Dermatology News

Tumor necrosis factor inhibitors have long been the go-to treatment of choice for patients with psoriasis and psoriatic arthritis (PsA). They’ve served patients well since etanercept was first approved for PsA in 2002, but today, with the availability of more attractive interleukin-17 and IL-23 inhibitors, dermatologists and rheumatologists are asking whether it’s time to reconsider the use of TNF inhibitors as first-line therapy in psoriasis and PsA.

“TNF inhibitors have served psoriasis patients well for many years. The question is, ‘Is it time to move on from them as first-line agents for psoriasis?’ ” said April W. Armstrong, MD, MPH, a dermatologist and associate dean for clinical research at the University of Southern California, Los Angeles. Dr. Armstrong participated in a point/counterpoint debate about the merits of IL-17 and IL-23 inhibitors over TNF inhibitors at the annual meeting of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis. “For the majority of our patients, IL-17 and IL-23 inhibitors are probably rationally better than TNF inhibitors as first-line agents for moderate to severe plaque psoriasis,” she said.

In this debate, dermatologists and rheumatologists cited studies showing the safety and efficacy of IL-17 and IL-23 inhibitors over TNF inhibitors. TNF inhibitors include etanercept (Enbrel and biosimilars), infliximab (Remicade and biosimilars), adalimumab (Humira and biosimilars), certolizumab pegol (Cimzia), and golimumab (Simponi). IL-12/23 inhibitors are limited to ustekinumab (Stelara). IL-17 inhibitors include secukinumab (Cosentyx), ixekizumab (Taltz), and brodalumab (Siliq). IL-23 inhibitors include guselkumab (Tremfya), tildrakizumab (Ilumya), and risankizumab (Skyrizi).

TNF inhibitors are recommended by the American College of Rheumatology as first-line therapy for treatment-naive patients with active PsA, and they, along with IL-12/23, IL-17, and IL-23 inhibitors are all recommended by the American Academy of Dermatology as monotherapy treatment options in adult patients with moderate to severe plaque psoriasis. However, some studies have shown that non–TNF-inhibitor biologics have a higher efficacy than TNF inhibitors in some cases for some patients, such as those with moderate to severe psoriasis alone or for musculoskeletal efficacy in patients with PsA who have peripheral arthritis, enthesitis, dactylitis, or axial manifestations.

Favorable characteristics of non–TNF-inhibitor biologics

Dr. Armstrong cited a number of head-to-head trials to support her view that IL-17 and IL-23 inhibitors are better than TNF inhibitors as first-line agents for patients with moderate to severe plaque psoriasis. In the first head-to-head study of its kind in patients with moderate to severe psoriasis, ustekinumab proved superior to etanercept. Guselkumab was shown to be superior to adalimumab for patients with moderate to severe psoriasis. Tildrakizumab also proved superior to etanercept for patients with psoriasis. Risankizumab bested adalimumab in patients with moderate to severe psoriasis. Ixekizumab proved superior to etanercept in two pivotal studies of patients with widespread moderate-to-severe psoriasis.

IL-23 and IL-17 inhibitors tend to have less frequent maintenance dosing, with IL-17 inhibitors being once every 2 or 4 weeks and IL-23 inhibitors once every 8 or 12 weeks, compared with frequencies ranging from every week to every 8 weeks with TNF inhibitors, Dr. Armstrong said.

IL-17 and IL-23 inhibitors also appear to have fewer safety concerns than TNF inhibitors, although there is less long-term data for them overall and there are some notable exceptions in certain patient populations. TNF inhibitors should be avoided in patients with a history of demyelinating disease or hepatitis B virus infection, and they are not preferred in patients who have a history of latent tuberculosis or advanced heart failure. IL-17 inhibitors should not be used in patients with a history of inflammatory bowel disease, and their use is associated with a higher rate of oral candidiasis. IL-23 inhibitors have a good safety profile overall, she said.

“The IL-17/23 axis is very important to psoriatic arthritis and should be the focus of our treatments” for PsA, said Deepak Jadon, MBBCh, MRCP, PhD, a rheumatologist and director of the rheumatology research unit at Addenbrooke’s Hospital, Cambridge (England) University Hospitals NHS Foundation Trust. In his presentation, he proposed that IL-17 inhibitors and IL-23 inhibitors be used as first-line therapies in PsA ahead of TNF inhibitors.

One reason to go with IL-17 and IL-23 inhibitors may be to ”get it right immunologically the first time,” Dr. Jadon said. He cited evidence showing substantially better response to guselkumab when given to biologic-naive patients with PsA versus those who had a inadequate response to TNF inhibitors, as well as data indicating better response with secukinumab regardless of previous TNF inhibitor use.

IL-17 inhibitors target more domains of psoriatic disease than do TNF inhibitors, he said, noting that “they have excellent musculoskeletal efficacy in patients with moderate skin psoriasis, not just those with severe psoriasis.” Ixekizumab proved superior to adalimumab in biologic-naive patients with PsA. The results of this study also indicated that IL-17 inhibitors should not be reserved only for patients with severe psoriasis since a higher percentage of patients with moderate psoriasis who were taking ixekizumab achieved very low PsA activity. Secukinumab also beat adalimumab in a head-to-head comparison and showed a greater impact on some measures of health-related quality of life.

IL-17 inhibitors also do not require concomitant methotrexate, he said, “which is a major bonus for our patients. All of my patients wish to stop methotrexate even if tolerated. Not having to cope with prescribed methotrexate improves risk of adverse events and frequency of blood test monitoring.”

IL-17 and IL-23 inhibitors appear to have good efficacy against axial disease in patients with PsA. Randomized trial results for secukinumab versus placebo show high percentages of patients improving either 20% or 40% in Assessment in Spondyloarthritis International Society response criteria and reduced inflammatory MRI lesions in the spine and sacroiliac joints. Analyses of trial results in guselkumab-treated patients with axial manifestations of PsA have shown the IL-23 inhibitor’s efficacy versus placebo across different measures of disease activity.

Dr. Jadon also cited real-world data showing that patients stay longer on IL-17 and IL-12/23 inhibitors versus TNF inhibitors. A 2016 study of patients with psoriasis in the PSOLAR registry showed that patients persisted on treatment longer with ustekinumab than with adalimumab, etanercept, or infliximab. Similarly, a 2020 study of patients with psoriasis from the British Association of Dermatologists Biologics and Immunomodulators Register found that both ustekinumab and secukinumab had better sustained drug survival than did adalimumab.


Accessibility weighs heavily in using TNF inhibitor first

Clinical trials data show that IL-17 inhibitors outperform TNF inhibitors for psoriasis, but in clinical practice, TNF inhibitors still perform very well in individual patients and are well tolerated, said Amit Garg, MD, founding chair of the department of dermatology at Hofstra University, Hempstead, N.Y.

He argued in favor of TNF inhibitors as first-line therapy over IL-17 inhibitors for psoriasis. In this case, treatment decisions often come down to accessibility, Dr. Garg said. Not all insurance companies cover the cost of the newer IL-23 inhibitors. Plus, access to TNF inhibitors is widespread and costs are generally lower.

“As a physician, I don’t have complete autonomy in prescribing what I want. The reality is whether it be because of cross indication or discount pricing, [TNF inhibitors] – in particular adalimumab – is widely available on all plans and is usually the preferred treatment plan, at least in our area,” he said. “I’m not a big fan of plans that allow drugs at low or no cost for a year or 2, and then abandon the patients at that point thereafter. I like to use something that insurance will cover sustainably, and, quite frankly, TNFs have served well in that regard.”

However, TNF inhibitors are associated with more safety signals, plus they carry a greater risk of infection, leading to tolerability and persistence issues with patients.

“Psoriasis is a lifelong disease. I wish I could tell you that every drug is going to work well forever for individual patients, but I don’t think we know that yet. From my perspective, for efficacy, general well tolerance, convenience, and access, TNFs are still an important part of our ability to treat psoriasis effectively. I have no problem starting there and transitioning as needed for individual patients.

“In my experience, I think patients on TNFs generally do well. We don’t always get the patients clear and certainly there’s drop off of efficacy over time, but I’m not sure that’s a rationale for [changing treatment],” Dr. Garg said.

Ying Ying (Katy) Leung, MD, a rheumatologist with Singapore General Hospital, and a member of the GRAPPA peripheral arthritis working group, argued against the use of IL-17 and IL-23 inhibitors as first-line treatment for PsA over TNF inhibitors. She reasoned that TNF blockers are more accessible, have more long-term safety data (including data indicating safety during pregnancy), and have better cardiovascular protection. She also noted that GRAPPA treatment recommendations strongly advise using TNF blockers (or IL-17 inhibitors) for treatment-naive patients with PsA.

“Accessibility is very important as I learned along the way of leading the peripheral arthritis [GRAPPA] working group. Accessibility [issues] can be coming from a lot of sources, but if you don’t take good care of accessibility, you might be developing a guideline that is way out of reality and nobody is going to use it,” she said.

In her native Singapore, Dr. Leung said that patients pay for biologics out of pocket, so cost is a key factor for her patients. She stated that adalimumab is available as a biosimilar at about $200 monthly for patients with PsA in Singapore, while the average monthly costs are $1,400 for originator infliximab and $1,500 for originator etanercept. By comparison, secukinumab sells for about $750 monthly, ixekizumab $540 monthly, and guselkumab $2,000 monthly.

Treatment choices should be aligned with the disease manifestations of PsA, Dr. Leung said, keeping in mind that accessibility and individual patient needs and preferences should be considered as well. She conducted an informal comparison that found TNF inhibitors are most effective for patients with uveitis or inflammatory bowel disease. Evidence from head-to-head studies indicates that TNF inhibitors and IL-17 inhibitors have similar efficacy for peripheral arthritis, enthesitis, and dactylitis. But caution is warranted, she suggested, for determining the best biologics for axial disease because no head-to-head comparison trials have been conducted for IL-17 or IL-23 inhibitors versus TNF inhibitors.

Dr. Armstrong has been a consultant to AbbVie, Bristol-Myers Squibb, Dermira, Genzyme, Incyte, Janssen, Leo Pharma, Eli Lilly, Novartis, Pfizer, and UCB. Dr. Jadon has been a consultant to, has been on speakers bureaus for, and has received grant/research support from AbbVie, Amgen, Celgene, Celltrion, Gilead, Janssen, Eli Lilly, MSD, Novartis, Pfizer, Roche, Sandoz, and UCB. Dr. Garg has consulted for AbbVie, Boehringer Ingelheim, Janssen, and UCB. Dr. Leung has been a consultant to AbbVie, Boehringer Ingelheim, Janssen, Eli Lilly, Novartis, and Pfizer. She has been on speakers bureaus for AbbVie, Janssen Eli Lilly, and Novartis. She has received grant/research support from Pfizer and conference support from AbbVie,

Tumor necrosis factor inhibitors have long been the go-to treatment of choice for patients with psoriasis and psoriatic arthritis (PsA). They’ve served patients well since etanercept was first approved for PsA in 2002, but today, with the availability of more attractive interleukin-17 and IL-23 inhibitors, dermatologists and rheumatologists are asking whether it’s time to reconsider the use of TNF inhibitors as first-line therapy in psoriasis and PsA.

“TNF inhibitors have served psoriasis patients well for many years. The question is, ‘Is it time to move on from them as first-line agents for psoriasis?’ ” said April W. Armstrong, MD, MPH, a dermatologist and associate dean for clinical research at the University of Southern California, Los Angeles. Dr. Armstrong participated in a point/counterpoint debate about the merits of IL-17 and IL-23 inhibitors over TNF inhibitors at the annual meeting of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis. “For the majority of our patients, IL-17 and IL-23 inhibitors are probably rationally better than TNF inhibitors as first-line agents for moderate to severe plaque psoriasis,” she said.

In this debate, dermatologists and rheumatologists cited studies showing the safety and efficacy of IL-17 and IL-23 inhibitors over TNF inhibitors. TNF inhibitors include etanercept (Enbrel and biosimilars), infliximab (Remicade and biosimilars), adalimumab (Humira and biosimilars), certolizumab pegol (Cimzia), and golimumab (Simponi). IL-12/23 inhibitors are limited to ustekinumab (Stelara). IL-17 inhibitors include secukinumab (Cosentyx), ixekizumab (Taltz), and brodalumab (Siliq). IL-23 inhibitors include guselkumab (Tremfya), tildrakizumab (Ilumya), and risankizumab (Skyrizi).

TNF inhibitors are recommended by the American College of Rheumatology as first-line therapy for treatment-naive patients with active PsA, and they, along with IL-12/23, IL-17, and IL-23 inhibitors are all recommended by the American Academy of Dermatology as monotherapy treatment options in adult patients with moderate to severe plaque psoriasis. However, some studies have shown that non–TNF-inhibitor biologics have a higher efficacy than TNF inhibitors in some cases for some patients, such as those with moderate to severe psoriasis alone or for musculoskeletal efficacy in patients with PsA who have peripheral arthritis, enthesitis, dactylitis, or axial manifestations.

Favorable characteristics of non–TNF-inhibitor biologics

Dr. Armstrong cited a number of head-to-head trials to support her view that IL-17 and IL-23 inhibitors are better than TNF inhibitors as first-line agents for patients with moderate to severe plaque psoriasis. In the first head-to-head study of its kind in patients with moderate to severe psoriasis, ustekinumab proved superior to etanercept. Guselkumab was shown to be superior to adalimumab for patients with moderate to severe psoriasis. Tildrakizumab also proved superior to etanercept for patients with psoriasis. Risankizumab bested adalimumab in patients with moderate to severe psoriasis. Ixekizumab proved superior to etanercept in two pivotal studies of patients with widespread moderate-to-severe psoriasis.

IL-23 and IL-17 inhibitors tend to have less frequent maintenance dosing, with IL-17 inhibitors being once every 2 or 4 weeks and IL-23 inhibitors once every 8 or 12 weeks, compared with frequencies ranging from every week to every 8 weeks with TNF inhibitors, Dr. Armstrong said.

IL-17 and IL-23 inhibitors also appear to have fewer safety concerns than TNF inhibitors, although there is less long-term data for them overall and there are some notable exceptions in certain patient populations. TNF inhibitors should be avoided in patients with a history of demyelinating disease or hepatitis B virus infection, and they are not preferred in patients who have a history of latent tuberculosis or advanced heart failure. IL-17 inhibitors should not be used in patients with a history of inflammatory bowel disease, and their use is associated with a higher rate of oral candidiasis. IL-23 inhibitors have a good safety profile overall, she said.

“The IL-17/23 axis is very important to psoriatic arthritis and should be the focus of our treatments” for PsA, said Deepak Jadon, MBBCh, MRCP, PhD, a rheumatologist and director of the rheumatology research unit at Addenbrooke’s Hospital, Cambridge (England) University Hospitals NHS Foundation Trust. In his presentation, he proposed that IL-17 inhibitors and IL-23 inhibitors be used as first-line therapies in PsA ahead of TNF inhibitors.

One reason to go with IL-17 and IL-23 inhibitors may be to ”get it right immunologically the first time,” Dr. Jadon said. He cited evidence showing substantially better response to guselkumab when given to biologic-naive patients with PsA versus those who had a inadequate response to TNF inhibitors, as well as data indicating better response with secukinumab regardless of previous TNF inhibitor use.

IL-17 inhibitors target more domains of psoriatic disease than do TNF inhibitors, he said, noting that “they have excellent musculoskeletal efficacy in patients with moderate skin psoriasis, not just those with severe psoriasis.” Ixekizumab proved superior to adalimumab in biologic-naive patients with PsA. The results of this study also indicated that IL-17 inhibitors should not be reserved only for patients with severe psoriasis since a higher percentage of patients with moderate psoriasis who were taking ixekizumab achieved very low PsA activity. Secukinumab also beat adalimumab in a head-to-head comparison and showed a greater impact on some measures of health-related quality of life.

IL-17 inhibitors also do not require concomitant methotrexate, he said, “which is a major bonus for our patients. All of my patients wish to stop methotrexate even if tolerated. Not having to cope with prescribed methotrexate improves risk of adverse events and frequency of blood test monitoring.”

IL-17 and IL-23 inhibitors appear to have good efficacy against axial disease in patients with PsA. Randomized trial results for secukinumab versus placebo show high percentages of patients improving either 20% or 40% in Assessment in Spondyloarthritis International Society response criteria and reduced inflammatory MRI lesions in the spine and sacroiliac joints. Analyses of trial results in guselkumab-treated patients with axial manifestations of PsA have shown the IL-23 inhibitor’s efficacy versus placebo across different measures of disease activity.

Dr. Jadon also cited real-world data showing that patients stay longer on IL-17 and IL-12/23 inhibitors versus TNF inhibitors. A 2016 study of patients with psoriasis in the PSOLAR registry showed that patients persisted on treatment longer with ustekinumab than with adalimumab, etanercept, or infliximab. Similarly, a 2020 study of patients with psoriasis from the British Association of Dermatologists Biologics and Immunomodulators Register found that both ustekinumab and secukinumab had better sustained drug survival than did adalimumab.


Accessibility weighs heavily in using TNF inhibitor first

Clinical trials data show that IL-17 inhibitors outperform TNF inhibitors for psoriasis, but in clinical practice, TNF inhibitors still perform very well in individual patients and are well tolerated, said Amit Garg, MD, founding chair of the department of dermatology at Hofstra University, Hempstead, N.Y.

He argued in favor of TNF inhibitors as first-line therapy over IL-17 inhibitors for psoriasis. In this case, treatment decisions often come down to accessibility, Dr. Garg said. Not all insurance companies cover the cost of the newer IL-23 inhibitors. Plus, access to TNF inhibitors is widespread and costs are generally lower.

“As a physician, I don’t have complete autonomy in prescribing what I want. The reality is whether it be because of cross indication or discount pricing, [TNF inhibitors] – in particular adalimumab – is widely available on all plans and is usually the preferred treatment plan, at least in our area,” he said. “I’m not a big fan of plans that allow drugs at low or no cost for a year or 2, and then abandon the patients at that point thereafter. I like to use something that insurance will cover sustainably, and, quite frankly, TNFs have served well in that regard.”

However, TNF inhibitors are associated with more safety signals, plus they carry a greater risk of infection, leading to tolerability and persistence issues with patients.

“Psoriasis is a lifelong disease. I wish I could tell you that every drug is going to work well forever for individual patients, but I don’t think we know that yet. From my perspective, for efficacy, general well tolerance, convenience, and access, TNFs are still an important part of our ability to treat psoriasis effectively. I have no problem starting there and transitioning as needed for individual patients.

“In my experience, I think patients on TNFs generally do well. We don’t always get the patients clear and certainly there’s drop off of efficacy over time, but I’m not sure that’s a rationale for [changing treatment],” Dr. Garg said.

Ying Ying (Katy) Leung, MD, a rheumatologist with Singapore General Hospital, and a member of the GRAPPA peripheral arthritis working group, argued against the use of IL-17 and IL-23 inhibitors as first-line treatment for PsA over TNF inhibitors. She reasoned that TNF blockers are more accessible, have more long-term safety data (including data indicating safety during pregnancy), and have better cardiovascular protection. She also noted that GRAPPA treatment recommendations strongly advise using TNF blockers (or IL-17 inhibitors) for treatment-naive patients with PsA.

“Accessibility is very important as I learned along the way of leading the peripheral arthritis [GRAPPA] working group. Accessibility [issues] can be coming from a lot of sources, but if you don’t take good care of accessibility, you might be developing a guideline that is way out of reality and nobody is going to use it,” she said.

