News from the FDA/CDC

The director of the Centers for Disease Control and Prevention late Thursday overruled the recommendation of the agency’s advisory panel to broaden the number of Americans who are now eligible for a third dose of the Pfizer COVID-19 vaccine.

The CDC’s Advisory Committee on Immunization Practices earlier Thursday voted to allow several groups of Americans to get a booster shot, but voted not to recommend it for adults age 18 to 64 who live or work in a place where the risk of COVID-19 is high. That would have included health care workers and other frontline employees.

But CDC Director Rochelle Walensky, MD, decided to reverse that recommendation and include the 18-to-64-year-olds in her final decision.

“As CDC Director, it is my job to recognize where our actions can have the greatest impact,” Dr. Walensky said in a statement late Thursday night, according to published reports. “At CDC, we are tasked with analyzing complex, often imperfect data to make concrete recommendations that optimize health. In a pandemic, even with uncertainty, we must take actions that we anticipate will do the greatest good.”

Dr. Walensky agreed with the rest of the advisory committee's decisions, which included recommendations that the following groups also be eligible for a booster shot:

• Adults ages 65 and up and residents of long-term care facilities
• Adults ages 50 to 64 who have an underlying medical condition that may increase their risk from a COVID infection
• Adults ages 18 to 49 who may be at increased risk from a COVID-19 infection because of an underlying medical condition, if a person feels like they need one based on a consideration of their individual benefit and risks.

About 26 million Americans are at least 6 months past the last dose of the Pfizer vaccines, making them eligible to receive a third dose.  About 13.6 million of them are over the age of 65.  Another 5.3 million are ages 50 to 64.

In making the recommendations, the committee left out healthcare workers. This was a departure from the Food and Drug Administration’s authorization which included boosters for those 65 and over, and for people 18 through 64 years of age who are at high risk for severe illness from the coronavirus, including essential workers – such as those in healthcare -- whose jobs increase their risk for infection.

This is the group Dr. Walensky added to the eligible list on her own.

Committee members “did not buy the need in occupational or institutional settings,” said William Schaffner, MD, an infectious disease specialist at Vanderbilt University in Nashville.  Dr. Schaffner sits on the ACIP workgroup that considered the evidence behind boosters. He said that he would have voted yes to offer boosters to healthcare and other essential workers.

“There was a real split in the committee,” he said.

The vote on boosters for healthcare and other high-risk workers was rejected 9 to 6.

“I think that there is ample evidence that people such as healthcare workers do not have repeated exposure in the workplace,” said Beth Bell, MD, a clinical professor at the University of Washington. “They’re using PPE as they should and they’re following the other policies within the healthcare setting. There’s lots of evidence that suggest that health care workers who become infected become infected because of exposures in the community.”

She was not alone in feeling cautious.

“I think this is an extremely slippery slope,” said Sarah Long, MD, a pediatric infectious disease specialist at Drexel University in Philadelphia, before her vote to reject boosters for healthcare and other high-risk workers.

“We might as well just say, ‘Give it to everybody 18 and over.’ We have an extremely effective vaccine. It’s like saying it’s not working, and it is working.”

The committee saw data showing that all of the vaccines remain highly protective against hospitalization and death for all age groups, though protection against getting sick with COVID has waned slightly over time and with the dominance of the more contagious Delta variant. Those at highest risk for a severe breakthrough infection — those that cause hospitalization or death — are older adults.
 

How much will the U.S. benefit from boosters?

Some felt squeamish about broadly recommending boosters at all.

“We have too much hope on the line with these boosters,” said James Loehr, MD, who is a family physician in Ithaca, N.Y. Dr. Loehr said he felt the goal of giving boosters in the United States should be to decrease hospitalizations, and he felt they would, but that the impact would likely be smaller than appreciated.

Based on his calculations of the benefits of boosters for each age group, Dr. Loehr said if boosters were given to all 13 million seniors previously vaccinated with the Pfizer vaccine, we might prevent 200 hospitalizations a day, “which would be a lot,” he noted. But, he said, “considering that we have 10,000 hospitalizations a day now, it’s probably not that much.”

Others agreed.

“I really think this is a solution looking for a problem,” said Jason Goldman, MD, an associate professor at Florida Atlantic University who was representing the American College of Physicians. “You know, I don’t think it’s going to address the issue of the pandemic. I really think it’s just going to create more confusion on the provider from the position of implementation, and I really think it’s going really far afield of the data.”

ACIP Chair Grace Lee, MD, a pediatric infectious disease specialist at Stanford, said she had cared for children who had died of COVID.

“I can tell you that their family members really wished they had extra protection for their kids, because they weren’t symptomatic. Nobody else was sick at home,” she said.

Dr. Lee said for her, access was paramount, and she was in favor of expanding access to boosters for as many people as possible.
 

Next steps

People who were initially vaccinated with either Moderna or Johnson & Johnson vaccines are excluded from booster recommendations, something many on the committee were uncomfortable with.

The FDA is still considering Moderna’s application to market booster doses. Johnson & Johnson hasn’t yet applied to the FDA for permission to offer second doses in the United States.

While the ACIP’s recommendations are important, in this case, they may not have a huge practical effect, said Schaffner. The CDC has already approved third shots for people who are immunocompromised, and no proof of a medical condition is required to get one.

More than 2 million people have already gotten a third dose, he noted, and not all of them are immunocompromised.

“They have heard the president say that, you know, everybody should get a booster, and they’ve taken that at face value,” he said.

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

The director of the Centers for Disease Control and Prevention late Thursday overruled the recommendation of the agency’s advisory panel to broaden the number of Americans who are now eligible for a third dose of the Pfizer COVID-19 vaccine.

The CDC’s Advisory Committee on Immunization Practices earlier Thursday voted to allow several groups of Americans to get a booster shot, but voted not to recommend it for adults age 18 to 64 who live or work in a place where the risk of COVID-19 is high. That would have included health care workers and other frontline employees.

But CDC Director Rochelle Walensky, MD, decided to reverse that recommendation and include the 18-to-64-year-olds in her final decision.

“As CDC Director, it is my job to recognize where our actions can have the greatest impact,” Dr. Walensky said in a statement late Thursday night, according to published reports. “At CDC, we are tasked with analyzing complex, often imperfect data to make concrete recommendations that optimize health. In a pandemic, even with uncertainty, we must take actions that we anticipate will do the greatest good.”

Dr. Walensky agreed with the rest of the advisory committee's decisions, which included recommendations that the following groups also be eligible for a booster shot:

• Adults ages 65 and up and residents of long-term care facilities
• Adults ages 50 to 64 who have an underlying medical condition that may increase their risk from a COVID infection
• Adults ages 18 to 49 who may be at increased risk from a COVID-19 infection because of an underlying medical condition, if a person feels like they need one based on a consideration of their individual benefit and risks.

About 26 million Americans are at least 6 months past the last dose of the Pfizer vaccines, making them eligible to receive a third dose.  About 13.6 million of them are over the age of 65.  Another 5.3 million are ages 50 to 64.

In making the recommendations, the committee left out healthcare workers. This was a departure from the Food and Drug Administration’s authorization which included boosters for those 65 and over, and for people 18 through 64 years of age who are at high risk for severe illness from the coronavirus, including essential workers – such as those in healthcare -- whose jobs increase their risk for infection.

This is the group Dr. Walensky added to the eligible list on her own.

Committee members “did not buy the need in occupational or institutional settings,” said William Schaffner, MD, an infectious disease specialist at Vanderbilt University in Nashville.  Dr. Schaffner sits on the ACIP workgroup that considered the evidence behind boosters. He said that he would have voted yes to offer boosters to healthcare and other essential workers.

“There was a real split in the committee,” he said.

The vote on boosters for healthcare and other high-risk workers was rejected 9 to 6.

“I think that there is ample evidence that people such as healthcare workers do not have repeated exposure in the workplace,” said Beth Bell, MD, a clinical professor at the University of Washington. “They’re using PPE as they should and they’re following the other policies within the healthcare setting. There’s lots of evidence that suggest that health care workers who become infected become infected because of exposures in the community.”

She was not alone in feeling cautious.

“I think this is an extremely slippery slope,” said Sarah Long, MD, a pediatric infectious disease specialist at Drexel University in Philadelphia, before her vote to reject boosters for healthcare and other high-risk workers.

“We might as well just say, ‘Give it to everybody 18 and over.’ We have an extremely effective vaccine. It’s like saying it’s not working, and it is working.”

The committee saw data showing that all of the vaccines remain highly protective against hospitalization and death for all age groups, though protection against getting sick with COVID has waned slightly over time and with the dominance of the more contagious Delta variant. Those at highest risk for a severe breakthrough infection — those that cause hospitalization or death — are older adults.
 

How much will the U.S. benefit from boosters?

Some felt squeamish about broadly recommending boosters at all.

“We have too much hope on the line with these boosters,” said James Loehr, MD, who is a family physician in Ithaca, N.Y. Dr. Loehr said he felt the goal of giving boosters in the United States should be to decrease hospitalizations, and he felt they would, but that the impact would likely be smaller than appreciated.

Based on his calculations of the benefits of boosters for each age group, Dr. Loehr said if boosters were given to all 13 million seniors previously vaccinated with the Pfizer vaccine, we might prevent 200 hospitalizations a day, “which would be a lot,” he noted. But, he said, “considering that we have 10,000 hospitalizations a day now, it’s probably not that much.”

Others agreed.

“I really think this is a solution looking for a problem,” said Jason Goldman, MD, an associate professor at Florida Atlantic University who was representing the American College of Physicians. “You know, I don’t think it’s going to address the issue of the pandemic. I really think it’s just going to create more confusion on the provider from the position of implementation, and I really think it’s going really far afield of the data.”

ACIP Chair Grace Lee, MD, a pediatric infectious disease specialist at Stanford, said she had cared for children who had died of COVID.

“I can tell you that their family members really wished they had extra protection for their kids, because they weren’t symptomatic. Nobody else was sick at home,” she said.

Dr. Lee said for her, access was paramount, and she was in favor of expanding access to boosters for as many people as possible.
 

Next steps

People who were initially vaccinated with either Moderna or Johnson & Johnson vaccines are excluded from booster recommendations, something many on the committee were uncomfortable with.

The FDA is still considering Moderna’s application to market booster doses. Johnson & Johnson hasn’t yet applied to the FDA for permission to offer second doses in the United States.

While the ACIP’s recommendations are important, in this case, they may not have a huge practical effect, said Schaffner. The CDC has already approved third shots for people who are immunocompromised, and no proof of a medical condition is required to get one.

More than 2 million people have already gotten a third dose, he noted, and not all of them are immunocompromised.

“They have heard the president say that, you know, everybody should get a booster, and they’ve taken that at face value,” he said.

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

The director of the Centers for Disease Control and Prevention late Thursday overruled the recommendation of the agency’s advisory panel to broaden the number of Americans who are now eligible for a third dose of the Pfizer COVID-19 vaccine.

The CDC’s Advisory Committee on Immunization Practices earlier Thursday voted to allow several groups of Americans to get a booster shot, but voted not to recommend it for adults age 18 to 64 who live or work in a place where the risk of COVID-19 is high. That would have included health care workers and other frontline employees.

But CDC Director Rochelle Walensky, MD, decided to reverse that recommendation and include the 18-to-64-year-olds in her final decision.

“As CDC Director, it is my job to recognize where our actions can have the greatest impact,” Dr. Walensky said in a statement late Thursday night, according to published reports. “At CDC, we are tasked with analyzing complex, often imperfect data to make concrete recommendations that optimize health. In a pandemic, even with uncertainty, we must take actions that we anticipate will do the greatest good.”

Dr. Walensky agreed with the rest of the advisory committee's decisions, which included recommendations that the following groups also be eligible for a booster shot:

• Adults ages 65 and up and residents of long-term care facilities
• Adults ages 50 to 64 who have an underlying medical condition that may increase their risk from a COVID infection
• Adults ages 18 to 49 who may be at increased risk from a COVID-19 infection because of an underlying medical condition, if a person feels like they need one based on a consideration of their individual benefit and risks.

About 26 million Americans are at least 6 months past the last dose of the Pfizer vaccines, making them eligible to receive a third dose.  About 13.6 million of them are over the age of 65.  Another 5.3 million are ages 50 to 64.

In making the recommendations, the committee left out healthcare workers. This was a departure from the Food and Drug Administration’s authorization which included boosters for those 65 and over, and for people 18 through 64 years of age who are at high risk for severe illness from the coronavirus, including essential workers – such as those in healthcare -- whose jobs increase their risk for infection.

This is the group Dr. Walensky added to the eligible list on her own.

Committee members “did not buy the need in occupational or institutional settings,” said William Schaffner, MD, an infectious disease specialist at Vanderbilt University in Nashville.  Dr. Schaffner sits on the ACIP workgroup that considered the evidence behind boosters. He said that he would have voted yes to offer boosters to healthcare and other essential workers.

“There was a real split in the committee,” he said.

The vote on boosters for healthcare and other high-risk workers was rejected 9 to 6.

“I think that there is ample evidence that people such as healthcare workers do not have repeated exposure in the workplace,” said Beth Bell, MD, a clinical professor at the University of Washington. “They’re using PPE as they should and they’re following the other policies within the healthcare setting. There’s lots of evidence that suggest that health care workers who become infected become infected because of exposures in the community.”

She was not alone in feeling cautious.

“I think this is an extremely slippery slope,” said Sarah Long, MD, a pediatric infectious disease specialist at Drexel University in Philadelphia, before her vote to reject boosters for healthcare and other high-risk workers.

“We might as well just say, ‘Give it to everybody 18 and over.’ We have an extremely effective vaccine. It’s like saying it’s not working, and it is working.”

The committee saw data showing that all of the vaccines remain highly protective against hospitalization and death for all age groups, though protection against getting sick with COVID has waned slightly over time and with the dominance of the more contagious Delta variant. Those at highest risk for a severe breakthrough infection — those that cause hospitalization or death — are older adults.
 

How much will the U.S. benefit from boosters?

Some felt squeamish about broadly recommending boosters at all.

