszewski had no financial conflicts to disclose.

Physicians are active on social media with contact dermatitis content, but they can take more advantage of this opportunity to educate patients, according to a review of posts on YouTube, Facebook, Instagram, Google, Twitter, and Reddit.

Data on social media use suggest that approximately 65% of U.S. adults regularly use social media, and 40% of individuals use it in making medical decisions, Morgan Nguyen, a medical student at Northwestern University, Chicago, said at the annual meeting of the American Contact Dermatitis Society, held virtually this year.

“Dermatologists’ awareness of social media discussions can further their understanding of where patients go for information and what they might encounter,” she said. In particular, “contact dermatitis practitioners can tailor their counseling by knowing what their patients are seeing online.”

To characterize the social media landscape for content related to allergic contact dermatitis (ACD), Ms. Nguyen and colleagues assessed metrics on content and authorship on six different platforms.

For YouTube, the authors reviewed 15 videos related to ACD with views ranging from 24,262 to 232,300. Of these videos, two were produced as medical education, four were produced by patients, and nine were produced by physicians. The content of many videos was poor quality, with an average QUEST score of 7.4/28 overall and 8.7 for physician videos. Video quality was not associated with increased views. Video titles included “What to do if you have a rash on your face,” and “Contact dermatitis on lips!”

Overall, Instagram was more popular than Twitter, particularly among patients. The investigators searched using the hashtags #ContactDermatitis, #AllergicContactDermatitis, and #ContactDerm and reviewed the 100 most recent posts for authorship. The most recent 100 posts occurred over 16 days; physicians, patients, and companies each contributed approximately one-third of the content, but patient content was more focused on symptoms, treatment progress, and advice.

For Instagram, the hashtag search phrase made a notable difference in authorship, Ms. Nguyen said. Physicians were disproportionately more likely to use #AllergicContactDermatitis (43%) compared with patients (22%).

On Twitter, the most recent 100 posts were spread over 152 days, and professional organizations and companies generated approximately two-thirds of the posts. The #ContactDermatitis hashtag was the most common, and accounted for 94% of tweets.

Although patient support groups specific to ACD exist on Facebook, the researchers found none on Reddit. These two venues are designed for creating online communities, rather than simply providing information, and the researchers searched for support groups related to contact dermatitis. One of the main differences between the two is that Facebook allows for the creation of private groups, while Reddit is an open forum.

The largest contact dermatitis Facebook group, the “Eczema, Contact Dermatitis and Patch Testing Alliance,” had 4,665 members at the time of the study, and most groups were private. Although no support groups existed on Reddit, titles of Reddit forums discussing ACD included allergies, askdoctors, fragrance, haircarescience, legaladvice, skincareaddicts, beauty, dermatologyquestions, medical_advice, skincare_addiction, tretinoin, and vulvodynia.

For Google, the researchers used terms similar to “contact dermatitis” as generated by the Google Keyword Planner tool, and used Google Adwords data to estimate monthly searches. The top estimated term was “contact dermatitis,” with 8,322 searches, followed by “contact dermatitis pictures,” with 1,666 searches, and “contact dermatitis treatment” with 595 searches. By contrast, “allergic dermatitis” had an estimated 346 monthly searches, and “allergic contact dermatitis” had 194.

Overall, approximately 9,000 searches each month involve “contact dermatitis,” “allergic contact dermatitis,” or “allergic dermatitis,” said Ms. Nguyen. However, these estimated searches seemed comparatively low, given the high burden of ACD, she said. Although ACD ranks eighth among skin diseases based on health care costs, psoriasis (fourteenth based on health care costs) shows an estimated monthly Google search volume of 600,462, she pointed out.

The study findings were limited by several factors including the potential impact of the COVID-19 pandemic on social media use, and by the lack of specificity associated with the search term “contact dermatitis,” which is not unique to ACD, Ms. Nguyen said.

Although more research on quality assessment is needed, the results suggest that social media is a popular venue for ACD patients to seek and share information, Ms. Nguyen emphasized. There is an opportunity for patch testing physicians to create and disperse educational content for patients using these sites, she concluded.
 

Study highlights education opportunities

“Due to the pandemic, patients have been increasingly interacting with online resources in lieu of coming to a physician’s office,” corresponding author Walter J. Liszewski, MD, of the department of dermatology, Northwestern University, Chicago, said in an interview. “As social media is increasingly used by patients and physicians, it is important to get a sense of its footprint,” he said.

He and Ms. Nguyen were surprised by several of their findings: First, searches for ACD on Google were not particularly common given its relatively high prevalence and economic cost to society. In addition, they found that physicians often used different language than that of patients to describe ACD on Twitter and Instagram. They were also surprised at how often ACD appeared in Reddit posts, which they noted highlights that ACD impacts multiple sections of society.

The greatest challenge in studying social media and medicine is the quality of material available, Dr. Liszewski and Ms. Nguyen observed, emphasizing that while there are numerous videos on ACD on YouTube, the quality is highly variable, and there is a need for more patient-centered, educational materials. However, the results of their study highlight the opportunity for physicians and industry to create medically-accurate educational materials, they added.

Ms. Nguyen and Dr. Liszewski had no financial conflicts to disclose.

Physicians are active on social media with contact dermatitis content, but they can take more advantage of this opportunity to educate patients, according to a review of posts on YouTube, Facebook, Instagram, Google, Twitter, and Reddit.

Data on social media use suggest that approximately 65% of U.S. adults regularly use social media, and 40% of individuals use it in making medical decisions, Morgan Nguyen, a medical student at Northwestern University, Chicago, said at the annual meeting of the American Contact Dermatitis Society, held virtually this year.

“Dermatologists’ awareness of social media discussions can further their understanding of where patients go for information and what they might encounter,” she said. In particular, “contact dermatitis practitioners can tailor their counseling by knowing what their patients are seeing online.”

To characterize the social media landscape for content related to allergic contact dermatitis (ACD), Ms. Nguyen and colleagues assessed metrics on content and authorship on six different platforms.

For YouTube, the authors reviewed 15 videos related to ACD with views ranging from 24,262 to 232,300. Of these videos, two were produced as medical education, four were produced by patients, and nine were produced by physicians. The content of many videos was poor quality, with an average QUEST score of 7.4/28 overall and 8.7 for physician videos. Video quality was not associated with increased views. Video titles included “What to do if you have a rash on your face,” and “Contact dermatitis on lips!”

Overall, Instagram was more popular than Twitter, particularly among patients. The investigators searched using the hashtags #ContactDermatitis, #AllergicContactDermatitis, and #ContactDerm and reviewed the 100 most recent posts for authorship. The most recent 100 posts occurred over 16 days; physicians, patients, and companies each contributed approximately one-third of the content, but patient content was more focused on symptoms, treatment progress, and advice.

For Instagram, the hashtag search phrase made a notable difference in authorship, Ms. Nguyen said. Physicians were disproportionately more likely to use #AllergicContactDermatitis (43%) compared with patients (22%).

On Twitter, the most recent 100 posts were spread over 152 days, and professional organizations and companies generated approximately two-thirds of the posts. The #ContactDermatitis hashtag was the most common, and accounted for 94% of tweets.

Although patient support groups specific to ACD exist on Facebook, the researchers found none on Reddit. These two venues are designed for creating online communities, rather than simply providing information, and the researchers searched for support groups related to contact dermatitis. One of the main differences between the two is that Facebook allows for the creation of private groups, while Reddit is an open forum.

The largest contact dermatitis Facebook group, the “Eczema, Contact Dermatitis and Patch Testing Alliance,” had 4,665 members at the time of the study, and most groups were private. Although no support groups existed on Reddit, titles of Reddit forums discussing ACD included allergies, askdoctors, fragrance, haircarescience, legaladvice, skincareaddicts, beauty, dermatologyquestions, medical_advice, skincare_addiction, tretinoin, and vulvodynia.

For Google, the researchers used terms similar to “contact dermatitis” as generated by the Google Keyword Planner tool, and used Google Adwords data to estimate monthly searches. The top estimated term was “contact dermatitis,” with 8,322 searches, followed by “contact dermatitis pictures,” with 1,666 searches, and “contact dermatitis treatment” with 595 searches. By contrast, “allergic dermatitis” had an estimated 346 monthly searches, and “allergic contact dermatitis” had 194.

Overall, approximately 9,000 searches each month involve “contact dermatitis,” “allergic contact dermatitis,” or “allergic dermatitis,” said Ms. Nguyen. However, these estimated searches seemed comparatively low, given the high burden of ACD, she said. Although ACD ranks eighth among skin diseases based on health care costs, psoriasis (fourteenth based on health care costs) shows an estimated monthly Google search volume of 600,462, she pointed out.

The study findings were limited by several factors including the potential impact of the COVID-19 pandemic on social media use, and by the lack of specificity associated with the search term “contact dermatitis,” which is not unique to ACD, Ms. Nguyen said.

Although more research on quality assessment is needed, the results suggest that social media is a popular venue for ACD patients to seek and share information, Ms. Nguyen emphasized. There is an opportunity for patch testing physicians to create and disperse educational content for patients using these sites, she concluded.
 

Study highlights education opportunities

“Due to the pandemic, patients have been increasingly interacting with online resources in lieu of coming to a physician’s office,” corresponding author Walter J. Liszewski, MD, of the department of dermatology, Northwestern University, Chicago, said in an interview. “As social media is increasingly used by patients and physicians, it is important to get a sense of its footprint,” he said.

He and Ms. Nguyen were surprised by several of their findings: First, searches for ACD on Google were not particularly common given its relatively high prevalence and economic cost to society. In addition, they found that physicians often used different language than that of patients to describe ACD on Twitter and Instagram. They were also surprised at how often ACD appeared in Reddit posts, which they noted highlights that ACD impacts multiple sections of society.

The greatest challenge in studying social media and medicine is the quality of material available, Dr. Liszewski and Ms. Nguyen observed, emphasizing that while there are numerous videos on ACD on YouTube, the quality is highly variable, and there is a need for more patient-centered, educational materials. However, the results of their study highlight the opportunity for physicians and industry to create medically-accurate educational materials, they added.

Ms. Nguyen and Dr. Liszewski had no financial conflicts to disclose.

Approximately 20% of shoe allergens are not detected with the current screening series, according to a retrospective study of more than 30,000 patients.

Contact allergy to shoes remains a common but difficult problem for many reasons, including the limited information from shoe manufacturers, differences in shoe manufacturing processes, and changes in shoe trends, said Raina Bembry, MD, a dermatitis research fellow at Duke University, Durham, N.C., in a presentation at the annual meeting of the American Contact Dermatitis Society.

The North American Contact Dermatitis Group (NACDG) published data on shoe allergens from 2001-2004 in a 2007 review. To update this information to reflect changes in shoe manufacturing and trends, she and her coinvestigators characterized demographics, clinical characteristics, patch test results, and occupational data for NACDG patients with shoe contact allergy. They identified 33,661 patients who were patch tested with the standard series with or without a supplemental allergen between 2005 and 2018; over half were over aged 40.

The primary focus was individuals with a confirmed shoe (defined as shoes, boots, sandals, or slippers) as the source of a screening allergen or supplemental allergen, a positive patch test, and the foot as one of three sites of involvement. A total of 352 individuals met these criteria and had a confirmed final diagnosis of allergic contact dermatitis, Dr. Bembry said. Compared with individuals who had positive patch tests without a confirmed diagnosis, those with confirmed allergic dermatitis were significantly more likely to be male (odds ratio, 3.36) and less likely to be over aged 40 years (OR, 0.49).

The most common NACDG screening allergen, potassium dichromate, was found in 29.8% of the study population, followed by p-tert-butylphenol formaldehyde resin in 20.1%, thiuram mix (13.3%), mixed dialkyl thioureas (12.6%) and carba mix (12%).

Notably, 29.8% of the patients showed positive patch test reactions to supplemental allergens, and 12.2% only reacted to supplemental allergens, Dr. Bembry said.

The results were limited by several factors, including referral selection bias, reliance on clinical judgment for patch test interpretations, and lack of data on the specifics of the supplemental allergens other than the source code, she said. In addition, the study does not identify nonshoe sources of foot contact allergy, and six screening allergens were not testing during this study period.

Overall, the findings were similar to those from previous studies in that patients affected with contact dermatitis from shoe allergens tended to be younger and male, with no occupational relevance to the reaction, said Dr. Bembry.

The finding that almost 20% of allergens were not found with the screening series emphasizes the value of testing not only relevant supplemental allergens, but also patient products and shoe components, she concluded.

Dr. Bembry had no financial conflicts to disclose. Coauthor Amber Atwater, MD, the immediate past president of the ACDS, and associate professor of dermatology at Duke University, disclosed receiving the Pfizer Independent Grant for Learning & Change and consulting for Henkel.

