Federal Practitioner

Cirrhosis hospitalizations are declining during the coronavirus pandemic, according to researchers from the University of Pennsylvania and Corporal Michael J. Crescenz US Department of Veterans Affairs Medical Center in Philadelphia. They found a “clear drop-off” among patients who ordinarily would meet acute care criteria.

Using data from the Veterans Outcomes and Costs Associated with Liver Disease (VOCAL) cohort, the researchers collected data that included length of stay, type of hospital, and region for 7,216 patients and 12,467 hospitalizations between January 1 and April 15 in 2019 and 2020. They designated 3 2020 subgroups: pre-COVID (before February 29), early COVID (February 29 - March 25), and late COVID (March 26 - April 15). The breakpoints were chosen because the Veterans Health Administration announced a COVID-19 Response Plan on March 23 that was implemented widely within 3 days.

Analyzing the differences in data from the 2 years, the researchers found weekly cirrhosis hospitalizations were on average 159.5 fewer in the late-COVID era, while admissions for end-stage liver disease were significantly higher. Patients also had shorter lengths of stay in 2020 when compared with 2019 (median, 2 days vs 3), and fewer hospital transfers (7.5% vs 11.1%).

The late-COVID era also was characterized by significantly fewer academic hospital admissions (63.6% vs 68.1% pre-COVID). And more patients were discharged to home in the late-COVID era (91.1% vs 88.8% pre-COVID) and fewer to facilities (5.1% vs 9.0% pre-COVID).

The changes likely reflect initiatives to preserve inpatient resources, the researchers say. “Importantly,” they suggest, their findings probably “parallel changes in other inpatient resource-intensive conditions,” such as congestive heart failure, chronic obstructive pulmonary disease, and myocardial infarction.

The pandemic response also may be sending conflicting messages to people who already have serious illnesses: Patients may be following guidance encouraging them to stay home, or avoiding going to the hospital until their symptoms are severe, perhaps from fears about COVID-19.

It is unclear how these patients are being managed, the researchers add. “Given the baseline vulnerability of patients with cirrhosis, it is likely that many do not currently have adequate healthcare access.”

Cirrhosis hospitalizations are declining during the coronavirus pandemic, according to researchers from the University of Pennsylvania and Corporal Michael J. Crescenz US Department of Veterans Affairs Medical Center in Philadelphia. They found a “clear drop-off” among patients who ordinarily would meet acute care criteria.

Using data from the Veterans Outcomes and Costs Associated with Liver Disease (VOCAL) cohort, the researchers collected data that included length of stay, type of hospital, and region for 7,216 patients and 12,467 hospitalizations between January 1 and April 15 in 2019 and 2020. They designated 3 2020 subgroups: pre-COVID (before February 29), early COVID (February 29 - March 25), and late COVID (March 26 - April 15). The breakpoints were chosen because the Veterans Health Administration announced a COVID-19 Response Plan on March 23 that was implemented widely within 3 days.

Analyzing the differences in data from the 2 years, the researchers found weekly cirrhosis hospitalizations were on average 159.5 fewer in the late-COVID era, while admissions for end-stage liver disease were significantly higher. Patients also had shorter lengths of stay in 2020 when compared with 2019 (median, 2 days vs 3), and fewer hospital transfers (7.5% vs 11.1%).

The late-COVID era also was characterized by significantly fewer academic hospital admissions (63.6% vs 68.1% pre-COVID). And more patients were discharged to home in the late-COVID era (91.1% vs 88.8% pre-COVID) and fewer to facilities (5.1% vs 9.0% pre-COVID).

The changes likely reflect initiatives to preserve inpatient resources, the researchers say. “Importantly,” they suggest, their findings probably “parallel changes in other inpatient resource-intensive conditions,” such as congestive heart failure, chronic obstructive pulmonary disease, and myocardial infarction.

The pandemic response also may be sending conflicting messages to people who already have serious illnesses: Patients may be following guidance encouraging them to stay home, or avoiding going to the hospital until their symptoms are severe, perhaps from fears about COVID-19.

It is unclear how these patients are being managed, the researchers add. “Given the baseline vulnerability of patients with cirrhosis, it is likely that many do not currently have adequate healthcare access.”

Cirrhosis hospitalizations are declining during the coronavirus pandemic, according to researchers from the University of Pennsylvania and Corporal Michael J. Crescenz US Department of Veterans Affairs Medical Center in Philadelphia. They found a “clear drop-off” among patients who ordinarily would meet acute care criteria.

Using data from the Veterans Outcomes and Costs Associated with Liver Disease (VOCAL) cohort, the researchers collected data that included length of stay, type of hospital, and region for 7,216 patients and 12,467 hospitalizations between January 1 and April 15 in 2019 and 2020. They designated 3 2020 subgroups: pre-COVID (before February 29), early COVID (February 29 - March 25), and late COVID (March 26 - April 15). The breakpoints were chosen because the Veterans Health Administration announced a COVID-19 Response Plan on March 23 that was implemented widely within 3 days.

Analyzing the differences in data from the 2 years, the researchers found weekly cirrhosis hospitalizations were on average 159.5 fewer in the late-COVID era, while admissions for end-stage liver disease were significantly higher. Patients also had shorter lengths of stay in 2020 when compared with 2019 (median, 2 days vs 3), and fewer hospital transfers (7.5% vs 11.1%).

The late-COVID era also was characterized by significantly fewer academic hospital admissions (63.6% vs 68.1% pre-COVID). And more patients were discharged to home in the late-COVID era (91.1% vs 88.8% pre-COVID) and fewer to facilities (5.1% vs 9.0% pre-COVID).

The changes likely reflect initiatives to preserve inpatient resources, the researchers say. “Importantly,” they suggest, their findings probably “parallel changes in other inpatient resource-intensive conditions,” such as congestive heart failure, chronic obstructive pulmonary disease, and myocardial infarction.

The pandemic response also may be sending conflicting messages to people who already have serious illnesses: Patients may be following guidance encouraging them to stay home, or avoiding going to the hospital until their symptoms are severe, perhaps from fears about COVID-19.

It is unclear how these patients are being managed, the researchers add. “Given the baseline vulnerability of patients with cirrhosis, it is likely that many do not currently have adequate healthcare access.”

Mainstream media outlets have been flooded recently with reports speculating on what role, if any, vitamin D may play in reducing the severity of COVID-19 infection.

Observational data comparing outcomes from various countries suggest inverse links between vitamin D levels and the severity of COVID-19 responses, as well as mortality, with the further suggestion of an effect of vitamin D on the immune response to infection.

But other studies question such a link, including any association between vitamin D concentration and differences in COVID-19 severity by ethnic group.

And while some researchers and clinicians believe people should get tested to see if they have adequate vitamin D levels during this pandemic – in particular frontline health care workers – most doctors say the best way to ensure that people have adequate levels of vitamin D during COVID-19 is to simply take supplements at currently recommended levels.

This is especially important given the fact that, during “lockdown” scenarios, many people are spending more time than usual indoors.

Clifford Rosen, MD, senior scientist at Maine Medical Center’s Research Institute in Scarborough, has been researching vitamin D for 25 years.

“There’s no randomized, controlled trial for sure, and that’s the gold standard,” he said in an interview, and “the observational data are so confounded, it’s difficult to know.”

Whether from diet or supplementation, having adequate vitamin D is important, especially for those at the highest risk of COVID-19, he said. Still, robust data supporting a role of vitamin D in prevention of COVID-19, or as any kind of “therapy” for the infection, are currently lacking.

Rose Anne Kenny, MD, professor of medical gerontology at Trinity College Dublin, recently coauthored an article detailing an inverse association between vitamin D levels and mortality from COVID-19 across countries in Europe.

“At no stage are any of us saying this is a given, but there’s a probability that [vitamin D] – a low-hanging fruit – is a contributory factor and we can do something about it now,” she said in an interview.

Dr. Kenny is calling for the Irish government to formally change their recommendations. “We call on the Irish government to update guidelines as a matter of urgency and encourage all adults to take [vitamin D] supplements during the COVID-19 crisis.” Northern Ireland, part of the United Kingdom, also has not yet made this recommendation, she said.

Meanwhile, Harpreet S. Bajaj, MD, MPH, a practicing endocrinologist from Mount Sinai Hospital, Toronto, said: “Vitamin D could have any of three potential roles in risk for COVID-19 and/or its severity: no role, simply a marker, or a causal factor.”

Dr. Bajaj said – as did Dr. Rosen and Dr. Kenny – that randomized, controlled trials (RCTs) are sorely needed to help ascertain whether there is a specific role of vitamin D.

“Until then, we should continue to follow established public health recommendations for vitamin D supplementation, in addition to following COVID-19 prevention guidance and evolving guidelines for COVID-19 treatment.”
 

What is the role of vitamin D fortification?

In their study in the Irish Medical Journal, Dr. Kenny and colleagues noted that, in Europe, despite being sunny, Spain and Northern Italy had high rates of vitamin D deficiency and have experienced some of the highest COVID-19 infection and mortality rates in the world.

But these countries do not formally fortify foods or recommend supplementation with vitamin D.

Conversely, the northern countries of Norway, Finland, and Sweden had higher vitamin D levels despite less UVB sunlight exposure, as a result of common supplementation and formal fortification of foods. These Nordic countries also had lower levels of COVID-19 infection and mortality.

Overall, the correlation between low vitamin D levels and mortality from COVID-19 was statistically significant (P = .046), the investigators reported.

“Optimizing vitamin D status to recommendations by national and international public health agencies will certainly have ... potential benefits for COVID-19,” they concluded.

“We’re not saying there aren’t any confounders. This can absolutely be the case, but this [finding] needs to be in the mix of evidence,” Dr. Kenny said.

Dr. Kenny also noted that countries in the Southern Hemisphere have been seeing a relatively low mortality from COVID-19, although she acknowledged the explanation could be that the virus spread later to those countries.

Dr. Rosen has doubts on this issue, too.

“Sure, vitamin D supplementation may have worked for [Nordic countries], their COVID-19 has been better controlled, but there’s no causality here; there’s another step to actually prove this. Other factors might be at play,” he said.

“Look at Brazil, it’s at the equator but the disease is devastating the country. Right now, I just don’t believe it.”

Does vitamin D have a role to play in immune modulation?

One theory currently circulating is that, if vitamin D does have any role to play in modulating response to COVID-19, this may be via a blunting of the immune system reaction to the virus.

In a recent preprint study, Ali Daneshkhah, PhD, and colleagues from Northwestern University, Chicago, interrogated hospital data from China, France, Germany, Italy, Iran, South Korea, Spain, Switzerland, the United Kingdom, and the United States.

Specifically, the risk of severe COVID-19 cases among patients with severe vitamin D deficiency was 17.3%, whereas the equivalent figure for patients with normal vitamin D levels was 14.6% (a reduction of 15.6%).

“This potential effect may be attributed to vitamin D’s ability to suppress the adaptive immune system, regulating cytokine levels and thereby reducing the risk of developing severe COVID-19,” said the researchers.

Likewise, JoAnn E. Manson, MD, chief of the division of preventive medicine at Brigham and Women’s Hospital in Boston, in a recent commentary, noted evidence from an observational study from three South Asian hospitals, in which the prevalence of vitamin D deficiency was much higher among those with severe COVID-19 illness compared with those with mild illness.

“We also know that vitamin D has an immune-modulating effect and can lower inflammation, and this may be relevant to the respiratory response during COVID-19 and the cytokine storm that’s been demonstrated,” she noted.

Dr. Rosen said he is willing to listen on the issue of a potential role of vitamin D in immune modulation.

“I’ve been a huge skeptic from the get-go, and loudly criticized the data for doing nothing. I am surprised at myself for saying there might be some effect,” he said.

“Clearly most people don’t get this [cytokine storm] but of those that do, it’s unclear why they do. Maybe if you are vitamin D sufficient, it might have some impact down the road on your response to an infection,” Dr. Rosen said. “Vitamin D may induce proteins important in modulating the function of macrophages of the immune system.”

Ethnic minorities disproportionately affected

It is also well recognized that COVID-19 disproportionately affects black and Asian minority ethnic individuals.

But on the issue of vitamin D in this context, one recent peer-reviewed study using UK Biobank data found no evidence to support a potential role for vitamin D concentration to explain susceptibility to COVID-19 infection either overall or in explaining differences between ethnic groups.

“Vitamin D is unlikely to be the underlying mechanism for the higher risk observed in black and minority ethnic individuals, and vitamin D supplements are unlikely to provide an effective intervention,” Claire Hastie, PhD, of the University of Glasgow and colleagues concluded.

But this hasn’t stopped two endocrinologists from appealing to members of the British Association of Physicians of Indian Origin (BAPIO) to get their vitamin D levels tested.

The black and Asian minority ethnic population, “especially frontline staff, should get their Vitamin D₃ levels checked and get appropriate replacement as required,” said Parag Singhal, MD, of Weston General Hospital, Weston-Super-Mare, England, and David C. Anderson, a retired endocrinologist, said in a letter to BAPIO members.

Indeed, they suggested a booster dose of 100,000 IU as a one-off for black and Asian minority ethnic health care staff that should raise vitamin D levels for 2-3 months. They referred to a systematic review that concludes that “single vitamin D₃ doses ≥300,000 IU are most effective at improving vitamin D status ... for up to 3 months”.

Commenting on the idea, Dr. Rosen remarked that, in general, the high-dose 50,000-500,000 IU given as a one-off does not confer any greater benefit than a single dose of 1,000 IU per day, except that the blood levels go up quicker and higher.