“We have too much hope on the line with these boosters,” said James Loehr, MD, who is a family physician in Ithaca, N.Y. Dr. Loehr said he felt the goal of giving boosters in the United States should be to decrease hospitalizations, and he felt they would, but that the impact would likely be smaller than appreciated.

Based on his calculations of the benefits of boosters for each age group, Dr. Loehr said if boosters were given to all 13 million seniors previously vaccinated with the Pfizer vaccine, we might prevent 200 hospitalizations a day, “which would be a lot,” he noted. But, he said, “considering that we have 10,000 hospitalizations a day now, it’s probably not that much.”

Others agreed.

“I really think this is a solution looking for a problem,” said Jason Goldman, MD, an associate professor at Florida Atlantic University who was representing the American College of Physicians. “You know, I don’t think it’s going to address the issue of the pandemic. I really think it’s just going to create more confusion on the provider from the position of implementation, and I really think it’s going really far afield of the data.”

ACIP Chair Grace Lee, MD, a pediatric infectious disease specialist at Stanford, said she had cared for children who had died of COVID.

“I can tell you that their family members really wished they had extra protection for their kids, because they weren’t symptomatic. Nobody else was sick at home,” she said.

Dr. Lee said for her, access was paramount, and she was in favor of expanding access to boosters for as many people as possible.
 

Next steps

People who were initially vaccinated with either Moderna or Johnson & Johnson vaccines are excluded from booster recommendations, something many on the committee were uncomfortable with.

The FDA is still considering Moderna’s application to market booster doses. Johnson & Johnson hasn’t yet applied to the FDA for permission to offer second doses in the United States.

While the ACIP’s recommendations are important, in this case, they may not have a huge practical effect, said Schaffner. The CDC has already approved third shots for people who are immunocompromised, and no proof of a medical condition is required to get one.

More than 2 million people have already gotten a third dose, he noted, and not all of them are immunocompromised.

“They have heard the president say that, you know, everybody should get a booster, and they’ve taken that at face value,” he said.

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

The Food and Drug Administration today gave the nod to topical ruxolitinib cream for the treatment of non-immunocompromised patients with mild to moderate atopic dermatitis ages 12 years and older, making it the first topical JAK inhibitor approved for AD – and the first JAK inhibitor approved for this indication – in the United States.

The approval is limited to patients whose AD is not adequately controlled with topical prescription therapies, or when those therapies are not advisable.

“Approval of topical ruxolitinib fills a major gap in the treatment of atopic dermatitis: a safe, effective, and tolerable non-steroidal topical therapy,” Eric L. Simpson, MD, professor of dermatology and director of the Oregon Health & Science University Dermatology Clinical Research Center, Portland, told this news organization. “This approval will allow for long-term treatment without the concern of steroid side effects. From earlier studies, ruxolitinib cream appears to be as effective as a medium-potency topical steroid. These efficacy levels and low incidence of burning will be a welcome addition to our current nonsteroidal therapies.”

The drug’s approval was based on results from two phase 3, randomized studies of identical design involving 1,249 patients aged 12 years and older with AD: TRuE-AD1 and TRuE-AD2. In these studies, ruxolitinib cream demonstrated anti-inflammatory activity, with rapid and sustained antipruritic action, compared with vehicle. In the trials, patients with an Investigator’s Global Assessment (IGA) score of 2 or 3 and 3%-20% of affected body surface area (BSA) were randomized (2:2:1) to twice-daily 0.75% ruxolitinib cream, 1.5% ruxolitinib cream, or vehicle cream for 8 continuous weeks. The 1.5% concentration was approved by the FDA.

A study first published in May of 2021 found that significantly more patients in TRuE-AD1 and TRuE-AD2 achieved IGA treatment success with 0.75% (50% vs. 39%, respectively) and 1.5% ruxolitinib cream (53.8% vs. 51.3%), compared with vehicle (15.1% vs. 7.6%; P < .0001) at week 8. In addition, significant reductions in itch, compared with vehicle, were reported within 12 hours of first applying 1.5% ruxolitinib cream (P < .05).

More key findings from TRuE-AD1 and TRuE-AD2 are scheduled to be presented during the upcoming European Academy of Dermatology and Venereology meeting Sept. 29-Oct. 2, but during the Revolutionizing Atopic Dermatitis Symposium on June 13, Kim Papp, MD, PhD, presented long-term safety data of ruxolitinib cream in patients who were followed for an additional 44 weeks. Dr. Papp, a dermatologist and founder of Probity Medical Research, Waterloo, Ont., reported that 543 patients from TRuE-AD1 and 530 from TRuE-AD2 entered the long-term analysis and that about 78% of these patients completed the study. From weeks 12 to 52, the proportion of patients with an IGA score of 0 or 1 with 0.75% and 1.5% ruxolitinib cream ranged from 62%-77% and 67%-77%, respectively, in TRuE-AD1, to 60%-77% and 72%-80% in TRuE-AD2.

The measured mean total affected BSA was less than 3% throughout the follow-up period in the 1.5% ruxolitinib cream arm in TRuE-AD1 and TRuE-AD2 and was less than 3% in the 0.75% ruxolitinib cream arm during most of the study period.

In a pooled safety analysis, treatment-emergent adverse events (TEAEs) were reported in 60% and 54% of patients who applied 0.75% and 1.5% ruxolitinib cream, respectively, over 44 weeks. The frequency of application-site reactions remained low. Specifically, treatment-related adverse events were reported in 5% of patients who applied 0.75% ruxolitinib cream and in 3% of patients who applied 1.5% ruxolitinib cream; none were serious. TEAEs led to discontinuation in 2% of patients in the 0.75% ruxolitinib cream group, and no patients in the 1.5% ruxolitinib cream group.

Dr. Papp and his colleagues observed that the most common treatment adverse events were upper respiratory tract infections and nasopharyngitis. According to Incyte’s press release, the most common treatment-emergent adverse reactions in patients treated with ruxolitinib during clinical trials were nasopharyngitis, diarrhea, bronchitis, ear infection, eosinophil count increases, urticaria, folliculitis, tonsillitis, and rhinorrhea. The labeling includes boxed warnings for serious infections, mortality, malignancy, major adverse cardiovascular events, and thrombosis, seen with oral JAK inhibitors for inflammatory conditions.

Incyte will market ruxolitinib under the trade name Opzelura.

Dr. Simpson disclosed that he is a consultant to and/or an investigator for several pharmaceutical companies, including Incyte, Regeneron/Sanofi, Eli Lilly and Company, AbbVie, and Pfizer.

Dr. Papp disclosed that he has received honoraria or clinical research grants as a consultant, speaker, scientific officer, advisory board member, and/or steering committee member for several pharmaceutical companies, including Incyte.

Commentary by Robert Sidbury, MD, MPH

Another nonsteroidal topical medication approved for atopic dermatitis (AD)? Thank goodness. Topical ruxolitinib 1.5% cream twice daily for mild to moderate AD demonstrated excellent efficacy vs. placebo in duplicative trials (53.8/51.3% vs. 15.1%/7.6%; P < .001), with a reassuring safety profile. Application site reactions were uncommon, though past experience with other new nonsteroidal agents suggests judgment be reserved on that score. More compelling was the fact that no patients discontinued therapy in the 1.5% arm, and adverse events were mild and self-limited such as nasopharyngitis and diarrhea. This stands in contradistinction to the boxed warning attached to JAK inhibitors (topical and systemic) against a daunting list of destructive possibilities: malignancy, infection, cardiovascular disease, and blood clots. None of these things was seen in these topical ruxolitinib trials.

Dr. Sidbury is chief of dermatology at Seattle Children's Hospital and professor, department of pediatrics, University of Washington, Seattle. He is a site principal investigator for dupilumab trials, for which the hospital has a contract with Regeneron.

This article was updated 6/16/22.

The Food and Drug Administration today gave the nod to topical ruxolitinib cream for the treatment of non-immunocompromised patients with mild to moderate atopic dermatitis ages 12 years and older, making it the first topical JAK inhibitor approved for AD – and the first JAK inhibitor approved for this indication – in the United States.

The approval is limited to patients whose AD is not adequately controlled with topical prescription therapies, or when those therapies are not advisable.

“Approval of topical ruxolitinib fills a major gap in the treatment of atopic dermatitis: a safe, effective, and tolerable non-steroidal topical therapy,” Eric L. Simpson, MD, professor of dermatology and director of the Oregon Health & Science University Dermatology Clinical Research Center, Portland, told this news organization. “This approval will allow for long-term treatment without the concern of steroid side effects. From earlier studies, ruxolitinib cream appears to be as effective as a medium-potency topical steroid. These efficacy levels and low incidence of burning will be a welcome addition to our current nonsteroidal therapies.”

The drug’s approval was based on results from two phase 3, randomized studies of identical design involving 1,249 patients aged 12 years and older with AD: TRuE-AD1 and TRuE-AD2. In these studies, ruxolitinib cream demonstrated anti-inflammatory activity, with rapid and sustained antipruritic action, compared with vehicle. In the trials, patients with an Investigator’s Global Assessment (IGA) score of 2 or 3 and 3%-20% of affected body surface area (BSA) were randomized (2:2:1) to twice-daily 0.75% ruxolitinib cream, 1.5% ruxolitinib cream, or vehicle cream for 8 continuous weeks. The 1.5% concentration was approved by the FDA.

A study first published in May of 2021 found that significantly more patients in TRuE-AD1 and TRuE-AD2 achieved IGA treatment success with 0.75% (50% vs. 39%, respectively) and 1.5% ruxolitinib cream (53.8% vs. 51.3%), compared with vehicle (15.1% vs. 7.6%; P < .0001) at week 8. In addition, significant reductions in itch, compared with vehicle, were reported within 12 hours of first applying 1.5% ruxolitinib cream (P < .05).

More key findings from TRuE-AD1 and TRuE-AD2 are scheduled to be presented during the upcoming European Academy of Dermatology and Venereology meeting Sept. 29-Oct. 2, but during the Revolutionizing Atopic Dermatitis Symposium on June 13, Kim Papp, MD, PhD, presented long-term safety data of ruxolitinib cream in patients who were followed for an additional 44 weeks. Dr. Papp, a dermatologist and founder of Probity Medical Research, Waterloo, Ont., reported that 543 patients from TRuE-AD1 and 530 from TRuE-AD2 entered the long-term analysis and that about 78% of these patients completed the study. From weeks 12 to 52, the proportion of patients with an IGA score of 0 or 1 with 0.75% and 1.5% ruxolitinib cream ranged from 62%-77% and 67%-77%, respectively, in TRuE-AD1, to 60%-77% and 72%-80% in TRuE-AD2.

The measured mean total affected BSA was less than 3% throughout the follow-up period in the 1.5% ruxolitinib cream arm in TRuE-AD1 and TRuE-AD2 and was less than 3% in the 0.75% ruxolitinib cream arm during most of the study period.

In a pooled safety analysis, treatment-emergent adverse events (TEAEs) were reported in 60% and 54% of patients who applied 0.75% and 1.5% ruxolitinib cream, respectively, over 44 weeks. The frequency of application-site reactions remained low. Specifically, treatment-related adverse events were reported in 5% of patients who applied 0.75% ruxolitinib cream and in 3% of patients who applied 1.5% ruxolitinib cream; none were serious. TEAEs led to discontinuation in 2% of patients in the 0.75% ruxolitinib cream group, and no patients in the 1.5% ruxolitinib cream group.

Dr. Papp and his colleagues observed that the most common treatment adverse events were upper respiratory tract infections and nasopharyngitis. According to Incyte’s press release, the most common treatment-emergent adverse reactions in patients treated with ruxolitinib during clinical trials were nasopharyngitis, diarrhea, bronchitis, ear infection, eosinophil count increases, urticaria, folliculitis, tonsillitis, and rhinorrhea. The labeling includes boxed warnings for serious infections, mortality, malignancy, major adverse cardiovascular events, and thrombosis, seen with oral JAK inhibitors for inflammatory conditions.

Incyte will market ruxolitinib under the trade name Opzelura.

Dr. Simpson disclosed that he is a consultant to and/or an investigator for several pharmaceutical companies, including Incyte, Regeneron/Sanofi, Eli Lilly and Company, AbbVie, and Pfizer.

Dr. Papp disclosed that he has received honoraria or clinical research grants as a consultant, speaker, scientific officer, advisory board member, and/or steering committee member for several pharmaceutical companies, including Incyte.

Commentary by Robert Sidbury, MD, MPH

Another nonsteroidal topical medication approved for atopic dermatitis (AD)? Thank goodness. Topical ruxolitinib 1.5% cream twice daily for mild to moderate AD demonstrated excellent efficacy vs. placebo in duplicative trials (53.8/51.3% vs. 15.1%/7.6%; P < .001), with a reassuring safety profile. Application site reactions were uncommon, though past experience with other new nonsteroidal agents suggests judgment be reserved on that score. More compelling was the fact that no patients discontinued therapy in the 1.5% arm, and adverse events were mild and self-limited such as nasopharyngitis and diarrhea. This stands in contradistinction to the boxed warning attached to JAK inhibitors (topical and systemic) against a daunting list of destructive possibilities: malignancy, infection, cardiovascular disease, and blood clots. None of these things was seen in these topical ruxolitinib trials.

Dr. Sidbury is chief of dermatology at Seattle Children's Hospital and professor, department of pediatrics, University of Washington, Seattle. He is a site principal investigator for dupilumab trials, for which the hospital has a contract with Regeneron.

This article was updated 6/16/22.

The Food and Drug Administration today gave the nod to topical ruxolitinib cream for the treatment of non-immunocompromised patients with mild to moderate atopic dermatitis ages 12 years and older, making it the first topical JAK inhibitor approved for AD – and the first JAK inhibitor approved for this indication – in the United States.

The approval is limited to patients whose AD is not adequately controlled with topical prescription therapies, or when those therapies are not advisable.

