Rheumatology News

The Lancet announced today that it has retracted a highly cited study that suggested hydroxychloroquine may cause more harm than benefit in patients with COVID-19. Hours later, the New England Journal of Medicine announced that it had retracted a second article by some of the same authors, also on heart disease and COVID-19.

The Lancet article, titled “Hydroxychloroquine or chloroquine with or without a macrolide for treatment of COVID-19: A multinational registry analysis” was originally published online May 22. The NEJM article, “Cardiovascular Disease, Drug Therapy, and Mortality in Covid-19” was initially published May 1.

Three authors of the Lancet article, Mandeep R. Mehra, MD, Frank Ruschitzka, MD, and Amit N. Patel, MD, wrote in a letter that the action came after concerns were raised about the integrity of the data, and about how the analysis was conducted by Chicago-based Surgisphere Corp and study coauthor Sapan Desai, MD, Surgisphere’s founder and CEO.

The authors asked for an independent third-party review of Surgisphere to evaluate the integrity of the trial elements and to replicate the analyses in the article.

“Our independent peer reviewers informed us that Surgisphere would not transfer the full dataset, client contracts, and the full ISO audit report to their servers for analysis, as such transfer would violate client agreements and confidentiality requirements,” the authors wrote.

Therefore, reviewers were not able to conduct the review and notified the authors they would withdraw from the peer-review process.

The Lancet said in a statement: “The Lancet takes issues of scientific integrity extremely seriously, and there are many outstanding questions about Surgisphere and the data that were allegedly included in this study. Following guidelines from the Committee on Publication Ethics and International Committee of Medical Journal Editors, institutional reviews of Surgisphere’s research collaborations are urgently needed.”

The authors wrote, “We can never forget the responsibility we have as researchers to scrupulously ensure that we rely on data sources that adhere to our high standards. Based on this development, we can no longer vouch for the veracity of the primary data sources. Due to this unfortunate development, the authors request that the paper be retracted.

“We all entered this collaboration to contribute in good faith and at a time of great need during the COVID-19 pandemic. We deeply apologize to you, the editors, and the journal readership for any embarrassment or inconvenience that this may have caused.”

In a similar, if briefer, note, the authors requested that the New England Journal of Medicine retract the earlier article as well. The retraction notice on the website reads: “Because all the authors were not granted access to the raw data and the raw data could not be made available to a third-party auditor, we are unable to validate the primary data sources underlying our article, ‘Cardiovascular Disease, Drug Therapy, and Mortality in Covid-19.’ We therefore request that the article be retracted. We apologize to the editors and to readers of the Journal for the difficulties that this has caused.”

Both journals had already published “Expression of Concern” notices about the articles. The expression of concern followed an open letter, endorsed by more than 200 scientists, ethicists, and clinicians and posted on May 28, questioning the data and ethics of the study.

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






 

The Lancet announced today that it has retracted a highly cited study that suggested hydroxychloroquine may cause more harm than benefit in patients with COVID-19. Hours later, the New England Journal of Medicine announced that it had retracted a second article by some of the same authors, also on heart disease and COVID-19.

The Lancet article, titled “Hydroxychloroquine or chloroquine with or without a macrolide for treatment of COVID-19: A multinational registry analysis” was originally published online May 22. The NEJM article, “Cardiovascular Disease, Drug Therapy, and Mortality in Covid-19” was initially published May 1.

Three authors of the Lancet article, Mandeep R. Mehra, MD, Frank Ruschitzka, MD, and Amit N. Patel, MD, wrote in a letter that the action came after concerns were raised about the integrity of the data, and about how the analysis was conducted by Chicago-based Surgisphere Corp and study coauthor Sapan Desai, MD, Surgisphere’s founder and CEO.

The authors asked for an independent third-party review of Surgisphere to evaluate the integrity of the trial elements and to replicate the analyses in the article.

“Our independent peer reviewers informed us that Surgisphere would not transfer the full dataset, client contracts, and the full ISO audit report to their servers for analysis, as such transfer would violate client agreements and confidentiality requirements,” the authors wrote.

Therefore, reviewers were not able to conduct the review and notified the authors they would withdraw from the peer-review process.

The Lancet said in a statement: “The Lancet takes issues of scientific integrity extremely seriously, and there are many outstanding questions about Surgisphere and the data that were allegedly included in this study. Following guidelines from the Committee on Publication Ethics and International Committee of Medical Journal Editors, institutional reviews of Surgisphere’s research collaborations are urgently needed.”

The authors wrote, “We can never forget the responsibility we have as researchers to scrupulously ensure that we rely on data sources that adhere to our high standards. Based on this development, we can no longer vouch for the veracity of the primary data sources. Due to this unfortunate development, the authors request that the paper be retracted.

“We all entered this collaboration to contribute in good faith and at a time of great need during the COVID-19 pandemic. We deeply apologize to you, the editors, and the journal readership for any embarrassment or inconvenience that this may have caused.”

In a similar, if briefer, note, the authors requested that the New England Journal of Medicine retract the earlier article as well. The retraction notice on the website reads: “Because all the authors were not granted access to the raw data and the raw data could not be made available to a third-party auditor, we are unable to validate the primary data sources underlying our article, ‘Cardiovascular Disease, Drug Therapy, and Mortality in Covid-19.’ We therefore request that the article be retracted. We apologize to the editors and to readers of the Journal for the difficulties that this has caused.”

Both journals had already published “Expression of Concern” notices about the articles. The expression of concern followed an open letter, endorsed by more than 200 scientists, ethicists, and clinicians and posted on May 28, questioning the data and ethics of the study.

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






 

The Lancet announced today that it has retracted a highly cited study that suggested hydroxychloroquine may cause more harm than benefit in patients with COVID-19. Hours later, the New England Journal of Medicine announced that it had retracted a second article by some of the same authors, also on heart disease and COVID-19.

The Lancet article, titled “Hydroxychloroquine or chloroquine with or without a macrolide for treatment of COVID-19: A multinational registry analysis” was originally published online May 22. The NEJM article, “Cardiovascular Disease, Drug Therapy, and Mortality in Covid-19” was initially published May 1.

Three authors of the Lancet article, Mandeep R. Mehra, MD, Frank Ruschitzka, MD, and Amit N. Patel, MD, wrote in a letter that the action came after concerns were raised about the integrity of the data, and about how the analysis was conducted by Chicago-based Surgisphere Corp and study coauthor Sapan Desai, MD, Surgisphere’s founder and CEO.

The authors asked for an independent third-party review of Surgisphere to evaluate the integrity of the trial elements and to replicate the analyses in the article.

“Our independent peer reviewers informed us that Surgisphere would not transfer the full dataset, client contracts, and the full ISO audit report to their servers for analysis, as such transfer would violate client agreements and confidentiality requirements,” the authors wrote.

Therefore, reviewers were not able to conduct the review and notified the authors they would withdraw from the peer-review process.

The Lancet said in a statement: “The Lancet takes issues of scientific integrity extremely seriously, and there are many outstanding questions about Surgisphere and the data that were allegedly included in this study. Following guidelines from the Committee on Publication Ethics and International Committee of Medical Journal Editors, institutional reviews of Surgisphere’s research collaborations are urgently needed.”

The authors wrote, “We can never forget the responsibility we have as researchers to scrupulously ensure that we rely on data sources that adhere to our high standards. Based on this development, we can no longer vouch for the veracity of the primary data sources. Due to this unfortunate development, the authors request that the paper be retracted.

“We all entered this collaboration to contribute in good faith and at a time of great need during the COVID-19 pandemic. We deeply apologize to you, the editors, and the journal readership for any embarrassment or inconvenience that this may have caused.”

In a similar, if briefer, note, the authors requested that the New England Journal of Medicine retract the earlier article as well. The retraction notice on the website reads: “Because all the authors were not granted access to the raw data and the raw data could not be made available to a third-party auditor, we are unable to validate the primary data sources underlying our article, ‘Cardiovascular Disease, Drug Therapy, and Mortality in Covid-19.’ We therefore request that the article be retracted. We apologize to the editors and to readers of the Journal for the difficulties that this has caused.”

Both journals had already published “Expression of Concern” notices about the articles. The expression of concern followed an open letter, endorsed by more than 200 scientists, ethicists, and clinicians and posted on May 28, questioning the data and ethics of the study.

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






 

Wearing a mask at home, even when everyone is feeling fine, might reduce the risk of frontline healthcare workers transmitting SARS-CoV-2 infection to their families, a recent study from China suggests. But the benefits might not outweigh the costs, according to several physicians interviewed.

“My gut reaction is that home mask use for healthcare workers would place an inordinately high burden on those healthcare workers and their families,” said Jeanne Noble, MD, an emergency care physician at the University of California, San Francisco. “Wearing a mask for a 10-hour shift already represents significant physical discomfort, causing sores across the nose and behind the ears. The emotional toll of the physical distance that comes with mask use, with limited facial expression, is also quite real.”

The suggested benefit of home mask use comes from research published online May 28 in BMJ Global Health. To assess predictors of household transmission of SARS-CoV-2 infection, Yu Wang, MD, of the Beijing Center for Disease Prevention and Control and colleagues conducted a retrospective study of 124 families in Beijing in which there was a confirmed case of COVID-19 as of February 21. The researchers surveyed family members by telephone about household hygiene and behaviors during the pandemic to examine risk factors for transmission.

During the 2 weeks following onset of the primary case, secondary transmission occurred in 41 families. Overall, 77 of 335 family members developed COVID-19.

A multivariable logistic regression analysis found that in households in which family members wore masks at home before the first person became ill, there was less likelihood of transmission of disease to a family member, compared with families in which no one wore a mask prior to illness onset.

“Facemasks were 79% effective and disinfection was 77% effective in preventing transmission,” the researchers report, “whilst close frequent contact in the household increased the risk of transmission 18 times, and diarrhea in the index patient increased the risk by four times.

However, wearing masks after symptom onset was not protective, according to the analysis. The findings support “universal face mask use, and also provides guidance on risk reduction for families living with someone in quarantine or isolation, and families of health workers, who may face ongoing risk,” the authors write.

Still, other precautions may be more important, experts say.

“I think by far the best way for healthcare professionals to protect their families is to carefully employ appropriate infection prevention measures at work,” said Mark E. Rupp, MD, chief of the Division of Infectious Diseases at Nebraska Medical Center in Omaha. “The combination of administrative interventions, engineering improvements, and personal protective equipment is very effective in preventing SARS-CoV-2 acquisition in the workplace.”

Many physicians already wear masks at home, and this study “only reemphasized the importance of doing so,” said Raghavendra Tirupathi, MD, medical director of Keystone Infectious Diseases in Chambersburg, Pennsylvania, who recently reviewed studies about masks and COVID-19.

Home mask use provides “one more layer of protection that might help mitigate the risk of transmission to family members,” Tirupathi said. But it does not obviate the need to follow other preventive measures, such as social distancing and proper hygiene.

But Rupp, whose advice on how healthcare workers can protect their families was recently highlighted by the American Medical Association, isn’t convinced. He said he won’t be adding home mask use to his list of recommendations. “It would be intrusive, cumbersome, and impractical to wear a mask in the home setting,” Rupp said in an interview.

However, when out in the community, all family members must protect one another by practicing social distancing, wearing masks, and practicing proper hand hygiene. “I also think that it is a good idea to have some masks on hand in case anyone does develop symptoms in the household and to wear them if a family member falls ill ― at least until testing can confirm COVID-19,” Rupp said. “If a family member does fall ill, masks for the ill person as well as the well persons would be indicated along with other home quarantine measures.”

For her part, Noble, who has provided guidance about proper mask use, said that targeted use of masks at home, such as around older visiting relatives or other more vulnerable family members, may be more realistic than continuous in-home use.

When a household member becomes ill, recommendations for preventing disease spread include having a sick family member sleep in a separate bedroom, using a separate bathroom, and wearing a mask when within 6 feet of other household members. They also should avoid sharing meals. “For a household member who is a medical provider, to follow these self-isolation precautions while at home for months on end would have a significant emotional toll,” Noble said in an email. “With no end in sight for the pandemic, perpetual mask use in both the private and public sphere strikes me as overwhelming ― I write this near the end of my 10-hour shift wearing both an N95 and surgical mask and counting the minutes before I can take them off!”

A limitation of the study was its reliance on telephone interviews, which are subject to recall bias, the authors note.

The study was funded by the Beijing Science and Technology Planning Project. The researchers have disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

Wearing a mask at home, even when everyone is feeling fine, might reduce the risk of frontline healthcare workers transmitting SARS-CoV-2 infection to their families, a recent study from China suggests. But the benefits might not outweigh the costs, according to several physicians interviewed.

“My gut reaction is that home mask use for healthcare workers would place an inordinately high burden on those healthcare workers and their families,” said Jeanne Noble, MD, an emergency care physician at the University of California, San Francisco. “Wearing a mask for a 10-hour shift already represents significant physical discomfort, causing sores across the nose and behind the ears. The emotional toll of the physical distance that comes with mask use, with limited facial expression, is also quite real.”