“Really there is no evidence that getting to super-high levels of vitamin D confer a greater benefit than normal levels,” he said. “So if health care workers suspect vitamin D deficiency, daily doses of 1,000 IU seem reasonable; even if they miss doses, the blood levels are relatively stable.”

On the specific question of vitamin D needs in ethnic minorities, Dr. Rosen said while such individuals do have lower serum levels of vitamin D, the issue is whether there are meaningful clinical implications related to this.

“The real question is whether [ethnic minority individuals] have physiologically adapted for this in other ways because these low levels have been so for thousands of years. In fact, African Americans have lower vitamin D levels but they absolutely have better bones than [whites],” he pointed out. 
 

Testing and governmental recommendations during COVID-19

The U.S. National Institutes of Health in general advises 400 IU to 800 IU per day intake of vitamin D, depending on age, with those over 70 years requiring the highest daily dose. This will result in blood levels that are sufficient to maintain bone health and normal calcium metabolism in healthy people. There are no additional recommendations specific to vitamin D intake during the COVID-19 pandemic, however.

And Dr. Rosen pointed out that there is no evidence for mass screening of vitamin D levels among the U.S. population.

“U.S. public health guidance was pre-COVID, and I think high-risk individuals might want to think about their levels; for example, someone with inflammatory bowel disease or liver or pancreatic disease. These people are at higher risk anyway, and it could be because their vitamin D is low,” he said.

“Skip the test and ensure you are getting adequate levels of vitamin D whether via diet or supplement [400-800 IU per day],” he suggested. “It won’t harm.”

The U.K.’s Public Health England (PHE) clarified its advice on vitamin D supplementation during COVID-19. Alison Tedstone, PhD, chief nutritionist at PHE, said: “Many people are spending more time indoors and may not get all the vitamin D they need from sunlight. To protect their bone and muscle health, they should consider taking a daily supplement containing 10 micrograms [400 IU] of vitamin D.”

However, “there is no sufficient evidence to support recommending Vitamin D for reducing the risk of COVID-19,” she stressed.

Dr. Bajaj is on the advisory board of Medscape Diabetes & Endocrinology. He has ties with Amgen, AstraZeneca Boehringer Ingelheim, Janssen, Merck, Novo Nordisk, Sanofi, Eli Lilly,Valeant, Canadian Collaborative Research Network, CMS Knowledge Translation, Diabetes Canada Scientific Group, LMC Healthcare,mdBriefCase,Medscape, andMeducom. Dr. Kenny, Dr. Rosen, and Dr. Singhal have disclosed no relevant financial relationships.

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

Mainstream media outlets have been flooded recently with reports speculating on what role, if any, vitamin D may play in reducing the severity of COVID-19 infection.

Observational data comparing outcomes from various countries suggest inverse links between vitamin D levels and the severity of COVID-19 responses, as well as mortality, with the further suggestion of an effect of vitamin D on the immune response to infection.

But other studies question such a link, including any association between vitamin D concentration and differences in COVID-19 severity by ethnic group.

And while some researchers and clinicians believe people should get tested to see if they have adequate vitamin D levels during this pandemic – in particular frontline health care workers – most doctors say the best way to ensure that people have adequate levels of vitamin D during COVID-19 is to simply take supplements at currently recommended levels.

This is especially important given the fact that, during “lockdown” scenarios, many people are spending more time than usual indoors.

Clifford Rosen, MD, senior scientist at Maine Medical Center’s Research Institute in Scarborough, has been researching vitamin D for 25 years.

“There’s no randomized, controlled trial for sure, and that’s the gold standard,” he said in an interview, and “the observational data are so confounded, it’s difficult to know.”

Whether from diet or supplementation, having adequate vitamin D is important, especially for those at the highest risk of COVID-19, he said. Still, robust data supporting a role of vitamin D in prevention of COVID-19, or as any kind of “therapy” for the infection, are currently lacking.

Rose Anne Kenny, MD, professor of medical gerontology at Trinity College Dublin, recently coauthored an article detailing an inverse association between vitamin D levels and mortality from COVID-19 across countries in Europe.

“At no stage are any of us saying this is a given, but there’s a probability that [vitamin D] – a low-hanging fruit – is a contributory factor and we can do something about it now,” she said in an interview.

Dr. Kenny is calling for the Irish government to formally change their recommendations. “We call on the Irish government to update guidelines as a matter of urgency and encourage all adults to take [vitamin D] supplements during the COVID-19 crisis.” Northern Ireland, part of the United Kingdom, also has not yet made this recommendation, she said.

Meanwhile, Harpreet S. Bajaj, MD, MPH, a practicing endocrinologist from Mount Sinai Hospital, Toronto, said: “Vitamin D could have any of three potential roles in risk for COVID-19 and/or its severity: no role, simply a marker, or a causal factor.”

Dr. Bajaj said – as did Dr. Rosen and Dr. Kenny – that randomized, controlled trials (RCTs) are sorely needed to help ascertain whether there is a specific role of vitamin D.

“Until then, we should continue to follow established public health recommendations for vitamin D supplementation, in addition to following COVID-19 prevention guidance and evolving guidelines for COVID-19 treatment.”
 

What is the role of vitamin D fortification?

In their study in the Irish Medical Journal, Dr. Kenny and colleagues noted that, in Europe, despite being sunny, Spain and Northern Italy had high rates of vitamin D deficiency and have experienced some of the highest COVID-19 infection and mortality rates in the world.

But these countries do not formally fortify foods or recommend supplementation with vitamin D.

Conversely, the northern countries of Norway, Finland, and Sweden had higher vitamin D levels despite less UVB sunlight exposure, as a result of common supplementation and formal fortification of foods. These Nordic countries also had lower levels of COVID-19 infection and mortality.

Overall, the correlation between low vitamin D levels and mortality from COVID-19 was statistically significant (P = .046), the investigators reported.

“Optimizing vitamin D status to recommendations by national and international public health agencies will certainly have ... potential benefits for COVID-19,” they concluded.

“We’re not saying there aren’t any confounders. This can absolutely be the case, but this [finding] needs to be in the mix of evidence,” Dr. Kenny said.

Dr. Kenny also noted that countries in the Southern Hemisphere have been seeing a relatively low mortality from COVID-19, although she acknowledged the explanation could be that the virus spread later to those countries.

Dr. Rosen has doubts on this issue, too.

“Sure, vitamin D supplementation may have worked for [Nordic countries], their COVID-19 has been better controlled, but there’s no causality here; there’s another step to actually prove this. Other factors might be at play,” he said.

“Look at Brazil, it’s at the equator but the disease is devastating the country. Right now, I just don’t believe it.”

Does vitamin D have a role to play in immune modulation?

One theory currently circulating is that, if vitamin D does have any role to play in modulating response to COVID-19, this may be via a blunting of the immune system reaction to the virus.

In a recent preprint study, Ali Daneshkhah, PhD, and colleagues from Northwestern University, Chicago, interrogated hospital data from China, France, Germany, Italy, Iran, South Korea, Spain, Switzerland, the United Kingdom, and the United States.

Specifically, the risk of severe COVID-19 cases among patients with severe vitamin D deficiency was 17.3%, whereas the equivalent figure for patients with normal vitamin D levels was 14.6% (a reduction of 15.6%).

“This potential effect may be attributed to vitamin D’s ability to suppress the adaptive immune system, regulating cytokine levels and thereby reducing the risk of developing severe COVID-19,” said the researchers.

Likewise, JoAnn E. Manson, MD, chief of the division of preventive medicine at Brigham and Women’s Hospital in Boston, in a recent commentary, noted evidence from an observational study from three South Asian hospitals, in which the prevalence of vitamin D deficiency was much higher among those with severe COVID-19 illness compared with those with mild illness.

“We also know that vitamin D has an immune-modulating effect and can lower inflammation, and this may be relevant to the respiratory response during COVID-19 and the cytokine storm that’s been demonstrated,” she noted.

Dr. Rosen said he is willing to listen on the issue of a potential role of vitamin D in immune modulation.

“I’ve been a huge skeptic from the get-go, and loudly criticized the data for doing nothing. I am surprised at myself for saying there might be some effect,” he said.

“Clearly most people don’t get this [cytokine storm] but of those that do, it’s unclear why they do. Maybe if you are vitamin D sufficient, it might have some impact down the road on your response to an infection,” Dr. Rosen said. “Vitamin D may induce proteins important in modulating the function of macrophages of the immune system.”

Ethnic minorities disproportionately affected

It is also well recognized that COVID-19 disproportionately affects black and Asian minority ethnic individuals.

But on the issue of vitamin D in this context, one recent peer-reviewed study using UK Biobank data found no evidence to support a potential role for vitamin D concentration to explain susceptibility to COVID-19 infection either overall or in explaining differences between ethnic groups.

“Vitamin D is unlikely to be the underlying mechanism for the higher risk observed in black and minority ethnic individuals, and vitamin D supplements are unlikely to provide an effective intervention,” Claire Hastie, PhD, of the University of Glasgow and colleagues concluded.

But this hasn’t stopped two endocrinologists from appealing to members of the British Association of Physicians of Indian Origin (BAPIO) to get their vitamin D levels tested.

The black and Asian minority ethnic population, “especially frontline staff, should get their Vitamin D₃ levels checked and get appropriate replacement as required,” said Parag Singhal, MD, of Weston General Hospital, Weston-Super-Mare, England, and David C. Anderson, a retired endocrinologist, said in a letter to BAPIO members.

Indeed, they suggested a booster dose of 100,000 IU as a one-off for black and Asian minority ethnic health care staff that should raise vitamin D levels for 2-3 months. They referred to a systematic review that concludes that “single vitamin D₃ doses ≥300,000 IU are most effective at improving vitamin D status ... for up to 3 months”.

Commenting on the idea, Dr. Rosen remarked that, in general, the high-dose 50,000-500,000 IU given as a one-off does not confer any greater benefit than a single dose of 1,000 IU per day, except that the blood levels go up quicker and higher.

“Really there is no evidence that getting to super-high levels of vitamin D confer a greater benefit than normal levels,” he said. “So if health care workers suspect vitamin D deficiency, daily doses of 1,000 IU seem reasonable; even if they miss doses, the blood levels are relatively stable.”

On the specific question of vitamin D needs in ethnic minorities, Dr. Rosen said while such individuals do have lower serum levels of vitamin D, the issue is whether there are meaningful clinical implications related to this.

“The real question is whether [ethnic minority individuals] have physiologically adapted for this in other ways because these low levels have been so for thousands of years. In fact, African Americans have lower vitamin D levels but they absolutely have better bones than [whites],” he pointed out. 
 

Testing and governmental recommendations during COVID-19

The U.S. National Institutes of Health in general advises 400 IU to 800 IU per day intake of vitamin D, depending on age, with those over 70 years requiring the highest daily dose. This will result in blood levels that are sufficient to maintain bone health and normal calcium metabolism in healthy people. There are no additional recommendations specific to vitamin D intake during the COVID-19 pandemic, however.

And Dr. Rosen pointed out that there is no evidence for mass screening of vitamin D levels among the U.S. population.

“U.S. public health guidance was pre-COVID, and I think high-risk individuals might want to think about their levels; for example, someone with inflammatory bowel disease or liver or pancreatic disease. These people are at higher risk anyway, and it could be because their vitamin D is low,” he said.

“Skip the test and ensure you are getting adequate levels of vitamin D whether via diet or supplement [400-800 IU per day],” he suggested. “It won’t harm.”

The U.K.’s Public Health England (PHE) clarified its advice on vitamin D supplementation during COVID-19. Alison Tedstone, PhD, chief nutritionist at PHE, said: “Many people are spending more time indoors and may not get all the vitamin D they need from sunlight. To protect their bone and muscle health, they should consider taking a daily supplement containing 10 micrograms [400 IU] of vitamin D.”

However, “there is no sufficient evidence to support recommending Vitamin D for reducing the risk of COVID-19,” she stressed.

Dr. Bajaj is on the advisory board of Medscape Diabetes & Endocrinology. He has ties with Amgen, AstraZeneca Boehringer Ingelheim, Janssen, Merck, Novo Nordisk, Sanofi, Eli Lilly,Valeant, Canadian Collaborative Research Network, CMS Knowledge Translation, Diabetes Canada Scientific Group, LMC Healthcare,mdBriefCase,Medscape, andMeducom. Dr. Kenny, Dr. Rosen, and Dr. Singhal have disclosed no relevant financial relationships.

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

Mainstream media outlets have been flooded recently with reports speculating on what role, if any, vitamin D may play in reducing the severity of COVID-19 infection.

Observational data comparing outcomes from various countries suggest inverse links between vitamin D levels and the severity of COVID-19 responses, as well as mortality, with the further suggestion of an effect of vitamin D on the immune response to infection.

But other studies question such a link, including any association between vitamin D concentration and differences in COVID-19 severity by ethnic group.

And while some researchers and clinicians believe people should get tested to see if they have adequate vitamin D levels during this pandemic – in particular frontline health care workers – most doctors say the best way to ensure that people have adequate levels of vitamin D during COVID-19 is to simply take supplements at currently recommended levels.

This is especially important given the fact that, during “lockdown” scenarios, many people are spending more time than usual indoors.

Clifford Rosen, MD, senior scientist at Maine Medical Center’s Research Institute in Scarborough, has been researching vitamin D for 25 years.

“There’s no randomized, controlled trial for sure, and that’s the gold standard,” he said in an interview, and “the observational data are so confounded, it’s difficult to know.”

Whether from diet or supplementation, having adequate vitamin D is important, especially for those at the highest risk of COVID-19, he said. Still, robust data supporting a role of vitamin D in prevention of COVID-19, or as any kind of “therapy” for the infection, are currently lacking.