“Approval of topical ruxolitinib fills a major gap in the treatment of atopic dermatitis: a safe, effective, and tolerable non-steroidal topical therapy,” Eric L. Simpson, MD, professor of dermatology and director of the Oregon Health & Science University Dermatology Clinical Research Center, Portland, told this news organization. “This approval will allow for long-term treatment without the concern of steroid side effects. From earlier studies, ruxolitinib cream appears to be as effective as a medium-potency topical steroid. These efficacy levels and low incidence of burning will be a welcome addition to our current nonsteroidal therapies.”

The drug’s approval was based on results from two phase 3, randomized studies of identical design involving 1,249 patients aged 12 years and older with AD: TRuE-AD1 and TRuE-AD2. In these studies, ruxolitinib cream demonstrated anti-inflammatory activity, with rapid and sustained antipruritic action, compared with vehicle. In the trials, patients with an Investigator’s Global Assessment (IGA) score of 2 or 3 and 3%-20% of affected body surface area (BSA) were randomized (2:2:1) to twice-daily 0.75% ruxolitinib cream, 1.5% ruxolitinib cream, or vehicle cream for 8 continuous weeks. The 1.5% concentration was approved by the FDA.

A study first published in May of 2021 found that significantly more patients in TRuE-AD1 and TRuE-AD2 achieved IGA treatment success with 0.75% (50% vs. 39%, respectively) and 1.5% ruxolitinib cream (53.8% vs. 51.3%), compared with vehicle (15.1% vs. 7.6%; P < .0001) at week 8. In addition, significant reductions in itch, compared with vehicle, were reported within 12 hours of first applying 1.5% ruxolitinib cream (P < .05).

More key findings from TRuE-AD1 and TRuE-AD2 are scheduled to be presented during the upcoming European Academy of Dermatology and Venereology meeting Sept. 29-Oct. 2, but during the Revolutionizing Atopic Dermatitis Symposium on June 13, Kim Papp, MD, PhD, presented long-term safety data of ruxolitinib cream in patients who were followed for an additional 44 weeks. Dr. Papp, a dermatologist and founder of Probity Medical Research, Waterloo, Ont., reported that 543 patients from TRuE-AD1 and 530 from TRuE-AD2 entered the long-term analysis and that about 78% of these patients completed the study. From weeks 12 to 52, the proportion of patients with an IGA score of 0 or 1 with 0.75% and 1.5% ruxolitinib cream ranged from 62%-77% and 67%-77%, respectively, in TRuE-AD1, to 60%-77% and 72%-80% in TRuE-AD2.

The measured mean total affected BSA was less than 3% throughout the follow-up period in the 1.5% ruxolitinib cream arm in TRuE-AD1 and TRuE-AD2 and was less than 3% in the 0.75% ruxolitinib cream arm during most of the study period.

In a pooled safety analysis, treatment-emergent adverse events (TEAEs) were reported in 60% and 54% of patients who applied 0.75% and 1.5% ruxolitinib cream, respectively, over 44 weeks. The frequency of application-site reactions remained low. Specifically, treatment-related adverse events were reported in 5% of patients who applied 0.75% ruxolitinib cream and in 3% of patients who applied 1.5% ruxolitinib cream; none were serious. TEAEs led to discontinuation in 2% of patients in the 0.75% ruxolitinib cream group, and no patients in the 1.5% ruxolitinib cream group.

Dr. Papp and his colleagues observed that the most common treatment adverse events were upper respiratory tract infections and nasopharyngitis. According to Incyte’s press release, the most common treatment-emergent adverse reactions in patients treated with ruxolitinib during clinical trials were nasopharyngitis, diarrhea, bronchitis, ear infection, eosinophil count increases, urticaria, folliculitis, tonsillitis, and rhinorrhea. The labeling includes boxed warnings for serious infections, mortality, malignancy, major adverse cardiovascular events, and thrombosis, seen with oral JAK inhibitors for inflammatory conditions.

Incyte will market ruxolitinib under the trade name Opzelura.

Dr. Simpson disclosed that he is a consultant to and/or an investigator for several pharmaceutical companies, including Incyte, Regeneron/Sanofi, Eli Lilly and Company, AbbVie, and Pfizer.

Dr. Papp disclosed that he has received honoraria or clinical research grants as a consultant, speaker, scientific officer, advisory board member, and/or steering committee member for several pharmaceutical companies, including Incyte.

Commentary by Robert Sidbury, MD, MPH

Another nonsteroidal topical medication approved for atopic dermatitis (AD)? Thank goodness. Topical ruxolitinib 1.5% cream twice daily for mild to moderate AD demonstrated excellent efficacy vs. placebo in duplicative trials (53.8/51.3% vs. 15.1%/7.6%; P < .001), with a reassuring safety profile. Application site reactions were uncommon, though past experience with other new nonsteroidal agents suggests judgment be reserved on that score. More compelling was the fact that no patients discontinued therapy in the 1.5% arm, and adverse events were mild and self-limited such as nasopharyngitis and diarrhea. This stands in contradistinction to the boxed warning attached to JAK inhibitors (topical and systemic) against a daunting list of destructive possibilities: malignancy, infection, cardiovascular disease, and blood clots. None of these things was seen in these topical ruxolitinib trials.

Dr. Sidbury is chief of dermatology at Seattle Children's Hospital and professor, department of pediatrics, University of Washington, Seattle. He is a site principal investigator for dupilumab trials, for which the hospital has a contract with Regeneron.

This article was updated 6/16/22.

A second consecutive week of falling COVID-19 cases in children, along with continued declines in new admissions, may indicate that the latest surge has peaked.

New child cases totaled 226,000 for the week of Sept. 10-16, down from 243,000 the previous week and from a pandemic high of 252,000 just 2 weeks earlier. Children made up over 25% of all new cases each week over that 3-week period covering the end of August and the first half of September, according to a report from the American Academy of Pediatrics and the Children’s Hospital Association.

New hospitalizations in children aged 0-17 years peaked on Sept. 4 – when the rate reached 0.51 per 100,000 population – and were down to 0.47 as of Sept. 11, the latest date for which data should be considered reliable, the Centers for Disease Control and Prevention said.

The CDC’s data largely agree with the AAP/CHA report, showing that cases peaked during the week of Aug. 22-28. Cases per 100,000 for children that week looked like this: 154.7 (age 0-4 years), 276.6 (5-11 years), 320.0 (12-15), and 334.1 (16-17). The highest rates that week among adults were 288.6 per 100,000 in 30- to 39-year-olds and 286.5 for those aged 18-29, the CDC said on its COVID Data Tracker.

By the week of Sept. 5-11 – reporting delays can affect more recent data – the rates in children were down more than 20% in each of the four age groups, according to the CDC.

Vaccinations among children, unfortunately, continue to decline. Vaccine initiations for 12- to 15-year-olds slipped from 199,000 (Sept. 7-13) to 179,000 during the week of Sept. 14-20, while the 16- to 17-year-olds went from almost 83,000 down to 75,000. Initiations have dropped for 6 straight weeks in both age groups, based on the CDC data.

Despite those declines, however, the 16- and 17-year-olds just passed a couple of vaccination milestones. More than 60% – 60.9%, to be exact – have now received at least one dose of COVID vaccine, and 50.3% can be considered fully vaccinated. For those aged 12-15, the corresponding figures are 53.1% and 42.0%, the CDC reported.

When children under age 12 years are included – through clinical trial involvement or incorrect birth dates – the CDC data put the total count of Americans under age 18 who have received at least one dose of vaccine at almost 12.8 million, with vaccination complete in 10.3 million.

Total cases, as calculated by the APA and CHA, are now over 5.5 million, although that figure includes cases in individuals as old as 20 years, since many states differ from the CDC on the age range for a child. The CDC’s COVID Data Tracker put the total for children aged 0-17 at nearly 4.6 million.

The total number of COVID-related deaths in children is 480 as of Sept. 16, the AAP and CHA said, based on data from 45 states, New York, City, Puerto Rico, and Guam, but the CDC provides a higher number, 548, since the pandemic began. Children aged 0-4 years represent the largest share (32.3%) of those 548 deaths, followed by the 12- to 15-year-olds (26.5%), based on the CDC data.

[email protected]

A second consecutive week of falling COVID-19 cases in children, along with continued declines in new admissions, may indicate that the latest surge has peaked.

New child cases totaled 226,000 for the week of Sept. 10-16, down from 243,000 the previous week and from a pandemic high of 252,000 just 2 weeks earlier. Children made up over 25% of all new cases each week over that 3-week period covering the end of August and the first half of September, according to a report from the American Academy of Pediatrics and the Children’s Hospital Association.

New hospitalizations in children aged 0-17 years peaked on Sept. 4 – when the rate reached 0.51 per 100,000 population – and were down to 0.47 as of Sept. 11, the latest date for which data should be considered reliable, the Centers for Disease Control and Prevention said.

The CDC’s data largely agree with the AAP/CHA report, showing that cases peaked during the week of Aug. 22-28. Cases per 100,000 for children that week looked like this: 154.7 (age 0-4 years), 276.6 (5-11 years), 320.0 (12-15), and 334.1 (16-17). The highest rates that week among adults were 288.6 per 100,000 in 30- to 39-year-olds and 286.5 for those aged 18-29, the CDC said on its COVID Data Tracker.

By the week of Sept. 5-11 – reporting delays can affect more recent data – the rates in children were down more than 20% in each of the four age groups, according to the CDC.

Vaccinations among children, unfortunately, continue to decline. Vaccine initiations for 12- to 15-year-olds slipped from 199,000 (Sept. 7-13) to 179,000 during the week of Sept. 14-20, while the 16- to 17-year-olds went from almost 83,000 down to 75,000. Initiations have dropped for 6 straight weeks in both age groups, based on the CDC data.

Despite those declines, however, the 16- and 17-year-olds just passed a couple of vaccination milestones. More than 60% – 60.9%, to be exact – have now received at least one dose of COVID vaccine, and 50.3% can be considered fully vaccinated. For those aged 12-15, the corresponding figures are 53.1% and 42.0%, the CDC reported.

When children under age 12 years are included – through clinical trial involvement or incorrect birth dates – the CDC data put the total count of Americans under age 18 who have received at least one dose of vaccine at almost 12.8 million, with vaccination complete in 10.3 million.

Total cases, as calculated by the APA and CHA, are now over 5.5 million, although that figure includes cases in individuals as old as 20 years, since many states differ from the CDC on the age range for a child. The CDC’s COVID Data Tracker put the total for children aged 0-17 at nearly 4.6 million.

The total number of COVID-related deaths in children is 480 as of Sept. 16, the AAP and CHA said, based on data from 45 states, New York, City, Puerto Rico, and Guam, but the CDC provides a higher number, 548, since the pandemic began. Children aged 0-4 years represent the largest share (32.3%) of those 548 deaths, followed by the 12- to 15-year-olds (26.5%), based on the CDC data.

[email protected]

A second consecutive week of falling COVID-19 cases in children, along with continued declines in new admissions, may indicate that the latest surge has peaked.

New child cases totaled 226,000 for the week of Sept. 10-16, down from 243,000 the previous week and from a pandemic high of 252,000 just 2 weeks earlier. Children made up over 25% of all new cases each week over that 3-week period covering the end of August and the first half of September, according to a report from the American Academy of Pediatrics and the Children’s Hospital Association.

New hospitalizations in children aged 0-17 years peaked on Sept. 4 – when the rate reached 0.51 per 100,000 population – and were down to 0.47 as of Sept. 11, the latest date for which data should be considered reliable, the Centers for Disease Control and Prevention said.

The CDC’s data largely agree with the AAP/CHA report, showing that cases peaked during the week of Aug. 22-28. Cases per 100,000 for children that week looked like this: 154.7 (age 0-4 years), 276.6 (5-11 years), 320.0 (12-15), and 334.1 (16-17). The highest rates that week among adults were 288.6 per 100,000 in 30- to 39-year-olds and 286.5 for those aged 18-29, the CDC said on its COVID Data Tracker.

By the week of Sept. 5-11 – reporting delays can affect more recent data – the rates in children were down more than 20% in each of the four age groups, according to the CDC.

Vaccinations among children, unfortunately, continue to decline. Vaccine initiations for 12- to 15-year-olds slipped from 199,000 (Sept. 7-13) to 179,000 during the week of Sept. 14-20, while the 16- to 17-year-olds went from almost 83,000 down to 75,000. Initiations have dropped for 6 straight weeks in both age groups, based on the CDC data.

Despite those declines, however, the 16- and 17-year-olds just passed a couple of vaccination milestones. More than 60% – 60.9%, to be exact – have now received at least one dose of COVID vaccine, and 50.3% can be considered fully vaccinated. For those aged 12-15, the corresponding figures are 53.1% and 42.0%, the CDC reported.

When children under age 12 years are included – through clinical trial involvement or incorrect birth dates – the CDC data put the total count of Americans under age 18 who have received at least one dose of vaccine at almost 12.8 million, with vaccination complete in 10.3 million.

Total cases, as calculated by the APA and CHA, are now over 5.5 million, although that figure includes cases in individuals as old as 20 years, since many states differ from the CDC on the age range for a child. The CDC’s COVID Data Tracker put the total for children aged 0-17 at nearly 4.6 million.

The total number of COVID-related deaths in children is 480 as of Sept. 16, the AAP and CHA said, based on data from 45 states, New York, City, Puerto Rico, and Guam, but the CDC provides a higher number, 548, since the pandemic began. Children aged 0-4 years represent the largest share (32.3%) of those 548 deaths, followed by the 12- to 15-year-olds (26.5%), based on the CDC data.

[email protected]

COVID-19 has now killed at least 675,000 Americans, a death toll that has surpassed the estimates of the number of Americans who died during the 1918 influenza pandemic, according to data collected by Johns Hopkins University.

Although the raw numbers match, epidemiologists point out that 675,000 deaths in 1918 was a much greater proportion of the population. In 1918, the U.S. population was 105 million, less than one third of what it is today.

The AIDS pandemic of the 1980s remains the deadliest of the 20th Century, claiming the lives of 700,000 Americans. But at our current pace of 2,000 COVID deaths a day, we could quickly eclipse that death toll, too.

