Holiday travel season is right around the corner, but coronavirus cases have already started to climb. But a new automated texting system could relieve pressure on emergency departments and reduce mortality rates if there were an uptick in COVID-19 this winter.

COVID Watch, a text message–based remote monitoring program developed by the University of Pennsylvania Health System, was associated with a 68% reduction in the risk of death, compared with those who received usual care. This was the main finding of a paper published in the Annals of Internal Medicine.

The investigators also determined that patients who enrolled in the program were more likely to seek care in the ED and when they did, they came in on average 2 days sooner than those who received usual care.

“When our clinical team designed COVID Watch the goal was to facilitate hospital care for patients who require it, while supporting access to care for patients who can safely remain at home,” study author M. Kit Delgado, MD, MS, an assistant professor of emergency medicine and epidemiology at Penn Presbyterian Medical Center in Philadelphia, said in an interview.

Researchers had initially hoped COVID Watch would relieve pressure on EDs, Dr. Delgado said.
 

Significantly lower mortality seen among COVID Watch group

For the study, Dr. Delgado and colleagues enrolled 3,488 patients in COVID Watch and 4,377 in the usual care group to compare outcomes at 30 and 60 days.

“We didn’t include patients who were diagnosed with COVID in the ER or hospital, so this is a lower-risk cohort of patients who test positive in outpatient settings,” Dr. Delgado noted. “Outpatients who received usual care and COVID Watch both had relatively low mortality, but it was significantly lower in those who were in COVID Watch.”

The researchers found that 3 patients in the COVID Watch group died within 30 days of their enrollment, compared with 12 in the control group. At 60 days after enrollment, 5 people within COVID Watch died, compared with 16 not using the system. More than one-third of the deaths in the usual care group occurred outside the hospital, compared with zero deaths among those in COVID Watch.
 

More than half of program participants were Black or Latino

The messaging system also reduced mortality rates among “all major racial and ethnic subgroups,” the researchers said, with more than 50% of the patients enrolled in COVID Watch having been Black or Latino.

“This is important because Black and Hispanic communities have experienced higher exposure and infection rates, decreased access to care, and have had higher mortality rates,” Dr. Delgado said. “Therefore, the results imply that this type of program could play a role in decreasing disparities in COVID outcomes if scaled more broadly.”
 

Outside expert: COVID Watch bring new approach to digital health monitoring

The study not only highlights the efficacy and sustainment of the COVID Watch program, but it sheds light on the possibility of using text message monitoring systems on other chronic disease conditions, said Jamie Faro, PhD, who was not involved in the study.

“It brings a new approach to health monitoring using digital means, which may lessen the burden on health care providers and be more cost effective than usual care approaches,” said Dr. Faro, who is assistant professor at the department of population and quantitative health sciences at the University of Massachusetts, Worcester. “Text messaging, which is used by over 80% of Americans, can allow us to reach a large percentage of the population for remote health care monitoring.”

Researchers of the current study said the findings “reveal a model for outpatient health system management of patients with COVID-19 and possibly other conditions where the early detection of clinical declines is critical.” Dr. Faro said that COVID Watch can have a measurable impact on an outcome that is truly life or death. However, it would be critical to understand how to reach those who either “were not offered or refused to take part in the program.”

The authors of the paper and Dr. Faro had no disclosures.

Holiday travel season is right around the corner, but coronavirus cases have already started to climb. But a new automated texting system could relieve pressure on emergency departments and reduce mortality rates if there were an uptick in COVID-19 this winter.

COVID Watch, a text message–based remote monitoring program developed by the University of Pennsylvania Health System, was associated with a 68% reduction in the risk of death, compared with those who received usual care. This was the main finding of a paper published in the Annals of Internal Medicine.

The investigators also determined that patients who enrolled in the program were more likely to seek care in the ED and when they did, they came in on average 2 days sooner than those who received usual care.

“When our clinical team designed COVID Watch the goal was to facilitate hospital care for patients who require it, while supporting access to care for patients who can safely remain at home,” study author M. Kit Delgado, MD, MS, an assistant professor of emergency medicine and epidemiology at Penn Presbyterian Medical Center in Philadelphia, said in an interview.

Researchers had initially hoped COVID Watch would relieve pressure on EDs, Dr. Delgado said.
 

Significantly lower mortality seen among COVID Watch group

For the study, Dr. Delgado and colleagues enrolled 3,488 patients in COVID Watch and 4,377 in the usual care group to compare outcomes at 30 and 60 days.