Rose Anne Kenny, MD, professor of medical gerontology at Trinity College Dublin, recently coauthored an article detailing an inverse association between vitamin D levels and mortality from COVID-19 across countries in Europe.

“At no stage are any of us saying this is a given, but there’s a probability that [vitamin D] – a low-hanging fruit – is a contributory factor and we can do something about it now,” she said in an interview.

Dr. Kenny is calling for the Irish government to formally change their recommendations. “We call on the Irish government to update guidelines as a matter of urgency and encourage all adults to take [vitamin D] supplements during the COVID-19 crisis.” Northern Ireland, part of the United Kingdom, also has not yet made this recommendation, she said.

Meanwhile, Harpreet S. Bajaj, MD, MPH, a practicing endocrinologist from Mount Sinai Hospital, Toronto, said: “Vitamin D could have any of three potential roles in risk for COVID-19 and/or its severity: no role, simply a marker, or a causal factor.”

Dr. Bajaj said – as did Dr. Rosen and Dr. Kenny – that randomized, controlled trials (RCTs) are sorely needed to help ascertain whether there is a specific role of vitamin D.

“Until then, we should continue to follow established public health recommendations for vitamin D supplementation, in addition to following COVID-19 prevention guidance and evolving guidelines for COVID-19 treatment.”
 

What is the role of vitamin D fortification?

In their study in the Irish Medical Journal, Dr. Kenny and colleagues noted that, in Europe, despite being sunny, Spain and Northern Italy had high rates of vitamin D deficiency and have experienced some of the highest COVID-19 infection and mortality rates in the world.

But these countries do not formally fortify foods or recommend supplementation with vitamin D.

Conversely, the northern countries of Norway, Finland, and Sweden had higher vitamin D levels despite less UVB sunlight exposure, as a result of common supplementation and formal fortification of foods. These Nordic countries also had lower levels of COVID-19 infection and mortality.

Overall, the correlation between low vitamin D levels and mortality from COVID-19 was statistically significant (P = .046), the investigators reported.

“Optimizing vitamin D status to recommendations by national and international public health agencies will certainly have ... potential benefits for COVID-19,” they concluded.

“We’re not saying there aren’t any confounders. This can absolutely be the case, but this [finding] needs to be in the mix of evidence,” Dr. Kenny said.

Dr. Kenny also noted that countries in the Southern Hemisphere have been seeing a relatively low mortality from COVID-19, although she acknowledged the explanation could be that the virus spread later to those countries.

Dr. Rosen has doubts on this issue, too.

“Sure, vitamin D supplementation may have worked for [Nordic countries], their COVID-19 has been better controlled, but there’s no causality here; there’s another step to actually prove this. Other factors might be at play,” he said.

“Look at Brazil, it’s at the equator but the disease is devastating the country. Right now, I just don’t believe it.”

Does vitamin D have a role to play in immune modulation?

One theory currently circulating is that, if vitamin D does have any role to play in modulating response to COVID-19, this may be via a blunting of the immune system reaction to the virus.

In a recent preprint study, Ali Daneshkhah, PhD, and colleagues from Northwestern University, Chicago, interrogated hospital data from China, France, Germany, Italy, Iran, South Korea, Spain, Switzerland, the United Kingdom, and the United States.

Specifically, the risk of severe COVID-19 cases among patients with severe vitamin D deficiency was 17.3%, whereas the equivalent figure for patients with normal vitamin D levels was 14.6% (a reduction of 15.6%).

“This potential effect may be attributed to vitamin D’s ability to suppress the adaptive immune system, regulating cytokine levels and thereby reducing the risk of developing severe COVID-19,” said the researchers.

Likewise, JoAnn E. Manson, MD, chief of the division of preventive medicine at Brigham and Women’s Hospital in Boston, in a recent commentary, noted evidence from an observational study from three South Asian hospitals, in which the prevalence of vitamin D deficiency was much higher among those with severe COVID-19 illness compared with those with mild illness.

“We also know that vitamin D has an immune-modulating effect and can lower inflammation, and this may be relevant to the respiratory response during COVID-19 and the cytokine storm that’s been demonstrated,” she noted.

Dr. Rosen said he is willing to listen on the issue of a potential role of vitamin D in immune modulation.

“I’ve been a huge skeptic from the get-go, and loudly criticized the data for doing nothing. I am surprised at myself for saying there might be some effect,” he said.

“Clearly most people don’t get this [cytokine storm] but of those that do, it’s unclear why they do. Maybe if you are vitamin D sufficient, it might have some impact down the road on your response to an infection,” Dr. Rosen said. “Vitamin D may induce proteins important in modulating the function of macrophages of the immune system.”

Ethnic minorities disproportionately affected

It is also well recognized that COVID-19 disproportionately affects black and Asian minority ethnic individuals.

But on the issue of vitamin D in this context, one recent peer-reviewed study using UK Biobank data found no evidence to support a potential role for vitamin D concentration to explain susceptibility to COVID-19 infection either overall or in explaining differences between ethnic groups.

“Vitamin D is unlikely to be the underlying mechanism for the higher risk observed in black and minority ethnic individuals, and vitamin D supplements are unlikely to provide an effective intervention,” Claire Hastie, PhD, of the University of Glasgow and colleagues concluded.

But this hasn’t stopped two endocrinologists from appealing to members of the British Association of Physicians of Indian Origin (BAPIO) to get their vitamin D levels tested.

The black and Asian minority ethnic population, “especially frontline staff, should get their Vitamin D₃ levels checked and get appropriate replacement as required,” said Parag Singhal, MD, of Weston General Hospital, Weston-Super-Mare, England, and David C. Anderson, a retired endocrinologist, said in a letter to BAPIO members.

Indeed, they suggested a booster dose of 100,000 IU as a one-off for black and Asian minority ethnic health care staff that should raise vitamin D levels for 2-3 months. They referred to a systematic review that concludes that “single vitamin D₃ doses ≥300,000 IU are most effective at improving vitamin D status ... for up to 3 months”.

Commenting on the idea, Dr. Rosen remarked that, in general, the high-dose 50,000-500,000 IU given as a one-off does not confer any greater benefit than a single dose of 1,000 IU per day, except that the blood levels go up quicker and higher.

“Really there is no evidence that getting to super-high levels of vitamin D confer a greater benefit than normal levels,” he said. “So if health care workers suspect vitamin D deficiency, daily doses of 1,000 IU seem reasonable; even if they miss doses, the blood levels are relatively stable.”

On the specific question of vitamin D needs in ethnic minorities, Dr. Rosen said while such individuals do have lower serum levels of vitamin D, the issue is whether there are meaningful clinical implications related to this.

“The real question is whether [ethnic minority individuals] have physiologically adapted for this in other ways because these low levels have been so for thousands of years. In fact, African Americans have lower vitamin D levels but they absolutely have better bones than [whites],” he pointed out. 
 

Testing and governmental recommendations during COVID-19

The U.S. National Institutes of Health in general advises 400 IU to 800 IU per day intake of vitamin D, depending on age, with those over 70 years requiring the highest daily dose. This will result in blood levels that are sufficient to maintain bone health and normal calcium metabolism in healthy people. There are no additional recommendations specific to vitamin D intake during the COVID-19 pandemic, however.

And Dr. Rosen pointed out that there is no evidence for mass screening of vitamin D levels among the U.S. population.

“U.S. public health guidance was pre-COVID, and I think high-risk individuals might want to think about their levels; for example, someone with inflammatory bowel disease or liver or pancreatic disease. These people are at higher risk anyway, and it could be because their vitamin D is low,” he said.

“Skip the test and ensure you are getting adequate levels of vitamin D whether via diet or supplement [400-800 IU per day],” he suggested. “It won’t harm.”

The U.K.’s Public Health England (PHE) clarified its advice on vitamin D supplementation during COVID-19. Alison Tedstone, PhD, chief nutritionist at PHE, said: “Many people are spending more time indoors and may not get all the vitamin D they need from sunlight. To protect their bone and muscle health, they should consider taking a daily supplement containing 10 micrograms [400 IU] of vitamin D.”

However, “there is no sufficient evidence to support recommending Vitamin D for reducing the risk of COVID-19,” she stressed.

Dr. Bajaj is on the advisory board of Medscape Diabetes & Endocrinology. He has ties with Amgen, AstraZeneca Boehringer Ingelheim, Janssen, Merck, Novo Nordisk, Sanofi, Eli Lilly,Valeant, Canadian Collaborative Research Network, CMS Knowledge Translation, Diabetes Canada Scientific Group, LMC Healthcare,mdBriefCase,Medscape, andMeducom. Dr. Kenny, Dr. Rosen, and Dr. Singhal have disclosed no relevant financial relationships.

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

Patients on a tumor necrosis factor inhibitor for their rheumatic disease when they became infected with COVID-19 were markedly less likely to subsequently require hospitalization, according to intriguing early evidence from the COVID-19 Global Rheumatology Alliance Registry.

On the other hand, those registry patients who were on 10 mg of prednisone or more daily when they got infected were more than twice as likely to be hospitalized than were those who were not on corticosteroids, even after controlling for the severity of their rheumatic disease and other potential confounders, Jinoos Yazdany, MD, reported at the virtual edition of the American College of Rheumatology’s 2020 State-of-the-Art Clinical Symposium.

“We saw a signal with moderate to high-dose steroids. I think it’s something we’re going to have to keep an eye out on as more data come in,” said Dr. Yazdany, professor of medicine at the University of California, San Francisco, and chief of rheumatology at San Francisco General Hospital.

The global registry launched on March 24, 2020, and was quickly embraced by rheumatologists from around the world. By May 12, the registry included more than 1,300 patients with a range of rheumatic diseases, all with confirmed COVID-19 infection as a requisite for enrollment; the cases were submitted by more than 300 rheumatologists in 40 countries. The registry is supported by the ACR and European League Against Rheumatism.

Dr. Yazdany, a member of the registry steering committee, described the project’s two main goals: To learn the outcomes of COVID-19–infected patients with various rheumatic diseases and to make inferences regarding the impact of the immunosuppressive and antimalarial medications widely prescribed by rheumatologists.

She presented soon-to-be-published data on the characteristics and disposition of the first 600 patients, 46% of whom were hospitalized and 9% died. A caveat regarding the registry, she noted, is that these are observational data and thus potentially subject to unrecognized confounders. Also, the registry population is skewed toward the sicker end of the COVID-19 disease spectrum because while all participants have confirmed infection, testing for the infection has been notoriously uneven. Many people are infected asymptomatically and thus may not undergo testing even where readily available.
 

Early key findings from registry

The risk factors for more severe infection resulting in hospitalization in patients with rheumatic diseases are by and large the same drivers described in the general population: older age and comorbid conditions including diabetes, hypertension, cardiovascular disease, obesity, chronic kidney disease, and lung disease. Notably, however, patients on the equivalent of 10 mg/day of prednisone or more were at a 105% increased risk for hospitalization, compared with those not on corticosteroids after adjustment for age, comorbid conditions, and rheumatic disease severity.

Patients on a background tumor necrosis factor (TNF) inhibitor had an adjusted 60% reduction in risk of hospitalization. This apparent protective effect against more severe COVID-19 disease is mechanistically plausible: In animal studies, being on a TNF inhibitor has been associated with less severe infection following exposure to influenza virus, Dr. Yazdany observed.

COVID-infected patients on any biologic disease-modifying antirheumatic drug had a 54% decreased risk of hospitalization. However, in this early analysis, the study was sufficiently powered only to specifically assess the impact of TNF inhibitors, since those agents were by far the most commonly used biologics. As the registry grows, it will be possible to analyze the impact of other antirheumatic medications.

Being on hydroxychloroquine or other antimalarials at the time of COVID-19 infection had no impact on hospitalization.

The only rheumatic disease diagnosis with an odds of hospitalization significantly different from that of RA patients was systemic lupus erythematosus (SLE). Lupus patients were at 80% increased risk of hospitalization. Although this was a statistically significant difference, Dr. Yazdany cautioned against making too much of it because of the strong potential for unmeasured confounding. In particular, lupus patients as a group are known to rate on the lower end of measures of social determinants of health, a status that is an established major risk factor for COVID-19 disease.

“A strength of the global registry has been that it provides timely data that’s been very helpful for rheumatologists to rapidly dispel misinformation that has been spread about hydroxychloroquine, especially statements about lupus patients not getting COVID-19. We know from these data that’s not true,” she said.

Being on background NSAIDs at the time of SARS-CoV-2 infection was not associated with increased risk of hospitalization; in fact, NSAID users were 36% less likely to be hospitalized for their COVID-19 disease, although this difference didn’t reach statistical significance.

Dr. Yazdany urged her fellow rheumatologists to enter their cases on the registry website: rheum-covid.org. There they can also join the registry mailing list and receive weekly updates.
 

Other recent insights on COVID-19 in rheumatology

An as-yet unpublished U.K. observational study involving electronic health record data on 17 million people included 885,000 individuals with RA, SLE, or psoriasis. After extensive statistical controlling for the known risk factors for severe COVID-19 infection, including a measure of socioeconomic deprivation, the group with one of these autoimmune diseases had an adjusted, statistically significant 23% increased risk of hospital death because of COVID-19 infection.

“This is the largest study of its kind to date. There’s potential for unmeasured confounding and selection bias here due to who gets tested. We’ll have to see where this study lands, but I think it does suggest there’s a slightly higher mortality risk in COVID-infected patients with rheumatic disease,” according to Dr. Yazdany.

On the other hand, there have been at least eight recently published patient surveys and case series of patients with rheumatic diseases in areas of the world hardest hit by the pandemic, and they paint a consistent picture.