Even though the 1918 epidemic is often called the “Spanish Flu,” there is no universal consensus regarding where the virus originated, according to the Centers for Disease Control and Prevention.

Still, the almost incomprehensible loss harkens back to a time when medicine and technology were far less advanced than they are today.

In 1918, the United States didn’t have access to a vaccine, or near real-time tools to trace the spread and communicate the threat.

In some ways, the United States has failed to learn from the mistakes of the past.

There are many similarities between the two pandemics. In the spring of 1918, when the first wave of influenza hit, the United States and its allies were nearing victory in Europe in World War I. Just this summer the United States has ended its longest war, the conflict in Afghanistan, as COVID cases surge.

In both pandemics, hospitals and funeral homes were overrun and makeshift clinics were opened where space was available. Mask mandates were installed; schools, churches, and theaters closed; and social distancing was encouraged.

As is the case today, different jurisdictions took different steps to fight the pandemic and some were more successful than others.

According to History.com, in 1918, Philadelphia’s mayor said a popular annual parade could be held, and an estimated 200,000 people attended. In less than 2 weeks, more than 1,000 local residents were dead. But in St. Louis, public gatherings were banned, schools and theaters closed, and the death toll there was one eighth of Philadelphia’s.

Just as in 1918, America has at times continued to fan the flames of the epidemic by relaxing restrictions too quickly and relying on unproven treatments. Poor communication allowed younger people to feel that they wouldn’t necessarily face the worst consequences of the virus, contributing to a false sense of security in the age group that was fueling the spread.

“A lot of the mistakes that we definitely fell into in 1918, we hoped we wouldn’t fall into in 2020,” epidemiologist Stephen Kissler, PhD, of the Harvard T.H. Chan School of Public Health, told CNN. “We did.”

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

COVID-19 has now killed at least 675,000 Americans, a death toll that has surpassed the estimates of the number of Americans who died during the 1918 influenza pandemic, according to data collected by Johns Hopkins University.

Although the raw numbers match, epidemiologists point out that 675,000 deaths in 1918 was a much greater proportion of the population. In 1918, the U.S. population was 105 million, less than one third of what it is today.

The AIDS pandemic of the 1980s remains the deadliest of the 20th Century, claiming the lives of 700,000 Americans. But at our current pace of 2,000 COVID deaths a day, we could quickly eclipse that death toll, too.

Even though the 1918 epidemic is often called the “Spanish Flu,” there is no universal consensus regarding where the virus originated, according to the Centers for Disease Control and Prevention.

Still, the almost incomprehensible loss harkens back to a time when medicine and technology were far less advanced than they are today.

In 1918, the United States didn’t have access to a vaccine, or near real-time tools to trace the spread and communicate the threat.

In some ways, the United States has failed to learn from the mistakes of the past.

There are many similarities between the two pandemics. In the spring of 1918, when the first wave of influenza hit, the United States and its allies were nearing victory in Europe in World War I. Just this summer the United States has ended its longest war, the conflict in Afghanistan, as COVID cases surge.

In both pandemics, hospitals and funeral homes were overrun and makeshift clinics were opened where space was available. Mask mandates were installed; schools, churches, and theaters closed; and social distancing was encouraged.

As is the case today, different jurisdictions took different steps to fight the pandemic and some were more successful than others.

According to History.com, in 1918, Philadelphia’s mayor said a popular annual parade could be held, and an estimated 200,000 people attended. In less than 2 weeks, more than 1,000 local residents were dead. But in St. Louis, public gatherings were banned, schools and theaters closed, and the death toll there was one eighth of Philadelphia’s.

Just as in 1918, America has at times continued to fan the flames of the epidemic by relaxing restrictions too quickly and relying on unproven treatments. Poor communication allowed younger people to feel that they wouldn’t necessarily face the worst consequences of the virus, contributing to a false sense of security in the age group that was fueling the spread.

“A lot of the mistakes that we definitely fell into in 1918, we hoped we wouldn’t fall into in 2020,” epidemiologist Stephen Kissler, PhD, of the Harvard T.H. Chan School of Public Health, told CNN. “We did.”

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

COVID-19 has now killed at least 675,000 Americans, a death toll that has surpassed the estimates of the number of Americans who died during the 1918 influenza pandemic, according to data collected by Johns Hopkins University.

Although the raw numbers match, epidemiologists point out that 675,000 deaths in 1918 was a much greater proportion of the population. In 1918, the U.S. population was 105 million, less than one third of what it is today.

The AIDS pandemic of the 1980s remains the deadliest of the 20th Century, claiming the lives of 700,000 Americans. But at our current pace of 2,000 COVID deaths a day, we could quickly eclipse that death toll, too.

Even though the 1918 epidemic is often called the “Spanish Flu,” there is no universal consensus regarding where the virus originated, according to the Centers for Disease Control and Prevention.

Still, the almost incomprehensible loss harkens back to a time when medicine and technology were far less advanced than they are today.

In 1918, the United States didn’t have access to a vaccine, or near real-time tools to trace the spread and communicate the threat.

In some ways, the United States has failed to learn from the mistakes of the past.

There are many similarities between the two pandemics. In the spring of 1918, when the first wave of influenza hit, the United States and its allies were nearing victory in Europe in World War I. Just this summer the United States has ended its longest war, the conflict in Afghanistan, as COVID cases surge.

In both pandemics, hospitals and funeral homes were overrun and makeshift clinics were opened where space was available. Mask mandates were installed; schools, churches, and theaters closed; and social distancing was encouraged.

As is the case today, different jurisdictions took different steps to fight the pandemic and some were more successful than others.

According to History.com, in 1918, Philadelphia’s mayor said a popular annual parade could be held, and an estimated 200,000 people attended. In less than 2 weeks, more than 1,000 local residents were dead. But in St. Louis, public gatherings were banned, schools and theaters closed, and the death toll there was one eighth of Philadelphia’s.

Just as in 1918, America has at times continued to fan the flames of the epidemic by relaxing restrictions too quickly and relying on unproven treatments. Poor communication allowed younger people to feel that they wouldn’t necessarily face the worst consequences of the virus, contributing to a false sense of security in the age group that was fueling the spread.

“A lot of the mistakes that we definitely fell into in 1918, we hoped we wouldn’t fall into in 2020,” epidemiologist Stephen Kissler, PhD, of the Harvard T.H. Chan School of Public Health, told CNN. “We did.”

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

Despite a decrease in reported adverse events after receiving the human papillomavirus (HPV) vaccine, among parents of unvaccinated adolescents, concerns about the vaccine’s safety rose 80% from 2015 to 2018, according to research published September 17 in JAMA Network Open.

Since its approval in 2006 by the U.S. Food and Drug Administration, uptake of the HPV vaccine has consistently lagged behind that of other routine vaccinations. According to the most recent data from the Centers for Disease Control and Prevention, released September 3, 58.6% of adolescents were considered up to date with their HPV vaccinations in 2020.

Trials prior to the vaccine’s FDA approval as well as an abundance of clinical and observational evidence after it hit the market demonstrate the vaccine’s efficacy and safety, said lead author Kalyani Sonawane, PhD, an assistant professor of management, policy, and community health at the UTHealth School of Public Health, in Houston, Texas, in an interview. Still, recent research suggests that safety concerns are a main reason why parents are hesitant to have their children vaccinated, she noted.

In the study, Dr. Sonawane and colleagues analyzed data from National Immunization Survey-Teen (NIS-Teen) from 2015 through 2018. NIS-Teen is a random-digit-dialed telephone survey conducted annually by the CDC to monitor routine vaccination coverage among adolescents aged 13 to 17. The researchers identified 39,364 adolescents who had not received any HPV shots and reviewed the caregivers’ reasons for vaccine hesitancy. The research team also reviewed the Vaccine Adverse Event Reporting System (VAERS). They identified 16,621 reports that listed the HPV vaccine from 2015 through 2018.

The top five reasons caregivers cited for avoiding the HPV vaccine were the following:

• not needed or necessary
• safety concerns
• not recommended
• lack of knowledge
• not sexually active

Of these, safety concerns were the only factor that increased during the study period. They increased from 13.0% in 2015 to 23.4% in 2018. Concerns over vaccine safety rose in 30 states, with increases of over 200% in California, Hawaii, South Dakota, and Mississippi.

The proportion of unvaccinated adolescents whose caregivers thought the HPV vaccine was not needed or necessary remained steady at around 25%. Those whose caregivers listed “not recommended,” “lack of knowledge,” and “not sexually active” as reasons for avoiding vaccination decreased over the study period.

The reporting rate for adverse events following HPV vaccination decreased from 44.7 per 100,000 doses in 2015 to 29.4 per 100,000 doses in 2018. Of the reported 16,621 adverse events following HPV vaccination that occurred over the study period, 4.6% were serious, resulting in hospitalizations, disability, life-threatening events, or death. From 2015 through 2018, reporting rates for serious adverse events remained level at around 0.3 events per 100,000 doses.

This mismatch between increasing vaccine safety concerns and decreasing adverse events suggests that disinformation may be driving these concerns more than scientific fact, Nosayaba Osazuwa-Peters, PhD, MPH, an assistant professor in head and neck surgery and communication sciences at the Duke University School of Medicine, in Durham, North Carolina, told this news organization. He co-wrote an invited commentary on the study and was not involved with the research. Although there have always been people who are hesitant to receive vaccinations, he said, social media and the internet have undoubtedly played a role in spreading concern.

Dr. Sonawane agreed. Online, “there are a lot of antivaccine groups that are making unwarranted claims about the vaccine’s safety,” such as that the HPV vaccine causes autism or fertility problems in women, she said. “We believe that this growing antivaccine movement in the U.S. and across the globe – which the World Health Organization has declared as one of the biggest threats right now – is also contributing to safety concerns among U.S. parents, particularly HPV vaccine safety.”

Although the study did not address strategies to combat this misinformation, Dr. Osazuwa-Peters said clinicians need to improve their communication with parents and patients. One way to do that, he said, is by bolstering an online presence and by countering vaccine disinformation with evidence-based responses on the internet. Most people get their medical information online. “Many people are just afraid because they don’t trust the messages coming from health care,” he said. “So, we need to a better job of not just providing the facts but providing the facts in a way that the end users can understand and appreciate.”

Dr. Sonawane and Dr. Osazuwa-Peters report no relevant financial relationships.

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

Despite a decrease in reported adverse events after receiving the human papillomavirus (HPV) vaccine, among parents of unvaccinated adolescents, concerns about the vaccine’s safety rose 80% from 2015 to 2018, according to research published September 17 in JAMA Network Open.

Since its approval in 2006 by the U.S. Food and Drug Administration, uptake of the HPV vaccine has consistently lagged behind that of other routine vaccinations. According to the most recent data from the Centers for Disease Control and Prevention, released September 3, 58.6% of adolescents were considered up to date with their HPV vaccinations in 2020.

Trials prior to the vaccine’s FDA approval as well as an abundance of clinical and observational evidence after it hit the market demonstrate the vaccine’s efficacy and safety, said lead author Kalyani Sonawane, PhD, an assistant professor of management, policy, and community health at the UTHealth School of Public Health, in Houston, Texas, in an interview. Still, recent research suggests that safety concerns are a main reason why parents are hesitant to have their children vaccinated, she noted.

In the study, Dr. Sonawane and colleagues analyzed data from National Immunization Survey-Teen (NIS-Teen) from 2015 through 2018. NIS-Teen is a random-digit-dialed telephone survey conducted annually by the CDC to monitor routine vaccination coverage among adolescents aged 13 to 17. The researchers identified 39,364 adolescents who had not received any HPV shots and reviewed the caregivers’ reasons for vaccine hesitancy. The research team also reviewed the Vaccine Adverse Event Reporting System (VAERS). They identified 16,621 reports that listed the HPV vaccine from 2015 through 2018.

The top five reasons caregivers cited for avoiding the HPV vaccine were the following:

• not needed or necessary
• safety concerns
• not recommended
• lack of knowledge
• not sexually active

Of these, safety concerns were the only factor that increased during the study period. They increased from 13.0% in 2015 to 23.4% in 2018. Concerns over vaccine safety rose in 30 states, with increases of over 200% in California, Hawaii, South Dakota, and Mississippi.

The proportion of unvaccinated adolescents whose caregivers thought the HPV vaccine was not needed or necessary remained steady at around 25%. Those whose caregivers listed “not recommended,” “lack of knowledge,” and “not sexually active” as reasons for avoiding vaccination decreased over the study period.

The reporting rate for adverse events following HPV vaccination decreased from 44.7 per 100,000 doses in 2015 to 29.4 per 100,000 doses in 2018. Of the reported 16,621 adverse events following HPV vaccination that occurred over the study period, 4.6% were serious, resulting in hospitalizations, disability, life-threatening events, or death. From 2015 through 2018, reporting rates for serious adverse events remained level at around 0.3 events per 100,000 doses.

This mismatch between increasing vaccine safety concerns and decreasing adverse events suggests that disinformation may be driving these concerns more than scientific fact, Nosayaba Osazuwa-Peters, PhD, MPH, an assistant professor in head and neck surgery and communication sciences at the Duke University School of Medicine, in Durham, North Carolina, told this news organization. He co-wrote an invited commentary on the study and was not involved with the research. Although there have always been people who are hesitant to receive vaccinations, he said, social media and the internet have undoubtedly played a role in spreading concern.

Dr. Sonawane agreed. Online, “there are a lot of antivaccine groups that are making unwarranted claims about the vaccine’s safety,” such as that the HPV vaccine causes autism or fertility problems in women, she said. “We believe that this growing antivaccine movement in the U.S. and across the globe – which the World Health Organization has declared as one of the biggest threats right now – is also contributing to safety concerns among U.S. parents, particularly HPV vaccine safety.”

Although the study did not address strategies to combat this misinformation, Dr. Osazuwa-Peters said clinicians need to improve their communication with parents and patients. One way to do that, he said, is by bolstering an online presence and by countering vaccine disinformation with evidence-based responses on the internet. Most people get their medical information online. “Many people are just afraid because they don’t trust the messages coming from health care,” he said. “So, we need to a better job of not just providing the facts but providing the facts in a way that the end users can understand and appreciate.”