Approximately 20% of shoe allergens are not detected with the current screening series, according to a retrospective study of more than 30,000 patients.

Contact allergy to shoes remains a common but difficult problem for many reasons, including the limited information from shoe manufacturers, differences in shoe manufacturing processes, and changes in shoe trends, said Raina Bembry, MD, a dermatitis research fellow at Duke University, Durham, N.C., in a presentation at the annual meeting of the American Contact Dermatitis Society.

The North American Contact Dermatitis Group (NACDG) published data on shoe allergens from 2001-2004 in a 2007 review. To update this information to reflect changes in shoe manufacturing and trends, she and her coinvestigators characterized demographics, clinical characteristics, patch test results, and occupational data for NACDG patients with shoe contact allergy. They identified 33,661 patients who were patch tested with the standard series with or without a supplemental allergen between 2005 and 2018; over half were over aged 40.

The primary focus was individuals with a confirmed shoe (defined as shoes, boots, sandals, or slippers) as the source of a screening allergen or supplemental allergen, a positive patch test, and the foot as one of three sites of involvement. A total of 352 individuals met these criteria and had a confirmed final diagnosis of allergic contact dermatitis, Dr. Bembry said. Compared with individuals who had positive patch tests without a confirmed diagnosis, those with confirmed allergic dermatitis were significantly more likely to be male (odds ratio, 3.36) and less likely to be over aged 40 years (OR, 0.49).

The most common NACDG screening allergen, potassium dichromate, was found in 29.8% of the study population, followed by p-tert-butylphenol formaldehyde resin in 20.1%, thiuram mix (13.3%), mixed dialkyl thioureas (12.6%) and carba mix (12%).

Notably, 29.8% of the patients showed positive patch test reactions to supplemental allergens, and 12.2% only reacted to supplemental allergens, Dr. Bembry said.

The results were limited by several factors, including referral selection bias, reliance on clinical judgment for patch test interpretations, and lack of data on the specifics of the supplemental allergens other than the source code, she said. In addition, the study does not identify nonshoe sources of foot contact allergy, and six screening allergens were not testing during this study period.

Overall, the findings were similar to those from previous studies in that patients affected with contact dermatitis from shoe allergens tended to be younger and male, with no occupational relevance to the reaction, said Dr. Bembry.

The finding that almost 20% of allergens were not found with the screening series emphasizes the value of testing not only relevant supplemental allergens, but also patient products and shoe components, she concluded.

Dr. Bembry had no financial conflicts to disclose. Coauthor Amber Atwater, MD, the immediate past president of the ACDS, and associate professor of dermatology at Duke University, disclosed receiving the Pfizer Independent Grant for Learning & Change and consulting for Henkel.

Approximately 20% of shoe allergens are not detected with the current screening series, according to a retrospective study of more than 30,000 patients.

Contact allergy to shoes remains a common but difficult problem for many reasons, including the limited information from shoe manufacturers, differences in shoe manufacturing processes, and changes in shoe trends, said Raina Bembry, MD, a dermatitis research fellow at Duke University, Durham, N.C., in a presentation at the annual meeting of the American Contact Dermatitis Society.

The North American Contact Dermatitis Group (NACDG) published data on shoe allergens from 2001-2004 in a 2007 review. To update this information to reflect changes in shoe manufacturing and trends, she and her coinvestigators characterized demographics, clinical characteristics, patch test results, and occupational data for NACDG patients with shoe contact allergy. They identified 33,661 patients who were patch tested with the standard series with or without a supplemental allergen between 2005 and 2018; over half were over aged 40.

The primary focus was individuals with a confirmed shoe (defined as shoes, boots, sandals, or slippers) as the source of a screening allergen or supplemental allergen, a positive patch test, and the foot as one of three sites of involvement. A total of 352 individuals met these criteria and had a confirmed final diagnosis of allergic contact dermatitis, Dr. Bembry said. Compared with individuals who had positive patch tests without a confirmed diagnosis, those with confirmed allergic dermatitis were significantly more likely to be male (odds ratio, 3.36) and less likely to be over aged 40 years (OR, 0.49).

The most common NACDG screening allergen, potassium dichromate, was found in 29.8% of the study population, followed by p-tert-butylphenol formaldehyde resin in 20.1%, thiuram mix (13.3%), mixed dialkyl thioureas (12.6%) and carba mix (12%).

Notably, 29.8% of the patients showed positive patch test reactions to supplemental allergens, and 12.2% only reacted to supplemental allergens, Dr. Bembry said.

The results were limited by several factors, including referral selection bias, reliance on clinical judgment for patch test interpretations, and lack of data on the specifics of the supplemental allergens other than the source code, she said. In addition, the study does not identify nonshoe sources of foot contact allergy, and six screening allergens were not testing during this study period.

Overall, the findings were similar to those from previous studies in that patients affected with contact dermatitis from shoe allergens tended to be younger and male, with no occupational relevance to the reaction, said Dr. Bembry.

The finding that almost 20% of allergens were not found with the screening series emphasizes the value of testing not only relevant supplemental allergens, but also patient products and shoe components, she concluded.

Dr. Bembry had no financial conflicts to disclose. Coauthor Amber Atwater, MD, the immediate past president of the ACDS, and associate professor of dermatology at Duke University, disclosed receiving the Pfizer Independent Grant for Learning & Change and consulting for Henkel.

The World Health Organization’s call for the elimination of cervical cancer worldwide is a laudable goal and one that many organizations across the globe have endorsed.

Yet some would say that this goal goes only halfway, and that the real finish line should be to eliminate all vaccine-type HPV infections that cause multiple cancers, in men as well as women.

One proponent of sweeping HPV prevention is Mark Jit, PhD, from the London School of Hygiene & Tropical Medicine.

In the long run, the WHO’s call to eliminate cervical cancer is “insufficiently ambitious” he writes in a special issue of Preventive Medicine.

“The point is, if you are trying to eliminate cervical cancer, you’ve run part of the race,” he said.

“But why not run that extra third and get rid of the virus, then you never have to worry about it again,” Dr. Jit elaborated in an interview.

Winning that race, however, is dependent on a gender-neutral HPV vaccination policy, he pointed out.

At present, the WHO advocates only for female vaccination and screening.

Some countries have already taken the matter into their own hands. As of May 2020, 33 countries and four territories have gender-neutral vaccination schedules.

Others are also calling for gender-neutral HPV vaccination to achieve a far wider public health good.

“I completely agree that our ultimate goal should be the elimination of all HPV-related cancers – but we will require gender-neutral vaccination to do it,” says Anna Giuliano, PhD, professor and director, Center for Immunization and Infection Research in Cancer, Moffitt Cancer Center, Tampa.

“The reason why WHO started with cervical cancer elimination is that it is likely to be the first cancer that we can achieve this with, and if you look internationally, cervical cancer has the highest burden,” Dr. Giuliano told this news organization.

“But it’s important to understand that it’s not just females who are at risk for HPV disease, men have serious consequences from HPV infection, too,” she said.

In fact, rates of HPV-related cancers and mortality in men exceed those for women in countries that have effective cervical cancer screening programs, she points out in an editorial in the same issue of Preventive Medicine.

Rates in men are driven largely by HPV-related oropharyngeal cancer, but not only, Dr. Giuliano noted in an interview.

Rates of anal cancer among men who have sex with men (MSM) are at least as high as rates of cervical cancer among women living in the poorest countries of the world, where 85% of cervical cancer deaths now occur, she noted. If MSM are HIV positive, rates of anal cancer are even higher.
 

Unethical to leave males out?

Arguments in favor of gender-neutral HPV vaccination abound, but the most compelling among them is that society really should give males an opportunity to receive direct protection against all types of HPV infection, Dr. Giuliano commented.

Indeed, in the U.K., experts argue that it is unethical to leave males out of achieving direct protection against HPV infection, she noted.

With a female-only vaccination strategy, “males are only protected if they stay in a population where there are high female vaccination rates – and very few countries have achieved high rates of vaccine dissemination and have sustained it,” she pointed out. But that applies only to heterosexual men, who develop some herd immunity from exposure to vaccinated females; this is not the case for MSM.

On a pragmatic note, a vaccine program that targets a larger number of people against HPV infection – which would be achieved with gender-neutral vaccination – is going to be more resilient against temporary changes in vaccine uptake, such as what has happened over the past year.

“During the pandemic, people may have had virtual clinic visits, but they haven’t had in-person visits, which is what you need for vaccination,” Dr. Giuliano pointed out. “So over the past year, there has been a major drop in vaccination rates,” she said.
 

Eliminating cervical cancer

Currently, the WHO plans for eliminating cervical cancer involve a strategy of vaccinating 90% of girls by the age of 15, screening 70% of women with a high performance test by the age of 35 and again at 45, and treating 90% of women with cervical disease – the so-called “90-70-90” strategy.

Dr. Jit agrees that very high levels of vaccine coverage would eradicate the HPV types causing almost all cases of cervical cancer. The same strategy would also sharply reduce the need for preventive measures in the future.

However, as Dr. Jit argues, 90% female-only coverage will not be sufficient to eliminate HPV 16 transmission, although 90% coverage in both males and females – namely a gender-neutral strategy – might. To show this, Dr. Jit and colleagues used the HPV-ADVISE transmission model in India.

Results from this modeling exercise suggest that 90% coverage of both sexes would bring the prevalence of HPV 16 close to elimination, defined as reducing the prevalence of HPV 16 to below 10 per 100,000 in the population.

In addition, because even at this low level, HPV transmission can be sustained in a small group of sex workers and their clients, achieving 95% coverage of 10-year-old girls who might become female sex workers in the future will likely achieve the goal of HPV 16 elimination, as Dr. Jit suggests.
 

OPSCC elimination

Elimination of another HPV-related cancer, oropharyngeal squamous cell carcinomas (OPSCCs), is discussed in another paper in the same journal.

HPV-related OPSCCs are mostly associated specifically with HPV 16.

There is currently an epidemic of this cancer among middle-aged men in the Nordic countries of Denmark, Finland, Norway, and Sweden; incidence rates have tripled over the past 30 years, note Tuomas Lehtinen, PhD, FICAN-MID, Tampere, Finland and colleagues.

They propose a two-step action plan – gender-neutral vaccination in adolescent boys and girls, and a screening program for adults born in 1995 or earlier.

The first step is already underway, and the recent implementation of school-based HPV vaccination programs in the Nordic countries is predicted to gradually decrease the incidence of HPV-related OPSCCs, they write.

“Even if HPV vaccination does not cure established infections, it can prevent re-infection/recurrence of associated lesions in 45% to 65% of individuals with anal or cervical intraepithelial neoplasia,” the authors write, “and there is high VE (vaccine efficacy) against oropharyngeal HPV infections as well.”

Furthermore, there is a tenfold relative risk of tonsillar and base of tongue cancers in spouses of women diagnosed with invasive anogenital cancer, researchers also point out. “This underlines the importance of breaking genito-oral transmission chains.”

The screening of adults born in 1995 for HPV-related OPSCC is still at a planning stage.

In a proof-of-concept study for the stepwise prevention of OPSCC, the authors suggest that target birth cohorts first be stratified and then randomized into serological HPV 16 E6 antibody screening or no screening. HPV 16 antibody-positive women and their spouses then could be invited for HPV vaccination followed by 2 HPV DNA tests.

Unscreened women and their spouses would serve as population-based controls. “Even if gender-neutral vaccination results in rapid elimination of HPV circulation, the effects of persistent, [prevalent] HPV infections on the most HPV-associated tonsillar cancer will continue for decades after HPV circulation has stopped,” the authors predict.

The Jit study was funded by the Bill & Melinda Gates Foundation and the National Institute for Health. The Lehtinen study was supported by grants from the Finnish Cancer Society and Tampere Tuberculosis Foundation. Dr. Jit and Dr. Lehtinen have disclosed no relevant financial relationships. Dr. Giuliano serves on the advisory board for Merck, which markets the HPV vaccine Gardasil.

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

The World Health Organization’s call for the elimination of cervical cancer worldwide is a laudable goal and one that many organizations across the globe have endorsed.

Yet some would say that this goal goes only halfway, and that the real finish line should be to eliminate all vaccine-type HPV infections that cause multiple cancers, in men as well as women.

One proponent of sweeping HPV prevention is Mark Jit, PhD, from the London School of Hygiene & Tropical Medicine.

In the long run, the WHO’s call to eliminate cervical cancer is “insufficiently ambitious” he writes in a special issue of Preventive Medicine.

“The point is, if you are trying to eliminate cervical cancer, you’ve run part of the race,” he said.

“But why not run that extra third and get rid of the virus, then you never have to worry about it again,” Dr. Jit elaborated in an interview.

Winning that race, however, is dependent on a gender-neutral HPV vaccination policy, he pointed out.

At present, the WHO advocates only for female vaccination and screening.