The suggested benefit of home mask use comes from research published online May 28 in BMJ Global Health. To assess predictors of household transmission of SARS-CoV-2 infection, Yu Wang, MD, of the Beijing Center for Disease Prevention and Control and colleagues conducted a retrospective study of 124 families in Beijing in which there was a confirmed case of COVID-19 as of February 21. The researchers surveyed family members by telephone about household hygiene and behaviors during the pandemic to examine risk factors for transmission.

During the 2 weeks following onset of the primary case, secondary transmission occurred in 41 families. Overall, 77 of 335 family members developed COVID-19.

A multivariable logistic regression analysis found that in households in which family members wore masks at home before the first person became ill, there was less likelihood of transmission of disease to a family member, compared with families in which no one wore a mask prior to illness onset.

“Facemasks were 79% effective and disinfection was 77% effective in preventing transmission,” the researchers report, “whilst close frequent contact in the household increased the risk of transmission 18 times, and diarrhea in the index patient increased the risk by four times.

However, wearing masks after symptom onset was not protective, according to the analysis. The findings support “universal face mask use, and also provides guidance on risk reduction for families living with someone in quarantine or isolation, and families of health workers, who may face ongoing risk,” the authors write.

Still, other precautions may be more important, experts say.

“I think by far the best way for healthcare professionals to protect their families is to carefully employ appropriate infection prevention measures at work,” said Mark E. Rupp, MD, chief of the Division of Infectious Diseases at Nebraska Medical Center in Omaha. “The combination of administrative interventions, engineering improvements, and personal protective equipment is very effective in preventing SARS-CoV-2 acquisition in the workplace.”

Many physicians already wear masks at home, and this study “only reemphasized the importance of doing so,” said Raghavendra Tirupathi, MD, medical director of Keystone Infectious Diseases in Chambersburg, Pennsylvania, who recently reviewed studies about masks and COVID-19.

Home mask use provides “one more layer of protection that might help mitigate the risk of transmission to family members,” Tirupathi said. But it does not obviate the need to follow other preventive measures, such as social distancing and proper hygiene.

But Rupp, whose advice on how healthcare workers can protect their families was recently highlighted by the American Medical Association, isn’t convinced. He said he won’t be adding home mask use to his list of recommendations. “It would be intrusive, cumbersome, and impractical to wear a mask in the home setting,” Rupp said in an interview.

However, when out in the community, all family members must protect one another by practicing social distancing, wearing masks, and practicing proper hand hygiene. “I also think that it is a good idea to have some masks on hand in case anyone does develop symptoms in the household and to wear them if a family member falls ill ― at least until testing can confirm COVID-19,” Rupp said. “If a family member does fall ill, masks for the ill person as well as the well persons would be indicated along with other home quarantine measures.”

For her part, Noble, who has provided guidance about proper mask use, said that targeted use of masks at home, such as around older visiting relatives or other more vulnerable family members, may be more realistic than continuous in-home use.

When a household member becomes ill, recommendations for preventing disease spread include having a sick family member sleep in a separate bedroom, using a separate bathroom, and wearing a mask when within 6 feet of other household members. They also should avoid sharing meals. “For a household member who is a medical provider, to follow these self-isolation precautions while at home for months on end would have a significant emotional toll,” Noble said in an email. “With no end in sight for the pandemic, perpetual mask use in both the private and public sphere strikes me as overwhelming ― I write this near the end of my 10-hour shift wearing both an N95 and surgical mask and counting the minutes before I can take them off!”

A limitation of the study was its reliance on telephone interviews, which are subject to recall bias, the authors note.

The study was funded by the Beijing Science and Technology Planning Project. The researchers have disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

Wearing a mask at home, even when everyone is feeling fine, might reduce the risk of frontline healthcare workers transmitting SARS-CoV-2 infection to their families, a recent study from China suggests. But the benefits might not outweigh the costs, according to several physicians interviewed.

“My gut reaction is that home mask use for healthcare workers would place an inordinately high burden on those healthcare workers and their families,” said Jeanne Noble, MD, an emergency care physician at the University of California, San Francisco. “Wearing a mask for a 10-hour shift already represents significant physical discomfort, causing sores across the nose and behind the ears. The emotional toll of the physical distance that comes with mask use, with limited facial expression, is also quite real.”

The suggested benefit of home mask use comes from research published online May 28 in BMJ Global Health. To assess predictors of household transmission of SARS-CoV-2 infection, Yu Wang, MD, of the Beijing Center for Disease Prevention and Control and colleagues conducted a retrospective study of 124 families in Beijing in which there was a confirmed case of COVID-19 as of February 21. The researchers surveyed family members by telephone about household hygiene and behaviors during the pandemic to examine risk factors for transmission.

During the 2 weeks following onset of the primary case, secondary transmission occurred in 41 families. Overall, 77 of 335 family members developed COVID-19.

A multivariable logistic regression analysis found that in households in which family members wore masks at home before the first person became ill, there was less likelihood of transmission of disease to a family member, compared with families in which no one wore a mask prior to illness onset.

“Facemasks were 79% effective and disinfection was 77% effective in preventing transmission,” the researchers report, “whilst close frequent contact in the household increased the risk of transmission 18 times, and diarrhea in the index patient increased the risk by four times.

However, wearing masks after symptom onset was not protective, according to the analysis. The findings support “universal face mask use, and also provides guidance on risk reduction for families living with someone in quarantine or isolation, and families of health workers, who may face ongoing risk,” the authors write.

Still, other precautions may be more important, experts say.

“I think by far the best way for healthcare professionals to protect their families is to carefully employ appropriate infection prevention measures at work,” said Mark E. Rupp, MD, chief of the Division of Infectious Diseases at Nebraska Medical Center in Omaha. “The combination of administrative interventions, engineering improvements, and personal protective equipment is very effective in preventing SARS-CoV-2 acquisition in the workplace.”

Many physicians already wear masks at home, and this study “only reemphasized the importance of doing so,” said Raghavendra Tirupathi, MD, medical director of Keystone Infectious Diseases in Chambersburg, Pennsylvania, who recently reviewed studies about masks and COVID-19.

Home mask use provides “one more layer of protection that might help mitigate the risk of transmission to family members,” Tirupathi said. But it does not obviate the need to follow other preventive measures, such as social distancing and proper hygiene.

But Rupp, whose advice on how healthcare workers can protect their families was recently highlighted by the American Medical Association, isn’t convinced. He said he won’t be adding home mask use to his list of recommendations. “It would be intrusive, cumbersome, and impractical to wear a mask in the home setting,” Rupp said in an interview.

However, when out in the community, all family members must protect one another by practicing social distancing, wearing masks, and practicing proper hand hygiene. “I also think that it is a good idea to have some masks on hand in case anyone does develop symptoms in the household and to wear them if a family member falls ill ― at least until testing can confirm COVID-19,” Rupp said. “If a family member does fall ill, masks for the ill person as well as the well persons would be indicated along with other home quarantine measures.”

For her part, Noble, who has provided guidance about proper mask use, said that targeted use of masks at home, such as around older visiting relatives or other more vulnerable family members, may be more realistic than continuous in-home use.

When a household member becomes ill, recommendations for preventing disease spread include having a sick family member sleep in a separate bedroom, using a separate bathroom, and wearing a mask when within 6 feet of other household members. They also should avoid sharing meals. “For a household member who is a medical provider, to follow these self-isolation precautions while at home for months on end would have a significant emotional toll,” Noble said in an email. “With no end in sight for the pandemic, perpetual mask use in both the private and public sphere strikes me as overwhelming ― I write this near the end of my 10-hour shift wearing both an N95 and surgical mask and counting the minutes before I can take them off!”

A limitation of the study was its reliance on telephone interviews, which are subject to recall bias, the authors note.

The study was funded by the Beijing Science and Technology Planning Project. The researchers have disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

Here are the stories our MDedge editors across specialties think you need to know about today:

More fatalities in heart transplant patients with COVID-19

COVID-19 infection appears to be associated with a high risk for mortality in heart transplant recipients. The conclusion is based on a case series with 28 patients with a confirmed diagnosis of COVID-19 who received a heart transplant during March and April 2020. There was a case-fatality rate of 25%, according to the study published in JAMA Cardiology. “The high case fatality in our case series should alert physicians to the vulnerability of heart transplant recipients during the COVID-19 pandemic,” senior author Nir Uriel, MD, professor of medicine at Columbia University, New York, said in an interview. “These patients require extra precautions to prevent the development of infection.” Read more.

High costs for type 1 diabetes patients: It’s not just insulin

For privately insured individuals with type 1 diabetes in the United States, out-of-pocket costs for insulin are typically lower than for other diabetes-related supplies. But overall out-of-pocket costs – taking into account everything that is needed to manage diabetes – are still very high. Two separate research letters recently published in JAMA Internal Medicine examined some of the drivers behind these high costs. The first research letter examined all costs for privately insured patients with type 1 diabetes, finding a mean out-of-pocket spend of approximately $2,500 a year. “Policymakers should improve the affordability of all care for type 1 diabetes,” said the lead author of the first research letter, Kao-Ping Chua, MD, PhD, of the department of pediatrics, University of Michigan, Ann Arbor. Read more.

Most rheumatology drugs don’t up COVID-19 hospitalizations

The vast majority of patients with rheumatic and musculoskeletal diseases who contract COVID-19 recover from the virus, regardless of which medication they receive for their rheumatic condition, new international research suggests. Researchers looked at 600 COVID-19 patients from 40 countries, and found that those taking TNF inhibitors for their rheumatic disease were less likely to be hospitalized for COVID-19. Treatment with more than 10 mg of prednisone daily – considered a moderate to high dose – was associated with a higher probability of hospitalization, however. “These results provide, for the first time, information about the outcome of COVID-19 in patients with rheumatic and musculoskeletal diseases,” said study investigator Pedro Machado, MD, PhD, from University College London. “They should provide some reassurance to patients and healthcare providers.” Read more.

A bumpy virtual #ASCO20

Some prominent oncologists gave up on the virtual meeting of the American Society of Clinical Oncology after facing technical problems with online sessions. Despite those glitches, dozens of virtual meeting attendees praised the online effort, which was assembled in just a few months, and called out virtues such as the quick availability of video transcripts as well as the obvious benefits of low cost, zero travel, and overall convenience. But one sentiment was nearly universal: there’s nothing like the real thing. This year’s meeting, which involved 40,000-plus attendees, was shortened to 3 days and limited to scientific presentations because of the COVID-19 pandemic. Education sessions will be held online August 8-10. Read more.

Parenting special needs children: An unlikely model

As families adjust to daily life during a pandemic, the parents of special needs children may be able to offer them some lessons. The chronic struggles of many special needs parents – from staying home often to taking on roles in which they have not been trained – strongly resemble the challenges facing most families in the COVID-19 pandemic, according to Migdalia Miranda Sotir, MD, a psychiatrist in private practice in Wheaton, Ill. “Parents may take on active roles supplementing their developmentally delayed children with educational experiences or therapeutic modalities in their own homes given that the needs might be too great to just rely on the school or therapy time,” she writes on MDedge. Read more.

For more on COVID-19, visit our Resource Center. All of our latest news is available on MDedge.com.

Here are the stories our MDedge editors across specialties think you need to know about today:

More fatalities in heart transplant patients with COVID-19

COVID-19 infection appears to be associated with a high risk for mortality in heart transplant recipients. The conclusion is based on a case series with 28 patients with a confirmed diagnosis of COVID-19 who received a heart transplant during March and April 2020. There was a case-fatality rate of 25%, according to the study published in JAMA Cardiology. “The high case fatality in our case series should alert physicians to the vulnerability of heart transplant recipients during the COVID-19 pandemic,” senior author Nir Uriel, MD, professor of medicine at Columbia University, New York, said in an interview. “These patients require extra precautions to prevent the development of infection.” Read more.

High costs for type 1 diabetes patients: It’s not just insulin

For privately insured individuals with type 1 diabetes in the United States, out-of-pocket costs for insulin are typically lower than for other diabetes-related supplies. But overall out-of-pocket costs – taking into account everything that is needed to manage diabetes – are still very high. Two separate research letters recently published in JAMA Internal Medicine examined some of the drivers behind these high costs. The first research letter examined all costs for privately insured patients with type 1 diabetes, finding a mean out-of-pocket spend of approximately $2,500 a year. “Policymakers should improve the affordability of all care for type 1 diabetes,” said the lead author of the first research letter, Kao-Ping Chua, MD, PhD, of the department of pediatrics, University of Michigan, Ann Arbor. Read more.

Most rheumatology drugs don’t up COVID-19 hospitalizations

The vast majority of patients with rheumatic and musculoskeletal diseases who contract COVID-19 recover from the virus, regardless of which medication they receive for their rheumatic condition, new international research suggests. Researchers looked at 600 COVID-19 patients from 40 countries, and found that those taking TNF inhibitors for their rheumatic disease were less likely to be hospitalized for COVID-19. Treatment with more than 10 mg of prednisone daily – considered a moderate to high dose – was associated with a higher probability of hospitalization, however. “These results provide, for the first time, information about the outcome of COVID-19 in patients with rheumatic and musculoskeletal diseases,” said study investigator Pedro Machado, MD, PhD, from University College London. “They should provide some reassurance to patients and healthcare providers.” Read more.