Dr. Sonawane and Dr. Osazuwa-Peters report no relevant financial relationships.

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

Despite a decrease in reported adverse events after receiving the human papillomavirus (HPV) vaccine, among parents of unvaccinated adolescents, concerns about the vaccine’s safety rose 80% from 2015 to 2018, according to research published September 17 in JAMA Network Open.

Since its approval in 2006 by the U.S. Food and Drug Administration, uptake of the HPV vaccine has consistently lagged behind that of other routine vaccinations. According to the most recent data from the Centers for Disease Control and Prevention, released September 3, 58.6% of adolescents were considered up to date with their HPV vaccinations in 2020.

Trials prior to the vaccine’s FDA approval as well as an abundance of clinical and observational evidence after it hit the market demonstrate the vaccine’s efficacy and safety, said lead author Kalyani Sonawane, PhD, an assistant professor of management, policy, and community health at the UTHealth School of Public Health, in Houston, Texas, in an interview. Still, recent research suggests that safety concerns are a main reason why parents are hesitant to have their children vaccinated, she noted.

In the study, Dr. Sonawane and colleagues analyzed data from National Immunization Survey-Teen (NIS-Teen) from 2015 through 2018. NIS-Teen is a random-digit-dialed telephone survey conducted annually by the CDC to monitor routine vaccination coverage among adolescents aged 13 to 17. The researchers identified 39,364 adolescents who had not received any HPV shots and reviewed the caregivers’ reasons for vaccine hesitancy. The research team also reviewed the Vaccine Adverse Event Reporting System (VAERS). They identified 16,621 reports that listed the HPV vaccine from 2015 through 2018.

The top five reasons caregivers cited for avoiding the HPV vaccine were the following:

• not needed or necessary
• safety concerns
• not recommended
• lack of knowledge
• not sexually active

Of these, safety concerns were the only factor that increased during the study period. They increased from 13.0% in 2015 to 23.4% in 2018. Concerns over vaccine safety rose in 30 states, with increases of over 200% in California, Hawaii, South Dakota, and Mississippi.

The proportion of unvaccinated adolescents whose caregivers thought the HPV vaccine was not needed or necessary remained steady at around 25%. Those whose caregivers listed “not recommended,” “lack of knowledge,” and “not sexually active” as reasons for avoiding vaccination decreased over the study period.

The reporting rate for adverse events following HPV vaccination decreased from 44.7 per 100,000 doses in 2015 to 29.4 per 100,000 doses in 2018. Of the reported 16,621 adverse events following HPV vaccination that occurred over the study period, 4.6% were serious, resulting in hospitalizations, disability, life-threatening events, or death. From 2015 through 2018, reporting rates for serious adverse events remained level at around 0.3 events per 100,000 doses.

This mismatch between increasing vaccine safety concerns and decreasing adverse events suggests that disinformation may be driving these concerns more than scientific fact, Nosayaba Osazuwa-Peters, PhD, MPH, an assistant professor in head and neck surgery and communication sciences at the Duke University School of Medicine, in Durham, North Carolina, told this news organization. He co-wrote an invited commentary on the study and was not involved with the research. Although there have always been people who are hesitant to receive vaccinations, he said, social media and the internet have undoubtedly played a role in spreading concern.

Dr. Sonawane agreed. Online, “there are a lot of antivaccine groups that are making unwarranted claims about the vaccine’s safety,” such as that the HPV vaccine causes autism or fertility problems in women, she said. “We believe that this growing antivaccine movement in the U.S. and across the globe – which the World Health Organization has declared as one of the biggest threats right now – is also contributing to safety concerns among U.S. parents, particularly HPV vaccine safety.”

Although the study did not address strategies to combat this misinformation, Dr. Osazuwa-Peters said clinicians need to improve their communication with parents and patients. One way to do that, he said, is by bolstering an online presence and by countering vaccine disinformation with evidence-based responses on the internet. Most people get their medical information online. “Many people are just afraid because they don’t trust the messages coming from health care,” he said. “So, we need to a better job of not just providing the facts but providing the facts in a way that the end users can understand and appreciate.”

Dr. Sonawane and Dr. Osazuwa-Peters report no relevant financial relationships.

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

A nationwide study of more than 3,600 adults found the Moderna vaccine does a better job at preventing COVID-19 hospitalizations than the two other vaccines being used in the United States, the Centers for Disease Control and Protection has said.

“Among U.S. adults without immunocompromising conditions, vaccine effectiveness against COVID-19 hospitalization during March 11–Aug. 15, 2021, was higher for the Moderna vaccine (93%) than the Pfizer-BioNTech vaccine (88%) and the Janssen vaccine (71%),” the agency’s Morbidity and Mortality Weekly Report said. Janssen refers to the Johnson & Johnson vaccine.

The CDC said the data could help people make informed decisions.

“Understanding differences in VE [vaccine effectiveness] by vaccine product can guide individual choices and policy recommendations regarding vaccine boosters. All Food and Drug Administration–approved or authorized COVID-19 vaccines provide substantial protection against COVID-19 hospitalization,” the report said.

The study also broke down effectiveness for longer periods. Moderna came out on top again.

After 120 days, the Moderna vaccine provided 92% effectiveness against hospitalization, whereas the Pfizer vaccine’s effectiveness dropped to 77%, the CDC said. There was no similar calculation for the Johnson & Johnson vaccine.

The CDC studied 3,689 adults at 21 hospitals in 18 states who got the two-shot Pfizer or Moderna vaccine or the one-shot Johnson & Johnson vaccine between March and August.

The agency noted some factors that could have come into play.

“Differences in vaccine effectiveness between the Moderna and Pfizer-BioNTech vaccine might be due to higher mRNA content in the Moderna vaccine, differences in timing between doses (3 weeks for Pfizer-BioNTech vs. 4 weeks for Moderna), or possible differences between groups that received each vaccine that were not accounted for in the analysis,” the report said.

The CDC noted limitations in the findings. Children, immunocompromised adults, and vaccine effectiveness against COVID-19 that did not result in hospitalization were not studied.

Other studies have shown all three U.S. vaccines provide a high rate of protection against coronavirus.

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

A nationwide study of more than 3,600 adults found the Moderna vaccine does a better job at preventing COVID-19 hospitalizations than the two other vaccines being used in the United States, the Centers for Disease Control and Protection has said.

“Among U.S. adults without immunocompromising conditions, vaccine effectiveness against COVID-19 hospitalization during March 11–Aug. 15, 2021, was higher for the Moderna vaccine (93%) than the Pfizer-BioNTech vaccine (88%) and the Janssen vaccine (71%),” the agency’s Morbidity and Mortality Weekly Report said. Janssen refers to the Johnson & Johnson vaccine.

The CDC said the data could help people make informed decisions.

“Understanding differences in VE [vaccine effectiveness] by vaccine product can guide individual choices and policy recommendations regarding vaccine boosters. All Food and Drug Administration–approved or authorized COVID-19 vaccines provide substantial protection against COVID-19 hospitalization,” the report said.

The study also broke down effectiveness for longer periods. Moderna came out on top again.

After 120 days, the Moderna vaccine provided 92% effectiveness against hospitalization, whereas the Pfizer vaccine’s effectiveness dropped to 77%, the CDC said. There was no similar calculation for the Johnson & Johnson vaccine.

The CDC studied 3,689 adults at 21 hospitals in 18 states who got the two-shot Pfizer or Moderna vaccine or the one-shot Johnson & Johnson vaccine between March and August.

The agency noted some factors that could have come into play.

“Differences in vaccine effectiveness between the Moderna and Pfizer-BioNTech vaccine might be due to higher mRNA content in the Moderna vaccine, differences in timing between doses (3 weeks for Pfizer-BioNTech vs. 4 weeks for Moderna), or possible differences between groups that received each vaccine that were not accounted for in the analysis,” the report said.

The CDC noted limitations in the findings. Children, immunocompromised adults, and vaccine effectiveness against COVID-19 that did not result in hospitalization were not studied.

Other studies have shown all three U.S. vaccines provide a high rate of protection against coronavirus.

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

A nationwide study of more than 3,600 adults found the Moderna vaccine does a better job at preventing COVID-19 hospitalizations than the two other vaccines being used in the United States, the Centers for Disease Control and Protection has said.

“Among U.S. adults without immunocompromising conditions, vaccine effectiveness against COVID-19 hospitalization during March 11–Aug. 15, 2021, was higher for the Moderna vaccine (93%) than the Pfizer-BioNTech vaccine (88%) and the Janssen vaccine (71%),” the agency’s Morbidity and Mortality Weekly Report said. Janssen refers to the Johnson & Johnson vaccine.

The CDC said the data could help people make informed decisions.

“Understanding differences in VE [vaccine effectiveness] by vaccine product can guide individual choices and policy recommendations regarding vaccine boosters. All Food and Drug Administration–approved or authorized COVID-19 vaccines provide substantial protection against COVID-19 hospitalization,” the report said.

The study also broke down effectiveness for longer periods. Moderna came out on top again.

After 120 days, the Moderna vaccine provided 92% effectiveness against hospitalization, whereas the Pfizer vaccine’s effectiveness dropped to 77%, the CDC said. There was no similar calculation for the Johnson & Johnson vaccine.

The CDC studied 3,689 adults at 21 hospitals in 18 states who got the two-shot Pfizer or Moderna vaccine or the one-shot Johnson & Johnson vaccine between March and August.

The agency noted some factors that could have come into play.

“Differences in vaccine effectiveness between the Moderna and Pfizer-BioNTech vaccine might be due to higher mRNA content in the Moderna vaccine, differences in timing between doses (3 weeks for Pfizer-BioNTech vs. 4 weeks for Moderna), or possible differences between groups that received each vaccine that were not accounted for in the analysis,” the report said.

The CDC noted limitations in the findings. Children, immunocompromised adults, and vaccine effectiveness against COVID-19 that did not result in hospitalization were not studied.

Other studies have shown all three U.S. vaccines provide a high rate of protection against coronavirus.

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

The U.S. Food and Drug Administration has granted an accelerated approval to zanubrutinib (Brukinsa) for the treatment of adult patients with relapsed or refractory (R/R) marginal zone lymphoma (MZL) who have received at least one anti-CD20–based regimen, the drug’s maker BeiGene announced in a press statement.  

The drug works as an inhibitor of Bruton’s tyrosine kinase (BTK), which plays a critical role in B-cell–receptor signaling, a driver in the development of marginal zone lymphoma, according to the company.

The new approval comes just 2 weeks after the oral drug received an accelerated approval for the treatment of adult patients with Waldenström’s macroglobulinemia, a rare non-Hodgkin lymphoma. The drug also has an accelerated approval for treating mantle cell lymphoma in patients who have received at least one prior therapy and is being studied in the treatment of chronic lymphocytic leukemia.

The latest indication is based on results from two single-arm clinical trials, with overall response rate (ORR) as the primary endpoint.

In the multicenter, phase 2 MAGNOLIA trial, zanubrutinib “demonstrated impressive overall response and complete remission rates, with responses observed in all MZL subtypes,” said Stephen Opat, MBBS, of Monash University in Melbourne, lead principal investigator of the study. “In addition, this next-generation BTK inhibitor was well-tolerated in these patients, with low rate of discontinuation due to adverse reactions.”

In the MAGNOLIA trial, 66 patients with R/R MZL who had received at least one anti-CD20–based regimen were treated with zanubrutinib. Among the patients were 26 with extranodal subtype, 26 with nodal subtype, 12 with splenic subtype, and 4 with unknown subtype.

The ORR was 56% with a complete response rate of 20%, based on CT scan assessment.

In addition, the ORR was 67% with a complete response rate of 26%, based on PET-CT scan assessment.

The median duration of response (DoR) was not reached at the median follow-up time of 8.3 months, with 85% of responders still in remission at 12 months. Responses were observed in all MZL subtypes.

In an earlier, phase 1/2 trial of the agent, 20 patients were evaluated, including 9 with extranodal subtype, 5 with nodal subtype, and 6 with splenic subtype. Based on CT scan assessment, the ORR was 80% with a complete remission rate of 20%. The median DoR was not reached at the median follow-up time of 31.4 months, with 72% of responders still in remission at 12 months.

The most common (≥30%) adverse reactions, including laboratory abnormalities, in the pooled safety population of 847 patients were decreased neutrophil count, upper respiratory tract infection, decreased platelet count, hemorrhage, decreased lymphocyte count, rash, and musculoskeletal pain, said the company.

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

The U.S. Food and Drug Administration has granted an accelerated approval to zanubrutinib (Brukinsa) for the treatment of adult patients with relapsed or refractory (R/R) marginal zone lymphoma (MZL) who have received at least one anti-CD20–based regimen, the drug’s maker BeiGene announced in a press statement.  

The drug works as an inhibitor of Bruton’s tyrosine kinase (BTK), which plays a critical role in B-cell–receptor signaling, a driver in the development of marginal zone lymphoma, according to the company.

The new approval comes just 2 weeks after the oral drug received an accelerated approval for the treatment of adult patients with Waldenström’s macroglobulinemia, a rare non-Hodgkin lymphoma. The drug also has an accelerated approval for treating mantle cell lymphoma in patients who have received at least one prior therapy and is being studied in the treatment of chronic lymphocytic leukemia.

The latest indication is based on results from two single-arm clinical trials, with overall response rate (ORR) as the primary endpoint.

In the multicenter, phase 2 MAGNOLIA trial, zanubrutinib “demonstrated impressive overall response and complete remission rates, with responses observed in all MZL subtypes,” said Stephen Opat, MBBS, of Monash University in Melbourne, lead principal investigator of the study. “In addition, this next-generation BTK inhibitor was well-tolerated in these patients, with low rate of discontinuation due to adverse reactions.”

In the MAGNOLIA trial, 66 patients with R/R MZL who had received at least one anti-CD20–based regimen were treated with zanubrutinib. Among the patients were 26 with extranodal subtype, 26 with nodal subtype, 12 with splenic subtype, and 4 with unknown subtype.