Some countries have already taken the matter into their own hands. As of May 2020, 33 countries and four territories have gender-neutral vaccination schedules.

Others are also calling for gender-neutral HPV vaccination to achieve a far wider public health good.

“I completely agree that our ultimate goal should be the elimination of all HPV-related cancers – but we will require gender-neutral vaccination to do it,” says Anna Giuliano, PhD, professor and director, Center for Immunization and Infection Research in Cancer, Moffitt Cancer Center, Tampa.

“The reason why WHO started with cervical cancer elimination is that it is likely to be the first cancer that we can achieve this with, and if you look internationally, cervical cancer has the highest burden,” Dr. Giuliano told this news organization.

“But it’s important to understand that it’s not just females who are at risk for HPV disease, men have serious consequences from HPV infection, too,” she said.

In fact, rates of HPV-related cancers and mortality in men exceed those for women in countries that have effective cervical cancer screening programs, she points out in an editorial in the same issue of Preventive Medicine.

Rates in men are driven largely by HPV-related oropharyngeal cancer, but not only, Dr. Giuliano noted in an interview.

Rates of anal cancer among men who have sex with men (MSM) are at least as high as rates of cervical cancer among women living in the poorest countries of the world, where 85% of cervical cancer deaths now occur, she noted. If MSM are HIV positive, rates of anal cancer are even higher.
 

Unethical to leave males out?

Arguments in favor of gender-neutral HPV vaccination abound, but the most compelling among them is that society really should give males an opportunity to receive direct protection against all types of HPV infection, Dr. Giuliano commented.

Indeed, in the U.K., experts argue that it is unethical to leave males out of achieving direct protection against HPV infection, she noted.

With a female-only vaccination strategy, “males are only protected if they stay in a population where there are high female vaccination rates – and very few countries have achieved high rates of vaccine dissemination and have sustained it,” she pointed out. But that applies only to heterosexual men, who develop some herd immunity from exposure to vaccinated females; this is not the case for MSM.

On a pragmatic note, a vaccine program that targets a larger number of people against HPV infection – which would be achieved with gender-neutral vaccination – is going to be more resilient against temporary changes in vaccine uptake, such as what has happened over the past year.

“During the pandemic, people may have had virtual clinic visits, but they haven’t had in-person visits, which is what you need for vaccination,” Dr. Giuliano pointed out. “So over the past year, there has been a major drop in vaccination rates,” she said.
 

Eliminating cervical cancer

Currently, the WHO plans for eliminating cervical cancer involve a strategy of vaccinating 90% of girls by the age of 15, screening 70% of women with a high performance test by the age of 35 and again at 45, and treating 90% of women with cervical disease – the so-called “90-70-90” strategy.

Dr. Jit agrees that very high levels of vaccine coverage would eradicate the HPV types causing almost all cases of cervical cancer. The same strategy would also sharply reduce the need for preventive measures in the future.

However, as Dr. Jit argues, 90% female-only coverage will not be sufficient to eliminate HPV 16 transmission, although 90% coverage in both males and females – namely a gender-neutral strategy – might. To show this, Dr. Jit and colleagues used the HPV-ADVISE transmission model in India.

Results from this modeling exercise suggest that 90% coverage of both sexes would bring the prevalence of HPV 16 close to elimination, defined as reducing the prevalence of HPV 16 to below 10 per 100,000 in the population.

In addition, because even at this low level, HPV transmission can be sustained in a small group of sex workers and their clients, achieving 95% coverage of 10-year-old girls who might become female sex workers in the future will likely achieve the goal of HPV 16 elimination, as Dr. Jit suggests.
 

OPSCC elimination

Elimination of another HPV-related cancer, oropharyngeal squamous cell carcinomas (OPSCCs), is discussed in another paper in the same journal.

HPV-related OPSCCs are mostly associated specifically with HPV 16.

There is currently an epidemic of this cancer among middle-aged men in the Nordic countries of Denmark, Finland, Norway, and Sweden; incidence rates have tripled over the past 30 years, note Tuomas Lehtinen, PhD, FICAN-MID, Tampere, Finland and colleagues.

They propose a two-step action plan – gender-neutral vaccination in adolescent boys and girls, and a screening program for adults born in 1995 or earlier.

The first step is already underway, and the recent implementation of school-based HPV vaccination programs in the Nordic countries is predicted to gradually decrease the incidence of HPV-related OPSCCs, they write.

“Even if HPV vaccination does not cure established infections, it can prevent re-infection/recurrence of associated lesions in 45% to 65% of individuals with anal or cervical intraepithelial neoplasia,” the authors write, “and there is high VE (vaccine efficacy) against oropharyngeal HPV infections as well.”

Furthermore, there is a tenfold relative risk of tonsillar and base of tongue cancers in spouses of women diagnosed with invasive anogenital cancer, researchers also point out. “This underlines the importance of breaking genito-oral transmission chains.”

The screening of adults born in 1995 for HPV-related OPSCC is still at a planning stage.

In a proof-of-concept study for the stepwise prevention of OPSCC, the authors suggest that target birth cohorts first be stratified and then randomized into serological HPV 16 E6 antibody screening or no screening. HPV 16 antibody-positive women and their spouses then could be invited for HPV vaccination followed by 2 HPV DNA tests.

Unscreened women and their spouses would serve as population-based controls. “Even if gender-neutral vaccination results in rapid elimination of HPV circulation, the effects of persistent, [prevalent] HPV infections on the most HPV-associated tonsillar cancer will continue for decades after HPV circulation has stopped,” the authors predict.

The Jit study was funded by the Bill & Melinda Gates Foundation and the National Institute for Health. The Lehtinen study was supported by grants from the Finnish Cancer Society and Tampere Tuberculosis Foundation. Dr. Jit and Dr. Lehtinen have disclosed no relevant financial relationships. Dr. Giuliano serves on the advisory board for Merck, which markets the HPV vaccine Gardasil.

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

The World Health Organization’s call for the elimination of cervical cancer worldwide is a laudable goal and one that many organizations across the globe have endorsed.

Yet some would say that this goal goes only halfway, and that the real finish line should be to eliminate all vaccine-type HPV infections that cause multiple cancers, in men as well as women.

One proponent of sweeping HPV prevention is Mark Jit, PhD, from the London School of Hygiene & Tropical Medicine.

In the long run, the WHO’s call to eliminate cervical cancer is “insufficiently ambitious” he writes in a special issue of Preventive Medicine.

“The point is, if you are trying to eliminate cervical cancer, you’ve run part of the race,” he said.

“But why not run that extra third and get rid of the virus, then you never have to worry about it again,” Dr. Jit elaborated in an interview.

Winning that race, however, is dependent on a gender-neutral HPV vaccination policy, he pointed out.

At present, the WHO advocates only for female vaccination and screening.

Some countries have already taken the matter into their own hands. As of May 2020, 33 countries and four territories have gender-neutral vaccination schedules.

Others are also calling for gender-neutral HPV vaccination to achieve a far wider public health good.

“I completely agree that our ultimate goal should be the elimination of all HPV-related cancers – but we will require gender-neutral vaccination to do it,” says Anna Giuliano, PhD, professor and director, Center for Immunization and Infection Research in Cancer, Moffitt Cancer Center, Tampa.

“The reason why WHO started with cervical cancer elimination is that it is likely to be the first cancer that we can achieve this with, and if you look internationally, cervical cancer has the highest burden,” Dr. Giuliano told this news organization.

“But it’s important to understand that it’s not just females who are at risk for HPV disease, men have serious consequences from HPV infection, too,” she said.

In fact, rates of HPV-related cancers and mortality in men exceed those for women in countries that have effective cervical cancer screening programs, she points out in an editorial in the same issue of Preventive Medicine.

Rates in men are driven largely by HPV-related oropharyngeal cancer, but not only, Dr. Giuliano noted in an interview.

Rates of anal cancer among men who have sex with men (MSM) are at least as high as rates of cervical cancer among women living in the poorest countries of the world, where 85% of cervical cancer deaths now occur, she noted. If MSM are HIV positive, rates of anal cancer are even higher.
 

Unethical to leave males out?

Arguments in favor of gender-neutral HPV vaccination abound, but the most compelling among them is that society really should give males an opportunity to receive direct protection against all types of HPV infection, Dr. Giuliano commented.

Indeed, in the U.K., experts argue that it is unethical to leave males out of achieving direct protection against HPV infection, she noted.

With a female-only vaccination strategy, “males are only protected if they stay in a population where there are high female vaccination rates – and very few countries have achieved high rates of vaccine dissemination and have sustained it,” she pointed out. But that applies only to heterosexual men, who develop some herd immunity from exposure to vaccinated females; this is not the case for MSM.

On a pragmatic note, a vaccine program that targets a larger number of people against HPV infection – which would be achieved with gender-neutral vaccination – is going to be more resilient against temporary changes in vaccine uptake, such as what has happened over the past year.

“During the pandemic, people may have had virtual clinic visits, but they haven’t had in-person visits, which is what you need for vaccination,” Dr. Giuliano pointed out. “So over the past year, there has been a major drop in vaccination rates,” she said.
 

Eliminating cervical cancer

Currently, the WHO plans for eliminating cervical cancer involve a strategy of vaccinating 90% of girls by the age of 15, screening 70% of women with a high performance test by the age of 35 and again at 45, and treating 90% of women with cervical disease – the so-called “90-70-90” strategy.

Dr. Jit agrees that very high levels of vaccine coverage would eradicate the HPV types causing almost all cases of cervical cancer. The same strategy would also sharply reduce the need for preventive measures in the future.

However, as Dr. Jit argues, 90% female-only coverage will not be sufficient to eliminate HPV 16 transmission, although 90% coverage in both males and females – namely a gender-neutral strategy – might. To show this, Dr. Jit and colleagues used the HPV-ADVISE transmission model in India.

Results from this modeling exercise suggest that 90% coverage of both sexes would bring the prevalence of HPV 16 close to elimination, defined as reducing the prevalence of HPV 16 to below 10 per 100,000 in the population.

In addition, because even at this low level, HPV transmission can be sustained in a small group of sex workers and their clients, achieving 95% coverage of 10-year-old girls who might become female sex workers in the future will likely achieve the goal of HPV 16 elimination, as Dr. Jit suggests.
 

OPSCC elimination

Elimination of another HPV-related cancer, oropharyngeal squamous cell carcinomas (OPSCCs), is discussed in another paper in the same journal.

HPV-related OPSCCs are mostly associated specifically with HPV 16.

There is currently an epidemic of this cancer among middle-aged men in the Nordic countries of Denmark, Finland, Norway, and Sweden; incidence rates have tripled over the past 30 years, note Tuomas Lehtinen, PhD, FICAN-MID, Tampere, Finland and colleagues.

They propose a two-step action plan – gender-neutral vaccination in adolescent boys and girls, and a screening program for adults born in 1995 or earlier.

The first step is already underway, and the recent implementation of school-based HPV vaccination programs in the Nordic countries is predicted to gradually decrease the incidence of HPV-related OPSCCs, they write.

“Even if HPV vaccination does not cure established infections, it can prevent re-infection/recurrence of associated lesions in 45% to 65% of individuals with anal or cervical intraepithelial neoplasia,” the authors write, “and there is high VE (vaccine efficacy) against oropharyngeal HPV infections as well.”

Furthermore, there is a tenfold relative risk of tonsillar and base of tongue cancers in spouses of women diagnosed with invasive anogenital cancer, researchers also point out. “This underlines the importance of breaking genito-oral transmission chains.”

The screening of adults born in 1995 for HPV-related OPSCC is still at a planning stage.

In a proof-of-concept study for the stepwise prevention of OPSCC, the authors suggest that target birth cohorts first be stratified and then randomized into serological HPV 16 E6 antibody screening or no screening. HPV 16 antibody-positive women and their spouses then could be invited for HPV vaccination followed by 2 HPV DNA tests.

Unscreened women and their spouses would serve as population-based controls. “Even if gender-neutral vaccination results in rapid elimination of HPV circulation, the effects of persistent, [prevalent] HPV infections on the most HPV-associated tonsillar cancer will continue for decades after HPV circulation has stopped,” the authors predict.

The Jit study was funded by the Bill & Melinda Gates Foundation and the National Institute for Health. The Lehtinen study was supported by grants from the Finnish Cancer Society and Tampere Tuberculosis Foundation. Dr. Jit and Dr. Lehtinen have disclosed no relevant financial relationships. Dr. Giuliano serves on the advisory board for Merck, which markets the HPV vaccine Gardasil.

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

People experiencing long-term symptoms following acute COVID-19 infection are increasingly meeting criteria for myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), a phenomenon that highlights the need for unified research and clinical approaches, speakers said at a press briefing March 25 held by the advocacy group MEAction.