In her native Singapore, Dr. Leung said that patients pay for biologics out of pocket, so cost is a key factor for her patients. She stated that adalimumab is available as a biosimilar at about $200 monthly for patients with PsA in Singapore, while the average monthly costs are $1,400 for originator infliximab and $1,500 for originator etanercept. By comparison, secukinumab sells for about $750 monthly, ixekizumab $540 monthly, and guselkumab $2,000 monthly.

Treatment choices should be aligned with the disease manifestations of PsA, Dr. Leung said, keeping in mind that accessibility and individual patient needs and preferences should be considered as well. She conducted an informal comparison that found TNF inhibitors are most effective for patients with uveitis or inflammatory bowel disease. Evidence from head-to-head studies indicates that TNF inhibitors and IL-17 inhibitors have similar efficacy for peripheral arthritis, enthesitis, and dactylitis. But caution is warranted, she suggested, for determining the best biologics for axial disease because no head-to-head comparison trials have been conducted for IL-17 or IL-23 inhibitors versus TNF inhibitors.

Dr. Armstrong has been a consultant to AbbVie, Bristol-Myers Squibb, Dermira, Genzyme, Incyte, Janssen, Leo Pharma, Eli Lilly, Novartis, Pfizer, and UCB. Dr. Jadon has been a consultant to, has been on speakers bureaus for, and has received grant/research support from AbbVie, Amgen, Celgene, Celltrion, Gilead, Janssen, Eli Lilly, MSD, Novartis, Pfizer, Roche, Sandoz, and UCB. Dr. Garg has consulted for AbbVie, Boehringer Ingelheim, Janssen, and UCB. Dr. Leung has been a consultant to AbbVie, Boehringer Ingelheim, Janssen, Eli Lilly, Novartis, and Pfizer. She has been on speakers bureaus for AbbVie, Janssen Eli Lilly, and Novartis. She has received grant/research support from Pfizer and conference support from AbbVie,

Tumor necrosis factor inhibitors have long been the go-to treatment of choice for patients with psoriasis and psoriatic arthritis (PsA). They’ve served patients well since etanercept was first approved for PsA in 2002, but today, with the availability of more attractive interleukin-17 and IL-23 inhibitors, dermatologists and rheumatologists are asking whether it’s time to reconsider the use of TNF inhibitors as first-line therapy in psoriasis and PsA.

“TNF inhibitors have served psoriasis patients well for many years. The question is, ‘Is it time to move on from them as first-line agents for psoriasis?’ ” said April W. Armstrong, MD, MPH, a dermatologist and associate dean for clinical research at the University of Southern California, Los Angeles. Dr. Armstrong participated in a point/counterpoint debate about the merits of IL-17 and IL-23 inhibitors over TNF inhibitors at the annual meeting of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis. “For the majority of our patients, IL-17 and IL-23 inhibitors are probably rationally better than TNF inhibitors as first-line agents for moderate to severe plaque psoriasis,” she said.

In this debate, dermatologists and rheumatologists cited studies showing the safety and efficacy of IL-17 and IL-23 inhibitors over TNF inhibitors. TNF inhibitors include etanercept (Enbrel and biosimilars), infliximab (Remicade and biosimilars), adalimumab (Humira and biosimilars), certolizumab pegol (Cimzia), and golimumab (Simponi). IL-12/23 inhibitors are limited to ustekinumab (Stelara). IL-17 inhibitors include secukinumab (Cosentyx), ixekizumab (Taltz), and brodalumab (Siliq). IL-23 inhibitors include guselkumab (Tremfya), tildrakizumab (Ilumya), and risankizumab (Skyrizi).

TNF inhibitors are recommended by the American College of Rheumatology as first-line therapy for treatment-naive patients with active PsA, and they, along with IL-12/23, IL-17, and IL-23 inhibitors are all recommended by the American Academy of Dermatology as monotherapy treatment options in adult patients with moderate to severe plaque psoriasis. However, some studies have shown that non–TNF-inhibitor biologics have a higher efficacy than TNF inhibitors in some cases for some patients, such as those with moderate to severe psoriasis alone or for musculoskeletal efficacy in patients with PsA who have peripheral arthritis, enthesitis, dactylitis, or axial manifestations.

Favorable characteristics of non–TNF-inhibitor biologics

Dr. Armstrong cited a number of head-to-head trials to support her view that IL-17 and IL-23 inhibitors are better than TNF inhibitors as first-line agents for patients with moderate to severe plaque psoriasis. In the first head-to-head study of its kind in patients with moderate to severe psoriasis, ustekinumab proved superior to etanercept. Guselkumab was shown to be superior to adalimumab for patients with moderate to severe psoriasis. Tildrakizumab also proved superior to etanercept for patients with psoriasis. Risankizumab bested adalimumab in patients with moderate to severe psoriasis. Ixekizumab proved superior to etanercept in two pivotal studies of patients with widespread moderate-to-severe psoriasis.

IL-23 and IL-17 inhibitors tend to have less frequent maintenance dosing, with IL-17 inhibitors being once every 2 or 4 weeks and IL-23 inhibitors once every 8 or 12 weeks, compared with frequencies ranging from every week to every 8 weeks with TNF inhibitors, Dr. Armstrong said.

IL-17 and IL-23 inhibitors also appear to have fewer safety concerns than TNF inhibitors, although there is less long-term data for them overall and there are some notable exceptions in certain patient populations. TNF inhibitors should be avoided in patients with a history of demyelinating disease or hepatitis B virus infection, and they are not preferred in patients who have a history of latent tuberculosis or advanced heart failure. IL-17 inhibitors should not be used in patients with a history of inflammatory bowel disease, and their use is associated with a higher rate of oral candidiasis. IL-23 inhibitors have a good safety profile overall, she said.

“The IL-17/23 axis is very important to psoriatic arthritis and should be the focus of our treatments” for PsA, said Deepak Jadon, MBBCh, MRCP, PhD, a rheumatologist and director of the rheumatology research unit at Addenbrooke’s Hospital, Cambridge (England) University Hospitals NHS Foundation Trust. In his presentation, he proposed that IL-17 inhibitors and IL-23 inhibitors be used as first-line therapies in PsA ahead of TNF inhibitors.

One reason to go with IL-17 and IL-23 inhibitors may be to ”get it right immunologically the first time,” Dr. Jadon said. He cited evidence showing substantially better response to guselkumab when given to biologic-naive patients with PsA versus those who had a inadequate response to TNF inhibitors, as well as data indicating better response with secukinumab regardless of previous TNF inhibitor use.

IL-17 inhibitors target more domains of psoriatic disease than do TNF inhibitors, he said, noting that “they have excellent musculoskeletal efficacy in patients with moderate skin psoriasis, not just those with severe psoriasis.” Ixekizumab proved superior to adalimumab in biologic-naive patients with PsA. The results of this study also indicated that IL-17 inhibitors should not be reserved only for patients with severe psoriasis since a higher percentage of patients with moderate psoriasis who were taking ixekizumab achieved very low PsA activity. Secukinumab also beat adalimumab in a head-to-head comparison and showed a greater impact on some measures of health-related quality of life.

IL-17 inhibitors also do not require concomitant methotrexate, he said, “which is a major bonus for our patients. All of my patients wish to stop methotrexate even if tolerated. Not having to cope with prescribed methotrexate improves risk of adverse events and frequency of blood test monitoring.”

IL-17 and IL-23 inhibitors appear to have good efficacy against axial disease in patients with PsA. Randomized trial results for secukinumab versus placebo show high percentages of patients improving either 20% or 40% in Assessment in Spondyloarthritis International Society response criteria and reduced inflammatory MRI lesions in the spine and sacroiliac joints. Analyses of trial results in guselkumab-treated patients with axial manifestations of PsA have shown the IL-23 inhibitor’s efficacy versus placebo across different measures of disease activity.

Dr. Jadon also cited real-world data showing that patients stay longer on IL-17 and IL-12/23 inhibitors versus TNF inhibitors. A 2016 study of patients with psoriasis in the PSOLAR registry showed that patients persisted on treatment longer with ustekinumab than with adalimumab, etanercept, or infliximab. Similarly, a 2020 study of patients with psoriasis from the British Association of Dermatologists Biologics and Immunomodulators Register found that both ustekinumab and secukinumab had better sustained drug survival than did adalimumab.


Accessibility weighs heavily in using TNF inhibitor first

Clinical trials data show that IL-17 inhibitors outperform TNF inhibitors for psoriasis, but in clinical practice, TNF inhibitors still perform very well in individual patients and are well tolerated, said Amit Garg, MD, founding chair of the department of dermatology at Hofstra University, Hempstead, N.Y.

He argued in favor of TNF inhibitors as first-line therapy over IL-17 inhibitors for psoriasis. In this case, treatment decisions often come down to accessibility, Dr. Garg said. Not all insurance companies cover the cost of the newer IL-23 inhibitors. Plus, access to TNF inhibitors is widespread and costs are generally lower.

“As a physician, I don’t have complete autonomy in prescribing what I want. The reality is whether it be because of cross indication or discount pricing, [TNF inhibitors] – in particular adalimumab – is widely available on all plans and is usually the preferred treatment plan, at least in our area,” he said. “I’m not a big fan of plans that allow drugs at low or no cost for a year or 2, and then abandon the patients at that point thereafter. I like to use something that insurance will cover sustainably, and, quite frankly, TNFs have served well in that regard.”

However, TNF inhibitors are associated with more safety signals, plus they carry a greater risk of infection, leading to tolerability and persistence issues with patients.

“Psoriasis is a lifelong disease. I wish I could tell you that every drug is going to work well forever for individual patients, but I don’t think we know that yet. From my perspective, for efficacy, general well tolerance, convenience, and access, TNFs are still an important part of our ability to treat psoriasis effectively. I have no problem starting there and transitioning as needed for individual patients.

“In my experience, I think patients on TNFs generally do well. We don’t always get the patients clear and certainly there’s drop off of efficacy over time, but I’m not sure that’s a rationale for [changing treatment],” Dr. Garg said.

Ying Ying (Katy) Leung, MD, a rheumatologist with Singapore General Hospital, and a member of the GRAPPA peripheral arthritis working group, argued against the use of IL-17 and IL-23 inhibitors as first-line treatment for PsA over TNF inhibitors. She reasoned that TNF blockers are more accessible, have more long-term safety data (including data indicating safety during pregnancy), and have better cardiovascular protection. She also noted that GRAPPA treatment recommendations strongly advise using TNF blockers (or IL-17 inhibitors) for treatment-naive patients with PsA.

“Accessibility is very important as I learned along the way of leading the peripheral arthritis [GRAPPA] working group. Accessibility [issues] can be coming from a lot of sources, but if you don’t take good care of accessibility, you might be developing a guideline that is way out of reality and nobody is going to use it,” she said.

In her native Singapore, Dr. Leung said that patients pay for biologics out of pocket, so cost is a key factor for her patients. She stated that adalimumab is available as a biosimilar at about $200 monthly for patients with PsA in Singapore, while the average monthly costs are $1,400 for originator infliximab and $1,500 for originator etanercept. By comparison, secukinumab sells for about $750 monthly, ixekizumab $540 monthly, and guselkumab $2,000 monthly.

Treatment choices should be aligned with the disease manifestations of PsA, Dr. Leung said, keeping in mind that accessibility and individual patient needs and preferences should be considered as well. She conducted an informal comparison that found TNF inhibitors are most effective for patients with uveitis or inflammatory bowel disease. Evidence from head-to-head studies indicates that TNF inhibitors and IL-17 inhibitors have similar efficacy for peripheral arthritis, enthesitis, and dactylitis. But caution is warranted, she suggested, for determining the best biologics for axial disease because no head-to-head comparison trials have been conducted for IL-17 or IL-23 inhibitors versus TNF inhibitors.

Dr. Armstrong has been a consultant to AbbVie, Bristol-Myers Squibb, Dermira, Genzyme, Incyte, Janssen, Leo Pharma, Eli Lilly, Novartis, Pfizer, and UCB. Dr. Jadon has been a consultant to, has been on speakers bureaus for, and has received grant/research support from AbbVie, Amgen, Celgene, Celltrion, Gilead, Janssen, Eli Lilly, MSD, Novartis, Pfizer, Roche, Sandoz, and UCB. Dr. Garg has consulted for AbbVie, Boehringer Ingelheim, Janssen, and UCB. Dr. Leung has been a consultant to AbbVie, Boehringer Ingelheim, Janssen, Eli Lilly, Novartis, and Pfizer. She has been on speakers bureaus for AbbVie, Janssen Eli Lilly, and Novartis. She has received grant/research support from Pfizer and conference support from AbbVie,

Over the 10 years we’ve been writing this column, we have often found inspiration for topics while traveling – especially while flying. This is not just because of the idle time spent in the air, but instead because of the many ways that air travel and health care experiences are similar. Both industries focus heavily on safety, are tightly regulated, and employ highly trained individuals.

Consumers may recognize the similarities as well – health care and air travel are both well-known for long waits, uncertainty, and implicit risk. Both sectors are also notorious drivers of innovation, constantly leveraging new technologies in pursuit of better outcomes and experiences. Occasionally, however, advancements in technology can present unforeseen challenges and even compromise safety, with the potential to produce unexpected consequences.

A familiar reminder of this potential was provided to us at the commencement of a recent flight, when we were instructed to turn off our personal electronic devices or flip them into “airplane mode.” This same admonishment is often given to patients and visitors in health care settings – everywhere from clinic waiting rooms to intensive care units – though the reason for this is typically left vague. This got us thinking. We wondered, what is the real risk of smart phones in medicine , or aviation, for that matter. More importantly, what other emerging technologies have the potential to create issues we may not have anticipated?

Mayo Clinic findings on radio communication used by mobile phones

Once our flight landed, we did some research to answer our initial question about personal communication technology and its ability to interfere with sensitive electronic devices. Specifically, we wanted to know whether radio communication used by mobile phones could affect the operation of medical equipment, potentially leading to dire consequences for patients. Spoiler alert: There is very little evidence that this can occur. In fact, a well-documented study performed by the Mayo Clinic in 2007 found interference in 0 out of 300 tests performed. To quote the authors, “the incidence of clinically important interference was 0%.”

We could find no other studies since 2007 that strongly contradict Mayo’s findings, except for several anecdotal reports and articles that postulate the theoretical possibility.

This is confirmed by the American Heart Association, who maintains a list of devices that may interfere with ICDs and pacemakers on their website. According to the AHA, “wireless transmissions from the antennae of phones available in the United States are a very small risk to ICDs and even less of a risk for pacemakers.” And in case you’re wondering, the story is quite similar for airplanes as well.

The latest publication from NASA’s Aviation Safety Reporting System (ASRS) documents incidents related to personal electronic devices during air travel. Most involve smoke production – or even small fires – caused by malfunctioning phone batteries during charging. Only a few entries reference wireless interference, and these were all minor and unconfirmed events. As with health care environments, airplanes don’t appear to face significant risks from radio interference. But that doesn’t mean personal electronics are completely harmless to patients.

Smartphones’ risks to patient with cardiac devices

On May 13 of 2021, the FDA issued a warning to cardiac patients about their smart phones and smart watches. Many current personal electronic devices and accessories are equipped with strong magnets, such as those contained in the “MagSafe” connector on the iPhone 12, that can deactivate pacemakers and implanted cardiac defibrillators. These medical devices are designed to be manipulated by magnets for diagnostic and therapeutic purposes, but strong magnetic fields can disable them unintentionally, leading to catastrophic results.

Apple and other manufacturers have acknowledged this risk and recommend that smartphones and other devices be kept at least 6 inches from cardiac devices. Given the ubiquity of offending products, it is also imperative that we warn our patients about this risk to their physical wellbeing.

Dr. Notte is a family physician and chief medical officer of Abington (Pa.) Hospital–Jefferson Health. Dr. Skolnik is professor of family and community medicine at Sidney Kimmel Medical College, Philadelphia, and associate director of the family medicine residency program at Abington Hospital–Jefferson Health. They have no conflicts related to the content of this piece.

Over the 10 years we’ve been writing this column, we have often found inspiration for topics while traveling – especially while flying. This is not just because of the idle time spent in the air, but instead because of the many ways that air travel and health care experiences are similar. Both industries focus heavily on safety, are tightly regulated, and employ highly trained individuals.

Consumers may recognize the similarities as well – health care and air travel are both well-known for long waits, uncertainty, and implicit risk. Both sectors are also notorious drivers of innovation, constantly leveraging new technologies in pursuit of better outcomes and experiences. Occasionally, however, advancements in technology can present unforeseen challenges and even compromise safety, with the potential to produce unexpected consequences.

A familiar reminder of this potential was provided to us at the commencement of a recent flight, when we were instructed to turn off our personal electronic devices or flip them into “airplane mode.” This same admonishment is often given to patients and visitors in health care settings – everywhere from clinic waiting rooms to intensive care units – though the reason for this is typically left vague. This got us thinking. We wondered, what is the real risk of smart phones in medicine , or aviation, for that matter. More importantly, what other emerging technologies have the potential to create issues we may not have anticipated?

Mayo Clinic findings on radio communication used by mobile phones

Once our flight landed, we did some research to answer our initial question about personal communication technology and its ability to interfere with sensitive electronic devices. Specifically, we wanted to know whether radio communication used by mobile phones could affect the operation of medical equipment, potentially leading to dire consequences for patients. Spoiler alert: There is very little evidence that this can occur. In fact, a well-documented study performed by the Mayo Clinic in 2007 found interference in 0 out of 300 tests performed. To quote the authors, “the incidence of clinically important interference was 0%.”

We could find no other studies since 2007 that strongly contradict Mayo’s findings, except for several anecdotal reports and articles that postulate the theoretical possibility.

This is confirmed by the American Heart Association, who maintains a list of devices that may interfere with ICDs and pacemakers on their website. According to the AHA, “wireless transmissions from the antennae of phones available in the United States are a very small risk to ICDs and even less of a risk for pacemakers.” And in case you’re wondering, the story is quite similar for airplanes as well.

The latest publication from NASA’s Aviation Safety Reporting System (ASRS) documents incidents related to personal electronic devices during air travel. Most involve smoke production – or even small fires – caused by malfunctioning phone batteries during charging. Only a few entries reference wireless interference, and these were all minor and unconfirmed events. As with health care environments, airplanes don’t appear to face significant risks from radio interference. But that doesn’t mean personal electronics are completely harmless to patients.

Smartphones’ risks to patient with cardiac devices

On May 13 of 2021, the FDA issued a warning to cardiac patients about their smart phones and smart watches. Many current personal electronic devices and accessories are equipped with strong magnets, such as those contained in the “MagSafe” connector on the iPhone 12, that can deactivate pacemakers and implanted cardiac defibrillators. These medical devices are designed to be manipulated by magnets for diagnostic and therapeutic purposes, but strong magnetic fields can disable them unintentionally, leading to catastrophic results.

Apple and other manufacturers have acknowledged this risk and recommend that smartphones and other devices be kept at least 6 inches from cardiac devices. Given the ubiquity of offending products, it is also imperative that we warn our patients about this risk to their physical wellbeing.

Dr. Notte is a family physician and chief medical officer of Abington (Pa.) Hospital–Jefferson Health. Dr. Skolnik is professor of family and community medicine at Sidney Kimmel Medical College, Philadelphia, and associate director of the family medicine residency program at Abington Hospital–Jefferson Health. They have no conflicts related to the content of this piece.

Over the 10 years we’ve been writing this column, we have often found inspiration for topics while traveling – especially while flying. This is not just because of the idle time spent in the air, but instead because of the many ways that air travel and health care experiences are similar. Both industries focus heavily on safety, are tightly regulated, and employ highly trained individuals.