A bumpy virtual #ASCO20

Some prominent oncologists gave up on the virtual meeting of the American Society of Clinical Oncology after facing technical problems with online sessions. Despite those glitches, dozens of virtual meeting attendees praised the online effort, which was assembled in just a few months, and called out virtues such as the quick availability of video transcripts as well as the obvious benefits of low cost, zero travel, and overall convenience. But one sentiment was nearly universal: there’s nothing like the real thing. This year’s meeting, which involved 40,000-plus attendees, was shortened to 3 days and limited to scientific presentations because of the COVID-19 pandemic. Education sessions will be held online August 8-10. Read more.

Parenting special needs children: An unlikely model

As families adjust to daily life during a pandemic, the parents of special needs children may be able to offer them some lessons. The chronic struggles of many special needs parents – from staying home often to taking on roles in which they have not been trained – strongly resemble the challenges facing most families in the COVID-19 pandemic, according to Migdalia Miranda Sotir, MD, a psychiatrist in private practice in Wheaton, Ill. “Parents may take on active roles supplementing their developmentally delayed children with educational experiences or therapeutic modalities in their own homes given that the needs might be too great to just rely on the school or therapy time,” she writes on MDedge. Read more.

For more on COVID-19, visit our Resource Center. All of our latest news is available on MDedge.com.

Here are the stories our MDedge editors across specialties think you need to know about today:

More fatalities in heart transplant patients with COVID-19

COVID-19 infection appears to be associated with a high risk for mortality in heart transplant recipients. The conclusion is based on a case series with 28 patients with a confirmed diagnosis of COVID-19 who received a heart transplant during March and April 2020. There was a case-fatality rate of 25%, according to the study published in JAMA Cardiology. “The high case fatality in our case series should alert physicians to the vulnerability of heart transplant recipients during the COVID-19 pandemic,” senior author Nir Uriel, MD, professor of medicine at Columbia University, New York, said in an interview. “These patients require extra precautions to prevent the development of infection.” Read more.

High costs for type 1 diabetes patients: It’s not just insulin

For privately insured individuals with type 1 diabetes in the United States, out-of-pocket costs for insulin are typically lower than for other diabetes-related supplies. But overall out-of-pocket costs – taking into account everything that is needed to manage diabetes – are still very high. Two separate research letters recently published in JAMA Internal Medicine examined some of the drivers behind these high costs. The first research letter examined all costs for privately insured patients with type 1 diabetes, finding a mean out-of-pocket spend of approximately $2,500 a year. “Policymakers should improve the affordability of all care for type 1 diabetes,” said the lead author of the first research letter, Kao-Ping Chua, MD, PhD, of the department of pediatrics, University of Michigan, Ann Arbor. Read more.

Most rheumatology drugs don’t up COVID-19 hospitalizations

The vast majority of patients with rheumatic and musculoskeletal diseases who contract COVID-19 recover from the virus, regardless of which medication they receive for their rheumatic condition, new international research suggests. Researchers looked at 600 COVID-19 patients from 40 countries, and found that those taking TNF inhibitors for their rheumatic disease were less likely to be hospitalized for COVID-19. Treatment with more than 10 mg of prednisone daily – considered a moderate to high dose – was associated with a higher probability of hospitalization, however. “These results provide, for the first time, information about the outcome of COVID-19 in patients with rheumatic and musculoskeletal diseases,” said study investigator Pedro Machado, MD, PhD, from University College London. “They should provide some reassurance to patients and healthcare providers.” Read more.

A bumpy virtual #ASCO20

Some prominent oncologists gave up on the virtual meeting of the American Society of Clinical Oncology after facing technical problems with online sessions. Despite those glitches, dozens of virtual meeting attendees praised the online effort, which was assembled in just a few months, and called out virtues such as the quick availability of video transcripts as well as the obvious benefits of low cost, zero travel, and overall convenience. But one sentiment was nearly universal: there’s nothing like the real thing. This year’s meeting, which involved 40,000-plus attendees, was shortened to 3 days and limited to scientific presentations because of the COVID-19 pandemic. Education sessions will be held online August 8-10. Read more.

Parenting special needs children: An unlikely model

As families adjust to daily life during a pandemic, the parents of special needs children may be able to offer them some lessons. The chronic struggles of many special needs parents – from staying home often to taking on roles in which they have not been trained – strongly resemble the challenges facing most families in the COVID-19 pandemic, according to Migdalia Miranda Sotir, MD, a psychiatrist in private practice in Wheaton, Ill. “Parents may take on active roles supplementing their developmentally delayed children with educational experiences or therapeutic modalities in their own homes given that the needs might be too great to just rely on the school or therapy time,” she writes on MDedge. Read more.

For more on COVID-19, visit our Resource Center. All of our latest news is available on MDedge.com.

The vast majority of patients with rheumatic and musculoskeletal diseases who contract COVID-19 recover from the virus, regardless of which medication they receive for their rheumatic condition, new international research suggests.

“These results provide, for the first time, information about the outcome of COVID-19 in patients with rheumatic and musculoskeletal diseases,” said study investigator Pedro Machado, MD, PhD, from University College London. “They should provide some reassurance to patients and healthcare providers.”

Machado and his colleagues looked at 600 COVID-19 patients from 40 countries, and found that those taking TNF inhibitors for their rheumatic disease were less likely to be hospitalized for COVID-19. However, treatment with more than 10 mg of prednisone daily — considered a moderate to high dose — was associated with a higher probability of hospitalization.

In addition, hospitalization was not associated with biologics; JAK inhibitors; conventional disease-modifying antirheumatic drugs (DMARDs), such as methotrexate; antimalarials, such as hydroxychloroquine; or nonsteroidal anti-inflammatory drugs (NSAIDs) — either alone or in combination with other biologics, such as TNF-alpha inhibitors.

The findings were presented at the virtual European League Against Rheumatism (EULAR) 2020 Congress and were published online in Annals of the Rheumatic Diseases.

“Initially, there was a huge concern that these drugs could affect the outcome of patients getting COVID-19, but what this is showing is that probably these drugs do not increase their risk of severe outcome,” Machado, who is chair of the EULAR standing committee on epidemiology and health services research, told Medscape Medical News.

As of June 1, 1061 patients from 28 participating countries had been entered into the EULAR COVID-19 database, which was launched as part of the international Global Rheumatology Alliance registry. Patient data are categorized by factors such as top rheumatology diagnosis, comorbidities, top-five COVID-19 symptoms, and DMARD therapy at the time of virus infection. Anonymized data will be shared with an international register based in the United States.

Machado’s team combined data from the EULAR and Global Rheumatology Alliance COVID-19 registries from March 24 to April 20. They looked at patient factors — such as age, sex, smoking status, rheumatic diagnosis, comorbidities, and rheumatic therapies — to examine the association of rheumatic therapies with hospitalization rates and COVID-19 disease course.

Of the 277 patients (46%) in the study cohort who required hospitalization, 55 (9%) died. But this finding shouldn’t be viewed as the true rate of hospitalization or death in patients with rheumatic disease and COVID-19, said Gerd Burmester, MD, from Charité–University Medicine Berlin.

“There’s tremendous bias in terms of more serious cases of COVID-19 being reported to the registries,” he explained, “because the mild cases won’t even show up at their rheumatologist’s office.”

“This can skew the idea that COVID-19 is much more dangerous to rheumatic patients than to the regular population,” Burmester told Medscape Medical News. “It scares the patients, obviously, but we believe this is not justified.”

It’s still unclear whether rituximab use raises the risk for severe COVID-19, he said. “It appears to be the only biologic for which the jury is still out,” he said.

“Anti-TNFs and anti-IL-6 drugs may even be beneficial, although we don’t have robust data,” he added.

The study can only highlight associations between rheumatic drugs and COVID-19 outcomes. “We cannot say there is a causal relationship between the findings,” Machado said.

Longer-term data, when available, should illuminate “more granular” aspects of COVID-19 outcomes in rheumatic patients, including their risks of requiring ventilation or developing a cytokine storm, he noted.

Burmester and Machado agree that research needs to continue as the pandemic rages on. But so far, “there are no data suggesting that, if you’re on a targeted, dedicated immunomodulator, your risk is higher to have a worse course of COVID-19 than the general population,” Burmester said.

“We simply didn’t know that when the pandemic started, and some patients even discontinued their drugs out of this fear,” he added. “It’s more reassuring than we originally thought.”

This article first appeared on Medscape.com.

The vast majority of patients with rheumatic and musculoskeletal diseases who contract COVID-19 recover from the virus, regardless of which medication they receive for their rheumatic condition, new international research suggests.

“These results provide, for the first time, information about the outcome of COVID-19 in patients with rheumatic and musculoskeletal diseases,” said study investigator Pedro Machado, MD, PhD, from University College London. “They should provide some reassurance to patients and healthcare providers.”

Machado and his colleagues looked at 600 COVID-19 patients from 40 countries, and found that those taking TNF inhibitors for their rheumatic disease were less likely to be hospitalized for COVID-19. However, treatment with more than 10 mg of prednisone daily — considered a moderate to high dose — was associated with a higher probability of hospitalization.

In addition, hospitalization was not associated with biologics; JAK inhibitors; conventional disease-modifying antirheumatic drugs (DMARDs), such as methotrexate; antimalarials, such as hydroxychloroquine; or nonsteroidal anti-inflammatory drugs (NSAIDs) — either alone or in combination with other biologics, such as TNF-alpha inhibitors.

The findings were presented at the virtual European League Against Rheumatism (EULAR) 2020 Congress and were published online in Annals of the Rheumatic Diseases.

“Initially, there was a huge concern that these drugs could affect the outcome of patients getting COVID-19, but what this is showing is that probably these drugs do not increase their risk of severe outcome,” Machado, who is chair of the EULAR standing committee on epidemiology and health services research, told Medscape Medical News.

As of June 1, 1061 patients from 28 participating countries had been entered into the EULAR COVID-19 database, which was launched as part of the international Global Rheumatology Alliance registry. Patient data are categorized by factors such as top rheumatology diagnosis, comorbidities, top-five COVID-19 symptoms, and DMARD therapy at the time of virus infection. Anonymized data will be shared with an international register based in the United States.

Machado’s team combined data from the EULAR and Global Rheumatology Alliance COVID-19 registries from March 24 to April 20. They looked at patient factors — such as age, sex, smoking status, rheumatic diagnosis, comorbidities, and rheumatic therapies — to examine the association of rheumatic therapies with hospitalization rates and COVID-19 disease course.

Of the 277 patients (46%) in the study cohort who required hospitalization, 55 (9%) died. But this finding shouldn’t be viewed as the true rate of hospitalization or death in patients with rheumatic disease and COVID-19, said Gerd Burmester, MD, from Charité–University Medicine Berlin.

“There’s tremendous bias in terms of more serious cases of COVID-19 being reported to the registries,” he explained, “because the mild cases won’t even show up at their rheumatologist’s office.”

“This can skew the idea that COVID-19 is much more dangerous to rheumatic patients than to the regular population,” Burmester told Medscape Medical News. “It scares the patients, obviously, but we believe this is not justified.”

It’s still unclear whether rituximab use raises the risk for severe COVID-19, he said. “It appears to be the only biologic for which the jury is still out,” he said.

“Anti-TNFs and anti-IL-6 drugs may even be beneficial, although we don’t have robust data,” he added.

The study can only highlight associations between rheumatic drugs and COVID-19 outcomes. “We cannot say there is a causal relationship between the findings,” Machado said.

Longer-term data, when available, should illuminate “more granular” aspects of COVID-19 outcomes in rheumatic patients, including their risks of requiring ventilation or developing a cytokine storm, he noted.

Burmester and Machado agree that research needs to continue as the pandemic rages on. But so far, “there are no data suggesting that, if you’re on a targeted, dedicated immunomodulator, your risk is higher to have a worse course of COVID-19 than the general population,” Burmester said.

“We simply didn’t know that when the pandemic started, and some patients even discontinued their drugs out of this fear,” he added. “It’s more reassuring than we originally thought.”

This article first appeared on Medscape.com.

The vast majority of patients with rheumatic and musculoskeletal diseases who contract COVID-19 recover from the virus, regardless of which medication they receive for their rheumatic condition, new international research suggests.

“These results provide, for the first time, information about the outcome of COVID-19 in patients with rheumatic and musculoskeletal diseases,” said study investigator Pedro Machado, MD, PhD, from University College London. “They should provide some reassurance to patients and healthcare providers.”

Machado and his colleagues looked at 600 COVID-19 patients from 40 countries, and found that those taking TNF inhibitors for their rheumatic disease were less likely to be hospitalized for COVID-19. However, treatment with more than 10 mg of prednisone daily — considered a moderate to high dose — was associated with a higher probability of hospitalization.