“Post-COVID lingering illness was predictable. Similar lingering fatigue syndromes have been reported in the scientific literature for nearly 100 years, following a variety of well-documented infections with viruses, bacteria, fungi, and even protozoa,” said Anthony Komaroff, MD, professor of medicine at Harvard Medical School, Boston.

Core criteria for ME/CFS established by the Institute of Medicine in 2015 include substantial decrement in functioning for at least 6 months, postexertional malaise (PEM), or a worsening of symptoms following even minor exertion (often described as “crashes”), unrefreshing sleep, and cognitive impairment and/or orthostatic intolerance.

Patients with ME/CFS also commonly experience painful headaches, muscle or joint aches, and allergies/other sensitivities. Although many patients can trace their symptoms to an initiating infection, “the cause is often unclear because the diagnosis is often delayed for months or years after symptom onset,” said Lucinda Bateman, MD, founder of the Bateman Horne Center, Salt Lake City, who leads a clinician coalition that aims to improve ME/CFS management.

In an international survey of 3762 COVID-19 “long-haulers” published in a preprint in December of 2020, the most frequent symptoms reported at least 6 months after illness onset were fatigue in 78%, PEM in 72%, and cognitive dysfunction (“brain fog”) in 55%. At the time of the survey, 45% reported requiring reduced work schedules because of their illness, and 22% reported being unable to work at all.

Dr. Bateman said those findings align with her experience so far with 12 COVID-19 “long haulers” who self-referred to her ME/CFS and fibromyalgia specialty clinic. Nine of the 12 met criteria for postural orthostatic tachycardia syndrome (POTS) based on the 10-minute NASA Lean Test, she said, and half also met the 2016 American College of Rheumatology criteria for fibromyalgia.

“Some were severely impaired. We suspect a small fiber polyneuropathy in about half, and mast cell activation syndrome in more than half. We look forward to doing more testing,” Dr. Bateman said.

To be sure, Dr. Komaroff noted, there are some differences. “Long COVID” patients will often experience breathlessness and ongoing anosmia (loss of taste and smell), which aren’t typical of ME/CFS.

But, he said, “many of the symptoms are quite similar ... My guess is that ME/CFS is an illness with a final common pathway that can be triggered by different things,” said Dr. Komaroff, a senior physician at Brigham and Women’s Hospital in Boston, and editor-in-chief of the Harvard Health Letter.

Based on previous data about CFS suggesting a 10% rate of symptoms persisting at least a year following a variety of infectious agents and the predicted 200 million COVID-19 cases globally by the end of 2021, Dr. Komaroff estimated that about 20 million cases of “long COVID” would be expected in the next year.

‘A huge investment’

On the research side, the National Institutes of Health recently appropriated $1.15 billion dollars over the next 4 years to investigate “the heterogeneity in the recovery process after COVID and to develop treatments for those suffering from [postacute COVID-19 syndrome]” according to a Feb. 5, 2021, blog from the National Institute of Neurological Disorders and Stroke (NINDS).

That same day, another NINDS blog announced “new resources for large-scale ME/CFS research” and emphasized the tie-in with long–COVID-19 syndrome.

“That’s a huge investment. In my opinion, there will be several lingering illnesses following COVID,” Dr. Komaroff said, adding, “It’s my bet that long COVID will prove to be caused by certain kinds of abnormalities in the brain, some of the same abnormalities already identified in ME/CFS. Research will determine whether that’s right or wrong.”

In 2017, NINDS had announced a large increase in funding for ME/CFS research, including the creation of four dedicated research centers. In April 2019, NINDS held a 2-day conference highlighting that ongoing work, as reported by Medscape Medical News.

During the briefing, NINDS clinical director Avindra Nath, MD, described a comprehensive ongoing ME/CFS intramural study he’s been leading since 2016.

He’s now also overseeing two long–COVID-19 studies, one of which has a protocol similar to that of the ME/CFS study and will include individuals who are still experiencing long-term symptoms following confirmed cases of COVID-19. The aim is to screen about 1,300 patients. Several task forces are now examining all of these data together.

“Each aspect is now being analyzed … What we learn from one applies to the other,” Dr. Nath said.  
 

Advice for clinicians

In interviews, Dr. Bateman and Dr. Nath offered clinical advice for managing patients who meet ME/CFS criteria, whether they had confirmed or suspected COVID-19, a different infection, or unknown trigger(s).

Dr. Bateman advised that clinicians assess patients for each of the symptoms individually. “Besides exercise intolerance and PEM, the most commonly missed is orthostatic intolerance. It really doesn’t matter what the cause is, it’s amenable to supportive treatment. It’s one aspect of the illness that contributes to severely impaired function. My plea to all physicians would be for sure to assess for [orthostatic intolerance], and gain an understanding about activity management and avoiding PEM symptoms.”

Dr. Nath noted that an often-challenging situation is when tests for the infectious agent and other blood work come back negative, yet the patient still reports multiple debilitating symptoms. This has been a particular issue with long COVID-19, since many patients became ill early in the pandemic before the polymerase chain reaction (PCR) tests for SARS-CoV-2 were widely available.

“The physician can only order tests that are available at their labs. I think what the physician should do is handle symptoms symptomatically but also refer patients to specialists who are taking care of these patients or to research studies,” he said.

Dr. Bateman added, “Whether they had a documented COVID infection – we just have to let go of that in 2020. Way too many people didn’t have access to a test or the timing wasn’t amenable. If people meet criteria for ME/CFS, it’s irrelevant … It’s mainly a clinical diagnosis. It’s not reliant on identifying the infectious trigger.” 

Dr. Komaroff, who began caring for then-termed “chronic fatigue syndrome” patients and researching the condition more than 30 years ago, said that “every cloud has its silver lining. The increased focus on postinfectious fatigue syndrome is a silver lining in my mind around the terrible dark cloud that is the pandemic of COVID.”

Dr. Komaroff has received personal fees from Serimmune Inc., Ono Pharma, and Deallus, and grants from the NIH. Dr. Bateman is employed by the Bateman Horne Center, which receives grants from the NIH, and fees from Exagen Inc., and Teva Pharmaceutical. Dr. Nath is an NIH employee.

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

People experiencing long-term symptoms following acute COVID-19 infection are increasingly meeting criteria for myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), a phenomenon that highlights the need for unified research and clinical approaches, speakers said at a press briefing March 25 held by the advocacy group MEAction.

“Post-COVID lingering illness was predictable. Similar lingering fatigue syndromes have been reported in the scientific literature for nearly 100 years, following a variety of well-documented infections with viruses, bacteria, fungi, and even protozoa,” said Anthony Komaroff, MD, professor of medicine at Harvard Medical School, Boston.

Core criteria for ME/CFS established by the Institute of Medicine in 2015 include substantial decrement in functioning for at least 6 months, postexertional malaise (PEM), or a worsening of symptoms following even minor exertion (often described as “crashes”), unrefreshing sleep, and cognitive impairment and/or orthostatic intolerance.

Patients with ME/CFS also commonly experience painful headaches, muscle or joint aches, and allergies/other sensitivities. Although many patients can trace their symptoms to an initiating infection, “the cause is often unclear because the diagnosis is often delayed for months or years after symptom onset,” said Lucinda Bateman, MD, founder of the Bateman Horne Center, Salt Lake City, who leads a clinician coalition that aims to improve ME/CFS management.

In an international survey of 3762 COVID-19 “long-haulers” published in a preprint in December of 2020, the most frequent symptoms reported at least 6 months after illness onset were fatigue in 78%, PEM in 72%, and cognitive dysfunction (“brain fog”) in 55%. At the time of the survey, 45% reported requiring reduced work schedules because of their illness, and 22% reported being unable to work at all.

Dr. Bateman said those findings align with her experience so far with 12 COVID-19 “long haulers” who self-referred to her ME/CFS and fibromyalgia specialty clinic. Nine of the 12 met criteria for postural orthostatic tachycardia syndrome (POTS) based on the 10-minute NASA Lean Test, she said, and half also met the 2016 American College of Rheumatology criteria for fibromyalgia.

“Some were severely impaired. We suspect a small fiber polyneuropathy in about half, and mast cell activation syndrome in more than half. We look forward to doing more testing,” Dr. Bateman said.

To be sure, Dr. Komaroff noted, there are some differences. “Long COVID” patients will often experience breathlessness and ongoing anosmia (loss of taste and smell), which aren’t typical of ME/CFS.

But, he said, “many of the symptoms are quite similar ... My guess is that ME/CFS is an illness with a final common pathway that can be triggered by different things,” said Dr. Komaroff, a senior physician at Brigham and Women’s Hospital in Boston, and editor-in-chief of the Harvard Health Letter.

Based on previous data about CFS suggesting a 10% rate of symptoms persisting at least a year following a variety of infectious agents and the predicted 200 million COVID-19 cases globally by the end of 2021, Dr. Komaroff estimated that about 20 million cases of “long COVID” would be expected in the next year.

‘A huge investment’

On the research side, the National Institutes of Health recently appropriated $1.15 billion dollars over the next 4 years to investigate “the heterogeneity in the recovery process after COVID and to develop treatments for those suffering from [postacute COVID-19 syndrome]” according to a Feb. 5, 2021, blog from the National Institute of Neurological Disorders and Stroke (NINDS).

That same day, another NINDS blog announced “new resources for large-scale ME/CFS research” and emphasized the tie-in with long–COVID-19 syndrome.

“That’s a huge investment. In my opinion, there will be several lingering illnesses following COVID,” Dr. Komaroff said, adding, “It’s my bet that long COVID will prove to be caused by certain kinds of abnormalities in the brain, some of the same abnormalities already identified in ME/CFS. Research will determine whether that’s right or wrong.”

In 2017, NINDS had announced a large increase in funding for ME/CFS research, including the creation of four dedicated research centers. In April 2019, NINDS held a 2-day conference highlighting that ongoing work, as reported by Medscape Medical News.

During the briefing, NINDS clinical director Avindra Nath, MD, described a comprehensive ongoing ME/CFS intramural study he’s been leading since 2016.

He’s now also overseeing two long–COVID-19 studies, one of which has a protocol similar to that of the ME/CFS study and will include individuals who are still experiencing long-term symptoms following confirmed cases of COVID-19. The aim is to screen about 1,300 patients. Several task forces are now examining all of these data together.

“Each aspect is now being analyzed … What we learn from one applies to the other,” Dr. Nath said.  
 

Advice for clinicians

In interviews, Dr. Bateman and Dr. Nath offered clinical advice for managing patients who meet ME/CFS criteria, whether they had confirmed or suspected COVID-19, a different infection, or unknown trigger(s).

Dr. Bateman advised that clinicians assess patients for each of the symptoms individually. “Besides exercise intolerance and PEM, the most commonly missed is orthostatic intolerance. It really doesn’t matter what the cause is, it’s amenable to supportive treatment. It’s one aspect of the illness that contributes to severely impaired function. My plea to all physicians would be for sure to assess for [orthostatic intolerance], and gain an understanding about activity management and avoiding PEM symptoms.”

Dr. Nath noted that an often-challenging situation is when tests for the infectious agent and other blood work come back negative, yet the patient still reports multiple debilitating symptoms. This has been a particular issue with long COVID-19, since many patients became ill early in the pandemic before the polymerase chain reaction (PCR) tests for SARS-CoV-2 were widely available.

“The physician can only order tests that are available at their labs. I think what the physician should do is handle symptoms symptomatically but also refer patients to specialists who are taking care of these patients or to research studies,” he said.

Dr. Bateman added, “Whether they had a documented COVID infection – we just have to let go of that in 2020. Way too many people didn’t have access to a test or the timing wasn’t amenable. If people meet criteria for ME/CFS, it’s irrelevant … It’s mainly a clinical diagnosis. It’s not reliant on identifying the infectious trigger.” 

Dr. Komaroff, who began caring for then-termed “chronic fatigue syndrome” patients and researching the condition more than 30 years ago, said that “every cloud has its silver lining. The increased focus on postinfectious fatigue syndrome is a silver lining in my mind around the terrible dark cloud that is the pandemic of COVID.”

Dr. Komaroff has received personal fees from Serimmune Inc., Ono Pharma, and Deallus, and grants from the NIH. Dr. Bateman is employed by the Bateman Horne Center, which receives grants from the NIH, and fees from Exagen Inc., and Teva Pharmaceutical. Dr. Nath is an NIH employee.

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

People experiencing long-term symptoms following acute COVID-19 infection are increasingly meeting criteria for myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), a phenomenon that highlights the need for unified research and clinical approaches, speakers said at a press briefing March 25 held by the advocacy group MEAction.

“Post-COVID lingering illness was predictable. Similar lingering fatigue syndromes have been reported in the scientific literature for nearly 100 years, following a variety of well-documented infections with viruses, bacteria, fungi, and even protozoa,” said Anthony Komaroff, MD, professor of medicine at Harvard Medical School, Boston.