“We didn’t include patients who were diagnosed with COVID in the ER or hospital, so this is a lower-risk cohort of patients who test positive in outpatient settings,” Dr. Delgado noted. “Outpatients who received usual care and COVID Watch both had relatively low mortality, but it was significantly lower in those who were in COVID Watch.”

The researchers found that 3 patients in the COVID Watch group died within 30 days of their enrollment, compared with 12 in the control group. At 60 days after enrollment, 5 people within COVID Watch died, compared with 16 not using the system. More than one-third of the deaths in the usual care group occurred outside the hospital, compared with zero deaths among those in COVID Watch.
 

More than half of program participants were Black or Latino

The messaging system also reduced mortality rates among “all major racial and ethnic subgroups,” the researchers said, with more than 50% of the patients enrolled in COVID Watch having been Black or Latino.

“This is important because Black and Hispanic communities have experienced higher exposure and infection rates, decreased access to care, and have had higher mortality rates,” Dr. Delgado said. “Therefore, the results imply that this type of program could play a role in decreasing disparities in COVID outcomes if scaled more broadly.”
 

Outside expert: COVID Watch bring new approach to digital health monitoring

The study not only highlights the efficacy and sustainment of the COVID Watch program, but it sheds light on the possibility of using text message monitoring systems on other chronic disease conditions, said Jamie Faro, PhD, who was not involved in the study.

“It brings a new approach to health monitoring using digital means, which may lessen the burden on health care providers and be more cost effective than usual care approaches,” said Dr. Faro, who is assistant professor at the department of population and quantitative health sciences at the University of Massachusetts, Worcester. “Text messaging, which is used by over 80% of Americans, can allow us to reach a large percentage of the population for remote health care monitoring.”

Researchers of the current study said the findings “reveal a model for outpatient health system management of patients with COVID-19 and possibly other conditions where the early detection of clinical declines is critical.” Dr. Faro said that COVID Watch can have a measurable impact on an outcome that is truly life or death. However, it would be critical to understand how to reach those who either “were not offered or refused to take part in the program.”

The authors of the paper and Dr. Faro had no disclosures.

Holiday travel season is right around the corner, but coronavirus cases have already started to climb. But a new automated texting system could relieve pressure on emergency departments and reduce mortality rates if there were an uptick in COVID-19 this winter.

COVID Watch, a text message–based remote monitoring program developed by the University of Pennsylvania Health System, was associated with a 68% reduction in the risk of death, compared with those who received usual care. This was the main finding of a paper published in the Annals of Internal Medicine.

The investigators also determined that patients who enrolled in the program were more likely to seek care in the ED and when they did, they came in on average 2 days sooner than those who received usual care.

“When our clinical team designed COVID Watch the goal was to facilitate hospital care for patients who require it, while supporting access to care for patients who can safely remain at home,” study author M. Kit Delgado, MD, MS, an assistant professor of emergency medicine and epidemiology at Penn Presbyterian Medical Center in Philadelphia, said in an interview.

Researchers had initially hoped COVID Watch would relieve pressure on EDs, Dr. Delgado said.
 

Significantly lower mortality seen among COVID Watch group

For the study, Dr. Delgado and colleagues enrolled 3,488 patients in COVID Watch and 4,377 in the usual care group to compare outcomes at 30 and 60 days.

“We didn’t include patients who were diagnosed with COVID in the ER or hospital, so this is a lower-risk cohort of patients who test positive in outpatient settings,” Dr. Delgado noted. “Outpatients who received usual care and COVID Watch both had relatively low mortality, but it was significantly lower in those who were in COVID Watch.”

The researchers found that 3 patients in the COVID Watch group died within 30 days of their enrollment, compared with 12 in the control group. At 60 days after enrollment, 5 people within COVID Watch died, compared with 16 not using the system. More than one-third of the deaths in the usual care group occurred outside the hospital, compared with zero deaths among those in COVID Watch.
 

More than half of program participants were Black or Latino

The messaging system also reduced mortality rates among “all major racial and ethnic subgroups,” the researchers said, with more than 50% of the patients enrolled in COVID Watch having been Black or Latino.

“This is important because Black and Hispanic communities have experienced higher exposure and infection rates, decreased access to care, and have had higher mortality rates,” Dr. Delgado said. “Therefore, the results imply that this type of program could play a role in decreasing disparities in COVID outcomes if scaled more broadly.”
 