“What we’ve learned from these studies was the infection rate was generally in the ballpark of people in the region. It doesn’t seem like there’s a dramatically higher infection rate in people with rheumatic disease in these surveys. The hospitalized rheumatology patients had many of the familiar comorbidities. This is the first glance at how likely people are to become infected and how they fared, and I think overall the data have been quite reassuring,” she said.

Dr. Yazdany reported serving as a consultant to AstraZeneca and Eli Lilly and receiving research funding from the National Institutes of Health, the Agency for Healthcare Research and Quality, and the Centers for Disease Control and Prevention.

[email protected]

Patients on a tumor necrosis factor inhibitor for their rheumatic disease when they became infected with COVID-19 were markedly less likely to subsequently require hospitalization, according to intriguing early evidence from the COVID-19 Global Rheumatology Alliance Registry.

On the other hand, those registry patients who were on 10 mg of prednisone or more daily when they got infected were more than twice as likely to be hospitalized than were those who were not on corticosteroids, even after controlling for the severity of their rheumatic disease and other potential confounders, Jinoos Yazdany, MD, reported at the virtual edition of the American College of Rheumatology’s 2020 State-of-the-Art Clinical Symposium.

“We saw a signal with moderate to high-dose steroids. I think it’s something we’re going to have to keep an eye out on as more data come in,” said Dr. Yazdany, professor of medicine at the University of California, San Francisco, and chief of rheumatology at San Francisco General Hospital.

The global registry launched on March 24, 2020, and was quickly embraced by rheumatologists from around the world. By May 12, the registry included more than 1,300 patients with a range of rheumatic diseases, all with confirmed COVID-19 infection as a requisite for enrollment; the cases were submitted by more than 300 rheumatologists in 40 countries. The registry is supported by the ACR and European League Against Rheumatism.

Dr. Yazdany, a member of the registry steering committee, described the project’s two main goals: To learn the outcomes of COVID-19–infected patients with various rheumatic diseases and to make inferences regarding the impact of the immunosuppressive and antimalarial medications widely prescribed by rheumatologists.

She presented soon-to-be-published data on the characteristics and disposition of the first 600 patients, 46% of whom were hospitalized and 9% died. A caveat regarding the registry, she noted, is that these are observational data and thus potentially subject to unrecognized confounders. Also, the registry population is skewed toward the sicker end of the COVID-19 disease spectrum because while all participants have confirmed infection, testing for the infection has been notoriously uneven. Many people are infected asymptomatically and thus may not undergo testing even where readily available.
 

Early key findings from registry

The risk factors for more severe infection resulting in hospitalization in patients with rheumatic diseases are by and large the same drivers described in the general population: older age and comorbid conditions including diabetes, hypertension, cardiovascular disease, obesity, chronic kidney disease, and lung disease. Notably, however, patients on the equivalent of 10 mg/day of prednisone or more were at a 105% increased risk for hospitalization, compared with those not on corticosteroids after adjustment for age, comorbid conditions, and rheumatic disease severity.

Patients on a background tumor necrosis factor (TNF) inhibitor had an adjusted 60% reduction in risk of hospitalization. This apparent protective effect against more severe COVID-19 disease is mechanistically plausible: In animal studies, being on a TNF inhibitor has been associated with less severe infection following exposure to influenza virus, Dr. Yazdany observed.

COVID-infected patients on any biologic disease-modifying antirheumatic drug had a 54% decreased risk of hospitalization. However, in this early analysis, the study was sufficiently powered only to specifically assess the impact of TNF inhibitors, since those agents were by far the most commonly used biologics. As the registry grows, it will be possible to analyze the impact of other antirheumatic medications.

Being on hydroxychloroquine or other antimalarials at the time of COVID-19 infection had no impact on hospitalization.

The only rheumatic disease diagnosis with an odds of hospitalization significantly different from that of RA patients was systemic lupus erythematosus (SLE). Lupus patients were at 80% increased risk of hospitalization. Although this was a statistically significant difference, Dr. Yazdany cautioned against making too much of it because of the strong potential for unmeasured confounding. In particular, lupus patients as a group are known to rate on the lower end of measures of social determinants of health, a status that is an established major risk factor for COVID-19 disease.

“A strength of the global registry has been that it provides timely data that’s been very helpful for rheumatologists to rapidly dispel misinformation that has been spread about hydroxychloroquine, especially statements about lupus patients not getting COVID-19. We know from these data that’s not true,” she said.

Being on background NSAIDs at the time of SARS-CoV-2 infection was not associated with increased risk of hospitalization; in fact, NSAID users were 36% less likely to be hospitalized for their COVID-19 disease, although this difference didn’t reach statistical significance.

Dr. Yazdany urged her fellow rheumatologists to enter their cases on the registry website: rheum-covid.org. There they can also join the registry mailing list and receive weekly updates.
 

Other recent insights on COVID-19 in rheumatology

An as-yet unpublished U.K. observational study involving electronic health record data on 17 million people included 885,000 individuals with RA, SLE, or psoriasis. After extensive statistical controlling for the known risk factors for severe COVID-19 infection, including a measure of socioeconomic deprivation, the group with one of these autoimmune diseases had an adjusted, statistically significant 23% increased risk of hospital death because of COVID-19 infection.

“This is the largest study of its kind to date. There’s potential for unmeasured confounding and selection bias here due to who gets tested. We’ll have to see where this study lands, but I think it does suggest there’s a slightly higher mortality risk in COVID-infected patients with rheumatic disease,” according to Dr. Yazdany.

On the other hand, there have been at least eight recently published patient surveys and case series of patients with rheumatic diseases in areas of the world hardest hit by the pandemic, and they paint a consistent picture.

“What we’ve learned from these studies was the infection rate was generally in the ballpark of people in the region. It doesn’t seem like there’s a dramatically higher infection rate in people with rheumatic disease in these surveys. The hospitalized rheumatology patients had many of the familiar comorbidities. This is the first glance at how likely people are to become infected and how they fared, and I think overall the data have been quite reassuring,” she said.

Dr. Yazdany reported serving as a consultant to AstraZeneca and Eli Lilly and receiving research funding from the National Institutes of Health, the Agency for Healthcare Research and Quality, and the Centers for Disease Control and Prevention.

[email protected]

Patients on a tumor necrosis factor inhibitor for their rheumatic disease when they became infected with COVID-19 were markedly less likely to subsequently require hospitalization, according to intriguing early evidence from the COVID-19 Global Rheumatology Alliance Registry.

On the other hand, those registry patients who were on 10 mg of prednisone or more daily when they got infected were more than twice as likely to be hospitalized than were those who were not on corticosteroids, even after controlling for the severity of their rheumatic disease and other potential confounders, Jinoos Yazdany, MD, reported at the virtual edition of the American College of Rheumatology’s 2020 State-of-the-Art Clinical Symposium.

“We saw a signal with moderate to high-dose steroids. I think it’s something we’re going to have to keep an eye out on as more data come in,” said Dr. Yazdany, professor of medicine at the University of California, San Francisco, and chief of rheumatology at San Francisco General Hospital.

The global registry launched on March 24, 2020, and was quickly embraced by rheumatologists from around the world. By May 12, the registry included more than 1,300 patients with a range of rheumatic diseases, all with confirmed COVID-19 infection as a requisite for enrollment; the cases were submitted by more than 300 rheumatologists in 40 countries. The registry is supported by the ACR and European League Against Rheumatism.

Dr. Yazdany, a member of the registry steering committee, described the project’s two main goals: To learn the outcomes of COVID-19–infected patients with various rheumatic diseases and to make inferences regarding the impact of the immunosuppressive and antimalarial medications widely prescribed by rheumatologists.

She presented soon-to-be-published data on the characteristics and disposition of the first 600 patients, 46% of whom were hospitalized and 9% died. A caveat regarding the registry, she noted, is that these are observational data and thus potentially subject to unrecognized confounders. Also, the registry population is skewed toward the sicker end of the COVID-19 disease spectrum because while all participants have confirmed infection, testing for the infection has been notoriously uneven. Many people are infected asymptomatically and thus may not undergo testing even where readily available.
 

Early key findings from registry

The risk factors for more severe infection resulting in hospitalization in patients with rheumatic diseases are by and large the same drivers described in the general population: older age and comorbid conditions including diabetes, hypertension, cardiovascular disease, obesity, chronic kidney disease, and lung disease. Notably, however, patients on the equivalent of 10 mg/day of prednisone or more were at a 105% increased risk for hospitalization, compared with those not on corticosteroids after adjustment for age, comorbid conditions, and rheumatic disease severity.

Patients on a background tumor necrosis factor (TNF) inhibitor had an adjusted 60% reduction in risk of hospitalization. This apparent protective effect against more severe COVID-19 disease is mechanistically plausible: In animal studies, being on a TNF inhibitor has been associated with less severe infection following exposure to influenza virus, Dr. Yazdany observed.

COVID-infected patients on any biologic disease-modifying antirheumatic drug had a 54% decreased risk of hospitalization. However, in this early analysis, the study was sufficiently powered only to specifically assess the impact of TNF inhibitors, since those agents were by far the most commonly used biologics. As the registry grows, it will be possible to analyze the impact of other antirheumatic medications.

Being on hydroxychloroquine or other antimalarials at the time of COVID-19 infection had no impact on hospitalization.

The only rheumatic disease diagnosis with an odds of hospitalization significantly different from that of RA patients was systemic lupus erythematosus (SLE). Lupus patients were at 80% increased risk of hospitalization. Although this was a statistically significant difference, Dr. Yazdany cautioned against making too much of it because of the strong potential for unmeasured confounding. In particular, lupus patients as a group are known to rate on the lower end of measures of social determinants of health, a status that is an established major risk factor for COVID-19 disease.

“A strength of the global registry has been that it provides timely data that’s been very helpful for rheumatologists to rapidly dispel misinformation that has been spread about hydroxychloroquine, especially statements about lupus patients not getting COVID-19. We know from these data that’s not true,” she said.

Being on background NSAIDs at the time of SARS-CoV-2 infection was not associated with increased risk of hospitalization; in fact, NSAID users were 36% less likely to be hospitalized for their COVID-19 disease, although this difference didn’t reach statistical significance.

Dr. Yazdany urged her fellow rheumatologists to enter their cases on the registry website: rheum-covid.org. There they can also join the registry mailing list and receive weekly updates.
 

Other recent insights on COVID-19 in rheumatology

An as-yet unpublished U.K. observational study involving electronic health record data on 17 million people included 885,000 individuals with RA, SLE, or psoriasis. After extensive statistical controlling for the known risk factors for severe COVID-19 infection, including a measure of socioeconomic deprivation, the group with one of these autoimmune diseases had an adjusted, statistically significant 23% increased risk of hospital death because of COVID-19 infection.

“This is the largest study of its kind to date. There’s potential for unmeasured confounding and selection bias here due to who gets tested. We’ll have to see where this study lands, but I think it does suggest there’s a slightly higher mortality risk in COVID-infected patients with rheumatic disease,” according to Dr. Yazdany.

On the other hand, there have been at least eight recently published patient surveys and case series of patients with rheumatic diseases in areas of the world hardest hit by the pandemic, and they paint a consistent picture.

“What we’ve learned from these studies was the infection rate was generally in the ballpark of people in the region. It doesn’t seem like there’s a dramatically higher infection rate in people with rheumatic disease in these surveys. The hospitalized rheumatology patients had many of the familiar comorbidities. This is the first glance at how likely people are to become infected and how they fared, and I think overall the data have been quite reassuring,” she said.

Dr. Yazdany reported serving as a consultant to AstraZeneca and Eli Lilly and receiving research funding from the National Institutes of Health, the Agency for Healthcare Research and Quality, and the Centers for Disease Control and Prevention.

[email protected]

The number of COVID-19 infections in the community may be “substantially greater” than totals confirmed by authorities, based on SARS-CoV-2 antibody testing among a random sample of adults in Los Angeles County, Calif.

Testing of 863 people on April 10-11 revealed that 35 (4.06%) were positive for SARS-CoV-2–specific antibodies (IgM or IgG), and after adjustment for test sensitivity and specificity, the weighted prevalence for the entire sample was 4.65%, Neeraj Sood, PhD, of the University of Southern California, Los Angeles, and associates wrote in JAMA.

The estimate of 4.65% “implies that approximately 367,000 adults [in Los Angeles County] had SARS-CoV-2 antibodies, which is substantially greater than the 8,430 cumulative number of confirmed infections in the county on April 10,” they wrote.

It also suggests that fatality rates based on the larger number of infections may be lower than rates based on confirmed cases. “In addition, contact tracing methods to limit the spread of infection will face considerable challenges,” Dr. Sood and associates said.

Test positivity varied by race/ethnicity, sex, and income. The proportion of non-Hispanic blacks with a positive result was 6.94%, compared with 4.42% for non-Hispanic whites, 2.10% for Hispanics, and 3.85% for others. Men were much more likely than women to be positive for SARS-CoV-2: 5.18% vs. 3.31%, the investigators said.

Household income favored the middle ground. Those individuals making less than $50,000 a year had a positivity rate of 5.14% and those with an income of $100,000 or more had a rate of 4.90%, but only 1.58% of those making $50,000-$99,999 tested positive, they reported.

The authors reported numerous sources of nonprofit organization support.

[email protected]

SOURCE: Sood N et al. JAMA 2020 May 18. doi: 10.1001/jama.2020.8279.

The number of COVID-19 infections in the community may be “substantially greater” than totals confirmed by authorities, based on SARS-CoV-2 antibody testing among a random sample of adults in Los Angeles County, Calif.