Core criteria for ME/CFS established by the Institute of Medicine in 2015 include substantial decrement in functioning for at least 6 months, postexertional malaise (PEM), or a worsening of symptoms following even minor exertion (often described as “crashes”), unrefreshing sleep, and cognitive impairment and/or orthostatic intolerance.

Patients with ME/CFS also commonly experience painful headaches, muscle or joint aches, and allergies/other sensitivities. Although many patients can trace their symptoms to an initiating infection, “the cause is often unclear because the diagnosis is often delayed for months or years after symptom onset,” said Lucinda Bateman, MD, founder of the Bateman Horne Center, Salt Lake City, who leads a clinician coalition that aims to improve ME/CFS management.

In an international survey of 3762 COVID-19 “long-haulers” published in a preprint in December of 2020, the most frequent symptoms reported at least 6 months after illness onset were fatigue in 78%, PEM in 72%, and cognitive dysfunction (“brain fog”) in 55%. At the time of the survey, 45% reported requiring reduced work schedules because of their illness, and 22% reported being unable to work at all.

Dr. Bateman said those findings align with her experience so far with 12 COVID-19 “long haulers” who self-referred to her ME/CFS and fibromyalgia specialty clinic. Nine of the 12 met criteria for postural orthostatic tachycardia syndrome (POTS) based on the 10-minute NASA Lean Test, she said, and half also met the 2016 American College of Rheumatology criteria for fibromyalgia.

“Some were severely impaired. We suspect a small fiber polyneuropathy in about half, and mast cell activation syndrome in more than half. We look forward to doing more testing,” Dr. Bateman said.

To be sure, Dr. Komaroff noted, there are some differences. “Long COVID” patients will often experience breathlessness and ongoing anosmia (loss of taste and smell), which aren’t typical of ME/CFS.

But, he said, “many of the symptoms are quite similar ... My guess is that ME/CFS is an illness with a final common pathway that can be triggered by different things,” said Dr. Komaroff, a senior physician at Brigham and Women’s Hospital in Boston, and editor-in-chief of the Harvard Health Letter.

Based on previous data about CFS suggesting a 10% rate of symptoms persisting at least a year following a variety of infectious agents and the predicted 200 million COVID-19 cases globally by the end of 2021, Dr. Komaroff estimated that about 20 million cases of “long COVID” would be expected in the next year.

‘A huge investment’

On the research side, the National Institutes of Health recently appropriated $1.15 billion dollars over the next 4 years to investigate “the heterogeneity in the recovery process after COVID and to develop treatments for those suffering from [postacute COVID-19 syndrome]” according to a Feb. 5, 2021, blog from the National Institute of Neurological Disorders and Stroke (NINDS).

That same day, another NINDS blog announced “new resources for large-scale ME/CFS research” and emphasized the tie-in with long–COVID-19 syndrome.

“That’s a huge investment. In my opinion, there will be several lingering illnesses following COVID,” Dr. Komaroff said, adding, “It’s my bet that long COVID will prove to be caused by certain kinds of abnormalities in the brain, some of the same abnormalities already identified in ME/CFS. Research will determine whether that’s right or wrong.”

In 2017, NINDS had announced a large increase in funding for ME/CFS research, including the creation of four dedicated research centers. In April 2019, NINDS held a 2-day conference highlighting that ongoing work, as reported by Medscape Medical News.

During the briefing, NINDS clinical director Avindra Nath, MD, described a comprehensive ongoing ME/CFS intramural study he’s been leading since 2016.

He’s now also overseeing two long–COVID-19 studies, one of which has a protocol similar to that of the ME/CFS study and will include individuals who are still experiencing long-term symptoms following confirmed cases of COVID-19. The aim is to screen about 1,300 patients. Several task forces are now examining all of these data together.

“Each aspect is now being analyzed … What we learn from one applies to the other,” Dr. Nath said.  
 

Advice for clinicians

In interviews, Dr. Bateman and Dr. Nath offered clinical advice for managing patients who meet ME/CFS criteria, whether they had confirmed or suspected COVID-19, a different infection, or unknown trigger(s).

Dr. Bateman advised that clinicians assess patients for each of the symptoms individually. “Besides exercise intolerance and PEM, the most commonly missed is orthostatic intolerance. It really doesn’t matter what the cause is, it’s amenable to supportive treatment. It’s one aspect of the illness that contributes to severely impaired function. My plea to all physicians would be for sure to assess for [orthostatic intolerance], and gain an understanding about activity management and avoiding PEM symptoms.”

Dr. Nath noted that an often-challenging situation is when tests for the infectious agent and other blood work come back negative, yet the patient still reports multiple debilitating symptoms. This has been a particular issue with long COVID-19, since many patients became ill early in the pandemic before the polymerase chain reaction (PCR) tests for SARS-CoV-2 were widely available.

“The physician can only order tests that are available at their labs. I think what the physician should do is handle symptoms symptomatically but also refer patients to specialists who are taking care of these patients or to research studies,” he said.

Dr. Bateman added, “Whether they had a documented COVID infection – we just have to let go of that in 2020. Way too many people didn’t have access to a test or the timing wasn’t amenable. If people meet criteria for ME/CFS, it’s irrelevant … It’s mainly a clinical diagnosis. It’s not reliant on identifying the infectious trigger.” 

Dr. Komaroff, who began caring for then-termed “chronic fatigue syndrome” patients and researching the condition more than 30 years ago, said that “every cloud has its silver lining. The increased focus on postinfectious fatigue syndrome is a silver lining in my mind around the terrible dark cloud that is the pandemic of COVID.”

Dr. Komaroff has received personal fees from Serimmune Inc., Ono Pharma, and Deallus, and grants from the NIH. Dr. Bateman is employed by the Bateman Horne Center, which receives grants from the NIH, and fees from Exagen Inc., and Teva Pharmaceutical. Dr. Nath is an NIH employee.

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

Every day Melissa Fulton, RN, MSN, FNP, APRN-C, shows up to work, she’s ready for another fight. An advanced practice nurse who specializes in multiple sclerosis care, Ms. Fulton said she typically spends more than a third of her time battling it out with insurance companies over drugs she knows her patients need but that insurers don’t want to cover. Instead, they want the patient to first receive less expensive and often less efficacious drugs, even if that goes against recommendations and, in some cases, against the patient’s medical history.

The maddening protocol – familiar to health care providers everywhere – is known as “step therapy.” It forces patients to try alternative medications – medications that often fail – before receiving the one initially prescribed. The process can take weeks or months, which is time that some patients don’t have. Step therapy was sold as a way to lower costs. However, beyond the ethically problematic notion of forcing sick patients to receiver cheaper alternatives that are ineffective, research has also shown it may actually be more costly in the long run.

Ms. Fulton, who works at Saunders Medical Center in Wahoo, Neb., is a veteran in the war against step therapy. She is used to pushing her appeals up the insurance company chain of command, past nonmedical reviewers, until her patient’s case finally lands on the desk of someone with a neurology background. She said that can take three or four appeals – a judge might even get involved – and the patient could still lose. “This happens constantly,” she said, “but we fight like hell.”

Fortunately, life may soon get a little easier for Ms. Fulton. In late March, a bill to restrict step therapy made it through the Nebraska state legislature and is on its way to the governor’s desk. The Step Therapy Reform Act doesn’t outright ban the practice; however, it will put guardrails in place. It requires that insurers respond to appeals within certain time frames, and it creates key exemptions.

When the governor signs off, Nebraska will join more than two dozen other states that already have step therapy restrictions on the books, according to Hannah Lynch, MPS, associate director of federal government relations and health policy at the National Psoriasis Foundation, a leading advocate to reform and protect against the insurance practice. “There’s a lot of frustration out there,” Ms. Lynch said. “It really hinders providers’ ability to make decisions they think will have the best outcomes.”

Driven by coalitions of doctors, nurses, and patients, laws reining in step therapy have been adopted at a relatively quick clip, mostly within the past 5 years. Recent additions include South Dakota and North Carolina, which adopted step therapy laws in 2020, and Arkansas, which passed a law earlier this year.

Ms. Lynch attributed growing support to rising out-of-pocket drug costs and the introduction of biologic drugs, which are often more effective but also more expensive. Like Nebraska’s law, most step therapy reform legislation carves out exemptions and requires timely appeals processes; however, many of the laws still have significant gaps, such as not including certain types of insurance plans.

Ideally, Ms. Lynch said, the protections would apply to all types of health plans that are regulated at the state level, such as Medicaid, state employee health plans, and coverage sold through state insurance exchanges. Closing loopholes in the laws is a top priority for advocates, she added, pointing to work currently underway in Arkansas to extend its new protections to Medicaid expansion patients.

“With so many outside stakeholders, you have to compromise – it’s a give and take,” Ms. Lynch said. Still, when it comes to fighting step therapy, she says, “Any protection on the books is always our first goal when we go into a state.”

Putting patients first

Lisa Arkin, MD, a pediatric dermatologist at the University of Wisconsin–Madison, said she finds herself “swimming upstream every day in the fight with insurance.” Her patients are typically on their second or third stop and have more complex disorders. Dr. Arkin said that the problem with step therapy is that it tries to squeeze all patients into the same box, even if the circumstances don’t fit.

Her state passed restrictions on step therapy in 2019, but the measures only went into effect last year. Under the Wisconsin law, patients can be granted an exemption if an alternative treatment is contraindicated, likely to cause harm, or expected to be ineffective. Patients can also be exempt if their current treatment is working.

Dr. Arkin, an outspoken advocate for curbing step therapy, says the Wisconsin law is “very strong.” However, because it only applies to certain health plans – state employee health plans and those purchased in the state’s health insurance exchange – fewer than half the state’s patients benefit from its protections. She notes that some of the most severe presentations she treats occur in patients who rely on Medicaid coverage and already face barriers to care.

“I’m a doctor who puts up a fuss [with insurers], but that’s not fair – we shouldn’t have to do that,” Dr. Arkin said. “To me, it’s really critical to make this an even playing field so this law affords protection to everyone I see in the clinic.”

Major medical associations caution against step therapy as well. The American Society of Clinical Oncology and the American Medical Association have called out the risks to patient safety and health. In fact, in 2019, after the Centers for Medicare & Medicaid Services gave new authority to Medicare Advantage plans to start using step therapy, dozens of national medical groups called out the agency for allowing a practice that could potentially hurt patients and undercut the physician-patient decision-making process.

Last year, in a new position paper from the American College of Physicians, authors laid out recommendations for combating step therapy’s side effects. These recommendations included making related data transparent to the public and minimizing the policy’s disruptions to care. Jacqueline W. Fincher, MD, MACP, a member of the committee that issued the position paper and who is a primary care physician in Georgia, said such insurance practices need to be designed with “strong input from frontline physicians, not clipboard physicians.

“What we want from insurers is understanding, transparency, and the least burdensome protocol to provide patients the care they need at a cost-effective price they can afford,” said Dr. Fincher, who is also the current president of the ACP. “The focus needs to be on what’s in the patient’s best interest.”
 

Every year a new fight

“We all dread January,” said Dr. Fincher. That is the worst month, she added, because new health benefits go into effect, which means patients who are responding well to certain treatments may suddenly face new restrictions.

Another aggravating aspect of step therapy? It is often difficult – if not impossible – to access information on specific step therapy protocols in a patient’s health plan in real time in the exam room, where treatment conversations actually take place. In a more patient-centered world, Dr. Fincher said, she would be able to use the electronic health record system to quickly identify whether a patient’s plan covers a particular treatment and, if not, what the alternatives are.

Georgia’s new step therapy law went into effect last year. Like laws in other states, it spells out step therapy exemptions and sets time frames in which insurers must respond to exceptions and appeals. Dr. Fincher, who spoke in favor of the new law, said she’s “happy for any step forward.” Still, the growing burden of prior authorization rules are an utter “time sink” for her and her staff.

“I have to justify my decisions to nondoctors before I even get to a doctor, and that’s really frustrating,” she said. “We’re talking about people here, not widgets.”

Advocates in Nevada are hoping this is the year a step therapy bill will make it into law in their state. As of March, one had yet to be introduced in the state legislature. Tom McCoy, director of state government affairs at the Nevada Chronic Care Collaborative, said existing Nevada law already prohibits nonmedical drug switching during a policy year; however, insurers can still make changes the following year.

A bill to rein in step therapy was proposed previously, Mr. McCoy said, but it never got off the ground. The collaborative, as well as about two dozen organizations representing Nevada providers and patients, are now calling on state lawmakers to make the issue a priority in the current session.

“The health plans have a lot of power – a lot,” Mr. McCoy said. “We’re hoping to get a [legislative] sponsor in 2021 ... but it’s also been a really hard year to connect legislators with patients and doctors, and being able to hear their stories really does make a difference.”