The ORR was 56% with a complete response rate of 20%, based on CT scan assessment.

In addition, the ORR was 67% with a complete response rate of 26%, based on PET-CT scan assessment.

The median duration of response (DoR) was not reached at the median follow-up time of 8.3 months, with 85% of responders still in remission at 12 months. Responses were observed in all MZL subtypes.

In an earlier, phase 1/2 trial of the agent, 20 patients were evaluated, including 9 with extranodal subtype, 5 with nodal subtype, and 6 with splenic subtype. Based on CT scan assessment, the ORR was 80% with a complete remission rate of 20%. The median DoR was not reached at the median follow-up time of 31.4 months, with 72% of responders still in remission at 12 months.

The most common (≥30%) adverse reactions, including laboratory abnormalities, in the pooled safety population of 847 patients were decreased neutrophil count, upper respiratory tract infection, decreased platelet count, hemorrhage, decreased lymphocyte count, rash, and musculoskeletal pain, said the company.

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

The U.S. Food and Drug Administration has granted an accelerated approval to zanubrutinib (Brukinsa) for the treatment of adult patients with relapsed or refractory (R/R) marginal zone lymphoma (MZL) who have received at least one anti-CD20–based regimen, the drug’s maker BeiGene announced in a press statement.  

The drug works as an inhibitor of Bruton’s tyrosine kinase (BTK), which plays a critical role in B-cell–receptor signaling, a driver in the development of marginal zone lymphoma, according to the company.

The new approval comes just 2 weeks after the oral drug received an accelerated approval for the treatment of adult patients with Waldenström’s macroglobulinemia, a rare non-Hodgkin lymphoma. The drug also has an accelerated approval for treating mantle cell lymphoma in patients who have received at least one prior therapy and is being studied in the treatment of chronic lymphocytic leukemia.

The latest indication is based on results from two single-arm clinical trials, with overall response rate (ORR) as the primary endpoint.

In the multicenter, phase 2 MAGNOLIA trial, zanubrutinib “demonstrated impressive overall response and complete remission rates, with responses observed in all MZL subtypes,” said Stephen Opat, MBBS, of Monash University in Melbourne, lead principal investigator of the study. “In addition, this next-generation BTK inhibitor was well-tolerated in these patients, with low rate of discontinuation due to adverse reactions.”

In the MAGNOLIA trial, 66 patients with R/R MZL who had received at least one anti-CD20–based regimen were treated with zanubrutinib. Among the patients were 26 with extranodal subtype, 26 with nodal subtype, 12 with splenic subtype, and 4 with unknown subtype.

The ORR was 56% with a complete response rate of 20%, based on CT scan assessment.

In addition, the ORR was 67% with a complete response rate of 26%, based on PET-CT scan assessment.

The median duration of response (DoR) was not reached at the median follow-up time of 8.3 months, with 85% of responders still in remission at 12 months. Responses were observed in all MZL subtypes.

In an earlier, phase 1/2 trial of the agent, 20 patients were evaluated, including 9 with extranodal subtype, 5 with nodal subtype, and 6 with splenic subtype. Based on CT scan assessment, the ORR was 80% with a complete remission rate of 20%. The median DoR was not reached at the median follow-up time of 31.4 months, with 72% of responders still in remission at 12 months.

The most common (≥30%) adverse reactions, including laboratory abnormalities, in the pooled safety population of 847 patients were decreased neutrophil count, upper respiratory tract infection, decreased platelet count, hemorrhage, decreased lymphocyte count, rash, and musculoskeletal pain, said the company.

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

Long-term symptoms, like those linked with COVID-19, were common in people who had even just a single positive test, new Centers for Disease Control and Prevention data show.

The data show that symptoms in this group – including fatigue, cough, and headache – tended to last for more than a month. 

Frequency of symptoms in people with a positive test was 1.5 times higher, compared with people whose tests had always been negative, according to the research published in the CDC’s latest Morbidity and Mortality Weekly Report.

Lead author Valentine Wanga, PhD, with the CDC’s COVID-19 response team, and colleagues conducted a non–probability-based internet panel survey of about 6,000 U.S. adults to assess long-term symptoms often associated with COVID-19 among those who had ever tested positive or always tested negative for COVID-19 between January 2020 and April 2021.

William Schaffner, MD, an infectious disease expert at Vanderbilt University, Nashville, Tenn., said in an interview that this research “establishes more securely than before that you don’t have to be hospitalized with COVID in order to develop long COVID symptoms.”

That’s better known among infectious disease experts, he said, but added that “this survey really gives a firm database for that.”
 

Study results

The study’s results showed that, compared with respondents who had a negative test result, those who received a positive result reported a significantly higher prevalence of any long-term symptom (65.9% vs. 42.9%), fatigue (22.5% vs. 12.0%), change in sense of smell or taste (17.3% vs. 1.7%), shortness of breath (15.5% vs. 5.2%), cough (14.5% vs. 4.9%), and headache (13.8% vs. 9.9%).

More people who had a positive test result (76.2%) reported persistence for more than a month of at least one initially occurring symptom, compared with those whose test results were always negative (69.6%).

The numbers are further proof, Dr. Schaffner said, that COVID not only will be an acute stressor on the health care system but patients with long COVID will need help with managing care for the long term.

“We still don’t know what the COVID virus does that results in these long COVID symptoms,” he said. Vanderbilt and many other institutions have developed “long COVID” centers as a testament to how important the problem is.

Long COVID symptoms are not well understood and most studies have looked at the effects from patients who had been hospitalized with COVID-19.

In this survey, respondents self-reported whether they had ever had a positive SARS-CoV-2 test result (698), always received a negative test result (2,437), or never were tested for SARS-CoV-2 (2,750).

Compared with those who always tested negative, a larger proportion of those who tested positive (28.7% vs. 15.7%) reported believing that receiving a COVID-19 vaccine made their long-term symptoms better. No difference was found in reported beliefs that a vaccine made long-term symptoms worse.

Dr. Schaffner said he found that survey result interesting, but said that is not backed up by current data and would need further study.

“I would treat that with great caution,” he said. “I’m not dismissing it, but you can’t take that at face value. All of us who get sick and those of us who care for people who are sick – if there’s an intervention, we all hope for the best. We’re being optimistic. It’s when you do a randomized, double-blind, placebo-controlled study that you can find out whether your instincts or hopes were correct.”

The authors said that findings can inform public health preparedness, help guide care for people with post-COVID conditions, and help make the case for vaccines.

The study authors and Dr. Schaffner disclosed no relevant financial relationships.

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

Long-term symptoms, like those linked with COVID-19, were common in people who had even just a single positive test, new Centers for Disease Control and Prevention data show.

The data show that symptoms in this group – including fatigue, cough, and headache – tended to last for more than a month. 

Frequency of symptoms in people with a positive test was 1.5 times higher, compared with people whose tests had always been negative, according to the research published in the CDC’s latest Morbidity and Mortality Weekly Report.

Lead author Valentine Wanga, PhD, with the CDC’s COVID-19 response team, and colleagues conducted a non–probability-based internet panel survey of about 6,000 U.S. adults to assess long-term symptoms often associated with COVID-19 among those who had ever tested positive or always tested negative for COVID-19 between January 2020 and April 2021.

William Schaffner, MD, an infectious disease expert at Vanderbilt University, Nashville, Tenn., said in an interview that this research “establishes more securely than before that you don’t have to be hospitalized with COVID in order to develop long COVID symptoms.”

That’s better known among infectious disease experts, he said, but added that “this survey really gives a firm database for that.”
 

Study results

The study’s results showed that, compared with respondents who had a negative test result, those who received a positive result reported a significantly higher prevalence of any long-term symptom (65.9% vs. 42.9%), fatigue (22.5% vs. 12.0%), change in sense of smell or taste (17.3% vs. 1.7%), shortness of breath (15.5% vs. 5.2%), cough (14.5% vs. 4.9%), and headache (13.8% vs. 9.9%).

More people who had a positive test result (76.2%) reported persistence for more than a month of at least one initially occurring symptom, compared with those whose test results were always negative (69.6%).

The numbers are further proof, Dr. Schaffner said, that COVID not only will be an acute stressor on the health care system but patients with long COVID will need help with managing care for the long term.

“We still don’t know what the COVID virus does that results in these long COVID symptoms,” he said. Vanderbilt and many other institutions have developed “long COVID” centers as a testament to how important the problem is.

Long COVID symptoms are not well understood and most studies have looked at the effects from patients who had been hospitalized with COVID-19.

In this survey, respondents self-reported whether they had ever had a positive SARS-CoV-2 test result (698), always received a negative test result (2,437), or never were tested for SARS-CoV-2 (2,750).

Compared with those who always tested negative, a larger proportion of those who tested positive (28.7% vs. 15.7%) reported believing that receiving a COVID-19 vaccine made their long-term symptoms better. No difference was found in reported beliefs that a vaccine made long-term symptoms worse.

Dr. Schaffner said he found that survey result interesting, but said that is not backed up by current data and would need further study.

“I would treat that with great caution,” he said. “I’m not dismissing it, but you can’t take that at face value. All of us who get sick and those of us who care for people who are sick – if there’s an intervention, we all hope for the best. We’re being optimistic. It’s when you do a randomized, double-blind, placebo-controlled study that you can find out whether your instincts or hopes were correct.”

The authors said that findings can inform public health preparedness, help guide care for people with post-COVID conditions, and help make the case for vaccines.

The study authors and Dr. Schaffner disclosed no relevant financial relationships.

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

Long-term symptoms, like those linked with COVID-19, were common in people who had even just a single positive test, new Centers for Disease Control and Prevention data show.

The data show that symptoms in this group – including fatigue, cough, and headache – tended to last for more than a month. 

Frequency of symptoms in people with a positive test was 1.5 times higher, compared with people whose tests had always been negative, according to the research published in the CDC’s latest Morbidity and Mortality Weekly Report.

Lead author Valentine Wanga, PhD, with the CDC’s COVID-19 response team, and colleagues conducted a non–probability-based internet panel survey of about 6,000 U.S. adults to assess long-term symptoms often associated with COVID-19 among those who had ever tested positive or always tested negative for COVID-19 between January 2020 and April 2021.

William Schaffner, MD, an infectious disease expert at Vanderbilt University, Nashville, Tenn., said in an interview that this research “establishes more securely than before that you don’t have to be hospitalized with COVID in order to develop long COVID symptoms.”

That’s better known among infectious disease experts, he said, but added that “this survey really gives a firm database for that.”
 

Study results

The study’s results showed that, compared with respondents who had a negative test result, those who received a positive result reported a significantly higher prevalence of any long-term symptom (65.9% vs. 42.9%), fatigue (22.5% vs. 12.0%), change in sense of smell or taste (17.3% vs. 1.7%), shortness of breath (15.5% vs. 5.2%), cough (14.5% vs. 4.9%), and headache (13.8% vs. 9.9%).

More people who had a positive test result (76.2%) reported persistence for more than a month of at least one initially occurring symptom, compared with those whose test results were always negative (69.6%).

The numbers are further proof, Dr. Schaffner said, that COVID not only will be an acute stressor on the health care system but patients with long COVID will need help with managing care for the long term.

“We still don’t know what the COVID virus does that results in these long COVID symptoms,” he said. Vanderbilt and many other institutions have developed “long COVID” centers as a testament to how important the problem is.

Long COVID symptoms are not well understood and most studies have looked at the effects from patients who had been hospitalized with COVID-19.

In this survey, respondents self-reported whether they had ever had a positive SARS-CoV-2 test result (698), always received a negative test result (2,437), or never were tested for SARS-CoV-2 (2,750).

Compared with those who always tested negative, a larger proportion of those who tested positive (28.7% vs. 15.7%) reported believing that receiving a COVID-19 vaccine made their long-term symptoms better. No difference was found in reported beliefs that a vaccine made long-term symptoms worse.

Dr. Schaffner said he found that survey result interesting, but said that is not backed up by current data and would need further study.

“I would treat that with great caution,” he said. “I’m not dismissing it, but you can’t take that at face value. All of us who get sick and those of us who care for people who are sick – if there’s an intervention, we all hope for the best. We’re being optimistic. It’s when you do a randomized, double-blind, placebo-controlled study that you can find out whether your instincts or hopes were correct.”

The authors said that findings can inform public health preparedness, help guide care for people with post-COVID conditions, and help make the case for vaccines.

The study authors and Dr. Schaffner disclosed no relevant financial relationships.

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

The arthritis and ulcerative colitis medicine tofacitinib (Xeljanz, Xeljanz XR) poses an increased risk of serious cardiac events such as heart attack or stroke, cancer, blood clots, and death, the Food and Drug Administration announced Sept 1.

Manufacturers of this drug along with other Janus kinase (JAK) inhibitors baricitinib (Olumiant) and upadacitinib (Rinvoq) must update their boxed warnings to include information about these health risks. The FDA made the determination after new study data from Pfizer, which manufacturers Xeljanz, found an association between a lower dose of Xeljanz and increased risk of blood clots and death.

“Recommendations for healthcare professionals will include consideration of the benefits and risks for the individual patient prior to initiating or continuing therapy,” the agency stated.

The FDA is limiting all approved uses of these three medications to patients who have not responded well to tumor necrosis factor (TNF) blockers to ensure their benefits outweigh their risks. Tofacitinib is indicated for rheumatoid arthritis, psoriatic arthritis, ulcerative colitis, and polyarticular course juvenile idiopathic arthritis. Baricitinib and upadacitinib are approved only for RA. The FDA included baricitinib and upadacitinib in the warning because of the similar properties they share with tofacitinib, even though they haven’t been studied as extensively.

“We believe this update will bring important clarity for healthcare plans on the risk/benefit profile of Xeljanz, which is a medicine informed by more clinical data than any other JAK inhibitor,” Pfizer said in a statement.

Investigators for the ORAL Surveillance trial compared two doses of tofacitinib (5 mg twice daily and 10 mg twice daily) with TNF blockers in patients with rheumatoid arthritis who were aged 50 years or older with at least one additional cardiovascular risk factor.