In addition, hospitalization was not associated with biologics; JAK inhibitors; conventional disease-modifying antirheumatic drugs (DMARDs), such as methotrexate; antimalarials, such as hydroxychloroquine; or nonsteroidal anti-inflammatory drugs (NSAIDs) — either alone or in combination with other biologics, such as TNF-alpha inhibitors.

The findings were presented at the virtual European League Against Rheumatism (EULAR) 2020 Congress and were published online in Annals of the Rheumatic Diseases.

“Initially, there was a huge concern that these drugs could affect the outcome of patients getting COVID-19, but what this is showing is that probably these drugs do not increase their risk of severe outcome,” Machado, who is chair of the EULAR standing committee on epidemiology and health services research, told Medscape Medical News.

As of June 1, 1061 patients from 28 participating countries had been entered into the EULAR COVID-19 database, which was launched as part of the international Global Rheumatology Alliance registry. Patient data are categorized by factors such as top rheumatology diagnosis, comorbidities, top-five COVID-19 symptoms, and DMARD therapy at the time of virus infection. Anonymized data will be shared with an international register based in the United States.

Machado’s team combined data from the EULAR and Global Rheumatology Alliance COVID-19 registries from March 24 to April 20. They looked at patient factors — such as age, sex, smoking status, rheumatic diagnosis, comorbidities, and rheumatic therapies — to examine the association of rheumatic therapies with hospitalization rates and COVID-19 disease course.

Of the 277 patients (46%) in the study cohort who required hospitalization, 55 (9%) died. But this finding shouldn’t be viewed as the true rate of hospitalization or death in patients with rheumatic disease and COVID-19, said Gerd Burmester, MD, from Charité–University Medicine Berlin.

“There’s tremendous bias in terms of more serious cases of COVID-19 being reported to the registries,” he explained, “because the mild cases won’t even show up at their rheumatologist’s office.”

“This can skew the idea that COVID-19 is much more dangerous to rheumatic patients than to the regular population,” Burmester told Medscape Medical News. “It scares the patients, obviously, but we believe this is not justified.”

It’s still unclear whether rituximab use raises the risk for severe COVID-19, he said. “It appears to be the only biologic for which the jury is still out,” he said.

“Anti-TNFs and anti-IL-6 drugs may even be beneficial, although we don’t have robust data,” he added.

The study can only highlight associations between rheumatic drugs and COVID-19 outcomes. “We cannot say there is a causal relationship between the findings,” Machado said.

Longer-term data, when available, should illuminate “more granular” aspects of COVID-19 outcomes in rheumatic patients, including their risks of requiring ventilation or developing a cytokine storm, he noted.

Burmester and Machado agree that research needs to continue as the pandemic rages on. But so far, “there are no data suggesting that, if you’re on a targeted, dedicated immunomodulator, your risk is higher to have a worse course of COVID-19 than the general population,” Burmester said.

“We simply didn’t know that when the pandemic started, and some patients even discontinued their drugs out of this fear,” he added. “It’s more reassuring than we originally thought.”

This article first appeared on Medscape.com.

In patients with rheumatoid arthritis (RA), strategies to prevent cardiovascular events, such as treating hypertension, encouraging patients to stop smoking, and reinforcing statin therapy, may be especially important, regardless of whether they have a history of coronary artery disease because their risk for adverse cardiovascular outcomes is significantly greater than for patients who have neither RA nor coronary artery disease (CAD), a large population-based study from Denmark suggests.

“Among patients with RA, risk stratification by presence or absence of documented CAD may allow for screening and personalized treatment strategies,” wrote Brian B. Løgstrup, MD, PhD, DMSc, of Aarhus (Denmark) University Hospital, and his colleagues.

The study, published in Annals of the Rheumatic Diseases, analyzed 125,331 patients with and without CAD in the Western Denmark Heart Registry who had coronary angiography from 2003 through 2016. The cohort included 671 RA patients with no confirmed CAD and 1,061 RA patients who had CAD.

The study makes a significant contribution to the literature in reporting on the additive risk of RA and CAD, said Christie M. Bartels, MD, associate professor in the division of rheumatology at the University of Wisconsin, Madison. “Even among patients with both conditions [RA and CVD], they were less likely to get statin therapy,” she said, noting that the 82.6% of study patients with both CAD and RA were on statins vs. 86.5% of those with CAD alone, while the former had significantly higher rates of hypertension – 64.3% vs. 58.8%. “We’re doing a less effective job on secondary prevention,” she said. The anti-inflammatory properties of statins can also have an additive benefit in RA, she noted.

“This study shows that the rheumatologist can play a role in reinforcing the importance of primary and secondary cardiovascular disease prevention – meaning hypertension control, counseling patients to stop smoking and following up on statin therapy in RA,” Dr. Bartels added.

The study presents two novel findings, Dr. Løgstrup and colleagues noted:

• That RA confers a statistically significant, “but numerically marginally,” heightened risk of cardiovascular events other than stroke.
• Among patients with CAD, RA confers an increased risk of cardiac and all-cause death as well as MI and major adverse cardiovascular events (MACE).

“These finding indicate that RA may have a potential impact for precipitating cardiovascular events beyond CAD and, even more importantly, that RA seems to exacerbate the clinical risk of cardiovascular events in the presence of CAD,” Dr. Løgstrup and colleagues wrote.

The study found that patients with neither RA nor CAD had the lowest 10-year rates of MI (2.7%), ischemic stroke (2.9%), all-cause death (21.6%), cardiac death (2.3%), and MACE (7.3%).

By comparison, those with RA but no CAD had 10-year rates of 3.8% for MI, 5.5% for stroke, 35.6% for all-cause death, 3% for cardiac death, and 11.5% for MACE. Rates for those outcomes for people with CAD but no RA were 9.9% for MI, 4.6% for stroke, 33.3% for all-cause death, 7% for cardiac death, and 19.1% for MACE.

For patients with both RA and CAD, 10-year rates were 12.2% for MI, 4.4% for stroke, 49% for all-cause death, 10.9% for cardiac death, and 24.3% for MACE.

The researchers also performed a risk adjustment analysis based on potential confounding variables across the different groups, such as age, gender, comorbidities including diabetes and hypertension, active smoking status, and anticoagulant, antiplatelet, and statin therapy. The adjusted analysis revealed that patients with RA alone had a 63% greater risk of MI, 68% greater risk for stroke, 42% greater risk for all-cause death, 25% greater risk for cardiac death, and 60% greater risk for MACE than did people who had neither RA nor CAD.

For people with both RA and CAD, the adjusted risks were significantly higher when compared to people with neither: more than four times greater for MI and MACE, 55% greater for stroke, almost double for all-cause death, and 3.7 times greater for cardiac death. People with CAD but no RA also had higher adjusted risk rates compared to people with neither, but had variable rates when compared to people with RA but no CAD, and significantly lower adjusted rates compared to people with both.

The nature of CAD was also a factor, Dr. Løgstrup and colleagues noted. “We found more non-obstructive CAD but no increased incidence of one-vessel, two-vessel, and three-vessel disease in patients with RA than in patients without RA,” they wrote. That’s in line with other published studies (Semin Arthritis Rheum. 2010;40[3]:215–21 and J Rheumatol. 2007;34[5]:937–42), but counter to a study that found increased plaque burden and higher rates of multivessel disease among people with RA (Ann Rheum Dis. 2014;73:1797–804). Differences in methodology, vessel disease definitions, and study population may explain these deviations.

The study authors did not declare any outside source of funding or any competing interests.

Dr. Bartels disclosed receiving institutional grant funding through Pfizer.

SOURCE: Løgstrup BB et al. Ann Rheum Dis. 2020 May 29. doi: 10.1136/annrheumdis-2020-217154.

In patients with rheumatoid arthritis (RA), strategies to prevent cardiovascular events, such as treating hypertension, encouraging patients to stop smoking, and reinforcing statin therapy, may be especially important, regardless of whether they have a history of coronary artery disease because their risk for adverse cardiovascular outcomes is significantly greater than for patients who have neither RA nor coronary artery disease (CAD), a large population-based study from Denmark suggests.

“Among patients with RA, risk stratification by presence or absence of documented CAD may allow for screening and personalized treatment strategies,” wrote Brian B. Løgstrup, MD, PhD, DMSc, of Aarhus (Denmark) University Hospital, and his colleagues.

The study, published in Annals of the Rheumatic Diseases, analyzed 125,331 patients with and without CAD in the Western Denmark Heart Registry who had coronary angiography from 2003 through 2016. The cohort included 671 RA patients with no confirmed CAD and 1,061 RA patients who had CAD.

The study makes a significant contribution to the literature in reporting on the additive risk of RA and CAD, said Christie M. Bartels, MD, associate professor in the division of rheumatology at the University of Wisconsin, Madison. “Even among patients with both conditions [RA and CVD], they were less likely to get statin therapy,” she said, noting that the 82.6% of study patients with both CAD and RA were on statins vs. 86.5% of those with CAD alone, while the former had significantly higher rates of hypertension – 64.3% vs. 58.8%. “We’re doing a less effective job on secondary prevention,” she said. The anti-inflammatory properties of statins can also have an additive benefit in RA, she noted.

“This study shows that the rheumatologist can play a role in reinforcing the importance of primary and secondary cardiovascular disease prevention – meaning hypertension control, counseling patients to stop smoking and following up on statin therapy in RA,” Dr. Bartels added.

The study presents two novel findings, Dr. Løgstrup and colleagues noted:

• That RA confers a statistically significant, “but numerically marginally,” heightened risk of cardiovascular events other than stroke.
• Among patients with CAD, RA confers an increased risk of cardiac and all-cause death as well as MI and major adverse cardiovascular events (MACE).

“These finding indicate that RA may have a potential impact for precipitating cardiovascular events beyond CAD and, even more importantly, that RA seems to exacerbate the clinical risk of cardiovascular events in the presence of CAD,” Dr. Løgstrup and colleagues wrote.

The study found that patients with neither RA nor CAD had the lowest 10-year rates of MI (2.7%), ischemic stroke (2.9%), all-cause death (21.6%), cardiac death (2.3%), and MACE (7.3%).

By comparison, those with RA but no CAD had 10-year rates of 3.8% for MI, 5.5% for stroke, 35.6% for all-cause death, 3% for cardiac death, and 11.5% for MACE. Rates for those outcomes for people with CAD but no RA were 9.9% for MI, 4.6% for stroke, 33.3% for all-cause death, 7% for cardiac death, and 19.1% for MACE.

For patients with both RA and CAD, 10-year rates were 12.2% for MI, 4.4% for stroke, 49% for all-cause death, 10.9% for cardiac death, and 24.3% for MACE.

The researchers also performed a risk adjustment analysis based on potential confounding variables across the different groups, such as age, gender, comorbidities including diabetes and hypertension, active smoking status, and anticoagulant, antiplatelet, and statin therapy. The adjusted analysis revealed that patients with RA alone had a 63% greater risk of MI, 68% greater risk for stroke, 42% greater risk for all-cause death, 25% greater risk for cardiac death, and 60% greater risk for MACE than did people who had neither RA nor CAD.

For people with both RA and CAD, the adjusted risks were significantly higher when compared to people with neither: more than four times greater for MI and MACE, 55% greater for stroke, almost double for all-cause death, and 3.7 times greater for cardiac death. People with CAD but no RA also had higher adjusted risk rates compared to people with neither, but had variable rates when compared to people with RA but no CAD, and significantly lower adjusted rates compared to people with both.

The nature of CAD was also a factor, Dr. Løgstrup and colleagues noted. “We found more non-obstructive CAD but no increased incidence of one-vessel, two-vessel, and three-vessel disease in patients with RA than in patients without RA,” they wrote. That’s in line with other published studies (Semin Arthritis Rheum. 2010;40[3]:215–21 and J Rheumatol. 2007;34[5]:937–42), but counter to a study that found increased plaque burden and higher rates of multivessel disease among people with RA (Ann Rheum Dis. 2014;73:1797–804). Differences in methodology, vessel disease definitions, and study population may explain these deviations.

The study authors did not declare any outside source of funding or any competing interests.

Dr. Bartels disclosed receiving institutional grant funding through Pfizer.

SOURCE: Løgstrup BB et al. Ann Rheum Dis. 2020 May 29. doi: 10.1136/annrheumdis-2020-217154.

In patients with rheumatoid arthritis (RA), strategies to prevent cardiovascular events, such as treating hypertension, encouraging patients to stop smoking, and reinforcing statin therapy, may be especially important, regardless of whether they have a history of coronary artery disease because their risk for adverse cardiovascular outcomes is significantly greater than for patients who have neither RA nor coronary artery disease (CAD), a large population-based study from Denmark suggests.

“Among patients with RA, risk stratification by presence or absence of documented CAD may allow for screening and personalized treatment strategies,” wrote Brian B. Løgstrup, MD, PhD, DMSc, of Aarhus (Denmark) University Hospital, and his colleagues.