Consumers may recognize the similarities as well – health care and air travel are both well-known for long waits, uncertainty, and implicit risk. Both sectors are also notorious drivers of innovation, constantly leveraging new technologies in pursuit of better outcomes and experiences. Occasionally, however, advancements in technology can present unforeseen challenges and even compromise safety, with the potential to produce unexpected consequences.

A familiar reminder of this potential was provided to us at the commencement of a recent flight, when we were instructed to turn off our personal electronic devices or flip them into “airplane mode.” This same admonishment is often given to patients and visitors in health care settings – everywhere from clinic waiting rooms to intensive care units – though the reason for this is typically left vague. This got us thinking. We wondered, what is the real risk of smart phones in medicine , or aviation, for that matter. More importantly, what other emerging technologies have the potential to create issues we may not have anticipated?

Mayo Clinic findings on radio communication used by mobile phones

Once our flight landed, we did some research to answer our initial question about personal communication technology and its ability to interfere with sensitive electronic devices. Specifically, we wanted to know whether radio communication used by mobile phones could affect the operation of medical equipment, potentially leading to dire consequences for patients. Spoiler alert: There is very little evidence that this can occur. In fact, a well-documented study performed by the Mayo Clinic in 2007 found interference in 0 out of 300 tests performed. To quote the authors, “the incidence of clinically important interference was 0%.”

We could find no other studies since 2007 that strongly contradict Mayo’s findings, except for several anecdotal reports and articles that postulate the theoretical possibility.

This is confirmed by the American Heart Association, who maintains a list of devices that may interfere with ICDs and pacemakers on their website. According to the AHA, “wireless transmissions from the antennae of phones available in the United States are a very small risk to ICDs and even less of a risk for pacemakers.” And in case you’re wondering, the story is quite similar for airplanes as well.

The latest publication from NASA’s Aviation Safety Reporting System (ASRS) documents incidents related to personal electronic devices during air travel. Most involve smoke production – or even small fires – caused by malfunctioning phone batteries during charging. Only a few entries reference wireless interference, and these were all minor and unconfirmed events. As with health care environments, airplanes don’t appear to face significant risks from radio interference. But that doesn’t mean personal electronics are completely harmless to patients.

Smartphones’ risks to patient with cardiac devices

On May 13 of 2021, the FDA issued a warning to cardiac patients about their smart phones and smart watches. Many current personal electronic devices and accessories are equipped with strong magnets, such as those contained in the “MagSafe” connector on the iPhone 12, that can deactivate pacemakers and implanted cardiac defibrillators. These medical devices are designed to be manipulated by magnets for diagnostic and therapeutic purposes, but strong magnetic fields can disable them unintentionally, leading to catastrophic results.

Apple and other manufacturers have acknowledged this risk and recommend that smartphones and other devices be kept at least 6 inches from cardiac devices. Given the ubiquity of offending products, it is also imperative that we warn our patients about this risk to their physical wellbeing.

Dr. Notte is a family physician and chief medical officer of Abington (Pa.) Hospital–Jefferson Health. Dr. Skolnik is professor of family and community medicine at Sidney Kimmel Medical College, Philadelphia, and associate director of the family medicine residency program at Abington Hospital–Jefferson Health. They have no conflicts related to the content of this piece.

The U.S. health care system ranked last overall among 11 high-income countries in an analysis by the nonprofit Commonwealth Fund, according to a report released on Aug. 4.

The report is the seventh international comparison of countries’ health systems by the Commonwealth Fund since 2004, and the United States has ranked last in every edition, David Blumenthal, MD, president of the Commonwealth Fund, told reporters during a press briefing.

Researchers analyzed survey answers from tens of thousands of patients and physicians in 11 countries. They analyzed performance on 71 measures across five categories – access to care, care process, administrative efficiency, equity, and health care outcomes. Administrative data were gathered from the Organisation for Economic Cooperation and Development and the World Health Organization.

Among contributors to the poor showing by the United States is that half (50%) of lower-income U.S. adults and 27% of higher-income U.S. adults say costs keep them from getting needed health care.

“In no other country does income inequality so profoundly limit access to care,” Dr. Blumenthal said.

In the United Kingdom, only 12% with lower incomes and 7% with higher incomes said costs kept them from care.

In a stark comparison, the researchers found that “a high-income person in the U.S. was more likely to report financial barriers than a low-income person in nearly all the other countries surveyed: Australia, Canada, France, Germany, the Netherlands, New Zealand, Norway, Sweden, Switzerland, and the U.K.”

Norway, the Netherlands, and Australia were ranked at the top overall in that order. Rounding out the 11 in overall ranking were the U.K., Germany, New Zealand, Sweden, France, Switzerland, Canada, and the United States.

“What this report tells us is that our health care system is not working for Americans, particularly those with lower incomes, who are at a severe disadvantage compared to citizens of other countries. And they are paying the price with their health and their lives,” Dr. Blumenthal said in a press release.

“To catch up with other high-income countries, the administration and Congress would have to expand access to health care, equitably, to all Americans, act aggressively to control costs, and invest in the social services we know can lead to a healthier population.”
 

High infant mortality, low life expectancy in U.S.

Several factors contributed to the U.S. ranking at the bottom of the outcomes category. Among them are that the United States has the highest infant mortality rate (5.7 deaths per 1,000 live births) and lowest life expectancy at age 60 (living on average 23.1 years after age 60), compared with the other countries surveyed. The U.S. rate of preventable mortality (177 deaths per 100,000 population) is more than double that of the best-performing country, Switzerland.

Lead author Eric Schneider, MD, senior vice president for policy and research at the Commonwealth Fund, pointed out that, in terms of the change in avoidable mortality over a decade, not only did the United States have the highest rate, compared with the other countries surveyed, “it also experienced the smallest decline in avoidable mortality over that 10-year period.”

The U.S. maternal mortality rate of 17.4 deaths per 100,000 live births is twice that of France, the country with the next-highest rate (7.6 deaths per 100,000 live births).
 

U.S. excelled in only one category

The only category in which the United States did not rank last was in “care process,” where it ranked second behind only New Zealand.

The care process category combines preventive care, safe care, coordinated care, and patient engagement and preferences. The category includes indicators such as mammography screening and influenza vaccination for older adults as well as the percentage of adults counseled by a health care provider about nutrition, smoking, or alcohol use.

The United States and Germany performed best on engagement and patient preferences, although U.S. adults have the lowest rates of continuity with the same doctor.

New Zealand and the United States ranked highest in the safe care category, with higher reported use of computerized alerts and routine review of medications.
 

‘Too little, too late’: Key recommendations for U.S. to improve

Reginald Williams, vice president of International Health Policy and Practice Innovations at the Commonwealth Fund, pointed out that the U.S. shortcomings in health care come despite spending more than twice as much of its GDP (17% in 2019) as the average OECD country.

“It appears that the US delivers too little of the care that is most needed and often delivers that care too late, especially for people with chronic illnesses,” he said.

He then summarized the team’s recommendations on how the United States can change course.

First is expanding insurance coverage, he said, noting that the United States is the only one of the 11 countries that lacks universal coverage and nearly 30 million people remain uninsured.

Top-performing countries in the survey have universal coverage, annual out-of-pocket caps on covered benefits, and full coverage for primary care and treatment for chronic conditions, he said.

The United States must also improve access to care, he said.

“Top-ranking countries like the Netherlands and Norway ensure timely availability to care by telephone on nights and weekends, and in-person follow-up at home, if needed,” he said.

Mr. Williams said reducing administrative burdens is also critical to free up resources for improving health. He gave an example: “Norway determines patient copayments or physician fees on a regional basis, applying standardized copayments to all physicians within a specialty in a geographic area.”

Reducing income-related barriers is important as well, he said.

The fear of unpredictably high bills and other issues prevent people in the United States from getting the care they ultimately need, he said, adding that top-performing countries invest more in social services to reduce health risks.

That could have implications for the COVID-19 response.

Responding effectively to COVID-19 requires that patients can access affordable health care services, Mr. Williams noted.

“We know from our research that more than two-thirds of U.S. adults say their potential out-of-pocket costs would figure prominently in their decisions to get care if they had coronavirus symptoms,” he said.

Dr. Schneider summed up in the press release: “This study makes clear that higher U.S. spending on health care is not producing better health especially as the U.S. continues on a path of deepening inequality. A country that spends as much as we do should have the best health system in the world. We should adapt what works in other high-income countries to build a better health care system that provides affordable, high-quality health care for everyone.”

Dr. Blumenthal, Dr. Schneider, and Mr. Williams reported no relevant financial relationships outside their employment with the Commonwealth Fund. 

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

The U.S. health care system ranked last overall among 11 high-income countries in an analysis by the nonprofit Commonwealth Fund, according to a report released on Aug. 4.

The report is the seventh international comparison of countries’ health systems by the Commonwealth Fund since 2004, and the United States has ranked last in every edition, David Blumenthal, MD, president of the Commonwealth Fund, told reporters during a press briefing.

Researchers analyzed survey answers from tens of thousands of patients and physicians in 11 countries. They analyzed performance on 71 measures across five categories – access to care, care process, administrative efficiency, equity, and health care outcomes. Administrative data were gathered from the Organisation for Economic Cooperation and Development and the World Health Organization.

Among contributors to the poor showing by the United States is that half (50%) of lower-income U.S. adults and 27% of higher-income U.S. adults say costs keep them from getting needed health care.

“In no other country does income inequality so profoundly limit access to care,” Dr. Blumenthal said.

In the United Kingdom, only 12% with lower incomes and 7% with higher incomes said costs kept them from care.

In a stark comparison, the researchers found that “a high-income person in the U.S. was more likely to report financial barriers than a low-income person in nearly all the other countries surveyed: Australia, Canada, France, Germany, the Netherlands, New Zealand, Norway, Sweden, Switzerland, and the U.K.”

Norway, the Netherlands, and Australia were ranked at the top overall in that order. Rounding out the 11 in overall ranking were the U.K., Germany, New Zealand, Sweden, France, Switzerland, Canada, and the United States.

“What this report tells us is that our health care system is not working for Americans, particularly those with lower incomes, who are at a severe disadvantage compared to citizens of other countries. And they are paying the price with their health and their lives,” Dr. Blumenthal said in a press release.

“To catch up with other high-income countries, the administration and Congress would have to expand access to health care, equitably, to all Americans, act aggressively to control costs, and invest in the social services we know can lead to a healthier population.”
 

High infant mortality, low life expectancy in U.S.

Several factors contributed to the U.S. ranking at the bottom of the outcomes category. Among them are that the United States has the highest infant mortality rate (5.7 deaths per 1,000 live births) and lowest life expectancy at age 60 (living on average 23.1 years after age 60), compared with the other countries surveyed. The U.S. rate of preventable mortality (177 deaths per 100,000 population) is more than double that of the best-performing country, Switzerland.

Lead author Eric Schneider, MD, senior vice president for policy and research at the Commonwealth Fund, pointed out that, in terms of the change in avoidable mortality over a decade, not only did the United States have the highest rate, compared with the other countries surveyed, “it also experienced the smallest decline in avoidable mortality over that 10-year period.”

The U.S. maternal mortality rate of 17.4 deaths per 100,000 live births is twice that of France, the country with the next-highest rate (7.6 deaths per 100,000 live births).
 

U.S. excelled in only one category

The only category in which the United States did not rank last was in “care process,” where it ranked second behind only New Zealand.

The care process category combines preventive care, safe care, coordinated care, and patient engagement and preferences. The category includes indicators such as mammography screening and influenza vaccination for older adults as well as the percentage of adults counseled by a health care provider about nutrition, smoking, or alcohol use.

The United States and Germany performed best on engagement and patient preferences, although U.S. adults have the lowest rates of continuity with the same doctor.

New Zealand and the United States ranked highest in the safe care category, with higher reported use of computerized alerts and routine review of medications.
 

‘Too little, too late’: Key recommendations for U.S. to improve

Reginald Williams, vice president of International Health Policy and Practice Innovations at the Commonwealth Fund, pointed out that the U.S. shortcomings in health care come despite spending more than twice as much of its GDP (17% in 2019) as the average OECD country.

“It appears that the US delivers too little of the care that is most needed and often delivers that care too late, especially for people with chronic illnesses,” he said.

He then summarized the team’s recommendations on how the United States can change course.

First is expanding insurance coverage, he said, noting that the United States is the only one of the 11 countries that lacks universal coverage and nearly 30 million people remain uninsured.

Top-performing countries in the survey have universal coverage, annual out-of-pocket caps on covered benefits, and full coverage for primary care and treatment for chronic conditions, he said.

The United States must also improve access to care, he said.

“Top-ranking countries like the Netherlands and Norway ensure timely availability to care by telephone on nights and weekends, and in-person follow-up at home, if needed,” he said.

Mr. Williams said reducing administrative burdens is also critical to free up resources for improving health. He gave an example: “Norway determines patient copayments or physician fees on a regional basis, applying standardized copayments to all physicians within a specialty in a geographic area.”

Reducing income-related barriers is important as well, he said.

The fear of unpredictably high bills and other issues prevent people in the United States from getting the care they ultimately need, he said, adding that top-performing countries invest more in social services to reduce health risks.

That could have implications for the COVID-19 response.

Responding effectively to COVID-19 requires that patients can access affordable health care services, Mr. Williams noted.

“We know from our research that more than two-thirds of U.S. adults say their potential out-of-pocket costs would figure prominently in their decisions to get care if they had coronavirus symptoms,” he said.

Dr. Schneider summed up in the press release: “This study makes clear that higher U.S. spending on health care is not producing better health especially as the U.S. continues on a path of deepening inequality. A country that spends as much as we do should have the best health system in the world. We should adapt what works in other high-income countries to build a better health care system that provides affordable, high-quality health care for everyone.”

Dr. Blumenthal, Dr. Schneider, and Mr. Williams reported no relevant financial relationships outside their employment with the Commonwealth Fund. 

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

The U.S. health care system ranked last overall among 11 high-income countries in an analysis by the nonprofit Commonwealth Fund, according to a report released on Aug. 4.

The report is the seventh international comparison of countries’ health systems by the Commonwealth Fund since 2004, and the United States has ranked last in every edition, David Blumenthal, MD, president of the Commonwealth Fund, told reporters during a press briefing.

Researchers analyzed survey answers from tens of thousands of patients and physicians in 11 countries. They analyzed performance on 71 measures across five categories – access to care, care process, administrative efficiency, equity, and health care outcomes. Administrative data were gathered from the Organisation for Economic Cooperation and Development and the World Health Organization.

Among contributors to the poor showing by the United States is that half (50%) of lower-income U.S. adults and 27% of higher-income U.S. adults say costs keep them from getting needed health care.

“In no other country does income inequality so profoundly limit access to care,” Dr. Blumenthal said.

In the United Kingdom, only 12% with lower incomes and 7% with higher incomes said costs kept them from care.

In a stark comparison, the researchers found that “a high-income person in the U.S. was more likely to report financial barriers than a low-income person in nearly all the other countries surveyed: Australia, Canada, France, Germany, the Netherlands, New Zealand, Norway, Sweden, Switzerland, and the U.K.”

Norway, the Netherlands, and Australia were ranked at the top overall in that order. Rounding out the 11 in overall ranking were the U.K., Germany, New Zealand, Sweden, France, Switzerland, Canada, and the United States.

“What this report tells us is that our health care system is not working for Americans, particularly those with lower incomes, who are at a severe disadvantage compared to citizens of other countries. And they are paying the price with their health and their lives,” Dr. Blumenthal said in a press release.

“To catch up with other high-income countries, the administration and Congress would have to expand access to health care, equitably, to all Americans, act aggressively to control costs, and invest in the social services we know can lead to a healthier population.”
 

High infant mortality, low life expectancy in U.S.

Several factors contributed to the U.S. ranking at the bottom of the outcomes category. Among them are that the United States has the highest infant mortality rate (5.7 deaths per 1,000 live births) and lowest life expectancy at age 60 (living on average 23.1 years after age 60), compared with the other countries surveyed. The U.S. rate of preventable mortality (177 deaths per 100,000 population) is more than double that of the best-performing country, Switzerland.

Lead author Eric Schneider, MD, senior vice president for policy and research at the Commonwealth Fund, pointed out that, in terms of the change in avoidable mortality over a decade, not only did the United States have the highest rate, compared with the other countries surveyed, “it also experienced the smallest decline in avoidable mortality over that 10-year period.”

The U.S. maternal mortality rate of 17.4 deaths per 100,000 live births is twice that of France, the country with the next-highest rate (7.6 deaths per 100,000 live births).
 

U.S. excelled in only one category

The only category in which the United States did not rank last was in “care process,” where it ranked second behind only New Zealand.

The care process category combines preventive care, safe care, coordinated care, and patient engagement and preferences. The category includes indicators such as mammography screening and influenza vaccination for older adults as well as the percentage of adults counseled by a health care provider about nutrition, smoking, or alcohol use.

The United States and Germany performed best on engagement and patient preferences, although U.S. adults have the lowest rates of continuity with the same doctor.

New Zealand and the United States ranked highest in the safe care category, with higher reported use of computerized alerts and routine review of medications.
 

‘Too little, too late’: Key recommendations for U.S. to improve

Reginald Williams, vice president of International Health Policy and Practice Innovations at the Commonwealth Fund, pointed out that the U.S. shortcomings in health care come despite spending more than twice as much of its GDP (17% in 2019) as the average OECD country.

“It appears that the US delivers too little of the care that is most needed and often delivers that care too late, especially for people with chronic illnesses,” he said.

He then summarized the team’s recommendations on how the United States can change course.

First is expanding insurance coverage, he said, noting that the United States is the only one of the 11 countries that lacks universal coverage and nearly 30 million people remain uninsured.

Top-performing countries in the survey have universal coverage, annual out-of-pocket caps on covered benefits, and full coverage for primary care and treatment for chronic conditions, he said.

The United States must also improve access to care, he said.

“Top-ranking countries like the Netherlands and Norway ensure timely availability to care by telephone on nights and weekends, and in-person follow-up at home, if needed,” he said.

Mr. Williams said reducing administrative burdens is also critical to free up resources for improving health. He gave an example: “Norway determines patient copayments or physician fees on a regional basis, applying standardized copayments to all physicians within a specialty in a geographic area.”

Reducing income-related barriers is important as well, he said.

The fear of unpredictably high bills and other issues prevent people in the United States from getting the care they ultimately need, he said, adding that top-performing countries invest more in social services to reduce health risks.

That could have implications for the COVID-19 response.

Responding effectively to COVID-19 requires that patients can access affordable health care services, Mr. Williams noted.

“We know from our research that more than two-thirds of U.S. adults say their potential out-of-pocket costs would figure prominently in their decisions to get care if they had coronavirus symptoms,” he said.

Dr. Schneider summed up in the press release: “This study makes clear that higher U.S. spending on health care is not producing better health especially as the U.S. continues on a path of deepening inequality. A country that spends as much as we do should have the best health system in the world. We should adapt what works in other high-income countries to build a better health care system that provides affordable, high-quality health care for everyone.”

Dr. Blumenthal, Dr. Schneider, and Mr. Williams reported no relevant financial relationships outside their employment with the Commonwealth Fund. 

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

When the Delta variant of the coronavirus was first identified in India in December 2020, the threat may have seemed too remote to trigger worry in the United States, although the horror of it ripping through the country was soon hard to ignore.

Within months, the Delta variant had spread to more than 98 countries, including Scotland, the United Kingdom, Israel, and now, of course, the United States. The CDC said this week the Delta variant now accounts for 93% of all COVID cases.

Fueled by Delta, COVID-19 cases, hospitalizations, and deaths are increasing in nearly all states, according to the latest CDC data. After the 7-day average number of cases dipped by June 22 to about 11,000, it rose by Aug. 3 to more than 85,000.