Testing of 863 people on April 10-11 revealed that 35 (4.06%) were positive for SARS-CoV-2–specific antibodies (IgM or IgG), and after adjustment for test sensitivity and specificity, the weighted prevalence for the entire sample was 4.65%, Neeraj Sood, PhD, of the University of Southern California, Los Angeles, and associates wrote in JAMA.

The estimate of 4.65% “implies that approximately 367,000 adults [in Los Angeles County] had SARS-CoV-2 antibodies, which is substantially greater than the 8,430 cumulative number of confirmed infections in the county on April 10,” they wrote.

It also suggests that fatality rates based on the larger number of infections may be lower than rates based on confirmed cases. “In addition, contact tracing methods to limit the spread of infection will face considerable challenges,” Dr. Sood and associates said.

Test positivity varied by race/ethnicity, sex, and income. The proportion of non-Hispanic blacks with a positive result was 6.94%, compared with 4.42% for non-Hispanic whites, 2.10% for Hispanics, and 3.85% for others. Men were much more likely than women to be positive for SARS-CoV-2: 5.18% vs. 3.31%, the investigators said.

Household income favored the middle ground. Those individuals making less than $50,000 a year had a positivity rate of 5.14% and those with an income of $100,000 or more had a rate of 4.90%, but only 1.58% of those making $50,000-$99,999 tested positive, they reported.

The authors reported numerous sources of nonprofit organization support.

[email protected]

SOURCE: Sood N et al. JAMA 2020 May 18. doi: 10.1001/jama.2020.8279.

The number of COVID-19 infections in the community may be “substantially greater” than totals confirmed by authorities, based on SARS-CoV-2 antibody testing among a random sample of adults in Los Angeles County, Calif.

Testing of 863 people on April 10-11 revealed that 35 (4.06%) were positive for SARS-CoV-2–specific antibodies (IgM or IgG), and after adjustment for test sensitivity and specificity, the weighted prevalence for the entire sample was 4.65%, Neeraj Sood, PhD, of the University of Southern California, Los Angeles, and associates wrote in JAMA.

The estimate of 4.65% “implies that approximately 367,000 adults [in Los Angeles County] had SARS-CoV-2 antibodies, which is substantially greater than the 8,430 cumulative number of confirmed infections in the county on April 10,” they wrote.

It also suggests that fatality rates based on the larger number of infections may be lower than rates based on confirmed cases. “In addition, contact tracing methods to limit the spread of infection will face considerable challenges,” Dr. Sood and associates said.

Test positivity varied by race/ethnicity, sex, and income. The proportion of non-Hispanic blacks with a positive result was 6.94%, compared with 4.42% for non-Hispanic whites, 2.10% for Hispanics, and 3.85% for others. Men were much more likely than women to be positive for SARS-CoV-2: 5.18% vs. 3.31%, the investigators said.

Household income favored the middle ground. Those individuals making less than $50,000 a year had a positivity rate of 5.14% and those with an income of $100,000 or more had a rate of 4.90%, but only 1.58% of those making $50,000-$99,999 tested positive, they reported.

The authors reported numerous sources of nonprofit organization support.

[email protected]

SOURCE: Sood N et al. JAMA 2020 May 18. doi: 10.1001/jama.2020.8279.

A meta-analysis of relevant clinical trials has found that lowering blood pressure with antihypertensive agents was statistically significantly associated with reducing the risk of dementia or cognitive impairment, though the risk reduction was modest.

“Although observational studies report hypertension to be an important risk factor for dementia, the benefit of blood pressure lowering on dementia or cognitive impairment in clinical trials is modest and lower than the risk reduction for stroke,” wrote Diarmaid Hughes, MB, of the NUI Galway and Saolta University Hospital Group in Galway, Ireland, and coauthors. They added, however, that “these findings have the potential to inform public health strategies to reduce the burden of dementia globally.” The study was published online ahead of print May 19 in JAMA.
 

A rich data set

To assess the relationship between lowering blood pressure and cognitive issues, the researchers performed a systemic search of randomized, clinical trials that compared blood pressure lowering via antihypertensive agents with a control, had at least 1 year of follow-up, included more than 1,000 participants, and reported on either dementia, cognitive impairment, cognitive decline, or a change in cognitive test scores as outcomes. Of the 14 studies deemed eligible, 12 reported either the incidence of dementia (n = 9) or a composite of dementia or cognitive impairment (n = 3) at follow-up and thus were included in the primary meta-analysis. The other two studies were used for secondary outcomes only.

The studies included 96,158 participants in total – 42.2% were women – and their mean age was 69 years. At baseline, participants’ mean systolic blood pressure was 154 mm Hg and their mean diastolic blood pressure was 83.3 mm Hg. The mean duration of follow-up was 49.24 months.

In the 12 trials that reported dementia or cognitive impairment, blood pressure lowering via antihypertensive agents, compared with control, was significantly associated with a reduction in those two outcomes (7.0% vs. 7.5% over a mean trial follow-up of 4.1 years; odds ratio, 0.93; 95% confidence interval, 0.88-0.98; absolute risk reduction, 0.39%; 95% CI, 0.09%-0.68%). Blood pressure lowering, compared with control, was also significantly associated with a reduction in cognitive decline (20.2% vs. 21.1% over a mean trial follow-up of 4.1 years; OR, 0.93; 95% CI, 0.88-0.99; ARR, 0.71%; 95% CI, 0.19%-1.2%) in the eight trials that reported it as an outcome. An analysis of the eight trials that reported a change in cognitive scores did not find a significant association between that outcome and blood pressure lowering.
 

Subpopulations should be examined

“This is a very broad brush stroke study, albeit a definitive one,” Richard J. Caselli, MD, of the Mayo Clinic in Phoenix said in an interview. “With all the thousands of people in this meta-analysis, there are going to be subpopulations of patients with certain characteristics or common conditions in which blood pressure lowering might have a bigger or a lesser impact on their risk factor. Is there a difference between certain racial groups? Does it matter what antihypertensive strategies are used? You can look at the interactions between blood pressure lowering and other conditions: diabetes, head injuries, air pollution, certain genetic risk factors. There are a number of additional findings that could come from a very rich data set like this.”

The authors acknowledged their study’s limitations, including the challenges of performing a meta-analysis of studies that drew from different populations and had potentially different definitions of dementia, cognitive impairment, and cognitive decline outcomes. In addition, the low incidence of dementia across clinical trials limited the researchers, and its underdetection in trials and the potential of survivor bias for healthier participants with blood pressure reductions were noted as “unmeasured sources of potential error.”

Three authors reported receiving grants or personal fees from the Wellcome Trust and the Health Research Board, the Chief Scientist Office, and Bayer AG, respectively.

SOURCE: Hughes D et al. JAMA. 2020 May 19. doi: 10.1001/jama.2020.4249.

A meta-analysis of relevant clinical trials has found that lowering blood pressure with antihypertensive agents was statistically significantly associated with reducing the risk of dementia or cognitive impairment, though the risk reduction was modest.

“Although observational studies report hypertension to be an important risk factor for dementia, the benefit of blood pressure lowering on dementia or cognitive impairment in clinical trials is modest and lower than the risk reduction for stroke,” wrote Diarmaid Hughes, MB, of the NUI Galway and Saolta University Hospital Group in Galway, Ireland, and coauthors. They added, however, that “these findings have the potential to inform public health strategies to reduce the burden of dementia globally.” The study was published online ahead of print May 19 in JAMA.
 

A rich data set

To assess the relationship between lowering blood pressure and cognitive issues, the researchers performed a systemic search of randomized, clinical trials that compared blood pressure lowering via antihypertensive agents with a control, had at least 1 year of follow-up, included more than 1,000 participants, and reported on either dementia, cognitive impairment, cognitive decline, or a change in cognitive test scores as outcomes. Of the 14 studies deemed eligible, 12 reported either the incidence of dementia (n = 9) or a composite of dementia or cognitive impairment (n = 3) at follow-up and thus were included in the primary meta-analysis. The other two studies were used for secondary outcomes only.

The studies included 96,158 participants in total – 42.2% were women – and their mean age was 69 years. At baseline, participants’ mean systolic blood pressure was 154 mm Hg and their mean diastolic blood pressure was 83.3 mm Hg. The mean duration of follow-up was 49.24 months.

In the 12 trials that reported dementia or cognitive impairment, blood pressure lowering via antihypertensive agents, compared with control, was significantly associated with a reduction in those two outcomes (7.0% vs. 7.5% over a mean trial follow-up of 4.1 years; odds ratio, 0.93; 95% confidence interval, 0.88-0.98; absolute risk reduction, 0.39%; 95% CI, 0.09%-0.68%). Blood pressure lowering, compared with control, was also significantly associated with a reduction in cognitive decline (20.2% vs. 21.1% over a mean trial follow-up of 4.1 years; OR, 0.93; 95% CI, 0.88-0.99; ARR, 0.71%; 95% CI, 0.19%-1.2%) in the eight trials that reported it as an outcome. An analysis of the eight trials that reported a change in cognitive scores did not find a significant association between that outcome and blood pressure lowering.
 

Subpopulations should be examined

“This is a very broad brush stroke study, albeit a definitive one,” Richard J. Caselli, MD, of the Mayo Clinic in Phoenix said in an interview. “With all the thousands of people in this meta-analysis, there are going to be subpopulations of patients with certain characteristics or common conditions in which blood pressure lowering might have a bigger or a lesser impact on their risk factor. Is there a difference between certain racial groups? Does it matter what antihypertensive strategies are used? You can look at the interactions between blood pressure lowering and other conditions: diabetes, head injuries, air pollution, certain genetic risk factors. There are a number of additional findings that could come from a very rich data set like this.”

The authors acknowledged their study’s limitations, including the challenges of performing a meta-analysis of studies that drew from different populations and had potentially different definitions of dementia, cognitive impairment, and cognitive decline outcomes. In addition, the low incidence of dementia across clinical trials limited the researchers, and its underdetection in trials and the potential of survivor bias for healthier participants with blood pressure reductions were noted as “unmeasured sources of potential error.”

Three authors reported receiving grants or personal fees from the Wellcome Trust and the Health Research Board, the Chief Scientist Office, and Bayer AG, respectively.

SOURCE: Hughes D et al. JAMA. 2020 May 19. doi: 10.1001/jama.2020.4249.

A meta-analysis of relevant clinical trials has found that lowering blood pressure with antihypertensive agents was statistically significantly associated with reducing the risk of dementia or cognitive impairment, though the risk reduction was modest.

“Although observational studies report hypertension to be an important risk factor for dementia, the benefit of blood pressure lowering on dementia or cognitive impairment in clinical trials is modest and lower than the risk reduction for stroke,” wrote Diarmaid Hughes, MB, of the NUI Galway and Saolta University Hospital Group in Galway, Ireland, and coauthors. They added, however, that “these findings have the potential to inform public health strategies to reduce the burden of dementia globally.” The study was published online ahead of print May 19 in JAMA.
 

A rich data set

To assess the relationship between lowering blood pressure and cognitive issues, the researchers performed a systemic search of randomized, clinical trials that compared blood pressure lowering via antihypertensive agents with a control, had at least 1 year of follow-up, included more than 1,000 participants, and reported on either dementia, cognitive impairment, cognitive decline, or a change in cognitive test scores as outcomes. Of the 14 studies deemed eligible, 12 reported either the incidence of dementia (n = 9) or a composite of dementia or cognitive impairment (n = 3) at follow-up and thus were included in the primary meta-analysis. The other two studies were used for secondary outcomes only.

The studies included 96,158 participants in total – 42.2% were women – and their mean age was 69 years. At baseline, participants’ mean systolic blood pressure was 154 mm Hg and their mean diastolic blood pressure was 83.3 mm Hg. The mean duration of follow-up was 49.24 months.

In the 12 trials that reported dementia or cognitive impairment, blood pressure lowering via antihypertensive agents, compared with control, was significantly associated with a reduction in those two outcomes (7.0% vs. 7.5% over a mean trial follow-up of 4.1 years; odds ratio, 0.93; 95% confidence interval, 0.88-0.98; absolute risk reduction, 0.39%; 95% CI, 0.09%-0.68%). Blood pressure lowering, compared with control, was also significantly associated with a reduction in cognitive decline (20.2% vs. 21.1% over a mean trial follow-up of 4.1 years; OR, 0.93; 95% CI, 0.88-0.99; ARR, 0.71%; 95% CI, 0.19%-1.2%) in the eight trials that reported it as an outcome. An analysis of the eight trials that reported a change in cognitive scores did not find a significant association between that outcome and blood pressure lowering.
 

Subpopulations should be examined

“This is a very broad brush stroke study, albeit a definitive one,” Richard J. Caselli, MD, of the Mayo Clinic in Phoenix said in an interview. “With all the thousands of people in this meta-analysis, there are going to be subpopulations of patients with certain characteristics or common conditions in which blood pressure lowering might have a bigger or a lesser impact on their risk factor. Is there a difference between certain racial groups? Does it matter what antihypertensive strategies are used? You can look at the interactions between blood pressure lowering and other conditions: diabetes, head injuries, air pollution, certain genetic risk factors. There are a number of additional findings that could come from a very rich data set like this.”

The authors acknowledged their study’s limitations, including the challenges of performing a meta-analysis of studies that drew from different populations and had potentially different definitions of dementia, cognitive impairment, and cognitive decline outcomes. In addition, the low incidence of dementia across clinical trials limited the researchers, and its underdetection in trials and the potential of survivor bias for healthier participants with blood pressure reductions were noted as “unmeasured sources of potential error.”

Three authors reported receiving grants or personal fees from the Wellcome Trust and the Health Research Board, the Chief Scientist Office, and Bayer AG, respectively.

SOURCE: Hughes D et al. JAMA. 2020 May 19. doi: 10.1001/jama.2020.4249.