In Nebraska, Marcus Snow, MD, a rheumatologist at Nebraska Medicine, in Omaha, said that the state’s new step therapy law will be a “great first step in helping to provide some guardrails” around the practice. He noted that turnaround requirements for insurer responses are “sorely needed.” However, he said that, because the bill doesn’t apply to all health plans, many Nebraskans still won’t benefit.

Dealing with step therapy is a daily “headache” for Dr. Snow, who says navigating the bureaucracy of prior authorization seems to be getting worse every year. Like his peers around the country, he spends an inordinate amount of time pushing appeals up the insurance company ranks to get access to treatments he believes will be most effective. But Snow says that, more than just being a mountain of tiresome red tape, these practices also intrude on the patient-provider relationship, casting an unsettling sense of uncertainty that the ultimate decision about the best course of action isn’t up to the doctor and patient at all.

“In the end, the insurance company is the judge and jury of my prescription,” Dr. Snow said. “They’d argue I can still prescribe it, but if it costs $70,000 a year – I don’t know who can afford that.”

Ms. Lynch, at the National Psoriasis Foundation, said their step therapy advocacy will continue to take a two-pronged approach. They will push for new and expanded protections at both state and federal levels. Protections are needed at both levels to make sure that all health plans regulated by all entities are covered. In the U.S. Senate and the House, step therapy bills were reintroduced this year. They would apply to health plans subject to the federal Employee Retirement Income Security Act, which governs employer-sponsored health coverage, and could close a big gap in existing protections. Oregon, New Jersey, and Arizona are at the top of the foundation’s advocacy list this year, according to Ms. Lynch.

“Folks are really starting to pay more attention to this issue,” she said. “And hearing those real-world stories and frustrations is definitely one of the most effective tools we have.”

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

Every day Melissa Fulton, RN, MSN, FNP, APRN-C, shows up to work, she’s ready for another fight. An advanced practice nurse who specializes in multiple sclerosis care, Ms. Fulton said she typically spends more than a third of her time battling it out with insurance companies over drugs she knows her patients need but that insurers don’t want to cover. Instead, they want the patient to first receive less expensive and often less efficacious drugs, even if that goes against recommendations and, in some cases, against the patient’s medical history.

The maddening protocol – familiar to health care providers everywhere – is known as “step therapy.” It forces patients to try alternative medications – medications that often fail – before receiving the one initially prescribed. The process can take weeks or months, which is time that some patients don’t have. Step therapy was sold as a way to lower costs. However, beyond the ethically problematic notion of forcing sick patients to receiver cheaper alternatives that are ineffective, research has also shown it may actually be more costly in the long run.

Ms. Fulton, who works at Saunders Medical Center in Wahoo, Neb., is a veteran in the war against step therapy. She is used to pushing her appeals up the insurance company chain of command, past nonmedical reviewers, until her patient’s case finally lands on the desk of someone with a neurology background. She said that can take three or four appeals – a judge might even get involved – and the patient could still lose. “This happens constantly,” she said, “but we fight like hell.”

Fortunately, life may soon get a little easier for Ms. Fulton. In late March, a bill to restrict step therapy made it through the Nebraska state legislature and is on its way to the governor’s desk. The Step Therapy Reform Act doesn’t outright ban the practice; however, it will put guardrails in place. It requires that insurers respond to appeals within certain time frames, and it creates key exemptions.

When the governor signs off, Nebraska will join more than two dozen other states that already have step therapy restrictions on the books, according to Hannah Lynch, MPS, associate director of federal government relations and health policy at the National Psoriasis Foundation, a leading advocate to reform and protect against the insurance practice. “There’s a lot of frustration out there,” Ms. Lynch said. “It really hinders providers’ ability to make decisions they think will have the best outcomes.”

Driven by coalitions of doctors, nurses, and patients, laws reining in step therapy have been adopted at a relatively quick clip, mostly within the past 5 years. Recent additions include South Dakota and North Carolina, which adopted step therapy laws in 2020, and Arkansas, which passed a law earlier this year.

Ms. Lynch attributed growing support to rising out-of-pocket drug costs and the introduction of biologic drugs, which are often more effective but also more expensive. Like Nebraska’s law, most step therapy reform legislation carves out exemptions and requires timely appeals processes; however, many of the laws still have significant gaps, such as not including certain types of insurance plans.

Ideally, Ms. Lynch said, the protections would apply to all types of health plans that are regulated at the state level, such as Medicaid, state employee health plans, and coverage sold through state insurance exchanges. Closing loopholes in the laws is a top priority for advocates, she added, pointing to work currently underway in Arkansas to extend its new protections to Medicaid expansion patients.

“With so many outside stakeholders, you have to compromise – it’s a give and take,” Ms. Lynch said. Still, when it comes to fighting step therapy, she says, “Any protection on the books is always our first goal when we go into a state.”

Putting patients first

Lisa Arkin, MD, a pediatric dermatologist at the University of Wisconsin–Madison, said she finds herself “swimming upstream every day in the fight with insurance.” Her patients are typically on their second or third stop and have more complex disorders. Dr. Arkin said that the problem with step therapy is that it tries to squeeze all patients into the same box, even if the circumstances don’t fit.

Her state passed restrictions on step therapy in 2019, but the measures only went into effect last year. Under the Wisconsin law, patients can be granted an exemption if an alternative treatment is contraindicated, likely to cause harm, or expected to be ineffective. Patients can also be exempt if their current treatment is working.

Dr. Arkin, an outspoken advocate for curbing step therapy, says the Wisconsin law is “very strong.” However, because it only applies to certain health plans – state employee health plans and those purchased in the state’s health insurance exchange – fewer than half the state’s patients benefit from its protections. She notes that some of the most severe presentations she treats occur in patients who rely on Medicaid coverage and already face barriers to care.

“I’m a doctor who puts up a fuss [with insurers], but that’s not fair – we shouldn’t have to do that,” Dr. Arkin said. “To me, it’s really critical to make this an even playing field so this law affords protection to everyone I see in the clinic.”

Major medical associations caution against step therapy as well. The American Society of Clinical Oncology and the American Medical Association have called out the risks to patient safety and health. In fact, in 2019, after the Centers for Medicare & Medicaid Services gave new authority to Medicare Advantage plans to start using step therapy, dozens of national medical groups called out the agency for allowing a practice that could potentially hurt patients and undercut the physician-patient decision-making process.

Last year, in a new position paper from the American College of Physicians, authors laid out recommendations for combating step therapy’s side effects. These recommendations included making related data transparent to the public and minimizing the policy’s disruptions to care. Jacqueline W. Fincher, MD, MACP, a member of the committee that issued the position paper and who is a primary care physician in Georgia, said such insurance practices need to be designed with “strong input from frontline physicians, not clipboard physicians.

“What we want from insurers is understanding, transparency, and the least burdensome protocol to provide patients the care they need at a cost-effective price they can afford,” said Dr. Fincher, who is also the current president of the ACP. “The focus needs to be on what’s in the patient’s best interest.”
 

Every year a new fight

“We all dread January,” said Dr. Fincher. That is the worst month, she added, because new health benefits go into effect, which means patients who are responding well to certain treatments may suddenly face new restrictions.

Another aggravating aspect of step therapy? It is often difficult – if not impossible – to access information on specific step therapy protocols in a patient’s health plan in real time in the exam room, where treatment conversations actually take place. In a more patient-centered world, Dr. Fincher said, she would be able to use the electronic health record system to quickly identify whether a patient’s plan covers a particular treatment and, if not, what the alternatives are.

Georgia’s new step therapy law went into effect last year. Like laws in other states, it spells out step therapy exemptions and sets time frames in which insurers must respond to exceptions and appeals. Dr. Fincher, who spoke in favor of the new law, said she’s “happy for any step forward.” Still, the growing burden of prior authorization rules are an utter “time sink” for her and her staff.

“I have to justify my decisions to nondoctors before I even get to a doctor, and that’s really frustrating,” she said. “We’re talking about people here, not widgets.”

Advocates in Nevada are hoping this is the year a step therapy bill will make it into law in their state. As of March, one had yet to be introduced in the state legislature. Tom McCoy, director of state government affairs at the Nevada Chronic Care Collaborative, said existing Nevada law already prohibits nonmedical drug switching during a policy year; however, insurers can still make changes the following year.

A bill to rein in step therapy was proposed previously, Mr. McCoy said, but it never got off the ground. The collaborative, as well as about two dozen organizations representing Nevada providers and patients, are now calling on state lawmakers to make the issue a priority in the current session.

“The health plans have a lot of power – a lot,” Mr. McCoy said. “We’re hoping to get a [legislative] sponsor in 2021 ... but it’s also been a really hard year to connect legislators with patients and doctors, and being able to hear their stories really does make a difference.”

In Nebraska, Marcus Snow, MD, a rheumatologist at Nebraska Medicine, in Omaha, said that the state’s new step therapy law will be a “great first step in helping to provide some guardrails” around the practice. He noted that turnaround requirements for insurer responses are “sorely needed.” However, he said that, because the bill doesn’t apply to all health plans, many Nebraskans still won’t benefit.

Dealing with step therapy is a daily “headache” for Dr. Snow, who says navigating the bureaucracy of prior authorization seems to be getting worse every year. Like his peers around the country, he spends an inordinate amount of time pushing appeals up the insurance company ranks to get access to treatments he believes will be most effective. But Snow says that, more than just being a mountain of tiresome red tape, these practices also intrude on the patient-provider relationship, casting an unsettling sense of uncertainty that the ultimate decision about the best course of action isn’t up to the doctor and patient at all.

“In the end, the insurance company is the judge and jury of my prescription,” Dr. Snow said. “They’d argue I can still prescribe it, but if it costs $70,000 a year – I don’t know who can afford that.”

Ms. Lynch, at the National Psoriasis Foundation, said their step therapy advocacy will continue to take a two-pronged approach. They will push for new and expanded protections at both state and federal levels. Protections are needed at both levels to make sure that all health plans regulated by all entities are covered. In the U.S. Senate and the House, step therapy bills were reintroduced this year. They would apply to health plans subject to the federal Employee Retirement Income Security Act, which governs employer-sponsored health coverage, and could close a big gap in existing protections. Oregon, New Jersey, and Arizona are at the top of the foundation’s advocacy list this year, according to Ms. Lynch.

“Folks are really starting to pay more attention to this issue,” she said. “And hearing those real-world stories and frustrations is definitely one of the most effective tools we have.”

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

Every day Melissa Fulton, RN, MSN, FNP, APRN-C, shows up to work, she’s ready for another fight. An advanced practice nurse who specializes in multiple sclerosis care, Ms. Fulton said she typically spends more than a third of her time battling it out with insurance companies over drugs she knows her patients need but that insurers don’t want to cover. Instead, they want the patient to first receive less expensive and often less efficacious drugs, even if that goes against recommendations and, in some cases, against the patient’s medical history.

The maddening protocol – familiar to health care providers everywhere – is known as “step therapy.” It forces patients to try alternative medications – medications that often fail – before receiving the one initially prescribed. The process can take weeks or months, which is time that some patients don’t have. Step therapy was sold as a way to lower costs. However, beyond the ethically problematic notion of forcing sick patients to receiver cheaper alternatives that are ineffective, research has also shown it may actually be more costly in the long run.

Ms. Fulton, who works at Saunders Medical Center in Wahoo, Neb., is a veteran in the war against step therapy. She is used to pushing her appeals up the insurance company chain of command, past nonmedical reviewers, until her patient’s case finally lands on the desk of someone with a neurology background. She said that can take three or four appeals – a judge might even get involved – and the patient could still lose. “This happens constantly,” she said, “but we fight like hell.”

Fortunately, life may soon get a little easier for Ms. Fulton. In late March, a bill to restrict step therapy made it through the Nebraska state legislature and is on its way to the governor’s desk. The Step Therapy Reform Act doesn’t outright ban the practice; however, it will put guardrails in place. It requires that insurers respond to appeals within certain time frames, and it creates key exemptions.

When the governor signs off, Nebraska will join more than two dozen other states that already have step therapy restrictions on the books, according to Hannah Lynch, MPS, associate director of federal government relations and health policy at the National Psoriasis Foundation, a leading advocate to reform and protect against the insurance practice. “There’s a lot of frustration out there,” Ms. Lynch said. “It really hinders providers’ ability to make decisions they think will have the best outcomes.”

Driven by coalitions of doctors, nurses, and patients, laws reining in step therapy have been adopted at a relatively quick clip, mostly within the past 5 years. Recent additions include South Dakota and North Carolina, which adopted step therapy laws in 2020, and Arkansas, which passed a law earlier this year.

Ms. Lynch attributed growing support to rising out-of-pocket drug costs and the introduction of biologic drugs, which are often more effective but also more expensive. Like Nebraska’s law, most step therapy reform legislation carves out exemptions and requires timely appeals processes; however, many of the laws still have significant gaps, such as not including certain types of insurance plans.