The study, published in Annals of the Rheumatic Diseases, analyzed 125,331 patients with and without CAD in the Western Denmark Heart Registry who had coronary angiography from 2003 through 2016. The cohort included 671 RA patients with no confirmed CAD and 1,061 RA patients who had CAD.

The study makes a significant contribution to the literature in reporting on the additive risk of RA and CAD, said Christie M. Bartels, MD, associate professor in the division of rheumatology at the University of Wisconsin, Madison. “Even among patients with both conditions [RA and CVD], they were less likely to get statin therapy,” she said, noting that the 82.6% of study patients with both CAD and RA were on statins vs. 86.5% of those with CAD alone, while the former had significantly higher rates of hypertension – 64.3% vs. 58.8%. “We’re doing a less effective job on secondary prevention,” she said. The anti-inflammatory properties of statins can also have an additive benefit in RA, she noted.

“This study shows that the rheumatologist can play a role in reinforcing the importance of primary and secondary cardiovascular disease prevention – meaning hypertension control, counseling patients to stop smoking and following up on statin therapy in RA,” Dr. Bartels added.

The study presents two novel findings, Dr. Løgstrup and colleagues noted:

• That RA confers a statistically significant, “but numerically marginally,” heightened risk of cardiovascular events other than stroke.
• Among patients with CAD, RA confers an increased risk of cardiac and all-cause death as well as MI and major adverse cardiovascular events (MACE).

“These finding indicate that RA may have a potential impact for precipitating cardiovascular events beyond CAD and, even more importantly, that RA seems to exacerbate the clinical risk of cardiovascular events in the presence of CAD,” Dr. Løgstrup and colleagues wrote.

The study found that patients with neither RA nor CAD had the lowest 10-year rates of MI (2.7%), ischemic stroke (2.9%), all-cause death (21.6%), cardiac death (2.3%), and MACE (7.3%).

By comparison, those with RA but no CAD had 10-year rates of 3.8% for MI, 5.5% for stroke, 35.6% for all-cause death, 3% for cardiac death, and 11.5% for MACE. Rates for those outcomes for people with CAD but no RA were 9.9% for MI, 4.6% for stroke, 33.3% for all-cause death, 7% for cardiac death, and 19.1% for MACE.

For patients with both RA and CAD, 10-year rates were 12.2% for MI, 4.4% for stroke, 49% for all-cause death, 10.9% for cardiac death, and 24.3% for MACE.

The researchers also performed a risk adjustment analysis based on potential confounding variables across the different groups, such as age, gender, comorbidities including diabetes and hypertension, active smoking status, and anticoagulant, antiplatelet, and statin therapy. The adjusted analysis revealed that patients with RA alone had a 63% greater risk of MI, 68% greater risk for stroke, 42% greater risk for all-cause death, 25% greater risk for cardiac death, and 60% greater risk for MACE than did people who had neither RA nor CAD.

For people with both RA and CAD, the adjusted risks were significantly higher when compared to people with neither: more than four times greater for MI and MACE, 55% greater for stroke, almost double for all-cause death, and 3.7 times greater for cardiac death. People with CAD but no RA also had higher adjusted risk rates compared to people with neither, but had variable rates when compared to people with RA but no CAD, and significantly lower adjusted rates compared to people with both.

The nature of CAD was also a factor, Dr. Løgstrup and colleagues noted. “We found more non-obstructive CAD but no increased incidence of one-vessel, two-vessel, and three-vessel disease in patients with RA than in patients without RA,” they wrote. That’s in line with other published studies (Semin Arthritis Rheum. 2010;40[3]:215–21 and J Rheumatol. 2007;34[5]:937–42), but counter to a study that found increased plaque burden and higher rates of multivessel disease among people with RA (Ann Rheum Dis. 2014;73:1797–804). Differences in methodology, vessel disease definitions, and study population may explain these deviations.

The study authors did not declare any outside source of funding or any competing interests.

Dr. Bartels disclosed receiving institutional grant funding through Pfizer.

SOURCE: Løgstrup BB et al. Ann Rheum Dis. 2020 May 29. doi: 10.1136/annrheumdis-2020-217154.

Parents of children with significant special needs know a thing or two about what the population in general has been experiencing since the pandemic took hold of the nation. The last few months have tested the stamina of most families. Many people are struggling to keep some semblance of normalcy amid a radical transformation of everyday life. It seems as if everything changed overnight.

Jupiterimages/Thinkstock

In a similar way, when a child with many needs is born into a family, adjustments also have to take place to receive the new baby. Families are, in most cases, not prepared for what is to come. Their expectations usually are not in sync with how their lives end up. They are crunched for time. They need to adjust, and at the same time, they mourn the loss of their previous less demanding lifestyle. More importantly, these parents learn that this might be an adjustment that they might need to make for a long time – in some instances, for a lifetime.

Stress load over time can correlate with a sense of burnout, and mental health professionals need to be prepared to address these issues in our patients.

Here is a list of some chronic struggles with which many special needs parents must contend. These strongly resemble the challenges parents in the general population have been facing with their families during this pandemic:

• Bypassing breaks to unwind and having to be always “on” while at home: These parents take care of children who need to be chronically tube fed, can’t sleep well at night because they are often sick, have recurrent seizures or maladaptive behaviors that affect the caretakers and the rest of the family. For parents of children who are on the autism spectrum, these challenges can be a constant struggle. Almost 60% of children with autism spectrum disorder (ASD) experience bodily difficulties, such as trouble breathing. However, nearly 100% of children with ASD experienced difficulties with their abilities and activities, such as self-care tasks like eating and dressing, and emotional or behavioral health, according to a 2016 report on child and adolescent health by the Johns Hopkins Bloomberg School of Public Health.
• Taking on roles for which they are not trained: Parents may take on active roles supplementing their developmentally delayed children with educational experiences or therapeutic modalities in their own homes given that the needs might be too great to just rely on the school or therapy time. There are about 1.17 million children in the United States living with ASD and more than 12% of children with ASD have severe cases, the Hopkins report said. Parents frequently are forced to take on the role of “therapist” to meet the needs of their child.
• Staying home often: Some parents are unable to have a “regular sitter” to provide respite, because the needs of the child require a higher level of care, training, and consideration. Caring for a special child means parents often don’t have the option of leaving their older child alone. As a result, they may end up spending more time at home than their counterpart parents with children who are the same age.
• Struggling to meet everyone’s demands for attention while at home: The child might require full-time attention or prolonged hospitalizations, and the needs of other siblings are sometimes put on hold until time or energy are available for all.
• Not traveling unless absolutely necessary: Families have a hard time leaving home for vacations or for other reasons. They may have to travel with medical supplies and equipment. They need to make sure that their destination is ready to welcome their child with all needs taken into consideration (special diets, activities, and facilities). Will the vacation set them back because it might take more effort to go than to stay home?
• Avoiding unnecessary exposures: Trying to avoid infections (even the ones that may be innocuous to others) if their child is immunocompromised. These children may readily decompensate and end up hospitalized with a more serious medical complication.
• Being very aware of remaining physically distant from others: Parents must go to great lengths not to impinge on other people’s space if the child is being loud or moving in a disruptive way, or if other people negatively affect how the child responds. Some families are apprehensive because they have felt judged by others when they are in the community, restaurants, or other places of gathering.
• Feeling concerned about having the right food, medicines, and supplements in the house: Parents are constantly trying to fulfill special dietary requirements and have the reserve to make sure that all meals and treatments are accounted for in the near future. They might need oxygen or specialized formulas that are hard to find in local stores. Some treatments, when withdrawn or unavailable, can prove life threatening.
• Restricting social circles: Some families with children with severe autism may self-isolate when they feel it is hard to be around them and be friends with them, since they can’t readily participate in “usual family activities,” and the regular norms of socialization can’t apply to their family’s set of behaviors. Their child might seem to be disruptive, or loud, nonverbal, mute, or unable to easily relate to others.
• Experiencing a pervasive sense of uncertainty about the future: A child might continue to miss milestones, or might have a rare condition that hasn’t been diagnosed. When thinking of the future, parents can’t predict what level of care they need to plan and budget for.
• Being concerned about dying early and not being able to provide for their child: Parents worry about who would take care of their child for life. Who would take care of their aging adult “child” after parents are gone? They might have concerns about having a will in place early on.
• Facing financial stress secondary to losing a job or the cost of treatments: Absenteeism might be the end result of having to care for their child’s ongoing needs, appointments, and medical emergencies. Sometimes, they might depend on a caretaker who might be very difficult to replace. It might take extensive training once a candidate is found. Direct costs include medical care, hospitalizations, special education, special therapies (occupational, speech, and physical therapy), and paid caregivers. Indirect costs include lost productivity for family caregivers because of the inability to maintain employment while caring for affected individuals, as well as lost wages and benefits, the Hopkins report said.
• Struggling to coordinate daily schedules: Parents face this challenge not only with young children but with those who are chronically ill and might need ongoing 24/7 care. The schedule might include educational and therapeutic (physical, occupational, speech, language therapy, recreational) interventions regularly or daily. This schedule is to be superimposed on all the other necessary responsibilities parents already have to contend with. Forty-eight percent of school-aged children with ASD use three or more services. In addition, children with moderate or severe cases of ASD used three or more services at almost twice the rate of children with mild cases of ASD (60% vs. 35%).
• Longing for a cure or a medicine that will improve the outcome: Often, parents search for treatments so that their child could live a more comfortable or healthier life. For children who have a rare condition, there may not be sufficient research dedicated to their cause or diagnostic pursuits. Currently, it is estimated that 1 in 10 Americans has a rare disease – about 80% of which are genetically based. Of the nearly 7,000 rare diseases known to exist, less than 500 – roughly 5% – have a known treatment approved by the U.S. Food and Drug Administration, reports the National Center for Advancing Translational Diseases and the Genetic and Rare Diseases Information Center.
• Hoping for better times to come: It is difficult at times to appreciate the present when it happens to be so chronically challenging and exhausting for everyone.

Parents of children with significant special needs experience many hurdles that they learn to endure, overcome, and master. This pandemic can provide physicians with a window into the lives of these families.
 

Dr. Sotir is a psychiatrist in private practice in Wheaton, Ill. As a parent of three children, one with special needs, she has extensive experience helping parents challenged by having special needs children find balance, support, direction, and joy in all dimensions of individual and family life. This area is the focus of her practice and public speaking. In Part 2, she will explore how psychiatrists as a specialty can support these families. She has no disclosures.

Parents of children with significant special needs know a thing or two about what the population in general has been experiencing since the pandemic took hold of the nation. The last few months have tested the stamina of most families. Many people are struggling to keep some semblance of normalcy amid a radical transformation of everyday life. It seems as if everything changed overnight.

Jupiterimages/Thinkstock

In a similar way, when a child with many needs is born into a family, adjustments also have to take place to receive the new baby. Families are, in most cases, not prepared for what is to come. Their expectations usually are not in sync with how their lives end up. They are crunched for time. They need to adjust, and at the same time, they mourn the loss of their previous less demanding lifestyle. More importantly, these parents learn that this might be an adjustment that they might need to make for a long time – in some instances, for a lifetime.

Stress load over time can correlate with a sense of burnout, and mental health professionals need to be prepared to address these issues in our patients.