Some experts are heartened by the recent decrease in COVID-19 cases in the United Kingdom and India, both hard-hit with the Delta variant. COVID-19 cases in India peaked at more than 400,000 a day in May; by Aug. 2, that had dropped to about 30,500 daily.

Andy Slavitt, former Biden White House senior adviser for COVID-19 response, tweeted July 26 that, if the Delta variant acted the same in the United Kingdom as in India, it would have a quick rise and a quick drop.

The prediction seems to have come true. As of Aug. 3, U.K. cases have dropped to 7,467, compared with more than 46,800 July 19.

So the question of the summer has become: “When will Delta burn out here?”

Like other pandemic predictions, these are all over the board. Here are five predictions about when COVID cases will peak, then fall. They range from less than 2 weeks to more than 2 months:

• Mid-August: Among the most optimistic predictions of when the Delta-driven COVID-19 cases will decline is from Scott Gottlieb, MD, former FDA director. He told CNBC on July 28 that he would expect cases to decline in 2-3 weeks – so by August 11.
• Mid-August to mid-September: Ali Mokdad, PhD, chief strategy officer for population health at the University of Washington, Seattle, said that, “right now for the U.S. as a country, cases will peak mid-August” and then decline. He is citing projections by the university’s Institute for Health Metrics and Evaluation. In its “most likely” scenario, it predicts COVID deaths will peak at about 1,000 daily by mid-September, then decline. (As of Aug. 3, daily deaths averaged 371.)
• September: “I am hoping we get over this Delta hump [by then],” says Eric Topol, MD, founder and director of the Scripps Research Translational Institute in La Jolla, Calif., and editor-in-chief of Medscape. “But sometimes, I am too much of an optimist.”
• Mid-October: Experts at the COVID-19 Scenario Modeling Hub, a consortium of researchers from leading institutions who consult with the CDC, said the Delta-fueled pandemic will steadily increase through summer and fall, with a mid-October peak.
• Unclear: Because cases are underestimated, “I think it is unclear when we will see a peak of Delta,” says Amesh Adalja, MD, a senior scholar at the Johns Hopkins Center for Health Security, Baltimore. He predicts a decline in cases as “more people get infected and develop natural immunity.”

The predictions are based on different scenarios, such as most likely or worst case. Factors such as personal behaviors, public mandates, and vaccination rates could all alter the projections.
 

What a difference vaccination may make

An uptick in vaccinations could change all the models and predictions, experts agree. As of Aug. 3, almost half (49.7%) of the total U.S. population was fully vaccinated, the CDC said. (And 80.1% of those 65 and over were.)

But that’s a long way from the 70% or 80% figure often cited to reach herd immunity. Recently, Ricardo Franco, MD, of the University of Alabama at Birmingham, said at a briefing by the Infectious Diseases Society of America that the infectiousness of the Delta variant may mean the herd immunity threshold is actually closer to 90%.

Dr. Mokdad estimates that by Nov. 1, based on the current rate of infections, 64% of people in the United States will be immune to a variant like Delta, taking into account those already infected and those vaccinated against COVID-19.

Justin Lessler, PhD, a University of North Carolina at Chapel Hill epidemiologist involved in the modeling hub, says if enough people get vaccinated, it could stop the Delta variant in its tracks. But that percentage is high.

“I am relatively confident that if we could get 90% or more of the eligible population vaccinated that we would see the epidemic begin to recede,” he says.

It’s a huge leap from 50%, or even 64%, to 90%. Could the Delta surge really motivate that many people to head to a vaccination site?

That’s hard to predict, Dr. Topol said. Some unvaccinated people may feel like soldiers in a foxhole, especially if they are in hard-hit states like Louisiana, and rush to get the vaccine as soon as possible. Others, hearing about the “breakthrough” cases in the vaccinated, may dig in their heels and ask: “Why bother?” as they mistakenly conclude that the vaccine has not done its job.
 

Roles of public policy, individual behavior

Besides an increase in vaccinations, individual behaviors and mandates can change the scenario. Doctors can remind even vaccinated patients that behaviors such as social distancing and masks still matter, experts said.

“Don’t ‘stress test’ your vaccine, “ Dr. Topol said.

The vaccines against COVID are good but not perfect and, he notes, they offer less protection if many months have passed since the vaccines were given.

The best advice now, Dr. Topol said, is: “Don’t be inside without a mask.”

Even if outdoors, depending on how close others are and the level of the conversation, a mask might be wise, he says.

Dr. Mokdad finds that “when cases go up, people put on their best behavior,” such as going back to masks and social distancing.

“Unfortunately, we have two countries,” he said, referring to the way public health measures and mandates vary from state to state.
 

Once the Delta variant subsides, what’s next?

It’s not a matter of if there is another variant on the heels of Delta, but when, Dr. Topol and other experts said. A new variant, Lambda, was first identified in Peru in August 2020 but now makes up about 90% of the country’s infections.

There’s also Delta-plus, just found in two people in South Korea.

Future variants could be even more transmissible than Delta, “which would be a horror show,” Dr. Topol said. “This [Delta] is by far the worst version. The virus is going to keep evolving. It is not done with us.”
 

On the horizon: Variant-proof vaccines

What’s needed to tackle the next variant is another approach to vaccine development, according to Dr. Topol and his colleague, Dennis R. Burton, a professor of immunology and microbiology at Scripps Research Institute.

Writing a commentary in Nature published in 2021, the two propose using a special class of protective antibodies, known as broadly neutralizing antibodies, to develop these vaccines. The success of the current COVID-19 vaccines is likely because of the vaccine’s ability to prompt the body to make protective neutralizing antibodies. These proteins bind to the viruses and prevent them from infecting the body’s cells.

The broadly neutralizing antibodies, however, can act against many different strains of related viruses, Dr. Topol and Mr. Burton wrote. Using this approach, which is already under study, scientists could make vaccines that would be effective against a family of viruses. The goal: to stop future outbreaks from becoming epidemics and then pandemics.

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

When the Delta variant of the coronavirus was first identified in India in December 2020, the threat may have seemed too remote to trigger worry in the United States, although the horror of it ripping through the country was soon hard to ignore.

Within months, the Delta variant had spread to more than 98 countries, including Scotland, the United Kingdom, Israel, and now, of course, the United States. The CDC said this week the Delta variant now accounts for 93% of all COVID cases.

Fueled by Delta, COVID-19 cases, hospitalizations, and deaths are increasing in nearly all states, according to the latest CDC data. After the 7-day average number of cases dipped by June 22 to about 11,000, it rose by Aug. 3 to more than 85,000.

Some experts are heartened by the recent decrease in COVID-19 cases in the United Kingdom and India, both hard-hit with the Delta variant. COVID-19 cases in India peaked at more than 400,000 a day in May; by Aug. 2, that had dropped to about 30,500 daily.

Andy Slavitt, former Biden White House senior adviser for COVID-19 response, tweeted July 26 that, if the Delta variant acted the same in the United Kingdom as in India, it would have a quick rise and a quick drop.

The prediction seems to have come true. As of Aug. 3, U.K. cases have dropped to 7,467, compared with more than 46,800 July 19.

So the question of the summer has become: “When will Delta burn out here?”

Like other pandemic predictions, these are all over the board. Here are five predictions about when COVID cases will peak, then fall. They range from less than 2 weeks to more than 2 months:

• Mid-August: Among the most optimistic predictions of when the Delta-driven COVID-19 cases will decline is from Scott Gottlieb, MD, former FDA director. He told CNBC on July 28 that he would expect cases to decline in 2-3 weeks – so by August 11.
• Mid-August to mid-September: Ali Mokdad, PhD, chief strategy officer for population health at the University of Washington, Seattle, said that, “right now for the U.S. as a country, cases will peak mid-August” and then decline. He is citing projections by the university’s Institute for Health Metrics and Evaluation. In its “most likely” scenario, it predicts COVID deaths will peak at about 1,000 daily by mid-September, then decline. (As of Aug. 3, daily deaths averaged 371.)
• September: “I am hoping we get over this Delta hump [by then],” says Eric Topol, MD, founder and director of the Scripps Research Translational Institute in La Jolla, Calif., and editor-in-chief of Medscape. “But sometimes, I am too much of an optimist.”
• Mid-October: Experts at the COVID-19 Scenario Modeling Hub, a consortium of researchers from leading institutions who consult with the CDC, said the Delta-fueled pandemic will steadily increase through summer and fall, with a mid-October peak.
• Unclear: Because cases are underestimated, “I think it is unclear when we will see a peak of Delta,” says Amesh Adalja, MD, a senior scholar at the Johns Hopkins Center for Health Security, Baltimore. He predicts a decline in cases as “more people get infected and develop natural immunity.”

The predictions are based on different scenarios, such as most likely or worst case. Factors such as personal behaviors, public mandates, and vaccination rates could all alter the projections.
 

What a difference vaccination may make

An uptick in vaccinations could change all the models and predictions, experts agree. As of Aug. 3, almost half (49.7%) of the total U.S. population was fully vaccinated, the CDC said. (And 80.1% of those 65 and over were.)

But that’s a long way from the 70% or 80% figure often cited to reach herd immunity. Recently, Ricardo Franco, MD, of the University of Alabama at Birmingham, said at a briefing by the Infectious Diseases Society of America that the infectiousness of the Delta variant may mean the herd immunity threshold is actually closer to 90%.

Dr. Mokdad estimates that by Nov. 1, based on the current rate of infections, 64% of people in the United States will be immune to a variant like Delta, taking into account those already infected and those vaccinated against COVID-19.

Justin Lessler, PhD, a University of North Carolina at Chapel Hill epidemiologist involved in the modeling hub, says if enough people get vaccinated, it could stop the Delta variant in its tracks. But that percentage is high.

“I am relatively confident that if we could get 90% or more of the eligible population vaccinated that we would see the epidemic begin to recede,” he says.

It’s a huge leap from 50%, or even 64%, to 90%. Could the Delta surge really motivate that many people to head to a vaccination site?

That’s hard to predict, Dr. Topol said. Some unvaccinated people may feel like soldiers in a foxhole, especially if they are in hard-hit states like Louisiana, and rush to get the vaccine as soon as possible. Others, hearing about the “breakthrough” cases in the vaccinated, may dig in their heels and ask: “Why bother?” as they mistakenly conclude that the vaccine has not done its job.
 

Roles of public policy, individual behavior

Besides an increase in vaccinations, individual behaviors and mandates can change the scenario. Doctors can remind even vaccinated patients that behaviors such as social distancing and masks still matter, experts said.

“Don’t ‘stress test’ your vaccine, “ Dr. Topol said.

The vaccines against COVID are good but not perfect and, he notes, they offer less protection if many months have passed since the vaccines were given.

The best advice now, Dr. Topol said, is: “Don’t be inside without a mask.”

Even if outdoors, depending on how close others are and the level of the conversation, a mask might be wise, he says.

Dr. Mokdad finds that “when cases go up, people put on their best behavior,” such as going back to masks and social distancing.

“Unfortunately, we have two countries,” he said, referring to the way public health measures and mandates vary from state to state.
 

Once the Delta variant subsides, what’s next?

It’s not a matter of if there is another variant on the heels of Delta, but when, Dr. Topol and other experts said. A new variant, Lambda, was first identified in Peru in August 2020 but now makes up about 90% of the country’s infections.

There’s also Delta-plus, just found in two people in South Korea.

Future variants could be even more transmissible than Delta, “which would be a horror show,” Dr. Topol said. “This [Delta] is by far the worst version. The virus is going to keep evolving. It is not done with us.”
 

On the horizon: Variant-proof vaccines

What’s needed to tackle the next variant is another approach to vaccine development, according to Dr. Topol and his colleague, Dennis R. Burton, a professor of immunology and microbiology at Scripps Research Institute.

Writing a commentary in Nature published in 2021, the two propose using a special class of protective antibodies, known as broadly neutralizing antibodies, to develop these vaccines. The success of the current COVID-19 vaccines is likely because of the vaccine’s ability to prompt the body to make protective neutralizing antibodies. These proteins bind to the viruses and prevent them from infecting the body’s cells.

The broadly neutralizing antibodies, however, can act against many different strains of related viruses, Dr. Topol and Mr. Burton wrote. Using this approach, which is already under study, scientists could make vaccines that would be effective against a family of viruses. The goal: to stop future outbreaks from becoming epidemics and then pandemics.

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

When the Delta variant of the coronavirus was first identified in India in December 2020, the threat may have seemed too remote to trigger worry in the United States, although the horror of it ripping through the country was soon hard to ignore.

Within months, the Delta variant had spread to more than 98 countries, including Scotland, the United Kingdom, Israel, and now, of course, the United States. The CDC said this week the Delta variant now accounts for 93% of all COVID cases.

Fueled by Delta, COVID-19 cases, hospitalizations, and deaths are increasing in nearly all states, according to the latest CDC data. After the 7-day average number of cases dipped by June 22 to about 11,000, it rose by Aug. 3 to more than 85,000.

Some experts are heartened by the recent decrease in COVID-19 cases in the United Kingdom and India, both hard-hit with the Delta variant. COVID-19 cases in India peaked at more than 400,000 a day in May; by Aug. 2, that had dropped to about 30,500 daily.

Andy Slavitt, former Biden White House senior adviser for COVID-19 response, tweeted July 26 that, if the Delta variant acted the same in the United Kingdom as in India, it would have a quick rise and a quick drop.

The prediction seems to have come true. As of Aug. 3, U.K. cases have dropped to 7,467, compared with more than 46,800 July 19.

So the question of the summer has become: “When will Delta burn out here?”

Like other pandemic predictions, these are all over the board. Here are five predictions about when COVID cases will peak, then fall. They range from less than 2 weeks to more than 2 months:

• Mid-August: Among the most optimistic predictions of when the Delta-driven COVID-19 cases will decline is from Scott Gottlieb, MD, former FDA director. He told CNBC on July 28 that he would expect cases to decline in 2-3 weeks – so by August 11.
• Mid-August to mid-September: Ali Mokdad, PhD, chief strategy officer for population health at the University of Washington, Seattle, said that, “right now for the U.S. as a country, cases will peak mid-August” and then decline. He is citing projections by the university’s Institute for Health Metrics and Evaluation. In its “most likely” scenario, it predicts COVID deaths will peak at about 1,000 daily by mid-September, then decline. (As of Aug. 3, daily deaths averaged 371.)
• September: “I am hoping we get over this Delta hump [by then],” says Eric Topol, MD, founder and director of the Scripps Research Translational Institute in La Jolla, Calif., and editor-in-chief of Medscape. “But sometimes, I am too much of an optimist.”
• Mid-October: Experts at the COVID-19 Scenario Modeling Hub, a consortium of researchers from leading institutions who consult with the CDC, said the Delta-fueled pandemic will steadily increase through summer and fall, with a mid-October peak.
• Unclear: Because cases are underestimated, “I think it is unclear when we will see a peak of Delta,” says Amesh Adalja, MD, a senior scholar at the Johns Hopkins Center for Health Security, Baltimore. He predicts a decline in cases as “more people get infected and develop natural immunity.”

The predictions are based on different scenarios, such as most likely or worst case. Factors such as personal behaviors, public mandates, and vaccination rates could all alter the projections.
 

What a difference vaccination may make

An uptick in vaccinations could change all the models and predictions, experts agree. As of Aug. 3, almost half (49.7%) of the total U.S. population was fully vaccinated, the CDC said. (And 80.1% of those 65 and over were.)

But that’s a long way from the 70% or 80% figure often cited to reach herd immunity. Recently, Ricardo Franco, MD, of the University of Alabama at Birmingham, said at a briefing by the Infectious Diseases Society of America that the infectiousness of the Delta variant may mean the herd immunity threshold is actually closer to 90%.

Dr. Mokdad estimates that by Nov. 1, based on the current rate of infections, 64% of people in the United States will be immune to a variant like Delta, taking into account those already infected and those vaccinated against COVID-19.

Justin Lessler, PhD, a University of North Carolina at Chapel Hill epidemiologist involved in the modeling hub, says if enough people get vaccinated, it could stop the Delta variant in its tracks. But that percentage is high.

“I am relatively confident that if we could get 90% or more of the eligible population vaccinated that we would see the epidemic begin to recede,” he says.

It’s a huge leap from 50%, or even 64%, to 90%. Could the Delta surge really motivate that many people to head to a vaccination site?

That’s hard to predict, Dr. Topol said. Some unvaccinated people may feel like soldiers in a foxhole, especially if they are in hard-hit states like Louisiana, and rush to get the vaccine as soon as possible. Others, hearing about the “breakthrough” cases in the vaccinated, may dig in their heels and ask: “Why bother?” as they mistakenly conclude that the vaccine has not done its job.
 

Roles of public policy, individual behavior

Besides an increase in vaccinations, individual behaviors and mandates can change the scenario. Doctors can remind even vaccinated patients that behaviors such as social distancing and masks still matter, experts said.

“Don’t ‘stress test’ your vaccine, “ Dr. Topol said.

The vaccines against COVID are good but not perfect and, he notes, they offer less protection if many months have passed since the vaccines were given.

The best advice now, Dr. Topol said, is: “Don’t be inside without a mask.”

Even if outdoors, depending on how close others are and the level of the conversation, a mask might be wise, he says.

Dr. Mokdad finds that “when cases go up, people put on their best behavior,” such as going back to masks and social distancing.

“Unfortunately, we have two countries,” he said, referring to the way public health measures and mandates vary from state to state.
 

Once the Delta variant subsides, what’s next?

It’s not a matter of if there is another variant on the heels of Delta, but when, Dr. Topol and other experts said. A new variant, Lambda, was first identified in Peru in August 2020 but now makes up about 90% of the country’s infections.

There’s also Delta-plus, just found in two people in South Korea.

Future variants could be even more transmissible than Delta, “which would be a horror show,” Dr. Topol said. “This [Delta] is by far the worst version. The virus is going to keep evolving. It is not done with us.”
 

On the horizon: Variant-proof vaccines

What’s needed to tackle the next variant is another approach to vaccine development, according to Dr. Topol and his colleague, Dennis R. Burton, a professor of immunology and microbiology at Scripps Research Institute.

Writing a commentary in Nature published in 2021, the two propose using a special class of protective antibodies, known as broadly neutralizing antibodies, to develop these vaccines. The success of the current COVID-19 vaccines is likely because of the vaccine’s ability to prompt the body to make protective neutralizing antibodies. These proteins bind to the viruses and prevent them from infecting the body’s cells.

The broadly neutralizing antibodies, however, can act against many different strains of related viruses, Dr. Topol and Mr. Burton wrote. Using this approach, which is already under study, scientists could make vaccines that would be effective against a family of viruses. The goal: to stop future outbreaks from becoming epidemics and then pandemics.

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

Androgenetic alopecia significantly impairs patients’ overall quality of life and emotional health, but does not have a notable impact on the incidence of depression, according a systematic review and meta-analysis of 41 studies.

“Hair loss affects self-image, causes trichodynia, and plays a role in emotions and social activity, which may be associated with psychiatric problems and impaired health-related quality of life,” wrote Chun-Hsien Huang, MD, of Chang Gung Memorial Hospital, Linkou, Taiwan, and colleagues. However, systematic reviews of the associations between androgenetic alopecia (AGA) and health-related quality of life (HRQOL) are lacking, they said.

In a study published in JAMA Dermatology, the researchers reviewed data from a total of 7,995 AGA patients in 41 studies. The studies included 11 tools for HRQOL assessment and 29 tools for psychological assessment. Of these, the Dermatology Life Quality Index (DLQI) and the Hair-Specific Skindex-29 were used to assess quality of life, and the Center for Epidemiologic Studies Depression Scale (CES-D) was used for psychological assessment in the meta-analysis.