A completely new approach to the treatment of prostate cancer is now available to clinicians through the approval of the first PARP inhibitor for use in certain patients with this disease.

Rucaparib (Rubraca, Clovis Oncology) is the first PARP inhibitor approved for use in patients with metastatic castration-resistant prostate cancer (mCRPC) that harbors deleterious BRCA mutations (germline and/or somatic). The drug is indicated for use in patients who have already been treated with androgen receptor–directed therapy and a taxane-based chemotherapy.

The drug is already marketed for use in ovarian cancer.

The new prostate cancer indication was granted an accelerated approval by the US Food and Drug Administration (FDA) on the basis of response rates and effect on levels of prostate-specific antigen (PSA) from the TRITON2 clinical trial. A confirmatory phase 3 trial, TRITON3, is currently underway.

“Standard treatment options for men with mCRPC have been limited to androgen receptor–targeting therapies, taxane chemotherapy, radium-223, and sipuleucel-T,” said Wassim Abida, MD, a medical oncologist at Memorial Sloan Kettering Cancer Center in New York City, in a statement.

“Rucaparib is the first in a class of drugs to become newly available to patients with mCRPC who harbor a deleterious BRCA mutation,” said Abida, who is also the principal investigator of the TRITON2 study. “Given the level and duration of responses observed with rucaparib in men with mCRPC and these mutations, it represents an important and timely new treatment option for this patient population.”
 

Other indications, another PARP inhibitor

Rucaparib is already approved for the treatment of women with advanced BRCA mutation–positive ovarian cancer who have received two or more prior chemotherapies. It is also approved as maintenance treatment for patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who demonstrate a complete or partial response to platinum-based chemotherapy, regardless of BRCA status.

Another PARP inhibitor, olaparib (Lynparza, AstraZeneca), is awaiting approval for use in prostate cancer in men with BRCA mutations. That pending approval is based on results from the phase 3 PROfound trial, which was hailed as a “landmark trial” when it was presented last year. The results showed a significant improved in disease-free progression. The company recently announced that there was also a significant improvement in overall survival.

Olaparib is already approved for the maintenance treatment of platinum-sensitive relapsed ovarian cancer regardless of BRCA status and as first-line maintenance treatment in BRCA-mutated advanced ovarian cancer following response to platinum-based chemotherapy. It is also approved for germline BRCA-mutated HER2-negative metastatic breast cancer previously treated with chemotherapy and for the maintenance treatment of germline BRCA-mutated advanced pancreatic cancer following first-line platinum-based chemotherapy.
 

Details of the TRITON2 study

The accelerated approval for use of rucaparib in BRCA prostate cancer was based on efficacy data from the multicenter, single-arm TRITON2 clinical trial. The cohort included 62 patients with a BRCA (germline and/or somatic) mutation and measurable disease; 115 patients with a BRCA (germline and/or somatic) mutation and measurable or nonmeasurable disease; and 209 patients with homologous recombination deficiency (HRD)–positive mCRPC.

The major efficacy outcomes were objective response rate (ORR) and duration of response. Confirmed PSA response rate was also a prespecified endpoint. Data were assessed by independent radiologic review.

For the patients with measurable disease and a BRCA mutation, the ORR was 44%. The ORR was similar for patients with a germline BRCA mutation.

Median duration of response was not evaluable at data cutoff but ranged from 1.7 to 24+ months. Of the 27 patients with a confirmed objective response, 15 (56%) patients showed a response that lasted 6 months or longer.

In an analysis of 115 patients with a deleterious BRCA mutation (germline and/or somatic) and measurable or nonmeasurable disease, the confirmed PSA response rate was 55%.

The safety evaluation was based on an analysis of the 209 patients with HRD-positive mCRPC and included 115 with deleterious BRCA mutations. The most common adverse events (≥20%; grade 1-4) in the patients with BRCA mutations were fatigue/asthenia (62%), nausea (52%), anemia (43%), AST/ALT elevation (33%), decreased appetite (28%), rash (27%), constipation (27%), thrombocytopenia (25%), vomiting (22%), and diarrhea (20%).

Rucaparib has been associated with hematologic toxicity, including myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). However, MDS/AML was not observed in the TRITON2 study, regardless of HRD mutation.
 

Confirmation with TRITON3

A phase 3, randomized, open-label study, TRITON3, is currently underway and is expected to serve as the confirmatory study for the accelerated approval in mCRPC. TRITON3 is comparing rucaparib with physician’s choice of therapy in patients with mCRPC who have specific gene alterations, including BRCA and ATM alterations, and who have experienced disease progression after androgen receptor–directed therapy but have not yet received chemotherapy. The primary endpoint for TRITON3 is radiographic progression-free survival.

This article first appeared on Medscape.com.

A completely new approach to the treatment of prostate cancer is now available to clinicians through the approval of the first PARP inhibitor for use in certain patients with this disease.

Rucaparib (Rubraca, Clovis Oncology) is the first PARP inhibitor approved for use in patients with metastatic castration-resistant prostate cancer (mCRPC) that harbors deleterious BRCA mutations (germline and/or somatic). The drug is indicated for use in patients who have already been treated with androgen receptor–directed therapy and a taxane-based chemotherapy.

The drug is already marketed for use in ovarian cancer.

The new prostate cancer indication was granted an accelerated approval by the US Food and Drug Administration (FDA) on the basis of response rates and effect on levels of prostate-specific antigen (PSA) from the TRITON2 clinical trial. A confirmatory phase 3 trial, TRITON3, is currently underway.

“Standard treatment options for men with mCRPC have been limited to androgen receptor–targeting therapies, taxane chemotherapy, radium-223, and sipuleucel-T,” said Wassim Abida, MD, a medical oncologist at Memorial Sloan Kettering Cancer Center in New York City, in a statement.

“Rucaparib is the first in a class of drugs to become newly available to patients with mCRPC who harbor a deleterious BRCA mutation,” said Abida, who is also the principal investigator of the TRITON2 study. “Given the level and duration of responses observed with rucaparib in men with mCRPC and these mutations, it represents an important and timely new treatment option for this patient population.”
 

Other indications, another PARP inhibitor

Rucaparib is already approved for the treatment of women with advanced BRCA mutation–positive ovarian cancer who have received two or more prior chemotherapies. It is also approved as maintenance treatment for patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who demonstrate a complete or partial response to platinum-based chemotherapy, regardless of BRCA status.

Another PARP inhibitor, olaparib (Lynparza, AstraZeneca), is awaiting approval for use in prostate cancer in men with BRCA mutations. That pending approval is based on results from the phase 3 PROfound trial, which was hailed as a “landmark trial” when it was presented last year. The results showed a significant improved in disease-free progression. The company recently announced that there was also a significant improvement in overall survival.

Olaparib is already approved for the maintenance treatment of platinum-sensitive relapsed ovarian cancer regardless of BRCA status and as first-line maintenance treatment in BRCA-mutated advanced ovarian cancer following response to platinum-based chemotherapy. It is also approved for germline BRCA-mutated HER2-negative metastatic breast cancer previously treated with chemotherapy and for the maintenance treatment of germline BRCA-mutated advanced pancreatic cancer following first-line platinum-based chemotherapy.
 

Details of the TRITON2 study

The accelerated approval for use of rucaparib in BRCA prostate cancer was based on efficacy data from the multicenter, single-arm TRITON2 clinical trial. The cohort included 62 patients with a BRCA (germline and/or somatic) mutation and measurable disease; 115 patients with a BRCA (germline and/or somatic) mutation and measurable or nonmeasurable disease; and 209 patients with homologous recombination deficiency (HRD)–positive mCRPC.

The major efficacy outcomes were objective response rate (ORR) and duration of response. Confirmed PSA response rate was also a prespecified endpoint. Data were assessed by independent radiologic review.

For the patients with measurable disease and a BRCA mutation, the ORR was 44%. The ORR was similar for patients with a germline BRCA mutation.

Median duration of response was not evaluable at data cutoff but ranged from 1.7 to 24+ months. Of the 27 patients with a confirmed objective response, 15 (56%) patients showed a response that lasted 6 months or longer.

In an analysis of 115 patients with a deleterious BRCA mutation (germline and/or somatic) and measurable or nonmeasurable disease, the confirmed PSA response rate was 55%.

The safety evaluation was based on an analysis of the 209 patients with HRD-positive mCRPC and included 115 with deleterious BRCA mutations. The most common adverse events (≥20%; grade 1-4) in the patients with BRCA mutations were fatigue/asthenia (62%), nausea (52%), anemia (43%), AST/ALT elevation (33%), decreased appetite (28%), rash (27%), constipation (27%), thrombocytopenia (25%), vomiting (22%), and diarrhea (20%).

Rucaparib has been associated with hematologic toxicity, including myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). However, MDS/AML was not observed in the TRITON2 study, regardless of HRD mutation.
 

Confirmation with TRITON3

A phase 3, randomized, open-label study, TRITON3, is currently underway and is expected to serve as the confirmatory study for the accelerated approval in mCRPC. TRITON3 is comparing rucaparib with physician’s choice of therapy in patients with mCRPC who have specific gene alterations, including BRCA and ATM alterations, and who have experienced disease progression after androgen receptor–directed therapy but have not yet received chemotherapy. The primary endpoint for TRITON3 is radiographic progression-free survival.

This article first appeared on Medscape.com.

A completely new approach to the treatment of prostate cancer is now available to clinicians through the approval of the first PARP inhibitor for use in certain patients with this disease.

Rucaparib (Rubraca, Clovis Oncology) is the first PARP inhibitor approved for use in patients with metastatic castration-resistant prostate cancer (mCRPC) that harbors deleterious BRCA mutations (germline and/or somatic). The drug is indicated for use in patients who have already been treated with androgen receptor–directed therapy and a taxane-based chemotherapy.

The drug is already marketed for use in ovarian cancer.

The new prostate cancer indication was granted an accelerated approval by the US Food and Drug Administration (FDA) on the basis of response rates and effect on levels of prostate-specific antigen (PSA) from the TRITON2 clinical trial. A confirmatory phase 3 trial, TRITON3, is currently underway.

“Standard treatment options for men with mCRPC have been limited to androgen receptor–targeting therapies, taxane chemotherapy, radium-223, and sipuleucel-T,” said Wassim Abida, MD, a medical oncologist at Memorial Sloan Kettering Cancer Center in New York City, in a statement.

“Rucaparib is the first in a class of drugs to become newly available to patients with mCRPC who harbor a deleterious BRCA mutation,” said Abida, who is also the principal investigator of the TRITON2 study. “Given the level and duration of responses observed with rucaparib in men with mCRPC and these mutations, it represents an important and timely new treatment option for this patient population.”
 

Other indications, another PARP inhibitor

Rucaparib is already approved for the treatment of women with advanced BRCA mutation–positive ovarian cancer who have received two or more prior chemotherapies. It is also approved as maintenance treatment for patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who demonstrate a complete or partial response to platinum-based chemotherapy, regardless of BRCA status.

Another PARP inhibitor, olaparib (Lynparza, AstraZeneca), is awaiting approval for use in prostate cancer in men with BRCA mutations. That pending approval is based on results from the phase 3 PROfound trial, which was hailed as a “landmark trial” when it was presented last year. The results showed a significant improved in disease-free progression. The company recently announced that there was also a significant improvement in overall survival.

Olaparib is already approved for the maintenance treatment of platinum-sensitive relapsed ovarian cancer regardless of BRCA status and as first-line maintenance treatment in BRCA-mutated advanced ovarian cancer following response to platinum-based chemotherapy. It is also approved for germline BRCA-mutated HER2-negative metastatic breast cancer previously treated with chemotherapy and for the maintenance treatment of germline BRCA-mutated advanced pancreatic cancer following first-line platinum-based chemotherapy.
 

Details of the TRITON2 study

The accelerated approval for use of rucaparib in BRCA prostate cancer was based on efficacy data from the multicenter, single-arm TRITON2 clinical trial. The cohort included 62 patients with a BRCA (germline and/or somatic) mutation and measurable disease; 115 patients with a BRCA (germline and/or somatic) mutation and measurable or nonmeasurable disease; and 209 patients with homologous recombination deficiency (HRD)–positive mCRPC.

The major efficacy outcomes were objective response rate (ORR) and duration of response. Confirmed PSA response rate was also a prespecified endpoint. Data were assessed by independent radiologic review.

For the patients with measurable disease and a BRCA mutation, the ORR was 44%. The ORR was similar for patients with a germline BRCA mutation.

Median duration of response was not evaluable at data cutoff but ranged from 1.7 to 24+ months. Of the 27 patients with a confirmed objective response, 15 (56%) patients showed a response that lasted 6 months or longer.

In an analysis of 115 patients with a deleterious BRCA mutation (germline and/or somatic) and measurable or nonmeasurable disease, the confirmed PSA response rate was 55%.

The safety evaluation was based on an analysis of the 209 patients with HRD-positive mCRPC and included 115 with deleterious BRCA mutations. The most common adverse events (≥20%; grade 1-4) in the patients with BRCA mutations were fatigue/asthenia (62%), nausea (52%), anemia (43%), AST/ALT elevation (33%), decreased appetite (28%), rash (27%), constipation (27%), thrombocytopenia (25%), vomiting (22%), and diarrhea (20%).

Rucaparib has been associated with hematologic toxicity, including myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). However, MDS/AML was not observed in the TRITON2 study, regardless of HRD mutation.
 

Confirmation with TRITON3

A phase 3, randomized, open-label study, TRITON3, is currently underway and is expected to serve as the confirmatory study for the accelerated approval in mCRPC. TRITON3 is comparing rucaparib with physician’s choice of therapy in patients with mCRPC who have specific gene alterations, including BRCA and ATM alterations, and who have experienced disease progression after androgen receptor–directed therapy but have not yet received chemotherapy. The primary endpoint for TRITON3 is radiographic progression-free survival.