For both dose regimens of tofacitinib, they found an increased risk of major adverse cardiovascular events, malignancies, thrombosis, and death compared with the TNF blocker regimen. In addition, rates of lung cancers and lymphomas were higher with tofacitinib. In trial data released earlier this year, Pfizer revealed that the tofacitinib group had a much higher incidence of adjudicated malignancies compared with the TNF blocker group (1.13 vs. 0.77 per 100 person-years; hazard ratio, 1.48; 95% confidence interval, 1.04-2.09).

Impact on clinical practice

Physicians treating patients who have rheumatoid arthritis with tofacitinib may initially decrease prescriptions following the FDA’s drug safety communication, said Daniel E. Furst, MD, professor of medicine (emeritus) at the University of California, Los Angeles, adjunct professor at the University of Washington, Seattle, and a research professor at the University of Florence (Italy) – particularly those with a principal mechanism of action slightly different from that of tofacitinib, he added.

“Tofacitinib is principally a JAK 1,3 inhibitor at usual concentrations, whereas upadacitinib and baricitinib are JAK 1,2 inhibitors. Thus, I speculate that the tofacitinib prescriptions will go down more than the upadacitinib and baricitinib prescriptions,” he said in an interview.

Some patients may also be worried about taking tofacitinib, particularly those with previous events or predisposing conditions, Dr. Furst noted.

“First and foremost, I think we need to actually look at the data in a publication rather than just an FDA statement before making huge changes in our practice,” he advised.

“I am looking forward to the data finally being published ... It’s interesting that the full data still isn’t really out there beyond the press releases and an abstract. I think there’s a lot more to learn about how these drugs work and who is really at risk for harmful events,” said Alexis R. Ogdie, MD, MSCE, associate professor of medicine and epidemiology at the University of Pennsylvania, Philadelphia.

Pfizer’s data also may be affecting FDA approvals of other JAK inhibitors. This past summer, AbbVie and Eli Lilly stated that the FDA’s ongoing assessment of the safety trial was delaying the agency’s decisions about expanding use of their respective drugs upadacitinib and baricitinib.

“I think many rheumatologists have already taken this information in, and begun to incorporate it into their discussions with their patients” since it has been over a year since the first public release of information about the ORAL Surveillance trial, said Arthur Kavanaugh, MD, professor of medicine at the University of California, San Diego. “I don’t know that it will affect the approvals, but it will impact their labels.”

Wariness to prescribing tofacitinib may be lower for patients younger than those in the ORAL Surveillance trial without additional cardiovascular risk factors who are taking tofacitinib for non-RA indications, said gastroenterologist Miguel Regueiro, MD.

“The JAK inhibitor warning by the FDA is an important consideration for any prescriber or patient. The risk of cardiovascular disease and venous thromboembolism with this class of medicine appears higher in older rheumatoid arthritis patients with underlying cardiovascular disease. While the warning applies to all JAK inhibitors and likely the newer selective JAK inhibitors to come, we need to weigh the risk and benefit based on the indication for prescribing,” said Dr. Regueiro, chair of the Digestive Disease and Surgery Institute and of the department of gastroenterology, hepatology and nutrition at the Cleveland Clinic in Ohio.

“I do think that there will be a heightened awareness and wariness for older RA patients and for the prescribers. However, for inflammatory bowel disease (and other non-RA indications), it does not appear that the risk for cardiovascular disease and VTE are significantly increased. To that end, in my own practice, I still use tofacitinib for ulcerative colitis and will do the same for the selective JAK inhibitors to come for IBD. Of course, as with any medication, we need to have discussions with our patients, alert them to potential side effects and have an open line of communication for any questions or concerns.”

Gastroenterologist Stephen Hanauer, MD, professor of medicine at Northwestern University, Chicago, thought that while patients with RA have many other treatment options besides JAK inhibitors, fewer options available to patients with IBD “may motivate the use of oral [sphingosine-1-phosphate receptor modulator] agents such as ozanimod, although IBD patients are younger and [have fewer] MACE risk factors than RA patients, so absolute risk is very small in the ulcerative colitis population.”

Pfizer’s data may be affecting FDA approvals of other JAK inhibitors. This past summer, AbbVie and Eli Lilly stated that the FDA’s ongoing assessment of the safety trial was delaying the agency’s decisions about expanding use of their respective drugs upadacitinib and baricitinib.

The agency’s decision corroborates an earlier 2019 warning about the increased risk of blood clots and of death in patients with ulcerative colitis taking 10 mg tofacitinib twice daily.

The FDA said that two other JAK inhibitors, ruxolitinib (Jakafi) and fedratinib (Inrebic), are not indicated for the treatment of arthritis and other inflammatory conditions, and so are not a part of the updates being required.

Baricitinib, abrocitinib, and upadacitinib are currently under FDA review for treating atopic dermatitis (AD); a topical formulation of the JAK1/2 inhibitor ruxolitinib is under review for treating AD. Reviews for all 4 have been extended. In September 2020, baricitinib was approved for treating moderate to severe AD in Europe, at a dose of 4 mg once a day, with recommendations that the dose can be reduced to 2 mg once a day when the disease is under control, and that the dose may need to be reduced in patients with impaired kidney function, those with an increased risk of infections, and those older than aged 75 years.

In an interview, Jacob Thyssen, MD, PhD, professor of dermatology at the University of Copenhagen, said that in the EU, there has been “extensive education” about cardiovascular risks with baricitinib “and it is my impression that payers and dermatologists in Europe are confident that it is safe to use in AD.” In addition, there has been an emphasis on the differences in cardiovascular risk factors between RA and AD patients, “given that the latter group is generally young and lean.” In the United States, he added, it will be interesting to see which doses of the JAK inhibitors will be approved for AD.

Dr. Thyssen disclosed that he is a speaker, advisory board member and/or investigator for Regeneron, Sanofi-Genzyme, Eli Lilly, Pfizer, LEO Pharma, AbbVie, and Almirall.
 

*This story was updated 9/3/21 and 9/6/2021.

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

The arthritis and ulcerative colitis medicine tofacitinib (Xeljanz, Xeljanz XR) poses an increased risk of serious cardiac events such as heart attack or stroke, cancer, blood clots, and death, the Food and Drug Administration announced Sept 1.

Manufacturers of this drug along with other Janus kinase (JAK) inhibitors baricitinib (Olumiant) and upadacitinib (Rinvoq) must update their boxed warnings to include information about these health risks. The FDA made the determination after new study data from Pfizer, which manufacturers Xeljanz, found an association between a lower dose of Xeljanz and increased risk of blood clots and death.

“Recommendations for healthcare professionals will include consideration of the benefits and risks for the individual patient prior to initiating or continuing therapy,” the agency stated.

The FDA is limiting all approved uses of these three medications to patients who have not responded well to tumor necrosis factor (TNF) blockers to ensure their benefits outweigh their risks. Tofacitinib is indicated for rheumatoid arthritis, psoriatic arthritis, ulcerative colitis, and polyarticular course juvenile idiopathic arthritis. Baricitinib and upadacitinib are approved only for RA. The FDA included baricitinib and upadacitinib in the warning because of the similar properties they share with tofacitinib, even though they haven’t been studied as extensively.

“We believe this update will bring important clarity for healthcare plans on the risk/benefit profile of Xeljanz, which is a medicine informed by more clinical data than any other JAK inhibitor,” Pfizer said in a statement.

Investigators for the ORAL Surveillance trial compared two doses of tofacitinib (5 mg twice daily and 10 mg twice daily) with TNF blockers in patients with rheumatoid arthritis who were aged 50 years or older with at least one additional cardiovascular risk factor.

For both dose regimens of tofacitinib, they found an increased risk of major adverse cardiovascular events, malignancies, thrombosis, and death compared with the TNF blocker regimen. In addition, rates of lung cancers and lymphomas were higher with tofacitinib. In trial data released earlier this year, Pfizer revealed that the tofacitinib group had a much higher incidence of adjudicated malignancies compared with the TNF blocker group (1.13 vs. 0.77 per 100 person-years; hazard ratio, 1.48; 95% confidence interval, 1.04-2.09).

Impact on clinical practice

Physicians treating patients who have rheumatoid arthritis with tofacitinib may initially decrease prescriptions following the FDA’s drug safety communication, said Daniel E. Furst, MD, professor of medicine (emeritus) at the University of California, Los Angeles, adjunct professor at the University of Washington, Seattle, and a research professor at the University of Florence (Italy) – particularly those with a principal mechanism of action slightly different from that of tofacitinib, he added.

“Tofacitinib is principally a JAK 1,3 inhibitor at usual concentrations, whereas upadacitinib and baricitinib are JAK 1,2 inhibitors. Thus, I speculate that the tofacitinib prescriptions will go down more than the upadacitinib and baricitinib prescriptions,” he said in an interview.

Some patients may also be worried about taking tofacitinib, particularly those with previous events or predisposing conditions, Dr. Furst noted.

“First and foremost, I think we need to actually look at the data in a publication rather than just an FDA statement before making huge changes in our practice,” he advised.

“I am looking forward to the data finally being published ... It’s interesting that the full data still isn’t really out there beyond the press releases and an abstract. I think there’s a lot more to learn about how these drugs work and who is really at risk for harmful events,” said Alexis R. Ogdie, MD, MSCE, associate professor of medicine and epidemiology at the University of Pennsylvania, Philadelphia.

Pfizer’s data also may be affecting FDA approvals of other JAK inhibitors. This past summer, AbbVie and Eli Lilly stated that the FDA’s ongoing assessment of the safety trial was delaying the agency’s decisions about expanding use of their respective drugs upadacitinib and baricitinib.

“I think many rheumatologists have already taken this information in, and begun to incorporate it into their discussions with their patients” since it has been over a year since the first public release of information about the ORAL Surveillance trial, said Arthur Kavanaugh, MD, professor of medicine at the University of California, San Diego. “I don’t know that it will affect the approvals, but it will impact their labels.”

Wariness to prescribing tofacitinib may be lower for patients younger than those in the ORAL Surveillance trial without additional cardiovascular risk factors who are taking tofacitinib for non-RA indications, said gastroenterologist Miguel Regueiro, MD.

“The JAK inhibitor warning by the FDA is an important consideration for any prescriber or patient. The risk of cardiovascular disease and venous thromboembolism with this class of medicine appears higher in older rheumatoid arthritis patients with underlying cardiovascular disease. While the warning applies to all JAK inhibitors and likely the newer selective JAK inhibitors to come, we need to weigh the risk and benefit based on the indication for prescribing,” said Dr. Regueiro, chair of the Digestive Disease and Surgery Institute and of the department of gastroenterology, hepatology and nutrition at the Cleveland Clinic in Ohio.

“I do think that there will be a heightened awareness and wariness for older RA patients and for the prescribers. However, for inflammatory bowel disease (and other non-RA indications), it does not appear that the risk for cardiovascular disease and VTE are significantly increased. To that end, in my own practice, I still use tofacitinib for ulcerative colitis and will do the same for the selective JAK inhibitors to come for IBD. Of course, as with any medication, we need to have discussions with our patients, alert them to potential side effects and have an open line of communication for any questions or concerns.”

Gastroenterologist Stephen Hanauer, MD, professor of medicine at Northwestern University, Chicago, thought that while patients with RA have many other treatment options besides JAK inhibitors, fewer options available to patients with IBD “may motivate the use of oral [sphingosine-1-phosphate receptor modulator] agents such as ozanimod, although IBD patients are younger and [have fewer] MACE risk factors than RA patients, so absolute risk is very small in the ulcerative colitis population.”

Pfizer’s data may be affecting FDA approvals of other JAK inhibitors. This past summer, AbbVie and Eli Lilly stated that the FDA’s ongoing assessment of the safety trial was delaying the agency’s decisions about expanding use of their respective drugs upadacitinib and baricitinib.

The agency’s decision corroborates an earlier 2019 warning about the increased risk of blood clots and of death in patients with ulcerative colitis taking 10 mg tofacitinib twice daily.

The FDA said that two other JAK inhibitors, ruxolitinib (Jakafi) and fedratinib (Inrebic), are not indicated for the treatment of arthritis and other inflammatory conditions, and so are not a part of the updates being required.

Baricitinib, abrocitinib, and upadacitinib are currently under FDA review for treating atopic dermatitis (AD); a topical formulation of the JAK1/2 inhibitor ruxolitinib is under review for treating AD. Reviews for all 4 have been extended. In September 2020, baricitinib was approved for treating moderate to severe AD in Europe, at a dose of 4 mg once a day, with recommendations that the dose can be reduced to 2 mg once a day when the disease is under control, and that the dose may need to be reduced in patients with impaired kidney function, those with an increased risk of infections, and those older than aged 75 years.

In an interview, Jacob Thyssen, MD, PhD, professor of dermatology at the University of Copenhagen, said that in the EU, there has been “extensive education” about cardiovascular risks with baricitinib “and it is my impression that payers and dermatologists in Europe are confident that it is safe to use in AD.” In addition, there has been an emphasis on the differences in cardiovascular risk factors between RA and AD patients, “given that the latter group is generally young and lean.” In the United States, he added, it will be interesting to see which doses of the JAK inhibitors will be approved for AD.

Dr. Thyssen disclosed that he is a speaker, advisory board member and/or investigator for Regeneron, Sanofi-Genzyme, Eli Lilly, Pfizer, LEO Pharma, AbbVie, and Almirall.
 

*This story was updated 9/3/21 and 9/6/2021.

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

The arthritis and ulcerative colitis medicine tofacitinib (Xeljanz, Xeljanz XR) poses an increased risk of serious cardiac events such as heart attack or stroke, cancer, blood clots, and death, the Food and Drug Administration announced Sept 1.

Manufacturers of this drug along with other Janus kinase (JAK) inhibitors baricitinib (Olumiant) and upadacitinib (Rinvoq) must update their boxed warnings to include information about these health risks. The FDA made the determination after new study data from Pfizer, which manufacturers Xeljanz, found an association between a lower dose of Xeljanz and increased risk of blood clots and death.