Overall, 27 studies identified 18 factors associated with HRQOL; those with an inverse effect were higher self-rated hair loss severity, lower VAS score, and higher educational level. Of note, neither physician-rated hair loss severity nor treatment response were factors in HRQOL, the researchers said.

The pooled DLQI score across studies was 8.16, and subgroup analysis showed no differences in HRQOL between men and women or between patients from European vs. Asian countries. However, five studies showed significant differences in HRQOL between men and women when different assessment tools were used, which emphasized the need for more studies to examine the association of AGA with HRQOL by sex, the researchers said.

The meta-analysis of the Hair-Specific Skindex-29 scores showed pooled averages of 21.95 for symptom dimension, 18.52 in function dimension, and 29.22 in emotion dimension. Of these, the emotion dimension scores indicated moderate emotional impairment.

The average pooled score on the CES-D in the meta-analysis was 14.98, indicating no association between AGA and depression, the researchers said. However, “depression accounts for only a part of the emotion dimension,” they said. “Therefore, emotion dimension could be impaired even if no depressive symptoms were noted.”

The pooled DLQI scores for AGA (8.16) were higher than scores for other skin conditions including alopecia areata (6.3), contact dermatitis (7.35), and acne vulgaris (7.45), but lower than the pooled scores for vitiligo (9.11), urticaria (9.8), psoriasis (10.53), and atopic dermatitis (11.2), the researchers noted. “However, additional head-to-head studies are needed for direct comparisons of HRQOL in patients with various dermatoses,” they said.

The study findings were limited by the cross-sectional design of many of the included studies, and the limited number of assessment tools included in the analysis, the researchers noted. Other limitations were the lack of specific domain scores and the inclusion of only three studies from China, they said.

However, the results are consistent with findings from previous studies, and suggest that patients with AGA may benefit from psychological and psychosocial support, the researchers said.

Quality of life issues deserve attention

“Studies of the quality-of-life impact of various conditions are becoming more common in the medical literature,” Jamie B. MacKelfresh, MD, associate professor of dermatology, Emory University, Atlanta, said in an interview.

“Androgenetic alopecia is the most common type of hair loss in men and women,” she noted. “Hair loss can be labeled as a cosmetic concern, so it is important that providers understand the significant quality-of-life impact androgenetic alopecia has on the many people with this diagnosis,” she emphasized.

Dr. MacKelfresh, who was asked to comment on the study, said she was surprised that the subgroup analysis of the DLQI showed no significant difference between men and women. “This surprised me because a number of past studies have highlighted the relatively greater quality-of-life impact of hair loss on women compared to men,” she noted.

However, she added, “I was not surprised to see that androgenetic alopecia has a significant quality-of-life impact on many patients, and that physician objective assessments of the hair loss do not always correlate with the amount of quality-of-life impact,” said Dr. MacKelfresh. “In the patients I see, I find hair loss very often has a significant quality-of-life impact on patients, regardless of gender, and the amount of quality-of-life impact definitely does not always correlate with the objective amount of hair loss,” she noted.

A takeaway message for clinicians is to be aware that androgenetic alopecia frequently has a significant impact on patients, “particularly in the emotional dimension,” and can affect both men and women, Dr. MacKelfresh said. “Objective assessments of hair loss severity by providers may not accurately predict the degree of quality-of-life impact a patient may experience; therefore providers should include quality-of-life questions as part of their standard evaluation of patients with androgenetic alopecia,” she said. In addition to treating the hair loss, providers can help these patients by guiding them to psychological support resources, she emphasized.

More research is needed to assess the impact of androgenetic alopecia on “men, women, and the non-binary gender population,” as well as the relationship between self-esteem and hair loss, she said. “Finally, it would be helpful to understand what interventions can best help improve androgenetic alopecia patients’ quality of life,” she noted.

The study received no outside funding. The researchers had no financial conflicts to disclose. Dr. MacKelfresh had no financial conflicts to disclose.

Androgenetic alopecia significantly impairs patients’ overall quality of life and emotional health, but does not have a notable impact on the incidence of depression, according a systematic review and meta-analysis of 41 studies.

“Hair loss affects self-image, causes trichodynia, and plays a role in emotions and social activity, which may be associated with psychiatric problems and impaired health-related quality of life,” wrote Chun-Hsien Huang, MD, of Chang Gung Memorial Hospital, Linkou, Taiwan, and colleagues. However, systematic reviews of the associations between androgenetic alopecia (AGA) and health-related quality of life (HRQOL) are lacking, they said.

In a study published in JAMA Dermatology, the researchers reviewed data from a total of 7,995 AGA patients in 41 studies. The studies included 11 tools for HRQOL assessment and 29 tools for psychological assessment. Of these, the Dermatology Life Quality Index (DLQI) and the Hair-Specific Skindex-29 were used to assess quality of life, and the Center for Epidemiologic Studies Depression Scale (CES-D) was used for psychological assessment in the meta-analysis.

Overall, 27 studies identified 18 factors associated with HRQOL; those with an inverse effect were higher self-rated hair loss severity, lower VAS score, and higher educational level. Of note, neither physician-rated hair loss severity nor treatment response were factors in HRQOL, the researchers said.

The pooled DLQI score across studies was 8.16, and subgroup analysis showed no differences in HRQOL between men and women or between patients from European vs. Asian countries. However, five studies showed significant differences in HRQOL between men and women when different assessment tools were used, which emphasized the need for more studies to examine the association of AGA with HRQOL by sex, the researchers said.

The meta-analysis of the Hair-Specific Skindex-29 scores showed pooled averages of 21.95 for symptom dimension, 18.52 in function dimension, and 29.22 in emotion dimension. Of these, the emotion dimension scores indicated moderate emotional impairment.

The average pooled score on the CES-D in the meta-analysis was 14.98, indicating no association between AGA and depression, the researchers said. However, “depression accounts for only a part of the emotion dimension,” they said. “Therefore, emotion dimension could be impaired even if no depressive symptoms were noted.”

The pooled DLQI scores for AGA (8.16) were higher than scores for other skin conditions including alopecia areata (6.3), contact dermatitis (7.35), and acne vulgaris (7.45), but lower than the pooled scores for vitiligo (9.11), urticaria (9.8), psoriasis (10.53), and atopic dermatitis (11.2), the researchers noted. “However, additional head-to-head studies are needed for direct comparisons of HRQOL in patients with various dermatoses,” they said.

The study findings were limited by the cross-sectional design of many of the included studies, and the limited number of assessment tools included in the analysis, the researchers noted. Other limitations were the lack of specific domain scores and the inclusion of only three studies from China, they said.

However, the results are consistent with findings from previous studies, and suggest that patients with AGA may benefit from psychological and psychosocial support, the researchers said.

Quality of life issues deserve attention

“Studies of the quality-of-life impact of various conditions are becoming more common in the medical literature,” Jamie B. MacKelfresh, MD, associate professor of dermatology, Emory University, Atlanta, said in an interview.

“Androgenetic alopecia is the most common type of hair loss in men and women,” she noted. “Hair loss can be labeled as a cosmetic concern, so it is important that providers understand the significant quality-of-life impact androgenetic alopecia has on the many people with this diagnosis,” she emphasized.

Dr. MacKelfresh, who was asked to comment on the study, said she was surprised that the subgroup analysis of the DLQI showed no significant difference between men and women. “This surprised me because a number of past studies have highlighted the relatively greater quality-of-life impact of hair loss on women compared to men,” she noted.

However, she added, “I was not surprised to see that androgenetic alopecia has a significant quality-of-life impact on many patients, and that physician objective assessments of the hair loss do not always correlate with the amount of quality-of-life impact,” said Dr. MacKelfresh. “In the patients I see, I find hair loss very often has a significant quality-of-life impact on patients, regardless of gender, and the amount of quality-of-life impact definitely does not always correlate with the objective amount of hair loss,” she noted.

A takeaway message for clinicians is to be aware that androgenetic alopecia frequently has a significant impact on patients, “particularly in the emotional dimension,” and can affect both men and women, Dr. MacKelfresh said. “Objective assessments of hair loss severity by providers may not accurately predict the degree of quality-of-life impact a patient may experience; therefore providers should include quality-of-life questions as part of their standard evaluation of patients with androgenetic alopecia,” she said. In addition to treating the hair loss, providers can help these patients by guiding them to psychological support resources, she emphasized.

More research is needed to assess the impact of androgenetic alopecia on “men, women, and the non-binary gender population,” as well as the relationship between self-esteem and hair loss, she said. “Finally, it would be helpful to understand what interventions can best help improve androgenetic alopecia patients’ quality of life,” she noted.

The study received no outside funding. The researchers had no financial conflicts to disclose. Dr. MacKelfresh had no financial conflicts to disclose.

Androgenetic alopecia significantly impairs patients’ overall quality of life and emotional health, but does not have a notable impact on the incidence of depression, according a systematic review and meta-analysis of 41 studies.

“Hair loss affects self-image, causes trichodynia, and plays a role in emotions and social activity, which may be associated with psychiatric problems and impaired health-related quality of life,” wrote Chun-Hsien Huang, MD, of Chang Gung Memorial Hospital, Linkou, Taiwan, and colleagues. However, systematic reviews of the associations between androgenetic alopecia (AGA) and health-related quality of life (HRQOL) are lacking, they said.

In a study published in JAMA Dermatology, the researchers reviewed data from a total of 7,995 AGA patients in 41 studies. The studies included 11 tools for HRQOL assessment and 29 tools for psychological assessment. Of these, the Dermatology Life Quality Index (DLQI) and the Hair-Specific Skindex-29 were used to assess quality of life, and the Center for Epidemiologic Studies Depression Scale (CES-D) was used for psychological assessment in the meta-analysis.

Overall, 27 studies identified 18 factors associated with HRQOL; those with an inverse effect were higher self-rated hair loss severity, lower VAS score, and higher educational level. Of note, neither physician-rated hair loss severity nor treatment response were factors in HRQOL, the researchers said.

The pooled DLQI score across studies was 8.16, and subgroup analysis showed no differences in HRQOL between men and women or between patients from European vs. Asian countries. However, five studies showed significant differences in HRQOL between men and women when different assessment tools were used, which emphasized the need for more studies to examine the association of AGA with HRQOL by sex, the researchers said.

The meta-analysis of the Hair-Specific Skindex-29 scores showed pooled averages of 21.95 for symptom dimension, 18.52 in function dimension, and 29.22 in emotion dimension. Of these, the emotion dimension scores indicated moderate emotional impairment.

The average pooled score on the CES-D in the meta-analysis was 14.98, indicating no association between AGA and depression, the researchers said. However, “depression accounts for only a part of the emotion dimension,” they said. “Therefore, emotion dimension could be impaired even if no depressive symptoms were noted.”

The pooled DLQI scores for AGA (8.16) were higher than scores for other skin conditions including alopecia areata (6.3), contact dermatitis (7.35), and acne vulgaris (7.45), but lower than the pooled scores for vitiligo (9.11), urticaria (9.8), psoriasis (10.53), and atopic dermatitis (11.2), the researchers noted. “However, additional head-to-head studies are needed for direct comparisons of HRQOL in patients with various dermatoses,” they said.

The study findings were limited by the cross-sectional design of many of the included studies, and the limited number of assessment tools included in the analysis, the researchers noted. Other limitations were the lack of specific domain scores and the inclusion of only three studies from China, they said.

However, the results are consistent with findings from previous studies, and suggest that patients with AGA may benefit from psychological and psychosocial support, the researchers said.

Quality of life issues deserve attention

“Studies of the quality-of-life impact of various conditions are becoming more common in the medical literature,” Jamie B. MacKelfresh, MD, associate professor of dermatology, Emory University, Atlanta, said in an interview.

“Androgenetic alopecia is the most common type of hair loss in men and women,” she noted. “Hair loss can be labeled as a cosmetic concern, so it is important that providers understand the significant quality-of-life impact androgenetic alopecia has on the many people with this diagnosis,” she emphasized.

Dr. MacKelfresh, who was asked to comment on the study, said she was surprised that the subgroup analysis of the DLQI showed no significant difference between men and women. “This surprised me because a number of past studies have highlighted the relatively greater quality-of-life impact of hair loss on women compared to men,” she noted.

However, she added, “I was not surprised to see that androgenetic alopecia has a significant quality-of-life impact on many patients, and that physician objective assessments of the hair loss do not always correlate with the amount of quality-of-life impact,” said Dr. MacKelfresh. “In the patients I see, I find hair loss very often has a significant quality-of-life impact on patients, regardless of gender, and the amount of quality-of-life impact definitely does not always correlate with the objective amount of hair loss,” she noted.

A takeaway message for clinicians is to be aware that androgenetic alopecia frequently has a significant impact on patients, “particularly in the emotional dimension,” and can affect both men and women, Dr. MacKelfresh said. “Objective assessments of hair loss severity by providers may not accurately predict the degree of quality-of-life impact a patient may experience; therefore providers should include quality-of-life questions as part of their standard evaluation of patients with androgenetic alopecia,” she said. In addition to treating the hair loss, providers can help these patients by guiding them to psychological support resources, she emphasized.

More research is needed to assess the impact of androgenetic alopecia on “men, women, and the non-binary gender population,” as well as the relationship between self-esteem and hair loss, she said. “Finally, it would be helpful to understand what interventions can best help improve androgenetic alopecia patients’ quality of life,” she noted.

The study received no outside funding. The researchers had no financial conflicts to disclose. Dr. MacKelfresh had no financial conflicts to disclose.

The correlation between stress and graying of hair has long been hypothesized, but has been difficult to prove. In addition, reversal of hair graying has been thought of as a temporary phenomenon as hair pigment goes through its natural progression of senescence.

Noel Hendrickson/Getty Images

However, the recent publication that is a collaboration between the department of psychiatry at Columbia University, New York; and the departments of dermatology at the University College Dublin, University of Miami, and the University of Manchester (England); and the Monasterium Laboratory in Münster, Germany, demonstrates a quantitative mapping of human hair graying – and its reversal – in relation to stress.

In the study, hair color of single strands of hair from seven healthy females and seven healthy males, whose mean age was 35 years (range, 9-65 years), were analyzed. In addition to hair pigment analysis, study subjects documented the stress they were experiencing each week in diaries. Using either high resolution image scanners, electron microscopy, and/or hair shaft proteomics, the investigators were able to evaluate loss of pigment within fragments small enough to have grown over one hour.

When changes in hair color were noted, variations in up to 300 proteins were documented, including an up-regulation of the fatty acid synthesis and metabolism machinery in graying. Recent studies also corroborate that fatty acid synthesis by fatty acid synthase and “transport by CPT1A ... are sufficient drivers of cell senescence, and that fatty acid metabolism regulates melanocyte aging biology” the authors wrote.

Molecularly, the investigators found that gray hairs up-regulate proteins associated with energy metabolism, mitochondria, and antioxidant defenses. The graying correlated with stress was also reversible, “at least temporarily,” based on their retrospective analysis and analysis over the 2.5-year recruitment period, the investigators wrote. Specifically, they found that graying hair “may be acutely triggered by stressful life experiences, the removal of which can trigger reversal.” From the data, they also developed a mathematical model to predict what might happen to human hair over time.

Through this study, proof-of-concept evidence is provided indicating that biobehavioral factors are linked to human hair graying dynamics. Future analysis with larger sample sizes and incorporating neuroendocrine markers may further support these correlations. This is an interesting study that elucidates the mechanisms responsible for how stress and other life exposures manifest in human biology, and, if we as human beings effectively manage that stress, how it may both reverse the negative impact and outcomes affecting our body and health.

The study was supported by the Wharton Fund and grants from the National Institutes of Health.

Dr. Wesley and Dr. Lily Talakoub are cocontributors to this column. Dr. Wesley practices dermatology in Beverly Hills, Calif. Dr. Talakoub is in private practice in McLean, Va. This month’s column is by Dr. Wesley. Write to them at dermnews@mdedge.com. They have no relevant disclosures.

The correlation between stress and graying of hair has long been hypothesized, but has been difficult to prove. In addition, reversal of hair graying has been thought of as a temporary phenomenon as hair pigment goes through its natural progression of senescence.

Noel Hendrickson/Getty Images

However, the recent publication that is a collaboration between the department of psychiatry at Columbia University, New York; and the departments of dermatology at the University College Dublin, University of Miami, and the University of Manchester (England); and the Monasterium Laboratory in Münster, Germany, demonstrates a quantitative mapping of human hair graying – and its reversal – in relation to stress.

In the study, hair color of single strands of hair from seven healthy females and seven healthy males, whose mean age was 35 years (range, 9-65 years), were analyzed. In addition to hair pigment analysis, study subjects documented the stress they were experiencing each week in diaries. Using either high resolution image scanners, electron microscopy, and/or hair shaft proteomics, the investigators were able to evaluate loss of pigment within fragments small enough to have grown over one hour.

When changes in hair color were noted, variations in up to 300 proteins were documented, including an up-regulation of the fatty acid synthesis and metabolism machinery in graying. Recent studies also corroborate that fatty acid synthesis by fatty acid synthase and “transport by CPT1A ... are sufficient drivers of cell senescence, and that fatty acid metabolism regulates melanocyte aging biology” the authors wrote.

Molecularly, the investigators found that gray hairs up-regulate proteins associated with energy metabolism, mitochondria, and antioxidant defenses. The graying correlated with stress was also reversible, “at least temporarily,” based on their retrospective analysis and analysis over the 2.5-year recruitment period, the investigators wrote. Specifically, they found that graying hair “may be acutely triggered by stressful life experiences, the removal of which can trigger reversal.” From the data, they also developed a mathematical model to predict what might happen to human hair over time.

Through this study, proof-of-concept evidence is provided indicating that biobehavioral factors are linked to human hair graying dynamics. Future analysis with larger sample sizes and incorporating neuroendocrine markers may further support these correlations. This is an interesting study that elucidates the mechanisms responsible for how stress and other life exposures manifest in human biology, and, if we as human beings effectively manage that stress, how it may both reverse the negative impact and outcomes affecting our body and health.

The study was supported by the Wharton Fund and grants from the National Institutes of Health.

Dr. Wesley and Dr. Lily Talakoub are cocontributors to this column. Dr. Wesley practices dermatology in Beverly Hills, Calif. Dr. Talakoub is in private practice in McLean, Va. This month’s column is by Dr. Wesley. Write to them at dermnews@mdedge.com. They have no relevant disclosures.

The correlation between stress and graying of hair has long been hypothesized, but has been difficult to prove. In addition, reversal of hair graying has been thought of as a temporary phenomenon as hair pigment goes through its natural progression of senescence.

Noel Hendrickson/Getty Images

However, the recent publication that is a collaboration between the department of psychiatry at Columbia University, New York; and the departments of dermatology at the University College Dublin, University of Miami, and the University of Manchester (England); and the Monasterium Laboratory in Münster, Germany, demonstrates a quantitative mapping of human hair graying – and its reversal – in relation to stress.

In the study, hair color of single strands of hair from seven healthy females and seven healthy males, whose mean age was 35 years (range, 9-65 years), were analyzed. In addition to hair pigment analysis, study subjects documented the stress they were experiencing each week in diaries. Using either high resolution image scanners, electron microscopy, and/or hair shaft proteomics, the investigators were able to evaluate loss of pigment within fragments small enough to have grown over one hour.

When changes in hair color were noted, variations in up to 300 proteins were documented, including an up-regulation of the fatty acid synthesis and metabolism machinery in graying. Recent studies also corroborate that fatty acid synthesis by fatty acid synthase and “transport by CPT1A ... are sufficient drivers of cell senescence, and that fatty acid metabolism regulates melanocyte aging biology” the authors wrote.