Here is a list of some chronic struggles with which many special needs parents must contend. These strongly resemble the challenges parents in the general population have been facing with their families during this pandemic:

• Bypassing breaks to unwind and having to be always “on” while at home: These parents take care of children who need to be chronically tube fed, can’t sleep well at night because they are often sick, have recurrent seizures or maladaptive behaviors that affect the caretakers and the rest of the family. For parents of children who are on the autism spectrum, these challenges can be a constant struggle. Almost 60% of children with autism spectrum disorder (ASD) experience bodily difficulties, such as trouble breathing. However, nearly 100% of children with ASD experienced difficulties with their abilities and activities, such as self-care tasks like eating and dressing, and emotional or behavioral health, according to a 2016 report on child and adolescent health by the Johns Hopkins Bloomberg School of Public Health.
• Taking on roles for which they are not trained: Parents may take on active roles supplementing their developmentally delayed children with educational experiences or therapeutic modalities in their own homes given that the needs might be too great to just rely on the school or therapy time. There are about 1.17 million children in the United States living with ASD and more than 12% of children with ASD have severe cases, the Hopkins report said. Parents frequently are forced to take on the role of “therapist” to meet the needs of their child.
• Staying home often: Some parents are unable to have a “regular sitter” to provide respite, because the needs of the child require a higher level of care, training, and consideration. Caring for a special child means parents often don’t have the option of leaving their older child alone. As a result, they may end up spending more time at home than their counterpart parents with children who are the same age.
• Struggling to meet everyone’s demands for attention while at home: The child might require full-time attention or prolonged hospitalizations, and the needs of other siblings are sometimes put on hold until time or energy are available for all.
• Not traveling unless absolutely necessary: Families have a hard time leaving home for vacations or for other reasons. They may have to travel with medical supplies and equipment. They need to make sure that their destination is ready to welcome their child with all needs taken into consideration (special diets, activities, and facilities). Will the vacation set them back because it might take more effort to go than to stay home?
• Avoiding unnecessary exposures: Trying to avoid infections (even the ones that may be innocuous to others) if their child is immunocompromised. These children may readily decompensate and end up hospitalized with a more serious medical complication.
• Being very aware of remaining physically distant from others: Parents must go to great lengths not to impinge on other people’s space if the child is being loud or moving in a disruptive way, or if other people negatively affect how the child responds. Some families are apprehensive because they have felt judged by others when they are in the community, restaurants, or other places of gathering.
• Feeling concerned about having the right food, medicines, and supplements in the house: Parents are constantly trying to fulfill special dietary requirements and have the reserve to make sure that all meals and treatments are accounted for in the near future. They might need oxygen or specialized formulas that are hard to find in local stores. Some treatments, when withdrawn or unavailable, can prove life threatening.
• Restricting social circles: Some families with children with severe autism may self-isolate when they feel it is hard to be around them and be friends with them, since they can’t readily participate in “usual family activities,” and the regular norms of socialization can’t apply to their family’s set of behaviors. Their child might seem to be disruptive, or loud, nonverbal, mute, or unable to easily relate to others.
• Experiencing a pervasive sense of uncertainty about the future: A child might continue to miss milestones, or might have a rare condition that hasn’t been diagnosed. When thinking of the future, parents can’t predict what level of care they need to plan and budget for.
• Being concerned about dying early and not being able to provide for their child: Parents worry about who would take care of their child for life. Who would take care of their aging adult “child” after parents are gone? They might have concerns about having a will in place early on.
• Facing financial stress secondary to losing a job or the cost of treatments: Absenteeism might be the end result of having to care for their child’s ongoing needs, appointments, and medical emergencies. Sometimes, they might depend on a caretaker who might be very difficult to replace. It might take extensive training once a candidate is found. Direct costs include medical care, hospitalizations, special education, special therapies (occupational, speech, and physical therapy), and paid caregivers. Indirect costs include lost productivity for family caregivers because of the inability to maintain employment while caring for affected individuals, as well as lost wages and benefits, the Hopkins report said.
• Struggling to coordinate daily schedules: Parents face this challenge not only with young children but with those who are chronically ill and might need ongoing 24/7 care. The schedule might include educational and therapeutic (physical, occupational, speech, language therapy, recreational) interventions regularly or daily. This schedule is to be superimposed on all the other necessary responsibilities parents already have to contend with. Forty-eight percent of school-aged children with ASD use three or more services. In addition, children with moderate or severe cases of ASD used three or more services at almost twice the rate of children with mild cases of ASD (60% vs. 35%).
• Longing for a cure or a medicine that will improve the outcome: Often, parents search for treatments so that their child could live a more comfortable or healthier life. For children who have a rare condition, there may not be sufficient research dedicated to their cause or diagnostic pursuits. Currently, it is estimated that 1 in 10 Americans has a rare disease – about 80% of which are genetically based. Of the nearly 7,000 rare diseases known to exist, less than 500 – roughly 5% – have a known treatment approved by the U.S. Food and Drug Administration, reports the National Center for Advancing Translational Diseases and the Genetic and Rare Diseases Information Center.
• Hoping for better times to come: It is difficult at times to appreciate the present when it happens to be so chronically challenging and exhausting for everyone.

Parents of children with significant special needs experience many hurdles that they learn to endure, overcome, and master. This pandemic can provide physicians with a window into the lives of these families.
 

Dr. Sotir is a psychiatrist in private practice in Wheaton, Ill. As a parent of three children, one with special needs, she has extensive experience helping parents challenged by having special needs children find balance, support, direction, and joy in all dimensions of individual and family life. This area is the focus of her practice and public speaking. In Part 2, she will explore how psychiatrists as a specialty can support these families. She has no disclosures.

Parents of children with significant special needs know a thing or two about what the population in general has been experiencing since the pandemic took hold of the nation. The last few months have tested the stamina of most families. Many people are struggling to keep some semblance of normalcy amid a radical transformation of everyday life. It seems as if everything changed overnight.

Jupiterimages/Thinkstock

In a similar way, when a child with many needs is born into a family, adjustments also have to take place to receive the new baby. Families are, in most cases, not prepared for what is to come. Their expectations usually are not in sync with how their lives end up. They are crunched for time. They need to adjust, and at the same time, they mourn the loss of their previous less demanding lifestyle. More importantly, these parents learn that this might be an adjustment that they might need to make for a long time – in some instances, for a lifetime.

Stress load over time can correlate with a sense of burnout, and mental health professionals need to be prepared to address these issues in our patients.

Here is a list of some chronic struggles with which many special needs parents must contend. These strongly resemble the challenges parents in the general population have been facing with their families during this pandemic:

• Bypassing breaks to unwind and having to be always “on” while at home: These parents take care of children who need to be chronically tube fed, can’t sleep well at night because they are often sick, have recurrent seizures or maladaptive behaviors that affect the caretakers and the rest of the family. For parents of children who are on the autism spectrum, these challenges can be a constant struggle. Almost 60% of children with autism spectrum disorder (ASD) experience bodily difficulties, such as trouble breathing. However, nearly 100% of children with ASD experienced difficulties with their abilities and activities, such as self-care tasks like eating and dressing, and emotional or behavioral health, according to a 2016 report on child and adolescent health by the Johns Hopkins Bloomberg School of Public Health.
• Taking on roles for which they are not trained: Parents may take on active roles supplementing their developmentally delayed children with educational experiences or therapeutic modalities in their own homes given that the needs might be too great to just rely on the school or therapy time. There are about 1.17 million children in the United States living with ASD and more than 12% of children with ASD have severe cases, the Hopkins report said. Parents frequently are forced to take on the role of “therapist” to meet the needs of their child.
• Staying home often: Some parents are unable to have a “regular sitter” to provide respite, because the needs of the child require a higher level of care, training, and consideration. Caring for a special child means parents often don’t have the option of leaving their older child alone. As a result, they may end up spending more time at home than their counterpart parents with children who are the same age.
• Struggling to meet everyone’s demands for attention while at home: The child might require full-time attention or prolonged hospitalizations, and the needs of other siblings are sometimes put on hold until time or energy are available for all.
• Not traveling unless absolutely necessary: Families have a hard time leaving home for vacations or for other reasons. They may have to travel with medical supplies and equipment. They need to make sure that their destination is ready to welcome their child with all needs taken into consideration (special diets, activities, and facilities). Will the vacation set them back because it might take more effort to go than to stay home?
• Avoiding unnecessary exposures: Trying to avoid infections (even the ones that may be innocuous to others) if their child is immunocompromised. These children may readily decompensate and end up hospitalized with a more serious medical complication.
• Being very aware of remaining physically distant from others: Parents must go to great lengths not to impinge on other people’s space if the child is being loud or moving in a disruptive way, or if other people negatively affect how the child responds. Some families are apprehensive because they have felt judged by others when they are in the community, restaurants, or other places of gathering.
• Feeling concerned about having the right food, medicines, and supplements in the house: Parents are constantly trying to fulfill special dietary requirements and have the reserve to make sure that all meals and treatments are accounted for in the near future. They might need oxygen or specialized formulas that are hard to find in local stores. Some treatments, when withdrawn or unavailable, can prove life threatening.
• Restricting social circles: Some families with children with severe autism may self-isolate when they feel it is hard to be around them and be friends with them, since they can’t readily participate in “usual family activities,” and the regular norms of socialization can’t apply to their family’s set of behaviors. Their child might seem to be disruptive, or loud, nonverbal, mute, or unable to easily relate to others.
• Experiencing a pervasive sense of uncertainty about the future: A child might continue to miss milestones, or might have a rare condition that hasn’t been diagnosed. When thinking of the future, parents can’t predict what level of care they need to plan and budget for.
• Being concerned about dying early and not being able to provide for their child: Parents worry about who would take care of their child for life. Who would take care of their aging adult “child” after parents are gone? They might have concerns about having a will in place early on.
• Facing financial stress secondary to losing a job or the cost of treatments: Absenteeism might be the end result of having to care for their child’s ongoing needs, appointments, and medical emergencies. Sometimes, they might depend on a caretaker who might be very difficult to replace. It might take extensive training once a candidate is found. Direct costs include medical care, hospitalizations, special education, special therapies (occupational, speech, and physical therapy), and paid caregivers. Indirect costs include lost productivity for family caregivers because of the inability to maintain employment while caring for affected individuals, as well as lost wages and benefits, the Hopkins report said.
• Struggling to coordinate daily schedules: Parents face this challenge not only with young children but with those who are chronically ill and might need ongoing 24/7 care. The schedule might include educational and therapeutic (physical, occupational, speech, language therapy, recreational) interventions regularly or daily. This schedule is to be superimposed on all the other necessary responsibilities parents already have to contend with. Forty-eight percent of school-aged children with ASD use three or more services. In addition, children with moderate or severe cases of ASD used three or more services at almost twice the rate of children with mild cases of ASD (60% vs. 35%).
• Longing for a cure or a medicine that will improve the outcome: Often, parents search for treatments so that their child could live a more comfortable or healthier life. For children who have a rare condition, there may not be sufficient research dedicated to their cause or diagnostic pursuits. Currently, it is estimated that 1 in 10 Americans has a rare disease – about 80% of which are genetically based. Of the nearly 7,000 rare diseases known to exist, less than 500 – roughly 5% – have a known treatment approved by the U.S. Food and Drug Administration, reports the National Center for Advancing Translational Diseases and the Genetic and Rare Diseases Information Center.
• Hoping for better times to come: It is difficult at times to appreciate the present when it happens to be so chronically challenging and exhausting for everyone.

Parents of children with significant special needs experience many hurdles that they learn to endure, overcome, and master. This pandemic can provide physicians with a window into the lives of these families.
 

Dr. Sotir is a psychiatrist in private practice in Wheaton, Ill. As a parent of three children, one with special needs, she has extensive experience helping parents challenged by having special needs children find balance, support, direction, and joy in all dimensions of individual and family life. This area is the focus of her practice and public speaking. In Part 2, she will explore how psychiatrists as a specialty can support these families. She has no disclosures.

Avacopan, an investigational oral inhibitor of complement activation, is efficacious and safe for treating antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis, based on the results of the pivotal phase 3 ADVOCATE trial.

The trial results were reported in the opening plenary abstract session at the annual European Congress of Rheumatology, held online this year because of COVID-19.

“Standard of care for induction of remission includes high-dose glucocorticoids with either cyclophosphamide or rituximab. However, glucocorticoids are the major cause of treatment-related harm,” noted lead investigator Peter A. Merkel, MD, MPH, chief of the division of rheumatology at the University of Pennsylvania, Philadelphia.

The 331 patients in the trial had active ANCA-associated vasculitis (granulomatosis with polyangiitis or microscopic polyangiitis), either new onset or relapsed, with positivity for either proteinase 3 or myeloperoxidase antibodies and moderate to high disease activity.

They were randomized evenly to double-blind avacopan 30 mg or tapering prednisone from 60 mg/day to zero over 20 weeks, each combined either with rituximab (Rituxan) or with cyclophosphamide followed by azathioprine. Avacopan (formerly called CCX168) is a selective antagonist of the complement C5a receptor that has orphan-drug designation from the Food and Drug Administration for this disease.

Trial results showed that avacopan was noninferior to prednisone with respect to the week 26 rate of remission on the Birmingham Vasculitis Activity Score, with an estimate of common difference of 3.4%. And it was superior to prednisone with respect to the week 52 rate of sustained remission, which required remission from week 26 onward, with an estimate of common difference of 12.5%.

The avacopan group also had less glucocorticoid-related toxicity and, among patients with preexisting renal disease, greater improvement in renal function.

“This large, randomized trial met both of its primary endpoints. Important secondary endpoints were also achieved, with a very acceptable safety profile,” Dr. Merkel summarized.
 

Making sense of the results

The optimal duration of avacopan therapy is unclear, he noted. “We are still going to be learning how to use this drug, if it’s approved, in routine practice. But the data from the second 6 months – from week 26 to week 52 – implies that there is ongoing benefit to being on avacopan after remission is achieved.”

Avacopan worked similarly well regardless of disease status in ADVOCATE, according to Dr. Merkel. “We have not seen significant differences in efficacy of other drugs in our trials [by disease status], in the trials of ANCA-associated vasculitis. So I think we would treat moderate to serious disease similarly, whether it is new onset or recurrence, in terms of efficacy of the drug.”

“The topline phase 3 data from ADVOCATE sort of even exceeded my expectations in terms of the ability to show not just noninferiority, but superiority of avacopan at week 52 in maintaining sustained remission,” Lindsay S. Lally, MD, assistant professor of medicine at the Hospital for Special Surgery in New York, commented in an interview. “It’s spectacular to treat patients with this serious vasculitis without any steroids or with very minimal steroids, and see superiority at a year. That is really game changing.”

The ADVOCATE findings will likely pass muster with the FDA, according to Dr. Lally. “The bar that was set in terms of the coprimary endpoints was very stringent and in line with other registration trials, particularly the RAVE trial that led to the approval of rituximab,” she elaborated. “I don’t think there is any significant safety signal in the data related to avacopan.