“Recommendations for healthcare professionals will include consideration of the benefits and risks for the individual patient prior to initiating or continuing therapy,” the agency stated.

The FDA is limiting all approved uses of these three medications to patients who have not responded well to tumor necrosis factor (TNF) blockers to ensure their benefits outweigh their risks. Tofacitinib is indicated for rheumatoid arthritis, psoriatic arthritis, ulcerative colitis, and polyarticular course juvenile idiopathic arthritis. Baricitinib and upadacitinib are approved only for RA. The FDA included baricitinib and upadacitinib in the warning because of the similar properties they share with tofacitinib, even though they haven’t been studied as extensively.

“We believe this update will bring important clarity for healthcare plans on the risk/benefit profile of Xeljanz, which is a medicine informed by more clinical data than any other JAK inhibitor,” Pfizer said in a statement.

Investigators for the ORAL Surveillance trial compared two doses of tofacitinib (5 mg twice daily and 10 mg twice daily) with TNF blockers in patients with rheumatoid arthritis who were aged 50 years or older with at least one additional cardiovascular risk factor.

For both dose regimens of tofacitinib, they found an increased risk of major adverse cardiovascular events, malignancies, thrombosis, and death compared with the TNF blocker regimen. In addition, rates of lung cancers and lymphomas were higher with tofacitinib. In trial data released earlier this year, Pfizer revealed that the tofacitinib group had a much higher incidence of adjudicated malignancies compared with the TNF blocker group (1.13 vs. 0.77 per 100 person-years; hazard ratio, 1.48; 95% confidence interval, 1.04-2.09).

Impact on clinical practice

Physicians treating patients who have rheumatoid arthritis with tofacitinib may initially decrease prescriptions following the FDA’s drug safety communication, said Daniel E. Furst, MD, professor of medicine (emeritus) at the University of California, Los Angeles, adjunct professor at the University of Washington, Seattle, and a research professor at the University of Florence (Italy) – particularly those with a principal mechanism of action slightly different from that of tofacitinib, he added.

“Tofacitinib is principally a JAK 1,3 inhibitor at usual concentrations, whereas upadacitinib and baricitinib are JAK 1,2 inhibitors. Thus, I speculate that the tofacitinib prescriptions will go down more than the upadacitinib and baricitinib prescriptions,” he said in an interview.

Some patients may also be worried about taking tofacitinib, particularly those with previous events or predisposing conditions, Dr. Furst noted.

“First and foremost, I think we need to actually look at the data in a publication rather than just an FDA statement before making huge changes in our practice,” he advised.

“I am looking forward to the data finally being published ... It’s interesting that the full data still isn’t really out there beyond the press releases and an abstract. I think there’s a lot more to learn about how these drugs work and who is really at risk for harmful events,” said Alexis R. Ogdie, MD, MSCE, associate professor of medicine and epidemiology at the University of Pennsylvania, Philadelphia.

Pfizer’s data also may be affecting FDA approvals of other JAK inhibitors. This past summer, AbbVie and Eli Lilly stated that the FDA’s ongoing assessment of the safety trial was delaying the agency’s decisions about expanding use of their respective drugs upadacitinib and baricitinib.

“I think many rheumatologists have already taken this information in, and begun to incorporate it into their discussions with their patients” since it has been over a year since the first public release of information about the ORAL Surveillance trial, said Arthur Kavanaugh, MD, professor of medicine at the University of California, San Diego. “I don’t know that it will affect the approvals, but it will impact their labels.”

Wariness to prescribing tofacitinib may be lower for patients younger than those in the ORAL Surveillance trial without additional cardiovascular risk factors who are taking tofacitinib for non-RA indications, said gastroenterologist Miguel Regueiro, MD.

“The JAK inhibitor warning by the FDA is an important consideration for any prescriber or patient. The risk of cardiovascular disease and venous thromboembolism with this class of medicine appears higher in older rheumatoid arthritis patients with underlying cardiovascular disease. While the warning applies to all JAK inhibitors and likely the newer selective JAK inhibitors to come, we need to weigh the risk and benefit based on the indication for prescribing,” said Dr. Regueiro, chair of the Digestive Disease and Surgery Institute and of the department of gastroenterology, hepatology and nutrition at the Cleveland Clinic in Ohio.

“I do think that there will be a heightened awareness and wariness for older RA patients and for the prescribers. However, for inflammatory bowel disease (and other non-RA indications), it does not appear that the risk for cardiovascular disease and VTE are significantly increased. To that end, in my own practice, I still use tofacitinib for ulcerative colitis and will do the same for the selective JAK inhibitors to come for IBD. Of course, as with any medication, we need to have discussions with our patients, alert them to potential side effects and have an open line of communication for any questions or concerns.”

Gastroenterologist Stephen Hanauer, MD, professor of medicine at Northwestern University, Chicago, thought that while patients with RA have many other treatment options besides JAK inhibitors, fewer options available to patients with IBD “may motivate the use of oral [sphingosine-1-phosphate receptor modulator] agents such as ozanimod, although IBD patients are younger and [have fewer] MACE risk factors than RA patients, so absolute risk is very small in the ulcerative colitis population.”

Pfizer’s data may be affecting FDA approvals of other JAK inhibitors. This past summer, AbbVie and Eli Lilly stated that the FDA’s ongoing assessment of the safety trial was delaying the agency’s decisions about expanding use of their respective drugs upadacitinib and baricitinib.

The agency’s decision corroborates an earlier 2019 warning about the increased risk of blood clots and of death in patients with ulcerative colitis taking 10 mg tofacitinib twice daily.

The FDA said that two other JAK inhibitors, ruxolitinib (Jakafi) and fedratinib (Inrebic), are not indicated for the treatment of arthritis and other inflammatory conditions, and so are not a part of the updates being required.

Baricitinib, abrocitinib, and upadacitinib are currently under FDA review for treating atopic dermatitis (AD); a topical formulation of the JAK1/2 inhibitor ruxolitinib is under review for treating AD. Reviews for all 4 have been extended. In September 2020, baricitinib was approved for treating moderate to severe AD in Europe, at a dose of 4 mg once a day, with recommendations that the dose can be reduced to 2 mg once a day when the disease is under control, and that the dose may need to be reduced in patients with impaired kidney function, those with an increased risk of infections, and those older than aged 75 years.

In an interview, Jacob Thyssen, MD, PhD, professor of dermatology at the University of Copenhagen, said that in the EU, there has been “extensive education” about cardiovascular risks with baricitinib “and it is my impression that payers and dermatologists in Europe are confident that it is safe to use in AD.” In addition, there has been an emphasis on the differences in cardiovascular risk factors between RA and AD patients, “given that the latter group is generally young and lean.” In the United States, he added, it will be interesting to see which doses of the JAK inhibitors will be approved for AD.

Dr. Thyssen disclosed that he is a speaker, advisory board member and/or investigator for Regeneron, Sanofi-Genzyme, Eli Lilly, Pfizer, LEO Pharma, AbbVie, and Almirall.
 

*This story was updated 9/3/21 and 9/6/2021.

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

Weekly pediatric cases of COVID-19 exceeded 200,000 for just the second time during the pandemic, while new vaccinations in children continued to decline.

There were almost 204,000 new cases reported in children during the week of Aug. 20-26, the highest 1-week total since the peak of 211,000 in mid-January. The weekly count has now increased for 9 consecutive weeks, during which time it has risen by over 2,300%, the American Academy of Pediatrics and the Children’s Hospital Association said in their weekly COVID-19 report. Total cases in children number almost 4.8 million since the pandemic started.

Vaccinations in children are following a different trend. Vaccine initiation has dropped 3 weeks in a row for both of the eligible age groups: First doses administered were down by 29% among 12- to 15-year-olds over that span and by 32% in 16- to 17-year-olds, according to data from the Centers for Disease Control and Prevention.

Since vaccination for children aged 12-15 years started in May, 49% had received at least one dose, and just over 36% were fully vaccinated as of Aug. 30. Among children aged 16-17 years, who have been eligible since December, 57.5% had gotten at least one dose of the vaccine and 46% have completed the two-dose regimen. The total number of children with at least one dose, including those under age 12 who are involved in clinical trials, was about 12 million, the CDC said on its COVID Data Tracker.
 

Hospitalizations are higher than ever

The recent rise in new child cases has been accompanied by an unprecedented increase in hospitalizations. The daily rate in children aged 0-17 years, which did not surpass 0.30 new admissions per 100,000 population during the worst of the winter surge, had risen to 0.45 per 100,000 by Aug. 26. Since July 4, when the new-admission rate was at its low point of 0.07 per 100,000, hospitalizations in children have jumped by 543%, based on data reported to the CDC by 5,251 hospitals.

A total of 52,245 children were admitted with confirmed COVID-19 from Aug. 1, 2020, when the CDC dataset begins, to Aug. 28, 2021. Those children represent 1.9% of all COVID admissions (2.7 million) in the United States over that period, the CDC said.

Total COVID-related deaths in children are up to 425 in the 48 jurisdictions (45 states, New York City, Puerto Rico, and Guam) that provide mortality data by age, the AAP and the CHA said.

Record-high numbers for the previous 2 reporting weeks – 23 deaths during Aug. 20-26 and 24 deaths during Aug. 13-19, when the previous weekly high was 16 – at least partially reflect the recent addition of South Carolina and New Mexico to the AAP/CHA database, as the two states just started reporting age-related data.

[email protected]

Weekly pediatric cases of COVID-19 exceeded 200,000 for just the second time during the pandemic, while new vaccinations in children continued to decline.

There were almost 204,000 new cases reported in children during the week of Aug. 20-26, the highest 1-week total since the peak of 211,000 in mid-January. The weekly count has now increased for 9 consecutive weeks, during which time it has risen by over 2,300%, the American Academy of Pediatrics and the Children’s Hospital Association said in their weekly COVID-19 report. Total cases in children number almost 4.8 million since the pandemic started.

Vaccinations in children are following a different trend. Vaccine initiation has dropped 3 weeks in a row for both of the eligible age groups: First doses administered were down by 29% among 12- to 15-year-olds over that span and by 32% in 16- to 17-year-olds, according to data from the Centers for Disease Control and Prevention.

Since vaccination for children aged 12-15 years started in May, 49% had received at least one dose, and just over 36% were fully vaccinated as of Aug. 30. Among children aged 16-17 years, who have been eligible since December, 57.5% had gotten at least one dose of the vaccine and 46% have completed the two-dose regimen. The total number of children with at least one dose, including those under age 12 who are involved in clinical trials, was about 12 million, the CDC said on its COVID Data Tracker.
 

Hospitalizations are higher than ever

The recent rise in new child cases has been accompanied by an unprecedented increase in hospitalizations. The daily rate in children aged 0-17 years, which did not surpass 0.30 new admissions per 100,000 population during the worst of the winter surge, had risen to 0.45 per 100,000 by Aug. 26. Since July 4, when the new-admission rate was at its low point of 0.07 per 100,000, hospitalizations in children have jumped by 543%, based on data reported to the CDC by 5,251 hospitals.

A total of 52,245 children were admitted with confirmed COVID-19 from Aug. 1, 2020, when the CDC dataset begins, to Aug. 28, 2021. Those children represent 1.9% of all COVID admissions (2.7 million) in the United States over that period, the CDC said.

Total COVID-related deaths in children are up to 425 in the 48 jurisdictions (45 states, New York City, Puerto Rico, and Guam) that provide mortality data by age, the AAP and the CHA said.

Record-high numbers for the previous 2 reporting weeks – 23 deaths during Aug. 20-26 and 24 deaths during Aug. 13-19, when the previous weekly high was 16 – at least partially reflect the recent addition of South Carolina and New Mexico to the AAP/CHA database, as the two states just started reporting age-related data.

[email protected]

Weekly pediatric cases of COVID-19 exceeded 200,000 for just the second time during the pandemic, while new vaccinations in children continued to decline.

There were almost 204,000 new cases reported in children during the week of Aug. 20-26, the highest 1-week total since the peak of 211,000 in mid-January. The weekly count has now increased for 9 consecutive weeks, during which time it has risen by over 2,300%, the American Academy of Pediatrics and the Children’s Hospital Association said in their weekly COVID-19 report. Total cases in children number almost 4.8 million since the pandemic started.

Vaccinations in children are following a different trend. Vaccine initiation has dropped 3 weeks in a row for both of the eligible age groups: First doses administered were down by 29% among 12- to 15-year-olds over that span and by 32% in 16- to 17-year-olds, according to data from the Centers for Disease Control and Prevention.

Since vaccination for children aged 12-15 years started in May, 49% had received at least one dose, and just over 36% were fully vaccinated as of Aug. 30. Among children aged 16-17 years, who have been eligible since December, 57.5% had gotten at least one dose of the vaccine and 46% have completed the two-dose regimen. The total number of children with at least one dose, including those under age 12 who are involved in clinical trials, was about 12 million, the CDC said on its COVID Data Tracker.
 

Hospitalizations are higher than ever

The recent rise in new child cases has been accompanied by an unprecedented increase in hospitalizations. The daily rate in children aged 0-17 years, which did not surpass 0.30 new admissions per 100,000 population during the worst of the winter surge, had risen to 0.45 per 100,000 by Aug. 26. Since July 4, when the new-admission rate was at its low point of 0.07 per 100,000, hospitalizations in children have jumped by 543%, based on data reported to the CDC by 5,251 hospitals.

A total of 52,245 children were admitted with confirmed COVID-19 from Aug. 1, 2020, when the CDC dataset begins, to Aug. 28, 2021. Those children represent 1.9% of all COVID admissions (2.7 million) in the United States over that period, the CDC said.

Total COVID-related deaths in children are up to 425 in the 48 jurisdictions (45 states, New York City, Puerto Rico, and Guam) that provide mortality data by age, the AAP and the CHA said.

Record-high numbers for the previous 2 reporting weeks – 23 deaths during Aug. 20-26 and 24 deaths during Aug. 13-19, when the previous weekly high was 16 – at least partially reflect the recent addition of South Carolina and New Mexico to the AAP/CHA database, as the two states just started reporting age-related data.

[email protected]