Molecularly, the investigators found that gray hairs up-regulate proteins associated with energy metabolism, mitochondria, and antioxidant defenses. The graying correlated with stress was also reversible, “at least temporarily,” based on their retrospective analysis and analysis over the 2.5-year recruitment period, the investigators wrote. Specifically, they found that graying hair “may be acutely triggered by stressful life experiences, the removal of which can trigger reversal.” From the data, they also developed a mathematical model to predict what might happen to human hair over time.

Through this study, proof-of-concept evidence is provided indicating that biobehavioral factors are linked to human hair graying dynamics. Future analysis with larger sample sizes and incorporating neuroendocrine markers may further support these correlations. This is an interesting study that elucidates the mechanisms responsible for how stress and other life exposures manifest in human biology, and, if we as human beings effectively manage that stress, how it may both reverse the negative impact and outcomes affecting our body and health.

The study was supported by the Wharton Fund and grants from the National Institutes of Health.

Dr. Wesley and Dr. Lily Talakoub are cocontributors to this column. Dr. Wesley practices dermatology in Beverly Hills, Calif. Dr. Talakoub is in private practice in McLean, Va. This month’s column is by Dr. Wesley. Write to them at dermnews@mdedge.com. They have no relevant disclosures.

Bother me, I’m working 

Although some of us have been comfortably functioning in a virtual work environment, others are now trickling back into the office. And you know what that means? People come to your desk to show you pictures of their cat or tell you about their kid’s birthday party. You may sneer at the interruption, but a study shows you actually like it.

Rawpixel/Thinkstock

A team of researchers at the University of Cincinnati surveyed 111 full-time employees twice a day for 3 weeks about their work experience. They asked about mental exhaustion, workplace interruptions, sense of belonging, and overall job satisfaction. They found that employees had a higher sense of belonging and job satisfaction when interrupted with a social versus work interruption.

“Interruptions can actually benefit individuals from an interpersonal perspective – people feel like they belong when others come and talk to them or ask them questions, even while being distracted from their tasks,” said Heather C. Vough, senior investigator and a former university faculty member.

Chitchatting at work is often seen as a distraction, but this study suggests that it’s not like heating up fish in the breakroom microwave.

So the next time someone hits you with the “Hey, do you have a sec?,” do yourself a favor and enjoy the interruption.
 

A smorgasbord of science

It’s probably difficult to recruit patients for some medical trials. Try this new drug and potentially get all sorts of interesting and unpleasant side effects. Pass. We suggest the approach a group of researchers from the University of Kansas took for a recent study into weight gain: Invite a bunch of 20-something adults to an all-you-can-eat buffet. They’ll be beating down your door in no time.

pxfuel

Their study, published in Appetite, focused on hyperpalatable food – the sort of food you can keep eating – and compared it with high-energy-dense food and ultra processed food. The test patients had their body composition measured, were let loose on the buffet, and were measured again a year later.

The patients who favored salty/carbohydrate-filled hyperpalatable food (such as pretzels or popcorn) were much more likely to gain weight, compared with those who focused on salty/fat-filled food of any variety. As a matter of fact, those who stuck to fatty food during the buffet had no change in weight over the 1-year study period. The researchers noted that those who ate the carb-filled food tended more toward hedonic eating, or the act of eating simply for pleasure.

The study is no doubt helpful in the long battle against obesity and overeating, but it’s also a very helpful guide to getting the most bang for your buck at the buffet. Stay away from the cheap salty snack food. Go for the steak and seafood. Get your money’s worth. In the long run you won’t even gain any weight. No promises about tomorrow though.
 

There’s a cheat code for that

For a large percentage of kids and young adults, and maybe even older adults (we don’t judge), a storm warning means a cozy night in playing video games. Staying inside is probably the safest bet when there’s a storm, and the weatherman never says to avoid playing video games when there’s lightning.

xresch/Pixabay

Maybe he should, though, since a man from Tennessee reportedly got struck by lightning through his game controller. Emergency crews determined that lightning either hit the man’s house or struck near it and went through the controller. The type of console was not revealed, even though some people may want to know the specifics before playing during the next storm.

Luckily, the man was not seriously hurt and did not need to go to the hospital. This is apparently not unheard of, as a professional gamer was shocked through a wired controller last year, causing burns on her hands and a broken controller.

This might be our cue to do less electrical types of activities during thunderstorms, like knitting or reading by candlelight.
 

Freeze, squeeze, and enjoy … cramping

As you were ingesting last week’s installment of the never-ending buffet that is LOTME, you probably wondered: What’s going on? Where’s the latest bodily insult being perpetuated by the gang over at TikTok?

Daria-Yakovleva/Pixabay

Have no fear, good readers. We would never make you go 2 straight weeks without serving up some hyperpalatable TikTok tidbits.

Our bodily insult du jour is frozen honey, and it’s exploding all over TikTok … and a few other places. “The hashtag ‘#FrozenHoney’ has been viewed nearly 600 million times, and the hashtag ‘#FrozenHoneyChallenge’ has been viewed more than 80 million times,” NBC News recently reported.

After a few hours in the freezer, honey can be squeezed out of a plastic bottle as a semisolid, toothpastelike goo – it’s stiff enough to rise out of a container that’s pointed straight up – and bitten off in large chunks. And therein lies the problem.

Some people are overdoing it. “Honey is great, but having it in small amounts to sweeten is really a healthy relationship with food, and using it to get a lot of followers and a lot of attention and having it in excess amounts is crazy,” Kristin Kirkpatrick, a registered dietitian at the Cleveland Clinic, told NBC.

Besides the possible weight gain from eating massive amounts of sugar, experts warned that “gobbling up bottles of frozen honey” could lead to stomach cramping, bloating, and diarrhea. Some TikTokers, NBC noted, said that they “were running for the bathroom.”

As we said, it’s a trend that is exploding.

Be sure to tune in next week, when we learn how TikTokers use ground meat as a skin moisturizer.
 

Bother me, I’m working 

Although some of us have been comfortably functioning in a virtual work environment, others are now trickling back into the office. And you know what that means? People come to your desk to show you pictures of their cat or tell you about their kid’s birthday party. You may sneer at the interruption, but a study shows you actually like it.

Rawpixel/Thinkstock

A team of researchers at the University of Cincinnati surveyed 111 full-time employees twice a day for 3 weeks about their work experience. They asked about mental exhaustion, workplace interruptions, sense of belonging, and overall job satisfaction. They found that employees had a higher sense of belonging and job satisfaction when interrupted with a social versus work interruption.

“Interruptions can actually benefit individuals from an interpersonal perspective – people feel like they belong when others come and talk to them or ask them questions, even while being distracted from their tasks,” said Heather C. Vough, senior investigator and a former university faculty member.

Chitchatting at work is often seen as a distraction, but this study suggests that it’s not like heating up fish in the breakroom microwave.

So the next time someone hits you with the “Hey, do you have a sec?,” do yourself a favor and enjoy the interruption.
 

A smorgasbord of science

It’s probably difficult to recruit patients for some medical trials. Try this new drug and potentially get all sorts of interesting and unpleasant side effects. Pass. We suggest the approach a group of researchers from the University of Kansas took for a recent study into weight gain: Invite a bunch of 20-something adults to an all-you-can-eat buffet. They’ll be beating down your door in no time.

pxfuel

Their study, published in Appetite, focused on hyperpalatable food – the sort of food you can keep eating – and compared it with high-energy-dense food and ultra processed food. The test patients had their body composition measured, were let loose on the buffet, and were measured again a year later.

The patients who favored salty/carbohydrate-filled hyperpalatable food (such as pretzels or popcorn) were much more likely to gain weight, compared with those who focused on salty/fat-filled food of any variety. As a matter of fact, those who stuck to fatty food during the buffet had no change in weight over the 1-year study period. The researchers noted that those who ate the carb-filled food tended more toward hedonic eating, or the act of eating simply for pleasure.

The study is no doubt helpful in the long battle against obesity and overeating, but it’s also a very helpful guide to getting the most bang for your buck at the buffet. Stay away from the cheap salty snack food. Go for the steak and seafood. Get your money’s worth. In the long run you won’t even gain any weight. No promises about tomorrow though.
 

There’s a cheat code for that

For a large percentage of kids and young adults, and maybe even older adults (we don’t judge), a storm warning means a cozy night in playing video games. Staying inside is probably the safest bet when there’s a storm, and the weatherman never says to avoid playing video games when there’s lightning.

xresch/Pixabay

Maybe he should, though, since a man from Tennessee reportedly got struck by lightning through his game controller. Emergency crews determined that lightning either hit the man’s house or struck near it and went through the controller. The type of console was not revealed, even though some people may want to know the specifics before playing during the next storm.

Luckily, the man was not seriously hurt and did not need to go to the hospital. This is apparently not unheard of, as a professional gamer was shocked through a wired controller last year, causing burns on her hands and a broken controller.

This might be our cue to do less electrical types of activities during thunderstorms, like knitting or reading by candlelight.
 

Freeze, squeeze, and enjoy … cramping

As you were ingesting last week’s installment of the never-ending buffet that is LOTME, you probably wondered: What’s going on? Where’s the latest bodily insult being perpetuated by the gang over at TikTok?

Daria-Yakovleva/Pixabay

Have no fear, good readers. We would never make you go 2 straight weeks without serving up some hyperpalatable TikTok tidbits.

Our bodily insult du jour is frozen honey, and it’s exploding all over TikTok … and a few other places. “The hashtag ‘#FrozenHoney’ has been viewed nearly 600 million times, and the hashtag ‘#FrozenHoneyChallenge’ has been viewed more than 80 million times,” NBC News recently reported.

After a few hours in the freezer, honey can be squeezed out of a plastic bottle as a semisolid, toothpastelike goo – it’s stiff enough to rise out of a container that’s pointed straight up – and bitten off in large chunks. And therein lies the problem.

Some people are overdoing it. “Honey is great, but having it in small amounts to sweeten is really a healthy relationship with food, and using it to get a lot of followers and a lot of attention and having it in excess amounts is crazy,” Kristin Kirkpatrick, a registered dietitian at the Cleveland Clinic, told NBC.

Besides the possible weight gain from eating massive amounts of sugar, experts warned that “gobbling up bottles of frozen honey” could lead to stomach cramping, bloating, and diarrhea. Some TikTokers, NBC noted, said that they “were running for the bathroom.”

As we said, it’s a trend that is exploding.

Be sure to tune in next week, when we learn how TikTokers use ground meat as a skin moisturizer.
 

Bother me, I’m working 

Although some of us have been comfortably functioning in a virtual work environment, others are now trickling back into the office. And you know what that means? People come to your desk to show you pictures of their cat or tell you about their kid’s birthday party. You may sneer at the interruption, but a study shows you actually like it.

Rawpixel/Thinkstock

A team of researchers at the University of Cincinnati surveyed 111 full-time employees twice a day for 3 weeks about their work experience. They asked about mental exhaustion, workplace interruptions, sense of belonging, and overall job satisfaction. They found that employees had a higher sense of belonging and job satisfaction when interrupted with a social versus work interruption.

“Interruptions can actually benefit individuals from an interpersonal perspective – people feel like they belong when others come and talk to them or ask them questions, even while being distracted from their tasks,” said Heather C. Vough, senior investigator and a former university faculty member.

Chitchatting at work is often seen as a distraction, but this study suggests that it’s not like heating up fish in the breakroom microwave.

So the next time someone hits you with the “Hey, do you have a sec?,” do yourself a favor and enjoy the interruption.
 

A smorgasbord of science

It’s probably difficult to recruit patients for some medical trials. Try this new drug and potentially get all sorts of interesting and unpleasant side effects. Pass. We suggest the approach a group of researchers from the University of Kansas took for a recent study into weight gain: Invite a bunch of 20-something adults to an all-you-can-eat buffet. They’ll be beating down your door in no time.

pxfuel

Their study, published in Appetite, focused on hyperpalatable food – the sort of food you can keep eating – and compared it with high-energy-dense food and ultra processed food. The test patients had their body composition measured, were let loose on the buffet, and were measured again a year later.

The patients who favored salty/carbohydrate-filled hyperpalatable food (such as pretzels or popcorn) were much more likely to gain weight, compared with those who focused on salty/fat-filled food of any variety. As a matter of fact, those who stuck to fatty food during the buffet had no change in weight over the 1-year study period. The researchers noted that those who ate the carb-filled food tended more toward hedonic eating, or the act of eating simply for pleasure.

The study is no doubt helpful in the long battle against obesity and overeating, but it’s also a very helpful guide to getting the most bang for your buck at the buffet. Stay away from the cheap salty snack food. Go for the steak and seafood. Get your money’s worth. In the long run you won’t even gain any weight. No promises about tomorrow though.
 

There’s a cheat code for that

For a large percentage of kids and young adults, and maybe even older adults (we don’t judge), a storm warning means a cozy night in playing video games. Staying inside is probably the safest bet when there’s a storm, and the weatherman never says to avoid playing video games when there’s lightning.

xresch/Pixabay

Maybe he should, though, since a man from Tennessee reportedly got struck by lightning through his game controller. Emergency crews determined that lightning either hit the man’s house or struck near it and went through the controller. The type of console was not revealed, even though some people may want to know the specifics before playing during the next storm.

Luckily, the man was not seriously hurt and did not need to go to the hospital. This is apparently not unheard of, as a professional gamer was shocked through a wired controller last year, causing burns on her hands and a broken controller.

This might be our cue to do less electrical types of activities during thunderstorms, like knitting or reading by candlelight.
 

Freeze, squeeze, and enjoy … cramping

As you were ingesting last week’s installment of the never-ending buffet that is LOTME, you probably wondered: What’s going on? Where’s the latest bodily insult being perpetuated by the gang over at TikTok?

Daria-Yakovleva/Pixabay

Have no fear, good readers. We would never make you go 2 straight weeks without serving up some hyperpalatable TikTok tidbits.

Our bodily insult du jour is frozen honey, and it’s exploding all over TikTok … and a few other places. “The hashtag ‘#FrozenHoney’ has been viewed nearly 600 million times, and the hashtag ‘#FrozenHoneyChallenge’ has been viewed more than 80 million times,” NBC News recently reported.

After a few hours in the freezer, honey can be squeezed out of a plastic bottle as a semisolid, toothpastelike goo – it’s stiff enough to rise out of a container that’s pointed straight up – and bitten off in large chunks. And therein lies the problem.

Some people are overdoing it. “Honey is great, but having it in small amounts to sweeten is really a healthy relationship with food, and using it to get a lot of followers and a lot of attention and having it in excess amounts is crazy,” Kristin Kirkpatrick, a registered dietitian at the Cleveland Clinic, told NBC.

Besides the possible weight gain from eating massive amounts of sugar, experts warned that “gobbling up bottles of frozen honey” could lead to stomach cramping, bloating, and diarrhea. Some TikTokers, NBC noted, said that they “were running for the bathroom.”

As we said, it’s a trend that is exploding.

Be sure to tune in next week, when we learn how TikTokers use ground meat as a skin moisturizer.
 

Because the Delta variant of SARS-CoV-2 spreads more easily than the original virus, the proportion of the population that needs to be vaccinated to reach herd immunity could be upward of 80% or more, experts say.

Also, it could be time to consider wearing an N95 mask in public indoor spaces regardless of vaccination status, according to a media briefing on Aug. 3 sponsored by the Infectious Diseases Society of America.

Furthermore, giving booster shots to the fully vaccinated is not the top public health priority now. Instead, third vaccinations should be reserved for more vulnerable populations – and efforts should focus on getting first vaccinations to unvaccinated people in the United States and around the world.

“The problem here is that the Delta variant is ... more transmissible than the original virus. That pushes the overall population herd immunity threshold much higher,” Ricardo Franco, MD, assistant professor of medicine at the University of Alabama at Birmingham, said during the briefing.

“For Delta, those threshold estimates go well over 80% and may be approaching 90%,” he said.

To put that figure in context, the original SARS-CoV-2 virus required an estimated 67% of the population to be vaccinated to achieve herd immunity. Also, measles has one of the highest herd immunity thresholds at 95%, Dr. Franco added.

Herd immunity is the point at which enough people are immunized that the entire population gains protection. And it’s already happening. “Unvaccinated people are actually benefiting from greater herd immunity protection in high-vaccination counties compared to low-vaccination ones,” he said.
 

Maximize mask protection

Unlike early in the COVID-19 pandemic with widespread shortages of personal protective equipment, face masks are now readily available. This includes N95 masks, which offer enhanced protection against SARS-CoV-2, Ezekiel J. Emanuel, MD, PhD, said during the briefing.

Following the July 27 CDC recommendation that most Americans wear masks indoors when in public places, “I do think we need to upgrade our masks,” said Dr. Emanuel, who is Diane v.S. Levy & Robert M. Levy professor at the University of Pennsylvania, Philadelphia.

“It’s not just any mask,” he added. “Good masks make a big difference and are very important.”

Mask protection is about blocking 0.3-mcm particles, “and I think we need to make sure that people have masks that can filter that out,” he said. Although surgical masks are very good, he added, “they’re not quite as good as N95s.” As their name implies, N95s filter out 95% of these particles.

Dr. Emanuel acknowledged that people are tired of COVID-19 and complying with public health measures but urged perseverance. “We’ve sacrificed a lot. We should not throw it away in just a few months because we are tired. We’re all tired, but we do have to do the little bit extra getting vaccinated, wearing masks indoors, and protecting ourselves, our families, and our communities.”
 

Dealing with a disconnect

In response to a reporter’s question about the possibility that the large crowd at the Lollapalooza music festival in Chicago could become a superspreader event, Dr. Emanuel said, “it is worrisome.”

“I would say that, if you’re going to go to a gathering like that, wearing an N95 mask is wise, and not spending too long at any one place is also wise,” he said.

On the plus side, the event was held outdoors with lots of air circulation, Dr. Emanuel said.

However, “this is the kind of thing where we’ve got a sort of disconnect between people’s desire to get back to normal ... and the fact that we’re in the middle of this upsurge.”

Another potential problem is the event brought people together from many different locations, so when they travel home, they could be “potentially seeding lots of other communities.”
 

Boosters for some, for now

Even though not officially recommended, some fully vaccinated Americans are seeking a third or booster vaccination on their own.

Asked for his opinion, Dr. Emanuel said: “We’re probably going to have to be giving boosters to immunocompromised people and people who are susceptible. That’s where we are going to start.”

More research is needed regarding booster shots, he said. “There are very small studies – and the ‘very small’ should be emphasized – given that we’ve given shots to over 160 million people.”

“But it does appear that the boosters increase the antibodies and protection,” he said.

Instead of boosters, it is more important for people who haven’t been vaccinated to get fully vaccinated.

“We need to put our priorities in the right places,” he said.

Emanuel noted that, except for people in rural areas that might have to travel long distances, access to vaccines is no longer an issue. “It’s very hard not to find a vaccine if you want it.”

A remaining hurdle is “battling a major disinformation initiative. I don’t think this is misinformation. I think there’s very clear evidence that it is disinformation – false facts about the vaccines being spread,” Dr. Emanuel said.
 

The breakthrough infection dilemma

Breakthrough cases “remain the vast minority of infections at this time ... that is reassuring,” Dr. Franco said.

Also, tracking symptomatic breakthrough infections remains easier than studying fully vaccinated people who become infected with SARS-CoV-2 but remain symptom free.

“We really don’t have a good handle on the frequency of asymptomatic cases,” Dr. Emanuel said. “If you’re missing breakthrough infections, a lot of them, you may be missing some [virus] evolution that would be very important for us to follow.” This missing information could include the emergence of new variants.