“This study is going to move forward our ability to treat this disease effectively, as we have been able to do in some of our other vasculitis syndromes, by finding drugs that have significant steroid-sparing effects,” Dr. Lally predicted.
 

Study details

ADVOCATE results reported at the congress showed that the week 26 rate of disease remission was 72.3% with avacopan versus 70.1% with prednisone, with the difference falling within the 20% boundary for noninferiority (P < .0001) but missing the mark for superiority (P = .2387).

However, the week 52 rate of sustained disease remission was 65.7% versus 54.9%, respectively, yielding a difference in favor of avacopan that was statistically both noninferior (P < .0001) and superior (P = .0066).

At week 26, patients in the avacopan group had more favorable Glucocorticoid Toxicity Index scores for cumulative worsening (39.7 vs. 56.6; P = .0002) and for aggregate improvement (11.2 vs. 23.4; P = .008).

Among patients who had renal disease at baseline, those in the avacopan group had a greater increase in estimated glomerular filtration rate at week 52 (7.3 vs. 4.1 mL/min per 1.73 m²; P = .029).

“Particularly interesting is the fact that, even after week 26, when the patients were in remission, there was continued improvement in renal function,” Dr. Merkel noted.

Overall, avacopan had a good safety profile. “This was a sick population with many complications, but there were no important safety signals of the study medication,” he reported.

The avacopan and prednisone groups had a similar rate of severe adverse events (23.5% vs. 25.0%). But the former had lower rates of life-threatening adverse events (4.8% vs. 8.5%), adverse events potentially related to glucocorticoids (66.3% vs. 80.5%), deaths (1.2% vs. 2.4%), and deaths specifically caused by infection (0.6% vs. 1.2%).

The trial was sponsored by ChemoCentryx. Dr. Merkel disclosed receiving grant/research support from and consulting fees from ChemoCentryx, among other disclosures. Dr. Lally disclosed that she was an investigator in the trial.

SOURCE: Merkel PA et al. Ann Rheum Dis. 2020;79[suppl 1]:8, Abstract OP0011.

Avacopan, an investigational oral inhibitor of complement activation, is efficacious and safe for treating antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis, based on the results of the pivotal phase 3 ADVOCATE trial.

The trial results were reported in the opening plenary abstract session at the annual European Congress of Rheumatology, held online this year because of COVID-19.

“Standard of care for induction of remission includes high-dose glucocorticoids with either cyclophosphamide or rituximab. However, glucocorticoids are the major cause of treatment-related harm,” noted lead investigator Peter A. Merkel, MD, MPH, chief of the division of rheumatology at the University of Pennsylvania, Philadelphia.

The 331 patients in the trial had active ANCA-associated vasculitis (granulomatosis with polyangiitis or microscopic polyangiitis), either new onset or relapsed, with positivity for either proteinase 3 or myeloperoxidase antibodies and moderate to high disease activity.

They were randomized evenly to double-blind avacopan 30 mg or tapering prednisone from 60 mg/day to zero over 20 weeks, each combined either with rituximab (Rituxan) or with cyclophosphamide followed by azathioprine. Avacopan (formerly called CCX168) is a selective antagonist of the complement C5a receptor that has orphan-drug designation from the Food and Drug Administration for this disease.

Trial results showed that avacopan was noninferior to prednisone with respect to the week 26 rate of remission on the Birmingham Vasculitis Activity Score, with an estimate of common difference of 3.4%. And it was superior to prednisone with respect to the week 52 rate of sustained remission, which required remission from week 26 onward, with an estimate of common difference of 12.5%.

The avacopan group also had less glucocorticoid-related toxicity and, among patients with preexisting renal disease, greater improvement in renal function.

“This large, randomized trial met both of its primary endpoints. Important secondary endpoints were also achieved, with a very acceptable safety profile,” Dr. Merkel summarized.
 

Making sense of the results

The optimal duration of avacopan therapy is unclear, he noted. “We are still going to be learning how to use this drug, if it’s approved, in routine practice. But the data from the second 6 months – from week 26 to week 52 – implies that there is ongoing benefit to being on avacopan after remission is achieved.”

Avacopan worked similarly well regardless of disease status in ADVOCATE, according to Dr. Merkel. “We have not seen significant differences in efficacy of other drugs in our trials [by disease status], in the trials of ANCA-associated vasculitis. So I think we would treat moderate to serious disease similarly, whether it is new onset or recurrence, in terms of efficacy of the drug.”

“The topline phase 3 data from ADVOCATE sort of even exceeded my expectations in terms of the ability to show not just noninferiority, but superiority of avacopan at week 52 in maintaining sustained remission,” Lindsay S. Lally, MD, assistant professor of medicine at the Hospital for Special Surgery in New York, commented in an interview. “It’s spectacular to treat patients with this serious vasculitis without any steroids or with very minimal steroids, and see superiority at a year. That is really game changing.”

The ADVOCATE findings will likely pass muster with the FDA, according to Dr. Lally. “The bar that was set in terms of the coprimary endpoints was very stringent and in line with other registration trials, particularly the RAVE trial that led to the approval of rituximab,” she elaborated. “I don’t think there is any significant safety signal in the data related to avacopan.

“This study is going to move forward our ability to treat this disease effectively, as we have been able to do in some of our other vasculitis syndromes, by finding drugs that have significant steroid-sparing effects,” Dr. Lally predicted.
 

Study details

ADVOCATE results reported at the congress showed that the week 26 rate of disease remission was 72.3% with avacopan versus 70.1% with prednisone, with the difference falling within the 20% boundary for noninferiority (P < .0001) but missing the mark for superiority (P = .2387).

However, the week 52 rate of sustained disease remission was 65.7% versus 54.9%, respectively, yielding a difference in favor of avacopan that was statistically both noninferior (P < .0001) and superior (P = .0066).

At week 26, patients in the avacopan group had more favorable Glucocorticoid Toxicity Index scores for cumulative worsening (39.7 vs. 56.6; P = .0002) and for aggregate improvement (11.2 vs. 23.4; P = .008).

Among patients who had renal disease at baseline, those in the avacopan group had a greater increase in estimated glomerular filtration rate at week 52 (7.3 vs. 4.1 mL/min per 1.73 m²; P = .029).

“Particularly interesting is the fact that, even after week 26, when the patients were in remission, there was continued improvement in renal function,” Dr. Merkel noted.

Overall, avacopan had a good safety profile. “This was a sick population with many complications, but there were no important safety signals of the study medication,” he reported.

The avacopan and prednisone groups had a similar rate of severe adverse events (23.5% vs. 25.0%). But the former had lower rates of life-threatening adverse events (4.8% vs. 8.5%), adverse events potentially related to glucocorticoids (66.3% vs. 80.5%), deaths (1.2% vs. 2.4%), and deaths specifically caused by infection (0.6% vs. 1.2%).

The trial was sponsored by ChemoCentryx. Dr. Merkel disclosed receiving grant/research support from and consulting fees from ChemoCentryx, among other disclosures. Dr. Lally disclosed that she was an investigator in the trial.

SOURCE: Merkel PA et al. Ann Rheum Dis. 2020;79[suppl 1]:8, Abstract OP0011.

Avacopan, an investigational oral inhibitor of complement activation, is efficacious and safe for treating antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis, based on the results of the pivotal phase 3 ADVOCATE trial.

The trial results were reported in the opening plenary abstract session at the annual European Congress of Rheumatology, held online this year because of COVID-19.

“Standard of care for induction of remission includes high-dose glucocorticoids with either cyclophosphamide or rituximab. However, glucocorticoids are the major cause of treatment-related harm,” noted lead investigator Peter A. Merkel, MD, MPH, chief of the division of rheumatology at the University of Pennsylvania, Philadelphia.

The 331 patients in the trial had active ANCA-associated vasculitis (granulomatosis with polyangiitis or microscopic polyangiitis), either new onset or relapsed, with positivity for either proteinase 3 or myeloperoxidase antibodies and moderate to high disease activity.

They were randomized evenly to double-blind avacopan 30 mg or tapering prednisone from 60 mg/day to zero over 20 weeks, each combined either with rituximab (Rituxan) or with cyclophosphamide followed by azathioprine. Avacopan (formerly called CCX168) is a selective antagonist of the complement C5a receptor that has orphan-drug designation from the Food and Drug Administration for this disease.

Trial results showed that avacopan was noninferior to prednisone with respect to the week 26 rate of remission on the Birmingham Vasculitis Activity Score, with an estimate of common difference of 3.4%. And it was superior to prednisone with respect to the week 52 rate of sustained remission, which required remission from week 26 onward, with an estimate of common difference of 12.5%.

The avacopan group also had less glucocorticoid-related toxicity and, among patients with preexisting renal disease, greater improvement in renal function.

“This large, randomized trial met both of its primary endpoints. Important secondary endpoints were also achieved, with a very acceptable safety profile,” Dr. Merkel summarized.
 

Making sense of the results

The optimal duration of avacopan therapy is unclear, he noted. “We are still going to be learning how to use this drug, if it’s approved, in routine practice. But the data from the second 6 months – from week 26 to week 52 – implies that there is ongoing benefit to being on avacopan after remission is achieved.”

Avacopan worked similarly well regardless of disease status in ADVOCATE, according to Dr. Merkel. “We have not seen significant differences in efficacy of other drugs in our trials [by disease status], in the trials of ANCA-associated vasculitis. So I think we would treat moderate to serious disease similarly, whether it is new onset or recurrence, in terms of efficacy of the drug.”

“The topline phase 3 data from ADVOCATE sort of even exceeded my expectations in terms of the ability to show not just noninferiority, but superiority of avacopan at week 52 in maintaining sustained remission,” Lindsay S. Lally, MD, assistant professor of medicine at the Hospital for Special Surgery in New York, commented in an interview. “It’s spectacular to treat patients with this serious vasculitis without any steroids or with very minimal steroids, and see superiority at a year. That is really game changing.”

The ADVOCATE findings will likely pass muster with the FDA, according to Dr. Lally. “The bar that was set in terms of the coprimary endpoints was very stringent and in line with other registration trials, particularly the RAVE trial that led to the approval of rituximab,” she elaborated. “I don’t think there is any significant safety signal in the data related to avacopan.

“This study is going to move forward our ability to treat this disease effectively, as we have been able to do in some of our other vasculitis syndromes, by finding drugs that have significant steroid-sparing effects,” Dr. Lally predicted.
 

Study details

ADVOCATE results reported at the congress showed that the week 26 rate of disease remission was 72.3% with avacopan versus 70.1% with prednisone, with the difference falling within the 20% boundary for noninferiority (P < .0001) but missing the mark for superiority (P = .2387).

However, the week 52 rate of sustained disease remission was 65.7% versus 54.9%, respectively, yielding a difference in favor of avacopan that was statistically both noninferior (P < .0001) and superior (P = .0066).

At week 26, patients in the avacopan group had more favorable Glucocorticoid Toxicity Index scores for cumulative worsening (39.7 vs. 56.6; P = .0002) and for aggregate improvement (11.2 vs. 23.4; P = .008).

Among patients who had renal disease at baseline, those in the avacopan group had a greater increase in estimated glomerular filtration rate at week 52 (7.3 vs. 4.1 mL/min per 1.73 m²; P = .029).

“Particularly interesting is the fact that, even after week 26, when the patients were in remission, there was continued improvement in renal function,” Dr. Merkel noted.

Overall, avacopan had a good safety profile. “This was a sick population with many complications, but there were no important safety signals of the study medication,” he reported.

The avacopan and prednisone groups had a similar rate of severe adverse events (23.5% vs. 25.0%). But the former had lower rates of life-threatening adverse events (4.8% vs. 8.5%), adverse events potentially related to glucocorticoids (66.3% vs. 80.5%), deaths (1.2% vs. 2.4%), and deaths specifically caused by infection (0.6% vs. 1.2%).

The trial was sponsored by ChemoCentryx. Dr. Merkel disclosed receiving grant/research support from and consulting fees from ChemoCentryx, among other disclosures. Dr. Lally disclosed that she was an investigator in the trial.

SOURCE: Merkel PA et al. Ann Rheum Dis. 2020;79[suppl 1]:8, Abstract OP0011.

An alternative disease activity index for patients with systemic lupus erythematosus called the SLE-DAS (Disease Activity Score) has shown similar results to the Lupus Low Disease Activity State (LLDAS) in classifying low disease activity but may be easier to potentially apply in daily clinical practice in treat-to-target strategies, according to research presented at the annual European Congress of Rheumatology, held online this year because of COVID-19.

A treat-to-target approach, in which therapies are adjusted and the patient monitored to achieve the desired endpoint, has been proposed for patients with SLE. Clinical remission is the ideal goal, followed by achieving low disease activity (LDA) when clinical remission is unattainable, the first author of the SLE-DAS study, Helena Assunção, MD, of the department of rheumatology at Centro Hospitalar e Universitário de Coimbra (Portugal), said in an interview prior to the presentation of the study at the e-congress.