Ideally, Ms. Lynch said, the protections would apply to all types of health plans that are regulated at the state level, such as Medicaid, state employee health plans, and coverage sold through state insurance exchanges. Closing loopholes in the laws is a top priority for advocates, she added, pointing to work currently underway in Arkansas to extend its new protections to Medicaid expansion patients.

“With so many outside stakeholders, you have to compromise – it’s a give and take,” Ms. Lynch said. Still, when it comes to fighting step therapy, she says, “Any protection on the books is always our first goal when we go into a state.”

Putting patients first

Lisa Arkin, MD, a pediatric dermatologist at the University of Wisconsin–Madison, said she finds herself “swimming upstream every day in the fight with insurance.” Her patients are typically on their second or third stop and have more complex disorders. Dr. Arkin said that the problem with step therapy is that it tries to squeeze all patients into the same box, even if the circumstances don’t fit.

Her state passed restrictions on step therapy in 2019, but the measures only went into effect last year. Under the Wisconsin law, patients can be granted an exemption if an alternative treatment is contraindicated, likely to cause harm, or expected to be ineffective. Patients can also be exempt if their current treatment is working.

Dr. Arkin, an outspoken advocate for curbing step therapy, says the Wisconsin law is “very strong.” However, because it only applies to certain health plans – state employee health plans and those purchased in the state’s health insurance exchange – fewer than half the state’s patients benefit from its protections. She notes that some of the most severe presentations she treats occur in patients who rely on Medicaid coverage and already face barriers to care.

“I’m a doctor who puts up a fuss [with insurers], but that’s not fair – we shouldn’t have to do that,” Dr. Arkin said. “To me, it’s really critical to make this an even playing field so this law affords protection to everyone I see in the clinic.”

Major medical associations caution against step therapy as well. The American Society of Clinical Oncology and the American Medical Association have called out the risks to patient safety and health. In fact, in 2019, after the Centers for Medicare & Medicaid Services gave new authority to Medicare Advantage plans to start using step therapy, dozens of national medical groups called out the agency for allowing a practice that could potentially hurt patients and undercut the physician-patient decision-making process.

Last year, in a new position paper from the American College of Physicians, authors laid out recommendations for combating step therapy’s side effects. These recommendations included making related data transparent to the public and minimizing the policy’s disruptions to care. Jacqueline W. Fincher, MD, MACP, a member of the committee that issued the position paper and who is a primary care physician in Georgia, said such insurance practices need to be designed with “strong input from frontline physicians, not clipboard physicians.

“What we want from insurers is understanding, transparency, and the least burdensome protocol to provide patients the care they need at a cost-effective price they can afford,” said Dr. Fincher, who is also the current president of the ACP. “The focus needs to be on what’s in the patient’s best interest.”
 

Every year a new fight

“We all dread January,” said Dr. Fincher. That is the worst month, she added, because new health benefits go into effect, which means patients who are responding well to certain treatments may suddenly face new restrictions.

Another aggravating aspect of step therapy? It is often difficult – if not impossible – to access information on specific step therapy protocols in a patient’s health plan in real time in the exam room, where treatment conversations actually take place. In a more patient-centered world, Dr. Fincher said, she would be able to use the electronic health record system to quickly identify whether a patient’s plan covers a particular treatment and, if not, what the alternatives are.

Georgia’s new step therapy law went into effect last year. Like laws in other states, it spells out step therapy exemptions and sets time frames in which insurers must respond to exceptions and appeals. Dr. Fincher, who spoke in favor of the new law, said she’s “happy for any step forward.” Still, the growing burden of prior authorization rules are an utter “time sink” for her and her staff.

“I have to justify my decisions to nondoctors before I even get to a doctor, and that’s really frustrating,” she said. “We’re talking about people here, not widgets.”

Advocates in Nevada are hoping this is the year a step therapy bill will make it into law in their state. As of March, one had yet to be introduced in the state legislature. Tom McCoy, director of state government affairs at the Nevada Chronic Care Collaborative, said existing Nevada law already prohibits nonmedical drug switching during a policy year; however, insurers can still make changes the following year.

A bill to rein in step therapy was proposed previously, Mr. McCoy said, but it never got off the ground. The collaborative, as well as about two dozen organizations representing Nevada providers and patients, are now calling on state lawmakers to make the issue a priority in the current session.

“The health plans have a lot of power – a lot,” Mr. McCoy said. “We’re hoping to get a [legislative] sponsor in 2021 ... but it’s also been a really hard year to connect legislators with patients and doctors, and being able to hear their stories really does make a difference.”

In Nebraska, Marcus Snow, MD, a rheumatologist at Nebraska Medicine, in Omaha, said that the state’s new step therapy law will be a “great first step in helping to provide some guardrails” around the practice. He noted that turnaround requirements for insurer responses are “sorely needed.” However, he said that, because the bill doesn’t apply to all health plans, many Nebraskans still won’t benefit.

Dealing with step therapy is a daily “headache” for Dr. Snow, who says navigating the bureaucracy of prior authorization seems to be getting worse every year. Like his peers around the country, he spends an inordinate amount of time pushing appeals up the insurance company ranks to get access to treatments he believes will be most effective. But Snow says that, more than just being a mountain of tiresome red tape, these practices also intrude on the patient-provider relationship, casting an unsettling sense of uncertainty that the ultimate decision about the best course of action isn’t up to the doctor and patient at all.

“In the end, the insurance company is the judge and jury of my prescription,” Dr. Snow said. “They’d argue I can still prescribe it, but if it costs $70,000 a year – I don’t know who can afford that.”

Ms. Lynch, at the National Psoriasis Foundation, said their step therapy advocacy will continue to take a two-pronged approach. They will push for new and expanded protections at both state and federal levels. Protections are needed at both levels to make sure that all health plans regulated by all entities are covered. In the U.S. Senate and the House, step therapy bills were reintroduced this year. They would apply to health plans subject to the federal Employee Retirement Income Security Act, which governs employer-sponsored health coverage, and could close a big gap in existing protections. Oregon, New Jersey, and Arizona are at the top of the foundation’s advocacy list this year, according to Ms. Lynch.

“Folks are really starting to pay more attention to this issue,” she said. “And hearing those real-world stories and frustrations is definitely one of the most effective tools we have.”

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

Apremilast (Otezla) monotherapy may be an effective option in oligoarticular psoriatic arthritis, Alexis R. Ogdie, MD, reported at the 2021 Rheumatology Winter Clinical Symposium.

Her analysis of apremilast data from the CORRONA Registry was among several recent highlights in psoriatic arthritis (PsA) cited by speakers at the meeting. Other significant developments included a large pan-Scandinavian study that reassuringly found no increased risk of solid cancers in tumor necrosis factor (TNF) inhibitor–treated patients with PsA, and evidence to suggest a sex difference in the efficacy of both secukinumab (Cosentyx) and adalimumab (Humira), with men responding better than women to two biologics with differing mechanisms of action.
 

A role for apremilast in oligoarticular disease?

Dr. Ogdie presented an analysis of 150 patients in the U.S. observational CORRONA Registry who initiated monotherapy for oligoarticular PsA and were followed for 6 months. Thirty-four started on apremilast, 15 on methotrexate, and 101 on a biologic. Even though the apremilast group had higher baseline disease activity than did those who started on methotrexate, at 6 months a swollen joint count of 1 or 0 was present in 41% of the apremilast-treated patients, compared with none on methotrexate and 15% on a biologic agent.

A tender joint count of 0-1 was documented at 6 months in 24% of patients on apremilast, 13% with methotrexate, and 21% on a biologic agent. Apremilast’s numeric superiority in outcomes compared to methotrexate in this exploratory study wasn’t subjected to statistical analysis because of the small sample size. However, the ongoing phase 4, double-blind, placebo-controlled, multicenter FOREMOST trial in 330 patients with early oligoarticular PsA should provide more definitive efficacy data, noted Dr. Ogdie, a rheumatologist and epidemiologist at the University of Pennsylvania, Philadelphia.

RWCS program director Arthur Kavanaugh, MD, said, “The most recent EULAR [European Alliance of Associations for Rheumatology] PsA guidelines totally discount apremilast, and I think mostly on the basis of cost, but then they also say that in groups of people it’s not as effective as methotrexate.”

“This study shows to me that, even though it’s a registry, with all the caveats about getting data from registries, apremilast certainly can be an effective drug,” said Dr. Kavanaugh, a rheumatologist and professor of medicine at the University of California, San Diego.

Another valuable piece of information from the CORRONA analysis is that it zeros in on patients with oligoarticular PsA.

“Almost all of our PsA studies are focused on people with polyarticular disease. What about those who have lesser involvement? That, of course, is important in the clinic,” he noted.

Dr. Ogdie concurred.

“If we study only polyarticular disease and we make all of our assumptions based on polyarticular disease, we might be leaving out at least half of the patients with PsA. And those patients may not need a bigger gun. Apremilast and methotrexate are kind of in the same group for that mild oligoarticular disease, and they probably work just fine,” she said.

A final point: “We really don’t have good outcome measures to study oligoarticular disease well. The ACR20 is not good because a 20% improvement in three joints is not readily measurable. That’s why trialists enroll patients with high joint count numbers,” according to the rheumatologist.

No increased risk of solid cancers in PsA patients treated with TNF inhibitors

A new analysis of clinical rheumatology registries in five Nordic countries finally puts to rest any concerns that treatment of PsA with TNF inhibitors is associated with increased risk of solid cancers. The same group previously reported no link between TNF inhibitors and lymphoma in PsA.

The solid cancers study included 9,655 PsA patients who started a first TNF inhibitor during 2001-2017, 14,809 others not treated with biologics, and 31,350 matched general population controls. Linkage to Swedish, Norwegian, Danish, Icelandic, and Finnish national cancer registries showed that the adjusted risk for solid cancer in TNF inhibitor–treated, compared with biologic-naive PsA patients, was 1.0. Similarly, the pooled standardized incidence ratio of solid cancer in TNF inhibitor–treated PsA patients compared to the general population was 1.0. There was no signal of a differential risk for incident cancer for any of the eight malignancies studied: lung, colorectal, breast, prostate, uterine, brain, liver, and pancreatic cancer.

“I like this study a lot because it’s specific to PsA rather than extrapolating from rheumatoid arthritis data, where we have a bunch more information for a much longer period of time, but it’s a different population,” Dr. Kavanaugh said.

Dr. Ogdie said, “I talk to my patients about this particular study or the same group’s earlier lymphoma study all the time.”

“I have to say, these are important data for the dermatology world because there are dermatologists who are still not convinced that TNF inhibitors don’t have an increased risk of malignancy. This kind of information is going to be helpful,” observed Eric M. Ruderman, MD, professor of medicine (rheumatology) at Northwestern University, Chicago.
 

Greater efficacy for biologics in males than females with PsA?

A secondary analysis of the phase 3b EXCEED trial raised the intriguing possibility that both secukinumab, an interleukin-17A inhibitor, and adalimumab, a TNF inhibitor, have greater efficacy in men than in women with PsA. In this randomized trial of 853 biologic-naive patients with PsA, the ACR20 response rate to secukinumab at week 52 was 61% in females versus 74% in males, with ACR50 rates of 43% in females and 55.3% in males. The ACR20 rate with adalimumab was 51.5% in females and 70.2% in males. Similarly, the corresponding ACR50s were 32.6% and 55.3%, respectively. Minimal disease activity was achieved in 36.2% of women and 51% of men on secukinumab, and in 24.2% of women and 49.8% of men on adalimumab.

“These are randomized patients, so you really shouldn’t see these big differences in minimal disease activity,” Dr. Ogdie noted. “The question is why do men seem to respond better to therapy than women? I don’t think it’s the fibromyalgia-ness. There’s probably some biologic rationale for this that we just don’t understand yet. Maybe hormonal interactions.”

This gender difference in response is an important issue because it can potentially distort outcomes in head-to-head drug trials, Dr. Ruderman added.

“That gender difference is not likely to be huge if you’re looking at a placebo-controlled trial because the difference between the active drug and placebo is going to outweigh it. But when you have two active drugs, if there’s an imbalance in terms of how many men or women there are on each of the two drugs, you may end up with an efficacy difference that’s not real but is based on gender and not response to the drug,” he explained.

Roy M. Fleischmann, MD, a rheumatologist and clinical trialist at the University of Texas, Dallas, rose from the audience to pronounce the EXCEED male-versus-female analysis “very interesting.”

“We should go back and look at other trials and see if that occurred, and if it did, then we have to think about that going forward,” he proposed.

Dr. Ogdie, Dr. Kavanaugh, and Dr. Ruderman reported having financial relationships with numerous pharmaceutical companies.

[email protected]

Apremilast (Otezla) monotherapy may be an effective option in oligoarticular psoriatic arthritis, Alexis R. Ogdie, MD, reported at the 2021 Rheumatology Winter Clinical Symposium.