The asymptomatic breakthrough cases are the most worrisome group,” Dr. Emanuel said. “You get infected, you’re feeling fine. Maybe you’ve got a little sneeze or cough, but nothing unusual. And then you’re still able to transmit the Delta variant.”
 

The big picture

The upsurge in cases, hospitalizations, and deaths is a major challenge, Dr. Emanuel said. “We need to address that by getting many more people vaccinated right now with what are very good vaccines.”

“But it also means that we have to stop being U.S. focused alone.” He pointed out that Delta and other variants originated overseas, “so getting the world vaccinated ... has to be a top priority.”

“We are obviously all facing a challenge as we move into the fall,” Dr. Emanuel said. “With schools opening and employers bringing their employees back together, even if these groups are vaccinated, there are going to be major challenges for all of us.”

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

Because the Delta variant of SARS-CoV-2 spreads more easily than the original virus, the proportion of the population that needs to be vaccinated to reach herd immunity could be upward of 80% or more, experts say.

Also, it could be time to consider wearing an N95 mask in public indoor spaces regardless of vaccination status, according to a media briefing on Aug. 3 sponsored by the Infectious Diseases Society of America.

Furthermore, giving booster shots to the fully vaccinated is not the top public health priority now. Instead, third vaccinations should be reserved for more vulnerable populations – and efforts should focus on getting first vaccinations to unvaccinated people in the United States and around the world.

“The problem here is that the Delta variant is ... more transmissible than the original virus. That pushes the overall population herd immunity threshold much higher,” Ricardo Franco, MD, assistant professor of medicine at the University of Alabama at Birmingham, said during the briefing.

“For Delta, those threshold estimates go well over 80% and may be approaching 90%,” he said.

To put that figure in context, the original SARS-CoV-2 virus required an estimated 67% of the population to be vaccinated to achieve herd immunity. Also, measles has one of the highest herd immunity thresholds at 95%, Dr. Franco added.

Herd immunity is the point at which enough people are immunized that the entire population gains protection. And it’s already happening. “Unvaccinated people are actually benefiting from greater herd immunity protection in high-vaccination counties compared to low-vaccination ones,” he said.
 

Maximize mask protection

Unlike early in the COVID-19 pandemic with widespread shortages of personal protective equipment, face masks are now readily available. This includes N95 masks, which offer enhanced protection against SARS-CoV-2, Ezekiel J. Emanuel, MD, PhD, said during the briefing.

Following the July 27 CDC recommendation that most Americans wear masks indoors when in public places, “I do think we need to upgrade our masks,” said Dr. Emanuel, who is Diane v.S. Levy & Robert M. Levy professor at the University of Pennsylvania, Philadelphia.

“It’s not just any mask,” he added. “Good masks make a big difference and are very important.”

Mask protection is about blocking 0.3-mcm particles, “and I think we need to make sure that people have masks that can filter that out,” he said. Although surgical masks are very good, he added, “they’re not quite as good as N95s.” As their name implies, N95s filter out 95% of these particles.

Dr. Emanuel acknowledged that people are tired of COVID-19 and complying with public health measures but urged perseverance. “We’ve sacrificed a lot. We should not throw it away in just a few months because we are tired. We’re all tired, but we do have to do the little bit extra getting vaccinated, wearing masks indoors, and protecting ourselves, our families, and our communities.”
 

Dealing with a disconnect

In response to a reporter’s question about the possibility that the large crowd at the Lollapalooza music festival in Chicago could become a superspreader event, Dr. Emanuel said, “it is worrisome.”

“I would say that, if you’re going to go to a gathering like that, wearing an N95 mask is wise, and not spending too long at any one place is also wise,” he said.

On the plus side, the event was held outdoors with lots of air circulation, Dr. Emanuel said.

However, “this is the kind of thing where we’ve got a sort of disconnect between people’s desire to get back to normal ... and the fact that we’re in the middle of this upsurge.”

Another potential problem is the event brought people together from many different locations, so when they travel home, they could be “potentially seeding lots of other communities.”
 

Boosters for some, for now

Even though not officially recommended, some fully vaccinated Americans are seeking a third or booster vaccination on their own.

Asked for his opinion, Dr. Emanuel said: “We’re probably going to have to be giving boosters to immunocompromised people and people who are susceptible. That’s where we are going to start.”

More research is needed regarding booster shots, he said. “There are very small studies – and the ‘very small’ should be emphasized – given that we’ve given shots to over 160 million people.”

“But it does appear that the boosters increase the antibodies and protection,” he said.

Instead of boosters, it is more important for people who haven’t been vaccinated to get fully vaccinated.

“We need to put our priorities in the right places,” he said.

Emanuel noted that, except for people in rural areas that might have to travel long distances, access to vaccines is no longer an issue. “It’s very hard not to find a vaccine if you want it.”

A remaining hurdle is “battling a major disinformation initiative. I don’t think this is misinformation. I think there’s very clear evidence that it is disinformation – false facts about the vaccines being spread,” Dr. Emanuel said.
 

The breakthrough infection dilemma

Breakthrough cases “remain the vast minority of infections at this time ... that is reassuring,” Dr. Franco said.

Also, tracking symptomatic breakthrough infections remains easier than studying fully vaccinated people who become infected with SARS-CoV-2 but remain symptom free.

“We really don’t have a good handle on the frequency of asymptomatic cases,” Dr. Emanuel said. “If you’re missing breakthrough infections, a lot of them, you may be missing some [virus] evolution that would be very important for us to follow.” This missing information could include the emergence of new variants.

The asymptomatic breakthrough cases are the most worrisome group,” Dr. Emanuel said. “You get infected, you’re feeling fine. Maybe you’ve got a little sneeze or cough, but nothing unusual. And then you’re still able to transmit the Delta variant.”
 

The big picture

The upsurge in cases, hospitalizations, and deaths is a major challenge, Dr. Emanuel said. “We need to address that by getting many more people vaccinated right now with what are very good vaccines.”

“But it also means that we have to stop being U.S. focused alone.” He pointed out that Delta and other variants originated overseas, “so getting the world vaccinated ... has to be a top priority.”

“We are obviously all facing a challenge as we move into the fall,” Dr. Emanuel said. “With schools opening and employers bringing their employees back together, even if these groups are vaccinated, there are going to be major challenges for all of us.”

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

Because the Delta variant of SARS-CoV-2 spreads more easily than the original virus, the proportion of the population that needs to be vaccinated to reach herd immunity could be upward of 80% or more, experts say.

Also, it could be time to consider wearing an N95 mask in public indoor spaces regardless of vaccination status, according to a media briefing on Aug. 3 sponsored by the Infectious Diseases Society of America.

Furthermore, giving booster shots to the fully vaccinated is not the top public health priority now. Instead, third vaccinations should be reserved for more vulnerable populations – and efforts should focus on getting first vaccinations to unvaccinated people in the United States and around the world.

“The problem here is that the Delta variant is ... more transmissible than the original virus. That pushes the overall population herd immunity threshold much higher,” Ricardo Franco, MD, assistant professor of medicine at the University of Alabama at Birmingham, said during the briefing.

“For Delta, those threshold estimates go well over 80% and may be approaching 90%,” he said.

To put that figure in context, the original SARS-CoV-2 virus required an estimated 67% of the population to be vaccinated to achieve herd immunity. Also, measles has one of the highest herd immunity thresholds at 95%, Dr. Franco added.

Herd immunity is the point at which enough people are immunized that the entire population gains protection. And it’s already happening. “Unvaccinated people are actually benefiting from greater herd immunity protection in high-vaccination counties compared to low-vaccination ones,” he said.
 

Maximize mask protection

Unlike early in the COVID-19 pandemic with widespread shortages of personal protective equipment, face masks are now readily available. This includes N95 masks, which offer enhanced protection against SARS-CoV-2, Ezekiel J. Emanuel, MD, PhD, said during the briefing.

Following the July 27 CDC recommendation that most Americans wear masks indoors when in public places, “I do think we need to upgrade our masks,” said Dr. Emanuel, who is Diane v.S. Levy & Robert M. Levy professor at the University of Pennsylvania, Philadelphia.

“It’s not just any mask,” he added. “Good masks make a big difference and are very important.”

Mask protection is about blocking 0.3-mcm particles, “and I think we need to make sure that people have masks that can filter that out,” he said. Although surgical masks are very good, he added, “they’re not quite as good as N95s.” As their name implies, N95s filter out 95% of these particles.

Dr. Emanuel acknowledged that people are tired of COVID-19 and complying with public health measures but urged perseverance. “We’ve sacrificed a lot. We should not throw it away in just a few months because we are tired. We’re all tired, but we do have to do the little bit extra getting vaccinated, wearing masks indoors, and protecting ourselves, our families, and our communities.”
 

Dealing with a disconnect

In response to a reporter’s question about the possibility that the large crowd at the Lollapalooza music festival in Chicago could become a superspreader event, Dr. Emanuel said, “it is worrisome.”

“I would say that, if you’re going to go to a gathering like that, wearing an N95 mask is wise, and not spending too long at any one place is also wise,” he said.

On the plus side, the event was held outdoors with lots of air circulation, Dr. Emanuel said.

However, “this is the kind of thing where we’ve got a sort of disconnect between people’s desire to get back to normal ... and the fact that we’re in the middle of this upsurge.”

Another potential problem is the event brought people together from many different locations, so when they travel home, they could be “potentially seeding lots of other communities.”
 

Boosters for some, for now

Even though not officially recommended, some fully vaccinated Americans are seeking a third or booster vaccination on their own.

Asked for his opinion, Dr. Emanuel said: “We’re probably going to have to be giving boosters to immunocompromised people and people who are susceptible. That’s where we are going to start.”

More research is needed regarding booster shots, he said. “There are very small studies – and the ‘very small’ should be emphasized – given that we’ve given shots to over 160 million people.”

“But it does appear that the boosters increase the antibodies and protection,” he said.

Instead of boosters, it is more important for people who haven’t been vaccinated to get fully vaccinated.

“We need to put our priorities in the right places,” he said.

Emanuel noted that, except for people in rural areas that might have to travel long distances, access to vaccines is no longer an issue. “It’s very hard not to find a vaccine if you want it.”

A remaining hurdle is “battling a major disinformation initiative. I don’t think this is misinformation. I think there’s very clear evidence that it is disinformation – false facts about the vaccines being spread,” Dr. Emanuel said.
 

The breakthrough infection dilemma

Breakthrough cases “remain the vast minority of infections at this time ... that is reassuring,” Dr. Franco said.

Also, tracking symptomatic breakthrough infections remains easier than studying fully vaccinated people who become infected with SARS-CoV-2 but remain symptom free.

“We really don’t have a good handle on the frequency of asymptomatic cases,” Dr. Emanuel said. “If you’re missing breakthrough infections, a lot of them, you may be missing some [virus] evolution that would be very important for us to follow.” This missing information could include the emergence of new variants.

The asymptomatic breakthrough cases are the most worrisome group,” Dr. Emanuel said. “You get infected, you’re feeling fine. Maybe you’ve got a little sneeze or cough, but nothing unusual. And then you’re still able to transmit the Delta variant.”
 

The big picture

The upsurge in cases, hospitalizations, and deaths is a major challenge, Dr. Emanuel said. “We need to address that by getting many more people vaccinated right now with what are very good vaccines.”

“But it also means that we have to stop being U.S. focused alone.” He pointed out that Delta and other variants originated overseas, “so getting the world vaccinated ... has to be a top priority.”

“We are obviously all facing a challenge as we move into the fall,” Dr. Emanuel said. “With schools opening and employers bringing their employees back together, even if these groups are vaccinated, there are going to be major challenges for all of us.”

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

Like many colleagues, I have been working to change the minds and behaviors of acquaintances and patients who are opting to forgo a COVID vaccine. The large numbers of these unvaccinated Americans, combined with the surging Delta coronavirus variant, are endangering the health of us all.

When I spoke with the 22-year-old daughter of a family friend about what was holding her back, she told me that she would “never” get vaccinated. I shared my vaccination experience and told her that, except for a sore arm both times for a day, I felt no side effects. Likewise, I said, all of my adult family members are vaccinated, and everyone is fine. She was neither moved nor convinced.

Finally, I asked her whether she attended school (knowing that she was a college graduate), and she said “yes.” So I told her that all 50 states require children attending public schools to be vaccinated for diseases such as diphtheria, tetanus, polio, and the chickenpox – with certain religious, philosophical, and medical exemptions. Her response was simple: “I didn’t know that. Anyway, my parents were in charge.” Suddenly, her thinking shifted. “You’re right,” she said. She got a COVID shot the next day. Success for me.

When I asked another acquaintance whether he’d been vaccinated, he said he’d heard people were getting very sick from the vaccine – and was going to wait. Another gentleman I spoke with said that, at age 45, he was healthy. Besides, he added, he “doesn’t get sick.” When I asked another acquaintance about her vaccination status, her retort was that this was none of my business. So far, I’m batting about .300.

But as a physician, I believe that we – and other health care providers – must continue to encourage the people in our lives to care for themselves and others by getting vaccinated. One concrete step advised by the Centers for Disease Control and Prevention is to help people make an appointment for a shot. Some sites no longer require appointments, and New York City, for example, offers in-home vaccinations to all NYC residents.

Also, NYC Mayor Bill de Blasio announced Aug. 3 the “Key to NYC Pass,” which he called a “first-in-the-nation approach” to vaccination. Under this new policy, vaccine-eligible people aged 12 and older in New York City will need to prove with a vaccination card, an app, or an Excelsior Pass that they have received at least one dose of vaccine before participating in indoor venues such as restaurants, bars, gyms, and movie theaters within the city. Mayor de Blasio said the new initiative, which is still being finalized, will be phased in starting the week of Aug. 16. I see this as a major public health measure that will keep people healthy – and get them vaccinated.

The medical community should support this move by the city of New York and encourage people to follow CDC guidance on wearing face coverings in public settings, especially schools. New research shows that physicians continue to be among the most trusted sources of vaccine-related information.

Another strategy we might use is to point to the longtime practices of surgeons. We could ask: Why do surgeons wear face masks in the operating room? For years, these coverings have been used to protect patients from the nasal and oral bacteria generated by operating room staff. Likewise, we can tell those who remain on the fence that, by wearing face masks, we are protecting others from all variants, but specifically from Delta – which the CDC now says can be transmitted by people who are fully vaccinated.

Why did the CDC lift face mask guidance for fully vaccinated people in indoor spaces in May? It was clear to me and other colleagues back then that this was not a good idea. Despite that guidance, I continued to wear a mask in public places and advised anyone who would listen to do the same.

The development of vaccines in the 20th and 21st centuries has saved millions of lives. The World Health Organization reports that 4 million to 5 million lives a year are saved by immunizations. In addition, research shows that, before the emergence of SARS-CoV-2, vaccinations led to the eradication of smallpox and polio, and a 74% drop in measles-related deaths between 2004 and 2014.
 

Protecting the most vulnerable

With COVID cases surging, particularly in parts of the South and Midwest, I am concerned about children under age 12 who do not yet qualify for a vaccine. Certainly, unvaccinated parents could spread the virus to their young children, and unvaccinated children could transmit the illness to immediate and extended family. Now that the CDC has said that there is a risk of SARS-CoV-2 breakthrough infection among fully vaccinated people in areas with high community transmission, should we worry about unvaccinated young children with vaccinated parents? I recently spoke with James C. Fagin, MD, a board-certified pediatrician and immunologist, to get his views on this issue.

Dr. Fagin, who is retired, said he is in complete agreement with the Food and Drug Administration when it comes to approving medications for children. However, given the seriousness of the pandemic and the need to get our children back to in-person learning, he would like to see the approval process safely expedited. Large numbers of unvaccinated people increase the pool for the Delta variant and could increase the likelihood of a new variant that is more resistant to the vaccines, said Dr. Fagin, former chief of academic pediatrics at North Shore University Hospital and a former faculty member in the allergy/immunology division of Cohen Children’s Medical Center, both in New York.

Meanwhile, I agree with the American Academy of Pediatrics’ recommendations that children, teachers, and school staff and other adults in school settings should wear masks regardless of vaccination status. Kids adjust well to masks – as my grandchildren and their friends have.

The bottom line is that we need to get as many people as possible vaccinated as soon as possible, and while doing so, we must continue to wear face coverings in public spaces. As clinicians, we have a special responsibility to do all that we can to change minds – and behaviors.

Dr. London is a practicing psychiatrist who has been a newspaper columnist for 35 years, specializing in and writing about short-term therapy, including cognitive-behavioral therapy and guided imagery. He is author of “Find Freedom Fast” (New York: Kettlehole Publishing, 2019). He has no conflicts of interest.

Like many colleagues, I have been working to change the minds and behaviors of acquaintances and patients who are opting to forgo a COVID vaccine. The large numbers of these unvaccinated Americans, combined with the surging Delta coronavirus variant, are endangering the health of us all.

When I spoke with the 22-year-old daughter of a family friend about what was holding her back, she told me that she would “never” get vaccinated. I shared my vaccination experience and told her that, except for a sore arm both times for a day, I felt no side effects. Likewise, I said, all of my adult family members are vaccinated, and everyone is fine. She was neither moved nor convinced.

Finally, I asked her whether she attended school (knowing that she was a college graduate), and she said “yes.” So I told her that all 50 states require children attending public schools to be vaccinated for diseases such as diphtheria, tetanus, polio, and the chickenpox – with certain religious, philosophical, and medical exemptions. Her response was simple: “I didn’t know that. Anyway, my parents were in charge.” Suddenly, her thinking shifted. “You’re right,” she said. She got a COVID shot the next day. Success for me.

When I asked another acquaintance whether he’d been vaccinated, he said he’d heard people were getting very sick from the vaccine – and was going to wait. Another gentleman I spoke with said that, at age 45, he was healthy. Besides, he added, he “doesn’t get sick.” When I asked another acquaintance about her vaccination status, her retort was that this was none of my business. So far, I’m batting about .300.

But as a physician, I believe that we – and other health care providers – must continue to encourage the people in our lives to care for themselves and others by getting vaccinated. One concrete step advised by the Centers for Disease Control and Prevention is to help people make an appointment for a shot. Some sites no longer require appointments, and New York City, for example, offers in-home vaccinations to all NYC residents.

Also, NYC Mayor Bill de Blasio announced Aug. 3 the “Key to NYC Pass,” which he called a “first-in-the-nation approach” to vaccination. Under this new policy, vaccine-eligible people aged 12 and older in New York City will need to prove with a vaccination card, an app, or an Excelsior Pass that they have received at least one dose of vaccine before participating in indoor venues such as restaurants, bars, gyms, and movie theaters within the city. Mayor de Blasio said the new initiative, which is still being finalized, will be phased in starting the week of Aug. 16. I see this as a major public health measure that will keep people healthy – and get them vaccinated.

The medical community should support this move by the city of New York and encourage people to follow CDC guidance on wearing face coverings in public settings, especially schools. New research shows that physicians continue to be among the most trusted sources of vaccine-related information.

Another strategy we might use is to point to the longtime practices of surgeons. We could ask: Why do surgeons wear face masks in the operating room? For years, these coverings have been used to protect patients from the nasal and oral bacteria generated by operating room staff. Likewise, we can tell those who remain on the fence that, by wearing face masks, we are protecting others from all variants, but specifically from Delta – which the CDC now says can be transmitted by people who are fully vaccinated.

Why did the CDC lift face mask guidance for fully vaccinated people in indoor spaces in May? It was clear to me and other colleagues back then that this was not a good idea. Despite that guidance, I continued to wear a mask in public places and advised anyone who would listen to do the same.