This article first appeared on Medscape.com.

A leadless right-ventricular pacemaker continued to show an edge over conventional transvenous pacemakers by triggering a substantially reduced rate of complications during the 6 months following placement in a review of more than 10,000 Medicare patients treated over 2 years.

The “largest leadless pacemaker cohort to date” showed that in propensity score–matched cohorts, the 3,276 patients who received the Micra leadless transcatheter pacemaker during routine management and were followed for 6 months had a 3.3% rate of total complications, compared with a 9.4% rate among 7,256 patients who received a conventional VVI pacemaker with a transvenous lead, a statistically significant 66% relative risk reduction, Jonathan P. Piccini, MD, said at the annual scientific sessions of the Heart Rhythm Society, held online because of COVID-19.

The 66% reduced rate of complications – both acutely and with further follow-up – was similar to the complication reductions seen with Micra, compared with historical controls who received transvenous single-chamber pacemakers in both the pivotal study for the device (Heart Rhythm. 2017 May 1;14[3]:702-9) and in a postapproval registry study (Heart Rhythm. 2018 Dec 1;15[12]:1800-7). However, the newly reported advantage came in a population that was notably older and had significantly more comorbidities than in the prior leadless pacemaker studies, said Dr. Piccini, a cardiac electrophysiologist at Duke University, Durham, N.C.

The new Medicare data “tell us that physicians are reaching for these devices [leadless pacemakers] in patients with more comorbidities and a higher risk for complications to give them a [device with] better safety profile,” he said during a press briefing. “At Duke, and I suspect at other centers, when a patients is eligible for a leadless pacemaker that’s the preferred option.”

However, Dr. Piccini cited three examples of the small proportion of patients who are appropriate for the type of pacing the leadless pacemaker supplies but would be better candidates for a device with a transvenous lead: patients who failed treatment with a initial leadless pacemaker and have no suitable alternative subcutaneous spot to place the replacement device in a stable way, those with severe right ventricular enlargement that interferes with optimal placement, and those who don’t currently meet criteria for biventricular pacing but appear likely to switch to that pacing mode in the near term.

The 66% relative reduction in complications was “impressive; I hope this will be a message,” commented Nassir F. Marrouche, MD, a cardiac electrophysiologist and professor of medicine at Tulane University, New Orleans. Importantly, this reduced complication rate occurred in a real-world population that was sicker than any patient group previously studied with the device, he noted as a designated discussant for the report.

But the report’s second designated discussant, Roderick Tung, MD, highlighted some caveats when interpreting the lower complication rate with the leadless device compared with historical controls. He cited the absence of any episodes of pneumothorax among the patients reviewed by Dr. Piccini who received a leadless pacemaker, compared with a 5% rate among the control patients who had received a device with a transvenous lead, a major driver of the overall difference in complication rates. This difference “may not be relevant to operators who use either an axillary extrathoracic vein route for lead placement or a cephalic vein approach,” said Dr. Tung, director of cardiac electrophysiology at the University of Chicago. “There should not be a 5% rate of pneumothorax when implanting a VVI device.” The results reported by Dr. Piccini have the advantages of coming from many patients and from real-world practice, he acknowledged, but interpretation is limited by the lack of a randomized control group and the outsized impact of pneumothorax complications on the safety comparison.

The other major component of the 6-month complication tally was device-related events, which were twice as common in the historical controls who received a transvenous lead at a rate of 3.4%. The sole 6-month event more common among the patients who received a leadless pacemaker was pericarditis, at a rate of 1.3% in the Micra group and 0.5% in the transvenous lead controls, Dr. Piccini reported. The 6-month rate of device revisions was 1.7% with the leadless device and 2.8% with transvenous lead pacemakers, a difference that was not statistically significant. The two treatment arms had virtually identical 6-month mortality rates.

The rate of acute complications during the first 30 days after implant was also virtually the same in the two study arms. Patient who received the leadless device had significantly more puncture-site events, at a rate of 1.2%, and significantly more cardiac effusions or perforations, at a rate of 0.8%. The historical control patients who received devices with transvenous leads had significantly more device-related complications after 30 days, a 2.5% rate.

The 30-day cohorts examined had larger numbers of patients than at 6 months, 5,746 leadless pacemaker recipients and 9,662 matched historical controls who had received a transvenous lead pacemaker. The clinical and demographic profile of the 30-day cohort who received the leadless pacemaker highlighted the sicker nature of these patients compared with earlier studies of the device. They were an average age of 79 years, compared with average ages of 76 years in the two prior Micra studies, and they also had double the prevalence of coronary disease, triple the prevalence of heart failure, more than twice the rate of chronic obstructive pulmonary disease, and almost twice the prevalence of diabetes.

During the period examined in this report from Micra CED (Longitudinal Coverage With Evidence Development Study on Micra Leadless Pacemakers), in 2017-2018, the leadless pacemaker’s initial approved indications were for a circumscribed portion of the overall patient population that needs pacing. Essentially, they were elderly patients with persistent atrial fibrillation who only need ventricular pacing, roughly 15% of the overall cohort of pacing candidates. In January 2020, the FDA added an indication for high-grade atrioventricular block, an expanded population of candidates that roughly tripled the number of potentially appropriate recipients, said Larry A. Chinitz, MD, a cardiac electrophysiologist and a coinvestigator on some of the studies that led to the new indication, in an interview at the time of the revised labeling.

The study was sponsored by Medtronic, which markets the Micra leadless pacemaker. Dr. Piccini has received honoraria from Medtronic and several other companies. Dr. Marrouche has been a consultant to Medtronic as well as to Biosense Webster, Biotronik, Cardiac Design, and Preventice, and has received research funding from Abbott, Biosense Webster, Boston Scientific, and GE Healthcare. Dr. Tung has been a speaker on behalf of Abbott, Boston Scientific, and Biosense Webster. Dr. Chinitz has received fees and fellowship support from Medtronic, and has also received fees from Abbott, Biosense Webster, Biotronik, and Pfizer.

[email protected]

SOURCE: Piccini JP et al. Heart Rhythm 2020, Abstract D-LBCT04-01.

A leadless right-ventricular pacemaker continued to show an edge over conventional transvenous pacemakers by triggering a substantially reduced rate of complications during the 6 months following placement in a review of more than 10,000 Medicare patients treated over 2 years.

The “largest leadless pacemaker cohort to date” showed that in propensity score–matched cohorts, the 3,276 patients who received the Micra leadless transcatheter pacemaker during routine management and were followed for 6 months had a 3.3% rate of total complications, compared with a 9.4% rate among 7,256 patients who received a conventional VVI pacemaker with a transvenous lead, a statistically significant 66% relative risk reduction, Jonathan P. Piccini, MD, said at the annual scientific sessions of the Heart Rhythm Society, held online because of COVID-19.

The 66% reduced rate of complications – both acutely and with further follow-up – was similar to the complication reductions seen with Micra, compared with historical controls who received transvenous single-chamber pacemakers in both the pivotal study for the device (Heart Rhythm. 2017 May 1;14[3]:702-9) and in a postapproval registry study (Heart Rhythm. 2018 Dec 1;15[12]:1800-7). However, the newly reported advantage came in a population that was notably older and had significantly more comorbidities than in the prior leadless pacemaker studies, said Dr. Piccini, a cardiac electrophysiologist at Duke University, Durham, N.C.

The new Medicare data “tell us that physicians are reaching for these devices [leadless pacemakers] in patients with more comorbidities and a higher risk for complications to give them a [device with] better safety profile,” he said during a press briefing. “At Duke, and I suspect at other centers, when a patients is eligible for a leadless pacemaker that’s the preferred option.”

However, Dr. Piccini cited three examples of the small proportion of patients who are appropriate for the type of pacing the leadless pacemaker supplies but would be better candidates for a device with a transvenous lead: patients who failed treatment with a initial leadless pacemaker and have no suitable alternative subcutaneous spot to place the replacement device in a stable way, those with severe right ventricular enlargement that interferes with optimal placement, and those who don’t currently meet criteria for biventricular pacing but appear likely to switch to that pacing mode in the near term.

The 66% relative reduction in complications was “impressive; I hope this will be a message,” commented Nassir F. Marrouche, MD, a cardiac electrophysiologist and professor of medicine at Tulane University, New Orleans. Importantly, this reduced complication rate occurred in a real-world population that was sicker than any patient group previously studied with the device, he noted as a designated discussant for the report.

But the report’s second designated discussant, Roderick Tung, MD, highlighted some caveats when interpreting the lower complication rate with the leadless device compared with historical controls. He cited the absence of any episodes of pneumothorax among the patients reviewed by Dr. Piccini who received a leadless pacemaker, compared with a 5% rate among the control patients who had received a device with a transvenous lead, a major driver of the overall difference in complication rates. This difference “may not be relevant to operators who use either an axillary extrathoracic vein route for lead placement or a cephalic vein approach,” said Dr. Tung, director of cardiac electrophysiology at the University of Chicago. “There should not be a 5% rate of pneumothorax when implanting a VVI device.” The results reported by Dr. Piccini have the advantages of coming from many patients and from real-world practice, he acknowledged, but interpretation is limited by the lack of a randomized control group and the outsized impact of pneumothorax complications on the safety comparison.

The other major component of the 6-month complication tally was device-related events, which were twice as common in the historical controls who received a transvenous lead at a rate of 3.4%. The sole 6-month event more common among the patients who received a leadless pacemaker was pericarditis, at a rate of 1.3% in the Micra group and 0.5% in the transvenous lead controls, Dr. Piccini reported. The 6-month rate of device revisions was 1.7% with the leadless device and 2.8% with transvenous lead pacemakers, a difference that was not statistically significant. The two treatment arms had virtually identical 6-month mortality rates.

The rate of acute complications during the first 30 days after implant was also virtually the same in the two study arms. Patient who received the leadless device had significantly more puncture-site events, at a rate of 1.2%, and significantly more cardiac effusions or perforations, at a rate of 0.8%. The historical control patients who received devices with transvenous leads had significantly more device-related complications after 30 days, a 2.5% rate.

The 30-day cohorts examined had larger numbers of patients than at 6 months, 5,746 leadless pacemaker recipients and 9,662 matched historical controls who had received a transvenous lead pacemaker. The clinical and demographic profile of the 30-day cohort who received the leadless pacemaker highlighted the sicker nature of these patients compared with earlier studies of the device. They were an average age of 79 years, compared with average ages of 76 years in the two prior Micra studies, and they also had double the prevalence of coronary disease, triple the prevalence of heart failure, more than twice the rate of chronic obstructive pulmonary disease, and almost twice the prevalence of diabetes.

During the period examined in this report from Micra CED (Longitudinal Coverage With Evidence Development Study on Micra Leadless Pacemakers), in 2017-2018, the leadless pacemaker’s initial approved indications were for a circumscribed portion of the overall patient population that needs pacing. Essentially, they were elderly patients with persistent atrial fibrillation who only need ventricular pacing, roughly 15% of the overall cohort of pacing candidates. In January 2020, the FDA added an indication for high-grade atrioventricular block, an expanded population of candidates that roughly tripled the number of potentially appropriate recipients, said Larry A. Chinitz, MD, a cardiac electrophysiologist and a coinvestigator on some of the studies that led to the new indication, in an interview at the time of the revised labeling.

The study was sponsored by Medtronic, which markets the Micra leadless pacemaker. Dr. Piccini has received honoraria from Medtronic and several other companies. Dr. Marrouche has been a consultant to Medtronic as well as to Biosense Webster, Biotronik, Cardiac Design, and Preventice, and has received research funding from Abbott, Biosense Webster, Boston Scientific, and GE Healthcare. Dr. Tung has been a speaker on behalf of Abbott, Boston Scientific, and Biosense Webster. Dr. Chinitz has received fees and fellowship support from Medtronic, and has also received fees from Abbott, Biosense Webster, Biotronik, and Pfizer.

[email protected]

SOURCE: Piccini JP et al. Heart Rhythm 2020, Abstract D-LBCT04-01.

A leadless right-ventricular pacemaker continued to show an edge over conventional transvenous pacemakers by triggering a substantially reduced rate of complications during the 6 months following placement in a review of more than 10,000 Medicare patients treated over 2 years.

The “largest leadless pacemaker cohort to date” showed that in propensity score–matched cohorts, the 3,276 patients who received the Micra leadless transcatheter pacemaker during routine management and were followed for 6 months had a 3.3% rate of total complications, compared with a 9.4% rate among 7,256 patients who received a conventional VVI pacemaker with a transvenous lead, a statistically significant 66% relative risk reduction, Jonathan P. Piccini, MD, said at the annual scientific sessions of the Heart Rhythm Society, held online because of COVID-19.

The 66% reduced rate of complications – both acutely and with further follow-up – was similar to the complication reductions seen with Micra, compared with historical controls who received transvenous single-chamber pacemakers in both the pivotal study for the device (Heart Rhythm. 2017 May 1;14[3]:702-9) and in a postapproval registry study (Heart Rhythm. 2018 Dec 1;15[12]:1800-7). However, the newly reported advantage came in a population that was notably older and had significantly more comorbidities than in the prior leadless pacemaker studies, said Dr. Piccini, a cardiac electrophysiologist at Duke University, Durham, N.C.

The new Medicare data “tell us that physicians are reaching for these devices [leadless pacemakers] in patients with more comorbidities and a higher risk for complications to give them a [device with] better safety profile,” he said during a press briefing. “At Duke, and I suspect at other centers, when a patients is eligible for a leadless pacemaker that’s the preferred option.”