Her analysis of apremilast data from the CORRONA Registry was among several recent highlights in psoriatic arthritis (PsA) cited by speakers at the meeting. Other significant developments included a large pan-Scandinavian study that reassuringly found no increased risk of solid cancers in tumor necrosis factor (TNF) inhibitor–treated patients with PsA, and evidence to suggest a sex difference in the efficacy of both secukinumab (Cosentyx) and adalimumab (Humira), with men responding better than women to two biologics with differing mechanisms of action.
 

A role for apremilast in oligoarticular disease?

Dr. Ogdie presented an analysis of 150 patients in the U.S. observational CORRONA Registry who initiated monotherapy for oligoarticular PsA and were followed for 6 months. Thirty-four started on apremilast, 15 on methotrexate, and 101 on a biologic. Even though the apremilast group had higher baseline disease activity than did those who started on methotrexate, at 6 months a swollen joint count of 1 or 0 was present in 41% of the apremilast-treated patients, compared with none on methotrexate and 15% on a biologic agent.

A tender joint count of 0-1 was documented at 6 months in 24% of patients on apremilast, 13% with methotrexate, and 21% on a biologic agent. Apremilast’s numeric superiority in outcomes compared to methotrexate in this exploratory study wasn’t subjected to statistical analysis because of the small sample size. However, the ongoing phase 4, double-blind, placebo-controlled, multicenter FOREMOST trial in 330 patients with early oligoarticular PsA should provide more definitive efficacy data, noted Dr. Ogdie, a rheumatologist and epidemiologist at the University of Pennsylvania, Philadelphia.

RWCS program director Arthur Kavanaugh, MD, said, “The most recent EULAR [European Alliance of Associations for Rheumatology] PsA guidelines totally discount apremilast, and I think mostly on the basis of cost, but then they also say that in groups of people it’s not as effective as methotrexate.”

“This study shows to me that, even though it’s a registry, with all the caveats about getting data from registries, apremilast certainly can be an effective drug,” said Dr. Kavanaugh, a rheumatologist and professor of medicine at the University of California, San Diego.

Another valuable piece of information from the CORRONA analysis is that it zeros in on patients with oligoarticular PsA.

“Almost all of our PsA studies are focused on people with polyarticular disease. What about those who have lesser involvement? That, of course, is important in the clinic,” he noted.

Dr. Ogdie concurred.

“If we study only polyarticular disease and we make all of our assumptions based on polyarticular disease, we might be leaving out at least half of the patients with PsA. And those patients may not need a bigger gun. Apremilast and methotrexate are kind of in the same group for that mild oligoarticular disease, and they probably work just fine,” she said.

A final point: “We really don’t have good outcome measures to study oligoarticular disease well. The ACR20 is not good because a 20% improvement in three joints is not readily measurable. That’s why trialists enroll patients with high joint count numbers,” according to the rheumatologist.

No increased risk of solid cancers in PsA patients treated with TNF inhibitors

A new analysis of clinical rheumatology registries in five Nordic countries finally puts to rest any concerns that treatment of PsA with TNF inhibitors is associated with increased risk of solid cancers. The same group previously reported no link between TNF inhibitors and lymphoma in PsA.

The solid cancers study included 9,655 PsA patients who started a first TNF inhibitor during 2001-2017, 14,809 others not treated with biologics, and 31,350 matched general population controls. Linkage to Swedish, Norwegian, Danish, Icelandic, and Finnish national cancer registries showed that the adjusted risk for solid cancer in TNF inhibitor–treated, compared with biologic-naive PsA patients, was 1.0. Similarly, the pooled standardized incidence ratio of solid cancer in TNF inhibitor–treated PsA patients compared to the general population was 1.0. There was no signal of a differential risk for incident cancer for any of the eight malignancies studied: lung, colorectal, breast, prostate, uterine, brain, liver, and pancreatic cancer.

“I like this study a lot because it’s specific to PsA rather than extrapolating from rheumatoid arthritis data, where we have a bunch more information for a much longer period of time, but it’s a different population,” Dr. Kavanaugh said.

Dr. Ogdie said, “I talk to my patients about this particular study or the same group’s earlier lymphoma study all the time.”

“I have to say, these are important data for the dermatology world because there are dermatologists who are still not convinced that TNF inhibitors don’t have an increased risk of malignancy. This kind of information is going to be helpful,” observed Eric M. Ruderman, MD, professor of medicine (rheumatology) at Northwestern University, Chicago.
 

Greater efficacy for biologics in males than females with PsA?

A secondary analysis of the phase 3b EXCEED trial raised the intriguing possibility that both secukinumab, an interleukin-17A inhibitor, and adalimumab, a TNF inhibitor, have greater efficacy in men than in women with PsA. In this randomized trial of 853 biologic-naive patients with PsA, the ACR20 response rate to secukinumab at week 52 was 61% in females versus 74% in males, with ACR50 rates of 43% in females and 55.3% in males. The ACR20 rate with adalimumab was 51.5% in females and 70.2% in males. Similarly, the corresponding ACR50s were 32.6% and 55.3%, respectively. Minimal disease activity was achieved in 36.2% of women and 51% of men on secukinumab, and in 24.2% of women and 49.8% of men on adalimumab.

“These are randomized patients, so you really shouldn’t see these big differences in minimal disease activity,” Dr. Ogdie noted. “The question is why do men seem to respond better to therapy than women? I don’t think it’s the fibromyalgia-ness. There’s probably some biologic rationale for this that we just don’t understand yet. Maybe hormonal interactions.”

This gender difference in response is an important issue because it can potentially distort outcomes in head-to-head drug trials, Dr. Ruderman added.

“That gender difference is not likely to be huge if you’re looking at a placebo-controlled trial because the difference between the active drug and placebo is going to outweigh it. But when you have two active drugs, if there’s an imbalance in terms of how many men or women there are on each of the two drugs, you may end up with an efficacy difference that’s not real but is based on gender and not response to the drug,” he explained.

Roy M. Fleischmann, MD, a rheumatologist and clinical trialist at the University of Texas, Dallas, rose from the audience to pronounce the EXCEED male-versus-female analysis “very interesting.”

“We should go back and look at other trials and see if that occurred, and if it did, then we have to think about that going forward,” he proposed.

Dr. Ogdie, Dr. Kavanaugh, and Dr. Ruderman reported having financial relationships with numerous pharmaceutical companies.

[email protected]

Apremilast (Otezla) monotherapy may be an effective option in oligoarticular psoriatic arthritis, Alexis R. Ogdie, MD, reported at the 2021 Rheumatology Winter Clinical Symposium.

Her analysis of apremilast data from the CORRONA Registry was among several recent highlights in psoriatic arthritis (PsA) cited by speakers at the meeting. Other significant developments included a large pan-Scandinavian study that reassuringly found no increased risk of solid cancers in tumor necrosis factor (TNF) inhibitor–treated patients with PsA, and evidence to suggest a sex difference in the efficacy of both secukinumab (Cosentyx) and adalimumab (Humira), with men responding better than women to two biologics with differing mechanisms of action.
 

A role for apremilast in oligoarticular disease?

Dr. Ogdie presented an analysis of 150 patients in the U.S. observational CORRONA Registry who initiated monotherapy for oligoarticular PsA and were followed for 6 months. Thirty-four started on apremilast, 15 on methotrexate, and 101 on a biologic. Even though the apremilast group had higher baseline disease activity than did those who started on methotrexate, at 6 months a swollen joint count of 1 or 0 was present in 41% of the apremilast-treated patients, compared with none on methotrexate and 15% on a biologic agent.

A tender joint count of 0-1 was documented at 6 months in 24% of patients on apremilast, 13% with methotrexate, and 21% on a biologic agent. Apremilast’s numeric superiority in outcomes compared to methotrexate in this exploratory study wasn’t subjected to statistical analysis because of the small sample size. However, the ongoing phase 4, double-blind, placebo-controlled, multicenter FOREMOST trial in 330 patients with early oligoarticular PsA should provide more definitive efficacy data, noted Dr. Ogdie, a rheumatologist and epidemiologist at the University of Pennsylvania, Philadelphia.

RWCS program director Arthur Kavanaugh, MD, said, “The most recent EULAR [European Alliance of Associations for Rheumatology] PsA guidelines totally discount apremilast, and I think mostly on the basis of cost, but then they also say that in groups of people it’s not as effective as methotrexate.”

“This study shows to me that, even though it’s a registry, with all the caveats about getting data from registries, apremilast certainly can be an effective drug,” said Dr. Kavanaugh, a rheumatologist and professor of medicine at the University of California, San Diego.

Another valuable piece of information from the CORRONA analysis is that it zeros in on patients with oligoarticular PsA.

“Almost all of our PsA studies are focused on people with polyarticular disease. What about those who have lesser involvement? That, of course, is important in the clinic,” he noted.

Dr. Ogdie concurred.

“If we study only polyarticular disease and we make all of our assumptions based on polyarticular disease, we might be leaving out at least half of the patients with PsA. And those patients may not need a bigger gun. Apremilast and methotrexate are kind of in the same group for that mild oligoarticular disease, and they probably work just fine,” she said.

A final point: “We really don’t have good outcome measures to study oligoarticular disease well. The ACR20 is not good because a 20% improvement in three joints is not readily measurable. That’s why trialists enroll patients with high joint count numbers,” according to the rheumatologist.

No increased risk of solid cancers in PsA patients treated with TNF inhibitors

A new analysis of clinical rheumatology registries in five Nordic countries finally puts to rest any concerns that treatment of PsA with TNF inhibitors is associated with increased risk of solid cancers. The same group previously reported no link between TNF inhibitors and lymphoma in PsA.

The solid cancers study included 9,655 PsA patients who started a first TNF inhibitor during 2001-2017, 14,809 others not treated with biologics, and 31,350 matched general population controls. Linkage to Swedish, Norwegian, Danish, Icelandic, and Finnish national cancer registries showed that the adjusted risk for solid cancer in TNF inhibitor–treated, compared with biologic-naive PsA patients, was 1.0. Similarly, the pooled standardized incidence ratio of solid cancer in TNF inhibitor–treated PsA patients compared to the general population was 1.0. There was no signal of a differential risk for incident cancer for any of the eight malignancies studied: lung, colorectal, breast, prostate, uterine, brain, liver, and pancreatic cancer.

“I like this study a lot because it’s specific to PsA rather than extrapolating from rheumatoid arthritis data, where we have a bunch more information for a much longer period of time, but it’s a different population,” Dr. Kavanaugh said.

Dr. Ogdie said, “I talk to my patients about this particular study or the same group’s earlier lymphoma study all the time.”

“I have to say, these are important data for the dermatology world because there are dermatologists who are still not convinced that TNF inhibitors don’t have an increased risk of malignancy. This kind of information is going to be helpful,” observed Eric M. Ruderman, MD, professor of medicine (rheumatology) at Northwestern University, Chicago.
 

Greater efficacy for biologics in males than females with PsA?

A secondary analysis of the phase 3b EXCEED trial raised the intriguing possibility that both secukinumab, an interleukin-17A inhibitor, and adalimumab, a TNF inhibitor, have greater efficacy in men than in women with PsA. In this randomized trial of 853 biologic-naive patients with PsA, the ACR20 response rate to secukinumab at week 52 was 61% in females versus 74% in males, with ACR50 rates of 43% in females and 55.3% in males. The ACR20 rate with adalimumab was 51.5% in females and 70.2% in males. Similarly, the corresponding ACR50s were 32.6% and 55.3%, respectively. Minimal disease activity was achieved in 36.2% of women and 51% of men on secukinumab, and in 24.2% of women and 49.8% of men on adalimumab.

“These are randomized patients, so you really shouldn’t see these big differences in minimal disease activity,” Dr. Ogdie noted. “The question is why do men seem to respond better to therapy than women? I don’t think it’s the fibromyalgia-ness. There’s probably some biologic rationale for this that we just don’t understand yet. Maybe hormonal interactions.”

This gender difference in response is an important issue because it can potentially distort outcomes in head-to-head drug trials, Dr. Ruderman added.

“That gender difference is not likely to be huge if you’re looking at a placebo-controlled trial because the difference between the active drug and placebo is going to outweigh it. But when you have two active drugs, if there’s an imbalance in terms of how many men or women there are on each of the two drugs, you may end up with an efficacy difference that’s not real but is based on gender and not response to the drug,” he explained.

Roy M. Fleischmann, MD, a rheumatologist and clinical trialist at the University of Texas, Dallas, rose from the audience to pronounce the EXCEED male-versus-female analysis “very interesting.”

“We should go back and look at other trials and see if that occurred, and if it did, then we have to think about that going forward,” he proposed.

Dr. Ogdie, Dr. Kavanaugh, and Dr. Ruderman reported having financial relationships with numerous pharmaceutical companies.

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