But to conduct a treat-to-target approach in the clinical setting, clinicians must have reliable, user-friendly targets to assess a patient’s progress, she said. But that’s not available right now. Proposed definitions of LDA, such as the LLDAS, are based on the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K). This index doesn’t address some important manifestations of SLE and it is scored dichotomously – for example, giving a similar score for thrombocytopenia when platelet count is reduced to 100,000 or to 10,000.

To compensate for these limitations, the current LLDAS definition also requires the Physician Global Assessment and other steps, including a review of medication and changes to treatment or clinical status since the previous visit.

“It is not easy to apply,” Dr. Assunção said.

The SLE-DAS is a continuous index involving 17 parameters (4 continuous: arthritis, proteinuria, thrombocytopenia, and leukopenia), assigning higher scores when a manifestation is more severe, and has manifestation information that SLEDAI-2K lacks (cardiopulmonary involvement, lupus enteritis, and hemolytic anemia).

In contrast, the LLDAS is defined as:
 

• A SLEDAI-2k score of 4 or less with no major organ involvement
• No new disease activity
• A physician global assessment of the patient of 1 or less on a 0-3 scale
• Maintenance on a prednisolone dosage of 7.5 mg/day or less
• Maintenance on a standard immunosuppressive regimen

A previous study validated the SLE-DAS (Ann Rheum Dis. 2019 Mar;78[3]:365-71), and another exploratory study identified a cutoff SLE-DAS value of 3.77 or lower for LDA with SLE-DAS (Ann Rheum Dis. 2019;78:411-2).

Her group compared LDA status as measured with LLDAS versus the SLE-DAS in a cross-sectional study of 292 consecutive patients at their hospital. LDA on the SLE-DAS was defined as a score 3.77 or lower and a prednisolone dose of 7.5 mg/day or less. A total of 85% of patients were in LDA with SLE-DAS and 83.9% with LLDAS, and the agreement between LLDAS and SLE-DAS LDA was very high (Cohen’s kappa coefficient test; kappa = 0.831; P < .01). Out of 292 patients, only 13 were classified differently by the two definitions, 8 of which were classified as LDA by SLE-DAS, and 5 by LLDAS. Overall, 87% of patients were women and had a mean age of nearly 49 years, with a mean disease duration of about 14 years.

Dr. Assunção feels that the SLE-DAS LDA should be sufficient to monitor disease activity without adding the Physician Global Assessment and other steps, which would make it easier to apply than LLDAS. The fact that it is based on a continuous index is also an important difference. “Especially for low disease activity, it’s very good to be able to define it with a continuous index, because you are not that bad, but not that good, you’re in the middle,” she said.

The study should be regarded as exploratory, she said, but the results were encouraging. “We got similar results, and it’s definitely easier to apply.” She can also personally attest that the new model is easier to use, since she personally collected data for LLDAS assignment. “I had to check this, and this, and this … [SLE-DAS] is easier.”

Future work from her group will aim at deriving and validating a more robust definition of LDA, which will again be compared with the current LLDAS definition.

Her colleagues have already developed and validated a definition for clinical remission using SLE-DAS, although those results have not yet been published. They hope to define activity states using SLE-DAS, including mild, moderate, and high disease activity.

The team has produced an online SLE-DAS calculator (http://sle-das.eu/) where clinicians can score the 17 parameters. “You just input the values and it gives a number reflecting disease activity. Using this definition of SLE-DAS LDA you only need that number and to verify that the prednisolone dose is equal to or inferior to 7.5 mg/day,” said Dr. Assunção.

The study received no funding. Dr. Assunção has no financial disclosures, but one coauthor reported receiving grant/research support from Pfizer and AbbVie and serving as a consultant to Pfizer, AbbVie, Roche, Lilly, and Novartis.

SOURCE: Assunção H et al. Ann Rheum Dis 2020;79[suppl 1]:60, Abstract OP0092.

An alternative disease activity index for patients with systemic lupus erythematosus called the SLE-DAS (Disease Activity Score) has shown similar results to the Lupus Low Disease Activity State (LLDAS) in classifying low disease activity but may be easier to potentially apply in daily clinical practice in treat-to-target strategies, according to research presented at the annual European Congress of Rheumatology, held online this year because of COVID-19.

A treat-to-target approach, in which therapies are adjusted and the patient monitored to achieve the desired endpoint, has been proposed for patients with SLE. Clinical remission is the ideal goal, followed by achieving low disease activity (LDA) when clinical remission is unattainable, the first author of the SLE-DAS study, Helena Assunção, MD, of the department of rheumatology at Centro Hospitalar e Universitário de Coimbra (Portugal), said in an interview prior to the presentation of the study at the e-congress.

But to conduct a treat-to-target approach in the clinical setting, clinicians must have reliable, user-friendly targets to assess a patient’s progress, she said. But that’s not available right now. Proposed definitions of LDA, such as the LLDAS, are based on the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K). This index doesn’t address some important manifestations of SLE and it is scored dichotomously – for example, giving a similar score for thrombocytopenia when platelet count is reduced to 100,000 or to 10,000.

To compensate for these limitations, the current LLDAS definition also requires the Physician Global Assessment and other steps, including a review of medication and changes to treatment or clinical status since the previous visit.

“It is not easy to apply,” Dr. Assunção said.

The SLE-DAS is a continuous index involving 17 parameters (4 continuous: arthritis, proteinuria, thrombocytopenia, and leukopenia), assigning higher scores when a manifestation is more severe, and has manifestation information that SLEDAI-2K lacks (cardiopulmonary involvement, lupus enteritis, and hemolytic anemia).

In contrast, the LLDAS is defined as:
 

• A SLEDAI-2k score of 4 or less with no major organ involvement
• No new disease activity
• A physician global assessment of the patient of 1 or less on a 0-3 scale
• Maintenance on a prednisolone dosage of 7.5 mg/day or less
• Maintenance on a standard immunosuppressive regimen

A previous study validated the SLE-DAS (Ann Rheum Dis. 2019 Mar;78[3]:365-71), and another exploratory study identified a cutoff SLE-DAS value of 3.77 or lower for LDA with SLE-DAS (Ann Rheum Dis. 2019;78:411-2).

Her group compared LDA status as measured with LLDAS versus the SLE-DAS in a cross-sectional study of 292 consecutive patients at their hospital. LDA on the SLE-DAS was defined as a score 3.77 or lower and a prednisolone dose of 7.5 mg/day or less. A total of 85% of patients were in LDA with SLE-DAS and 83.9% with LLDAS, and the agreement between LLDAS and SLE-DAS LDA was very high (Cohen’s kappa coefficient test; kappa = 0.831; P < .01). Out of 292 patients, only 13 were classified differently by the two definitions, 8 of which were classified as LDA by SLE-DAS, and 5 by LLDAS. Overall, 87% of patients were women and had a mean age of nearly 49 years, with a mean disease duration of about 14 years.

Dr. Assunção feels that the SLE-DAS LDA should be sufficient to monitor disease activity without adding the Physician Global Assessment and other steps, which would make it easier to apply than LLDAS. The fact that it is based on a continuous index is also an important difference. “Especially for low disease activity, it’s very good to be able to define it with a continuous index, because you are not that bad, but not that good, you’re in the middle,” she said.

The study should be regarded as exploratory, she said, but the results were encouraging. “We got similar results, and it’s definitely easier to apply.” She can also personally attest that the new model is easier to use, since she personally collected data for LLDAS assignment. “I had to check this, and this, and this … [SLE-DAS] is easier.”

Future work from her group will aim at deriving and validating a more robust definition of LDA, which will again be compared with the current LLDAS definition.

Her colleagues have already developed and validated a definition for clinical remission using SLE-DAS, although those results have not yet been published. They hope to define activity states using SLE-DAS, including mild, moderate, and high disease activity.

The team has produced an online SLE-DAS calculator (http://sle-das.eu/) where clinicians can score the 17 parameters. “You just input the values and it gives a number reflecting disease activity. Using this definition of SLE-DAS LDA you only need that number and to verify that the prednisolone dose is equal to or inferior to 7.5 mg/day,” said Dr. Assunção.

The study received no funding. Dr. Assunção has no financial disclosures, but one coauthor reported receiving grant/research support from Pfizer and AbbVie and serving as a consultant to Pfizer, AbbVie, Roche, Lilly, and Novartis.

SOURCE: Assunção H et al. Ann Rheum Dis 2020;79[suppl 1]:60, Abstract OP0092.

An alternative disease activity index for patients with systemic lupus erythematosus called the SLE-DAS (Disease Activity Score) has shown similar results to the Lupus Low Disease Activity State (LLDAS) in classifying low disease activity but may be easier to potentially apply in daily clinical practice in treat-to-target strategies, according to research presented at the annual European Congress of Rheumatology, held online this year because of COVID-19.

A treat-to-target approach, in which therapies are adjusted and the patient monitored to achieve the desired endpoint, has been proposed for patients with SLE. Clinical remission is the ideal goal, followed by achieving low disease activity (LDA) when clinical remission is unattainable, the first author of the SLE-DAS study, Helena Assunção, MD, of the department of rheumatology at Centro Hospitalar e Universitário de Coimbra (Portugal), said in an interview prior to the presentation of the study at the e-congress.

But to conduct a treat-to-target approach in the clinical setting, clinicians must have reliable, user-friendly targets to assess a patient’s progress, she said. But that’s not available right now. Proposed definitions of LDA, such as the LLDAS, are based on the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K). This index doesn’t address some important manifestations of SLE and it is scored dichotomously – for example, giving a similar score for thrombocytopenia when platelet count is reduced to 100,000 or to 10,000.

To compensate for these limitations, the current LLDAS definition also requires the Physician Global Assessment and other steps, including a review of medication and changes to treatment or clinical status since the previous visit.

“It is not easy to apply,” Dr. Assunção said.

The SLE-DAS is a continuous index involving 17 parameters (4 continuous: arthritis, proteinuria, thrombocytopenia, and leukopenia), assigning higher scores when a manifestation is more severe, and has manifestation information that SLEDAI-2K lacks (cardiopulmonary involvement, lupus enteritis, and hemolytic anemia).

In contrast, the LLDAS is defined as:
 

• A SLEDAI-2k score of 4 or less with no major organ involvement
• No new disease activity
• A physician global assessment of the patient of 1 or less on a 0-3 scale
• Maintenance on a prednisolone dosage of 7.5 mg/day or less
• Maintenance on a standard immunosuppressive regimen

A previous study validated the SLE-DAS (Ann Rheum Dis. 2019 Mar;78[3]:365-71), and another exploratory study identified a cutoff SLE-DAS value of 3.77 or lower for LDA with SLE-DAS (Ann Rheum Dis. 2019;78:411-2).

Her group compared LDA status as measured with LLDAS versus the SLE-DAS in a cross-sectional study of 292 consecutive patients at their hospital. LDA on the SLE-DAS was defined as a score 3.77 or lower and a prednisolone dose of 7.5 mg/day or less. A total of 85% of patients were in LDA with SLE-DAS and 83.9% with LLDAS, and the agreement between LLDAS and SLE-DAS LDA was very high (Cohen’s kappa coefficient test; kappa = 0.831; P < .01). Out of 292 patients, only 13 were classified differently by the two definitions, 8 of which were classified as LDA by SLE-DAS, and 5 by LLDAS. Overall, 87% of patients were women and had a mean age of nearly 49 years, with a mean disease duration of about 14 years.

Dr. Assunção feels that the SLE-DAS LDA should be sufficient to monitor disease activity without adding the Physician Global Assessment and other steps, which would make it easier to apply than LLDAS. The fact that it is based on a continuous index is also an important difference. “Especially for low disease activity, it’s very good to be able to define it with a continuous index, because you are not that bad, but not that good, you’re in the middle,” she said.

The study should be regarded as exploratory, she said, but the results were encouraging. “We got similar results, and it’s definitely easier to apply.” She can also personally attest that the new model is easier to use, since she personally collected data for LLDAS assignment. “I had to check this, and this, and this … [SLE-DAS] is easier.”

Future work from her group will aim at deriving and validating a more robust definition of LDA, which will again be compared with the current LLDAS definition.

Her colleagues have already developed and validated a definition for clinical remission using SLE-DAS, although those results have not yet been published. They hope to define activity states using SLE-DAS, including mild, moderate, and high disease activity.

The team has produced an online SLE-DAS calculator (http://sle-das.eu/) where clinicians can score the 17 parameters. “You just input the values and it gives a number reflecting disease activity. Using this definition of SLE-DAS LDA you only need that number and to verify that the prednisolone dose is equal to or inferior to 7.5 mg/day,” said Dr. Assunção.

The study received no funding. Dr. Assunção has no financial disclosures, but one coauthor reported receiving grant/research support from Pfizer and AbbVie and serving as a consultant to Pfizer, AbbVie, Roche, Lilly, and Novartis.

SOURCE: Assunção H et al. Ann Rheum Dis 2020;79[suppl 1]:60, Abstract OP0092.