However, Dr. Piccini cited three examples of the small proportion of patients who are appropriate for the type of pacing the leadless pacemaker supplies but would be better candidates for a device with a transvenous lead: patients who failed treatment with a initial leadless pacemaker and have no suitable alternative subcutaneous spot to place the replacement device in a stable way, those with severe right ventricular enlargement that interferes with optimal placement, and those who don’t currently meet criteria for biventricular pacing but appear likely to switch to that pacing mode in the near term.

The 66% relative reduction in complications was “impressive; I hope this will be a message,” commented Nassir F. Marrouche, MD, a cardiac electrophysiologist and professor of medicine at Tulane University, New Orleans. Importantly, this reduced complication rate occurred in a real-world population that was sicker than any patient group previously studied with the device, he noted as a designated discussant for the report.

But the report’s second designated discussant, Roderick Tung, MD, highlighted some caveats when interpreting the lower complication rate with the leadless device compared with historical controls. He cited the absence of any episodes of pneumothorax among the patients reviewed by Dr. Piccini who received a leadless pacemaker, compared with a 5% rate among the control patients who had received a device with a transvenous lead, a major driver of the overall difference in complication rates. This difference “may not be relevant to operators who use either an axillary extrathoracic vein route for lead placement or a cephalic vein approach,” said Dr. Tung, director of cardiac electrophysiology at the University of Chicago. “There should not be a 5% rate of pneumothorax when implanting a VVI device.” The results reported by Dr. Piccini have the advantages of coming from many patients and from real-world practice, he acknowledged, but interpretation is limited by the lack of a randomized control group and the outsized impact of pneumothorax complications on the safety comparison.

The other major component of the 6-month complication tally was device-related events, which were twice as common in the historical controls who received a transvenous lead at a rate of 3.4%. The sole 6-month event more common among the patients who received a leadless pacemaker was pericarditis, at a rate of 1.3% in the Micra group and 0.5% in the transvenous lead controls, Dr. Piccini reported. The 6-month rate of device revisions was 1.7% with the leadless device and 2.8% with transvenous lead pacemakers, a difference that was not statistically significant. The two treatment arms had virtually identical 6-month mortality rates.

The rate of acute complications during the first 30 days after implant was also virtually the same in the two study arms. Patient who received the leadless device had significantly more puncture-site events, at a rate of 1.2%, and significantly more cardiac effusions or perforations, at a rate of 0.8%. The historical control patients who received devices with transvenous leads had significantly more device-related complications after 30 days, a 2.5% rate.

The 30-day cohorts examined had larger numbers of patients than at 6 months, 5,746 leadless pacemaker recipients and 9,662 matched historical controls who had received a transvenous lead pacemaker. The clinical and demographic profile of the 30-day cohort who received the leadless pacemaker highlighted the sicker nature of these patients compared with earlier studies of the device. They were an average age of 79 years, compared with average ages of 76 years in the two prior Micra studies, and they also had double the prevalence of coronary disease, triple the prevalence of heart failure, more than twice the rate of chronic obstructive pulmonary disease, and almost twice the prevalence of diabetes.

During the period examined in this report from Micra CED (Longitudinal Coverage With Evidence Development Study on Micra Leadless Pacemakers), in 2017-2018, the leadless pacemaker’s initial approved indications were for a circumscribed portion of the overall patient population that needs pacing. Essentially, they were elderly patients with persistent atrial fibrillation who only need ventricular pacing, roughly 15% of the overall cohort of pacing candidates. In January 2020, the FDA added an indication for high-grade atrioventricular block, an expanded population of candidates that roughly tripled the number of potentially appropriate recipients, said Larry A. Chinitz, MD, a cardiac electrophysiologist and a coinvestigator on some of the studies that led to the new indication, in an interview at the time of the revised labeling.

The study was sponsored by Medtronic, which markets the Micra leadless pacemaker. Dr. Piccini has received honoraria from Medtronic and several other companies. Dr. Marrouche has been a consultant to Medtronic as well as to Biosense Webster, Biotronik, Cardiac Design, and Preventice, and has received research funding from Abbott, Biosense Webster, Boston Scientific, and GE Healthcare. Dr. Tung has been a speaker on behalf of Abbott, Boston Scientific, and Biosense Webster. Dr. Chinitz has received fees and fellowship support from Medtronic, and has also received fees from Abbott, Biosense Webster, Biotronik, and Pfizer.

[email protected]

SOURCE: Piccini JP et al. Heart Rhythm 2020, Abstract D-LBCT04-01.

It is time to broaden the definition of osteoporosis used in clinical guidelines, states an article published in Age and Ageing, the official journal of the British Geriatrics Society.

The authors recommend that the World Health Organization and the International Society for Clinical Densitometry consider a broader definition of osteoporosis, which encompasses clinical diagnosis, providing clear guidance on communicating bone mineral density (BMD) results to patients.

The WHO definition of osteoporosis, which is endorsed as a diagnostic threshold in current U.K. and European guidance, still relies purely on BMD testing (T score of −2.5 SD or more). The authors say this definition no longer relates to the population for whom osteoporosis drugs are recommended.

In the past 15 years, they write, there has been a change in the field of osteoporosis, namely to base osteoporosis management not just on absolute values of BMD but also on broader consideration of future fracture risk. This change has been underpinned by observations that the majority of patients with a fragility fracture do not have osteoporotic BMD.

Coauthor Zoe Paskins, MBChB, a senior lecturer at Keele (England) University and clinical lead for the osteoporosis service in North Staffordshire, argues that many people with osteoporosis do not receive the treatment they need because of inconsistencies in how the condition is diagnosed around the world, resulting in confusion for both clinicians and patients.

“We think it is time for the WHO to reconsider the definition of osteoporosis, which is now more than 25 years old. A new definition is needed to acknowledge that it is possible, in some circumstances, to give a clinical diagnosis of osteoporosis in those who have osteoporotic fractures. In our view, this would help address current confusion and improve uptake of treatments,” she said.

This article first appeared on Univadis.

It is time to broaden the definition of osteoporosis used in clinical guidelines, states an article published in Age and Ageing, the official journal of the British Geriatrics Society.

The authors recommend that the World Health Organization and the International Society for Clinical Densitometry consider a broader definition of osteoporosis, which encompasses clinical diagnosis, providing clear guidance on communicating bone mineral density (BMD) results to patients.

The WHO definition of osteoporosis, which is endorsed as a diagnostic threshold in current U.K. and European guidance, still relies purely on BMD testing (T score of −2.5 SD or more). The authors say this definition no longer relates to the population for whom osteoporosis drugs are recommended.

In the past 15 years, they write, there has been a change in the field of osteoporosis, namely to base osteoporosis management not just on absolute values of BMD but also on broader consideration of future fracture risk. This change has been underpinned by observations that the majority of patients with a fragility fracture do not have osteoporotic BMD.

Coauthor Zoe Paskins, MBChB, a senior lecturer at Keele (England) University and clinical lead for the osteoporosis service in North Staffordshire, argues that many people with osteoporosis do not receive the treatment they need because of inconsistencies in how the condition is diagnosed around the world, resulting in confusion for both clinicians and patients.

“We think it is time for the WHO to reconsider the definition of osteoporosis, which is now more than 25 years old. A new definition is needed to acknowledge that it is possible, in some circumstances, to give a clinical diagnosis of osteoporosis in those who have osteoporotic fractures. In our view, this would help address current confusion and improve uptake of treatments,” she said.

This article first appeared on Univadis.

It is time to broaden the definition of osteoporosis used in clinical guidelines, states an article published in Age and Ageing, the official journal of the British Geriatrics Society.

The authors recommend that the World Health Organization and the International Society for Clinical Densitometry consider a broader definition of osteoporosis, which encompasses clinical diagnosis, providing clear guidance on communicating bone mineral density (BMD) results to patients.

The WHO definition of osteoporosis, which is endorsed as a diagnostic threshold in current U.K. and European guidance, still relies purely on BMD testing (T score of −2.5 SD or more). The authors say this definition no longer relates to the population for whom osteoporosis drugs are recommended.

In the past 15 years, they write, there has been a change in the field of osteoporosis, namely to base osteoporosis management not just on absolute values of BMD but also on broader consideration of future fracture risk. This change has been underpinned by observations that the majority of patients with a fragility fracture do not have osteoporotic BMD.

Coauthor Zoe Paskins, MBChB, a senior lecturer at Keele (England) University and clinical lead for the osteoporosis service in North Staffordshire, argues that many people with osteoporosis do not receive the treatment they need because of inconsistencies in how the condition is diagnosed around the world, resulting in confusion for both clinicians and patients.

“We think it is time for the WHO to reconsider the definition of osteoporosis, which is now more than 25 years old. A new definition is needed to acknowledge that it is possible, in some circumstances, to give a clinical diagnosis of osteoporosis in those who have osteoporotic fractures. In our view, this would help address current confusion and improve uptake of treatments,” she said.

This article first appeared on Univadis.

The dermatologic manifestations associated with SARS-CoV-2 are many and varied, with new information virtually daily. Graeme Lipper, MD, a member of the Medscape Dermatology advisory board, discussed what we know and what is still to be learned with Lindy Fox, MD, a professor of dermatology at University of California, San Francisco (UCSF) and a member of the American Academy of Dermatology’s COVID-19 Registry task force.

Graeme M. Lipper, MD

Earlier this spring, before there was any real talk about skin manifestations of COVID, my partner called me in to see an unusual case. His patient was a healthy 20-year-old who had just come back from college and had tender, purple discoloration and swelling on his toes. I shrugged and said “looks like chilblains,” but there was something weird about the case. It seemed more severe, with areas of blistering and erosions, and the discomfort was unusual for run-of-the-mill pernio. This young man had experienced a cough and shortness of breath a few weeks earlier but those symptoms had resolved when we saw him.

That evening, I was on a derm social media site and saw a series of pictures from Italy that blew me away. All of these pictures looked just like this kid’s toes. That’s the first I heard of “COVID toes,” but now they seem to be everywhere. How would you describe this presentation, and how does it differ from typical chilblains?

Lindy P. Fox, MD

I am so proud of dermatologists around the world who have really jumped into action to examine the pathophysiology and immunology behind these findings.

Your experience matches mine. Like you, I first heard about these pernio- or chilblains-like lesions when Europe was experiencing its surge in cases. And while it does indeed look like chilblains, I think the reality is that it is more severe and symptomatic than we would expect. I think your observation is exactly right. There are certainly clinicians who do not believe that this is an association with COVID-19 because the testing is often negative. But to my mind, there are just too many cases at the wrong time of year, all happening concomitantly, and simultaneous with a new virus for me to accept that they are not somehow related.
 

Dr. Lipper: Some have referred to this as “quarantine toes,” the result of more people at home and walking around barefoot. That doesn’t seem to make a whole lot of sense because it’s happening in both warm and cold climates.

Others have speculated that there is another, unrelated circulating virus causing these pernio cases, but that seems far-fetched.

But the idea of a reporting bias – more patients paying attention to these lesions because they’ve read something in the mass media or seen a report on television and are concerned, and thus present with mild lesions they might otherwise have ignored – may be contributing somewhat. But even that cannot be the sole reason behind the increase.

Dr. Fox: Agree.

Evaluation of the patient with chilblains – then and now

Dr. Lipper: In the past, how did you perform a workup for someone with chilblains?

Dr. Fox: Pre-COVID – and I think we all have divided our world into pre- and post-COVID – the most common thing that I’d be looking for would be a clotting disorder or an autoimmune disease, typically lupus. So I take a good history, review of systems, and look at the skin for signs of lupus or other autoimmune connective tissue diseases. My lab workup is probably limited to an antinuclear antibody (ANA). If the findings are severe and recurrent, I might check for hypercoagulability with an antiphospholipid antibody panel. But that was usually it unless there was something in the history or physical exam that would lead me to look for something less common – for example, cryoglobulins or an underlying hematologic disease that would lead to a predominance of lesions in acral sites.

My approach was the same. In New England, where I practice, I also always look at environmental factors. We would sometimes see chilblains in someone from a warmer climate who came home to the Northeast to ski.
 

Dr. Lipper: Now, in the post-COVID world, how do you assess these patients? What has changed?

Dr. Fox: That’s a great question. To be frank, our focus now is on not missing a secondary consequence of COVID infection that we might not have picked up before. I’m the first to admit that the workup that we have been doing at UCSF is extremely comprehensive. We may be ordering tests that don’t need to be done. But until we know better what might and might not be affected by COVID, we don’t actually have a sense of whether they’re worth looking for or not.

Right now, my workup includes nasal swab polymerase chain reaction (PCR) for COVID, as well as IgG and IgM serology if available. We have IgG easily available to us. IgM needs approval; at UCSF, it is primarily done in neonates as of now. I also do a workup for autoimmunity and cold-associated disease, which includes an ANA, rheumatoid factor, cryoglobulin, and cold agglutinins.

Because of reported concerns about hypercoagulability in COVID patients, particularly in those who are doing poorly in the hospital, we look for elevations in d-dimers and fibrinogen. We check antiphospholipid antibodies, anticardiolipin antibodies, erythrocyte sedimentation rate, and C-reactive protein. That is probably too much of a workup for the healthy young person, but as of yet, we are just unable to say that those things are universally normal.

There has also been concern that complement may be involved in patients who do poorly and tend to clot a lot. So we are also checking C3, C4, and CH50.

To date, in my patients who have had this workup, I have found one with a positive ANA that was significant (1:320) who also had low complements.

There have been a couple of patients at my institution, not my own patients, who are otherwise fine but have some slight elevation in d-dimers.