The development of vaccines in the 20th and 21st centuries has saved millions of lives. The World Health Organization reports that 4 million to 5 million lives a year are saved by immunizations. In addition, research shows that, before the emergence of SARS-CoV-2, vaccinations led to the eradication of smallpox and polio, and a 74% drop in measles-related deaths between 2004 and 2014.
 

Protecting the most vulnerable

With COVID cases surging, particularly in parts of the South and Midwest, I am concerned about children under age 12 who do not yet qualify for a vaccine. Certainly, unvaccinated parents could spread the virus to their young children, and unvaccinated children could transmit the illness to immediate and extended family. Now that the CDC has said that there is a risk of SARS-CoV-2 breakthrough infection among fully vaccinated people in areas with high community transmission, should we worry about unvaccinated young children with vaccinated parents? I recently spoke with James C. Fagin, MD, a board-certified pediatrician and immunologist, to get his views on this issue.

Dr. Fagin, who is retired, said he is in complete agreement with the Food and Drug Administration when it comes to approving medications for children. However, given the seriousness of the pandemic and the need to get our children back to in-person learning, he would like to see the approval process safely expedited. Large numbers of unvaccinated people increase the pool for the Delta variant and could increase the likelihood of a new variant that is more resistant to the vaccines, said Dr. Fagin, former chief of academic pediatrics at North Shore University Hospital and a former faculty member in the allergy/immunology division of Cohen Children’s Medical Center, both in New York.

Meanwhile, I agree with the American Academy of Pediatrics’ recommendations that children, teachers, and school staff and other adults in school settings should wear masks regardless of vaccination status. Kids adjust well to masks – as my grandchildren and their friends have.

The bottom line is that we need to get as many people as possible vaccinated as soon as possible, and while doing so, we must continue to wear face coverings in public spaces. As clinicians, we have a special responsibility to do all that we can to change minds – and behaviors.

Dr. London is a practicing psychiatrist who has been a newspaper columnist for 35 years, specializing in and writing about short-term therapy, including cognitive-behavioral therapy and guided imagery. He is author of “Find Freedom Fast” (New York: Kettlehole Publishing, 2019). He has no conflicts of interest.

Like many colleagues, I have been working to change the minds and behaviors of acquaintances and patients who are opting to forgo a COVID vaccine. The large numbers of these unvaccinated Americans, combined with the surging Delta coronavirus variant, are endangering the health of us all.

When I spoke with the 22-year-old daughter of a family friend about what was holding her back, she told me that she would “never” get vaccinated. I shared my vaccination experience and told her that, except for a sore arm both times for a day, I felt no side effects. Likewise, I said, all of my adult family members are vaccinated, and everyone is fine. She was neither moved nor convinced.

Finally, I asked her whether she attended school (knowing that she was a college graduate), and she said “yes.” So I told her that all 50 states require children attending public schools to be vaccinated for diseases such as diphtheria, tetanus, polio, and the chickenpox – with certain religious, philosophical, and medical exemptions. Her response was simple: “I didn’t know that. Anyway, my parents were in charge.” Suddenly, her thinking shifted. “You’re right,” she said. She got a COVID shot the next day. Success for me.

When I asked another acquaintance whether he’d been vaccinated, he said he’d heard people were getting very sick from the vaccine – and was going to wait. Another gentleman I spoke with said that, at age 45, he was healthy. Besides, he added, he “doesn’t get sick.” When I asked another acquaintance about her vaccination status, her retort was that this was none of my business. So far, I’m batting about .300.

But as a physician, I believe that we – and other health care providers – must continue to encourage the people in our lives to care for themselves and others by getting vaccinated. One concrete step advised by the Centers for Disease Control and Prevention is to help people make an appointment for a shot. Some sites no longer require appointments, and New York City, for example, offers in-home vaccinations to all NYC residents.

Also, NYC Mayor Bill de Blasio announced Aug. 3 the “Key to NYC Pass,” which he called a “first-in-the-nation approach” to vaccination. Under this new policy, vaccine-eligible people aged 12 and older in New York City will need to prove with a vaccination card, an app, or an Excelsior Pass that they have received at least one dose of vaccine before participating in indoor venues such as restaurants, bars, gyms, and movie theaters within the city. Mayor de Blasio said the new initiative, which is still being finalized, will be phased in starting the week of Aug. 16. I see this as a major public health measure that will keep people healthy – and get them vaccinated.

The medical community should support this move by the city of New York and encourage people to follow CDC guidance on wearing face coverings in public settings, especially schools. New research shows that physicians continue to be among the most trusted sources of vaccine-related information.

Another strategy we might use is to point to the longtime practices of surgeons. We could ask: Why do surgeons wear face masks in the operating room? For years, these coverings have been used to protect patients from the nasal and oral bacteria generated by operating room staff. Likewise, we can tell those who remain on the fence that, by wearing face masks, we are protecting others from all variants, but specifically from Delta – which the CDC now says can be transmitted by people who are fully vaccinated.

Why did the CDC lift face mask guidance for fully vaccinated people in indoor spaces in May? It was clear to me and other colleagues back then that this was not a good idea. Despite that guidance, I continued to wear a mask in public places and advised anyone who would listen to do the same.

The development of vaccines in the 20th and 21st centuries has saved millions of lives. The World Health Organization reports that 4 million to 5 million lives a year are saved by immunizations. In addition, research shows that, before the emergence of SARS-CoV-2, vaccinations led to the eradication of smallpox and polio, and a 74% drop in measles-related deaths between 2004 and 2014.
 

Protecting the most vulnerable

With COVID cases surging, particularly in parts of the South and Midwest, I am concerned about children under age 12 who do not yet qualify for a vaccine. Certainly, unvaccinated parents could spread the virus to their young children, and unvaccinated children could transmit the illness to immediate and extended family. Now that the CDC has said that there is a risk of SARS-CoV-2 breakthrough infection among fully vaccinated people in areas with high community transmission, should we worry about unvaccinated young children with vaccinated parents? I recently spoke with James C. Fagin, MD, a board-certified pediatrician and immunologist, to get his views on this issue.

Dr. Fagin, who is retired, said he is in complete agreement with the Food and Drug Administration when it comes to approving medications for children. However, given the seriousness of the pandemic and the need to get our children back to in-person learning, he would like to see the approval process safely expedited. Large numbers of unvaccinated people increase the pool for the Delta variant and could increase the likelihood of a new variant that is more resistant to the vaccines, said Dr. Fagin, former chief of academic pediatrics at North Shore University Hospital and a former faculty member in the allergy/immunology division of Cohen Children’s Medical Center, both in New York.

Meanwhile, I agree with the American Academy of Pediatrics’ recommendations that children, teachers, and school staff and other adults in school settings should wear masks regardless of vaccination status. Kids adjust well to masks – as my grandchildren and their friends have.

The bottom line is that we need to get as many people as possible vaccinated as soon as possible, and while doing so, we must continue to wear face coverings in public spaces. As clinicians, we have a special responsibility to do all that we can to change minds – and behaviors.

Dr. London is a practicing psychiatrist who has been a newspaper columnist for 35 years, specializing in and writing about short-term therapy, including cognitive-behavioral therapy and guided imagery. He is author of “Find Freedom Fast” (New York: Kettlehole Publishing, 2019). He has no conflicts of interest.

Anifrolumab, an inhibitor of type 1 interferons, received approval from the Food and Drug Administration for the treatment of adults with moderate to severe systemic lupus erythematosus (SLE) who are receiving standard therapy, according to a statement released Aug. 2 from its manufacturer, AstraZeneca.

Courtesy AstraZeneca

Anifrolumab will be marketed as Saphnelo. It is a fully human monoclonal antibody against subunit 1 of the type 1 interferon receptor, and its approval represents the only new treatment approved for patients with SLE in a decade. The recommended dosage is 300 mg as an intravenous infusion over a 30-minute period every 4 weeks, according to its prescribing information, and it will be sold in a single-dose vial containing 300 mg/2 mL (150 mg/mL).

Wikimedia Commons/FitzColinGerald/ Creative Commons License

Increased type I interferon (IFN) signaling is associated with increased disease activity in patients with SLE, and the option of a type I IFN receptor antagonist may allow physicians to treat patients with fewer corticosteroids, according to the statement.

The approval was based on data from three trials. The TULIP (Treatment of Uncontrolled Lupus via the Interferon Pathway) phase 3 research included two randomized, double-blind, placebo-controlled studies, TULIP-1 and TULIP-2. The TULIP trials each enrolled seropositive patients with moderate to severe active disease despite standard-of-care therapy (SOC), which included oral corticosteroids, antimalarials, and immunosuppressants (methotrexate, azathioprine, or mycophenolate mofetil). All patients met American College of Rheumatology criteria and had an SLE Disease Activity Index (SLEDAI)-2K of 6 or greater, as well as British Isles Lupus Assessment Group (BILAG) index scoring showing one or more organ systems with grade A involvement or two or more with grade B. Both trials required stable SOC therapy throughout the study except for mandatory attempts at oral corticosteroid tapering for patients who were receiving 10 mg/day or more of prednisone or its equivalent at study entry.

TULIP-1 failed to meet its primary endpoint of SLE Responder Index (SRI) at 52 weeks, but investigators determined after the trial that some patients taking anifrolumab had been inappropriately labeled as nonresponders because the trial automatically required any patient who used a restricted drug, including NSAIDs, to be classified as a nonresponder even if they used the medication for something unrelated to SLE. When these rules were amended in a post hoc analysis, differences between the groups treated with anifrolumab and placebo widened in secondary endpoints for oral corticosteroid dose reduction, Cutaneous Lupus Erythematosus Disease Activity Severity Index response, and BILAG-Based Composite Lupus Assessment (BICLA) response.

The TULIP-2 trial included 362 patients who received a fixed dose of 300 mg anifrolumab or a placebo intravenously every 4 weeks for 48 weeks. In this study, anifrolumab patients showed significant improvement in disease activity on the BICLA scale, compared with placebo patients. The BICLA response was 47.8% in patients taking anifrolumab and 31.5% in placebo-treated patients (P = .001).

In the MUSE phase 2 trial, 305 adults with SLE were randomized to a fixed-dose intravenous infusion of 300 mg or 1,000 mg of anifrolumab or a placebo every 4 weeks, plus SOC, for 48 weeks. Patients in this study showed significant improvement on either dose, compared with placebo.

The results from the MUSE trial were published online in Arthritis & Rheumatology Nov. 7, 2016, followed by the TULIP-1 trial in The Lancet Rheumatology Nov. 11, 2019, and the TULIP-2 trial in the New England Journal of Medicine Jan. 16, 2020.

The most common treatment-related adverse events in all three studies were nasopharyngitis, upper respiratory tract infection, bronchitis, infusion-related reactions, herpes zoster, and cough. Infusion-related reactions in the trials were similar in anifrolumab and placebo patients, and included headache, nausea, vomiting, fatigue, and dizziness.

Anifrolumab has not been evaluated in patients with severe active lupus nephritis or severe active central nervous system lupus and is not recommended for these patients, according to the statement.

AstraZeneca said in its statement that anifrolumab is also under regulatory review in Japan and the European Union, and it continues to evaluate anifrolumab in patients with SLE in a long-term extension phase 3 trial and a phase 3 trial assessing subcutaneous delivery. The company said it “is exploring the potential of Saphnelo in a variety of diseases where type I IFN plays a key role, including lupus nephritis, cutaneous lupus erythematosus, and myositis.”

Anifrolumab, an inhibitor of type 1 interferons, received approval from the Food and Drug Administration for the treatment of adults with moderate to severe systemic lupus erythematosus (SLE) who are receiving standard therapy, according to a statement released Aug. 2 from its manufacturer, AstraZeneca.

Courtesy AstraZeneca

Anifrolumab will be marketed as Saphnelo. It is a fully human monoclonal antibody against subunit 1 of the type 1 interferon receptor, and its approval represents the only new treatment approved for patients with SLE in a decade. The recommended dosage is 300 mg as an intravenous infusion over a 30-minute period every 4 weeks, according to its prescribing information, and it will be sold in a single-dose vial containing 300 mg/2 mL (150 mg/mL).

Wikimedia Commons/FitzColinGerald/ Creative Commons License

Increased type I interferon (IFN) signaling is associated with increased disease activity in patients with SLE, and the option of a type I IFN receptor antagonist may allow physicians to treat patients with fewer corticosteroids, according to the statement.

The approval was based on data from three trials. The TULIP (Treatment of Uncontrolled Lupus via the Interferon Pathway) phase 3 research included two randomized, double-blind, placebo-controlled studies, TULIP-1 and TULIP-2. The TULIP trials each enrolled seropositive patients with moderate to severe active disease despite standard-of-care therapy (SOC), which included oral corticosteroids, antimalarials, and immunosuppressants (methotrexate, azathioprine, or mycophenolate mofetil). All patients met American College of Rheumatology criteria and had an SLE Disease Activity Index (SLEDAI)-2K of 6 or greater, as well as British Isles Lupus Assessment Group (BILAG) index scoring showing one or more organ systems with grade A involvement or two or more with grade B. Both trials required stable SOC therapy throughout the study except for mandatory attempts at oral corticosteroid tapering for patients who were receiving 10 mg/day or more of prednisone or its equivalent at study entry.

TULIP-1 failed to meet its primary endpoint of SLE Responder Index (SRI) at 52 weeks, but investigators determined after the trial that some patients taking anifrolumab had been inappropriately labeled as nonresponders because the trial automatically required any patient who used a restricted drug, including NSAIDs, to be classified as a nonresponder even if they used the medication for something unrelated to SLE. When these rules were amended in a post hoc analysis, differences between the groups treated with anifrolumab and placebo widened in secondary endpoints for oral corticosteroid dose reduction, Cutaneous Lupus Erythematosus Disease Activity Severity Index response, and BILAG-Based Composite Lupus Assessment (BICLA) response.

The TULIP-2 trial included 362 patients who received a fixed dose of 300 mg anifrolumab or a placebo intravenously every 4 weeks for 48 weeks. In this study, anifrolumab patients showed significant improvement in disease activity on the BICLA scale, compared with placebo patients. The BICLA response was 47.8% in patients taking anifrolumab and 31.5% in placebo-treated patients (P = .001).

In the MUSE phase 2 trial, 305 adults with SLE were randomized to a fixed-dose intravenous infusion of 300 mg or 1,000 mg of anifrolumab or a placebo every 4 weeks, plus SOC, for 48 weeks. Patients in this study showed significant improvement on either dose, compared with placebo.

The results from the MUSE trial were published online in Arthritis & Rheumatology Nov. 7, 2016, followed by the TULIP-1 trial in The Lancet Rheumatology Nov. 11, 2019, and the TULIP-2 trial in the New England Journal of Medicine Jan. 16, 2020.

The most common treatment-related adverse events in all three studies were nasopharyngitis, upper respiratory tract infection, bronchitis, infusion-related reactions, herpes zoster, and cough. Infusion-related reactions in the trials were similar in anifrolumab and placebo patients, and included headache, nausea, vomiting, fatigue, and dizziness.

Anifrolumab has not been evaluated in patients with severe active lupus nephritis or severe active central nervous system lupus and is not recommended for these patients, according to the statement.

AstraZeneca said in its statement that anifrolumab is also under regulatory review in Japan and the European Union, and it continues to evaluate anifrolumab in patients with SLE in a long-term extension phase 3 trial and a phase 3 trial assessing subcutaneous delivery. The company said it “is exploring the potential of Saphnelo in a variety of diseases where type I IFN plays a key role, including lupus nephritis, cutaneous lupus erythematosus, and myositis.”

Anifrolumab, an inhibitor of type 1 interferons, received approval from the Food and Drug Administration for the treatment of adults with moderate to severe systemic lupus erythematosus (SLE) who are receiving standard therapy, according to a statement released Aug. 2 from its manufacturer, AstraZeneca.

Courtesy AstraZeneca

Anifrolumab will be marketed as Saphnelo. It is a fully human monoclonal antibody against subunit 1 of the type 1 interferon receptor, and its approval represents the only new treatment approved for patients with SLE in a decade. The recommended dosage is 300 mg as an intravenous infusion over a 30-minute period every 4 weeks, according to its prescribing information, and it will be sold in a single-dose vial containing 300 mg/2 mL (150 mg/mL).

Wikimedia Commons/FitzColinGerald/ Creative Commons License

Increased type I interferon (IFN) signaling is associated with increased disease activity in patients with SLE, and the option of a type I IFN receptor antagonist may allow physicians to treat patients with fewer corticosteroids, according to the statement.

The approval was based on data from three trials. The TULIP (Treatment of Uncontrolled Lupus via the Interferon Pathway) phase 3 research included two randomized, double-blind, placebo-controlled studies, TULIP-1 and TULIP-2. The TULIP trials each enrolled seropositive patients with moderate to severe active disease despite standard-of-care therapy (SOC), which included oral corticosteroids, antimalarials, and immunosuppressants (methotrexate, azathioprine, or mycophenolate mofetil). All patients met American College of Rheumatology criteria and had an SLE Disease Activity Index (SLEDAI)-2K of 6 or greater, as well as British Isles Lupus Assessment Group (BILAG) index scoring showing one or more organ systems with grade A involvement or two or more with grade B. Both trials required stable SOC therapy throughout the study except for mandatory attempts at oral corticosteroid tapering for patients who were receiving 10 mg/day or more of prednisone or its equivalent at study entry.

TULIP-1 failed to meet its primary endpoint of SLE Responder Index (SRI) at 52 weeks, but investigators determined after the trial that some patients taking anifrolumab had been inappropriately labeled as nonresponders because the trial automatically required any patient who used a restricted drug, including NSAIDs, to be classified as a nonresponder even if they used the medication for something unrelated to SLE. When these rules were amended in a post hoc analysis, differences between the groups treated with anifrolumab and placebo widened in secondary endpoints for oral corticosteroid dose reduction, Cutaneous Lupus Erythematosus Disease Activity Severity Index response, and BILAG-Based Composite Lupus Assessment (BICLA) response.

The TULIP-2 trial included 362 patients who received a fixed dose of 300 mg anifrolumab or a placebo intravenously every 4 weeks for 48 weeks. In this study, anifrolumab patients showed significant improvement in disease activity on the BICLA scale, compared with placebo patients. The BICLA response was 47.8% in patients taking anifrolumab and 31.5% in placebo-treated patients (P = .001).

In the MUSE phase 2 trial, 305 adults with SLE were randomized to a fixed-dose intravenous infusion of 300 mg or 1,000 mg of anifrolumab or a placebo every 4 weeks, plus SOC, for 48 weeks. Patients in this study showed significant improvement on either dose, compared with placebo.

The results from the MUSE trial were published online in Arthritis & Rheumatology Nov. 7, 2016, followed by the TULIP-1 trial in The Lancet Rheumatology Nov. 11, 2019, and the TULIP-2 trial in the New England Journal of Medicine Jan. 16, 2020.

The most common treatment-related adverse events in all three studies were nasopharyngitis, upper respiratory tract infection, bronchitis, infusion-related reactions, herpes zoster, and cough. Infusion-related reactions in the trials were similar in anifrolumab and placebo patients, and included headache, nausea, vomiting, fatigue, and dizziness.

Anifrolumab has not been evaluated in patients with severe active lupus nephritis or severe active central nervous system lupus and is not recommended for these patients, according to the statement.

AstraZeneca said in its statement that anifrolumab is also under regulatory review in Japan and the European Union, and it continues to evaluate anifrolumab in patients with SLE in a long-term extension phase 3 trial and a phase 3 trial assessing subcutaneous delivery. The company said it “is exploring the potential of Saphnelo in a variety of diseases where type I IFN plays a key role, including lupus nephritis, cutaneous lupus erythematosus, and myositis.”