Outside expert: COVID Watch bring new approach to digital health monitoring

The study not only highlights the efficacy and sustainment of the COVID Watch program, but it sheds light on the possibility of using text message monitoring systems on other chronic disease conditions, said Jamie Faro, PhD, who was not involved in the study.

“It brings a new approach to health monitoring using digital means, which may lessen the burden on health care providers and be more cost effective than usual care approaches,” said Dr. Faro, who is assistant professor at the department of population and quantitative health sciences at the University of Massachusetts, Worcester. “Text messaging, which is used by over 80% of Americans, can allow us to reach a large percentage of the population for remote health care monitoring.”

Researchers of the current study said the findings “reveal a model for outpatient health system management of patients with COVID-19 and possibly other conditions where the early detection of clinical declines is critical.” Dr. Faro said that COVID Watch can have a measurable impact on an outcome that is truly life or death. However, it would be critical to understand how to reach those who either “were not offered or refused to take part in the program.”

The authors of the paper and Dr. Faro had no disclosures.

Texas Senate Bill 8 (SB8) is the most extreme antiabortion legislation currently in effect in the United States. SB8 was introduced by the Texas legislature on March 11, 2021, and signed into law by Governor Greg Abbott on May 19, 2021.¹ The law went into effect on September 1, 2021, despite an appeal to the US Supreme Court to block the law until the courts could weigh in on its constitutionality. The bill prohibits all abortion care in the state of Texas after cardiac activity has been identified, typically at 6 weeks’ gestational age. The majority of pregnant people may be unaware at that point that they are pregnant, particularly if their menstrual cycles are irregular.² An estimated 85% of abortions in Texas occur after the 6-week mark, leaving millions of Texans without the constitutionally protected rights assured to them in Roe v Wade.^3,4 This has and will disproportionately impact communities of color and low-income people seeking abortion care.

SB8 does not contain exceptions in case of a pregnancy that results from rape, sexual assault, or incest, but it does contain an exemption for abortion care because of a medical emergency, as approved by a physician. The physician is required to note the medical emergency in the patient’s chart, stating that the “medical emergency necessitated the abortion” and “prevented compliance” with SB8.⁵ In practice, this exception is so vague as to leave clinicians concerned that routine management of medical conditions and complications, as in ectopic pregnancy, places them at risk of legal action against them and their colleagues should they authorize abortion care.

In Texas, abortion restrictions are nothing new. Texas patients are already subject to a 2-trip requirement: Since 2011 they have been required to have a mandatory ultrasound in one visit and schedule a second visit, 24 hours later, for the procedure.⁶ As of 2003, Texas law also mandates that providers discuss with patients the medical risks, adoption alternatives, and developmental stages of the pregnancy.⁶ There are no medical indications for either of these laws, and their impact is to delay patient care. Unfortunately, laws such as these have been increasingly common in the past decade, with 106 abortion restrictions enacted in 2021 alone.^7,8

What is different about SB8?

SB8 is unique in that it deputizes private citizens to enforce the law. This represents a major change in the antichoice movement’s tactics, as previous bills have made violations a criminal offense. SB8 allows a citizen to sue anyone associated with abortion care, with a minimum penalty of $10,000. In practice, a citizen of another state, who has no connection to the patient receiving care, can sue under this Texas law.⁹ Anyone “aiding and abetting a violation” can be found liable for up to 4 years after the date of care, including, for example, a ride-hailing driver called to ferry the patient to the appointment, the health care team providing abortion care, or insurance companies covering the costs of care. In addition, anyone found guilty of “aiding and abetting” a violation of the bill is responsible for all costs and attorney fees associated with the civil case.^5,10

Furthermore, SB8 outlines defenses that cannot be used to preempt a finding of civil liability, including “ignorance or mistake of the law,” “belief of the law’s unconstitutionality,” and “consent of the [patient] to the abortion.”⁵ This additional layer of restriction makes it difficult to appeal the bill and convolutes an individual’s ability to challenge the law. The law also forbids the state (Texas), a state official, a court, or a district attorney from intervening on behalf of the law—upending typical courses of appeal. This legislation also complicates both federal and state intervention regarding SB8’s constitutionality, as the state has no role in enforcing the law as it is written.⁵

Continue to: What has been the response?...

What has been the response?

As expected, abortion foes reacted positively to SB8, while abortion advocates expressed outrage that the law went into effect. Many were additionally confused that the Supreme Court chose not to intervene to stay the law while the courts adjudicate its constitutionality, as is typical in other cases concerning abortion restrictions.¹¹

In a 5-4 ruling, the US Supreme Court allowed SB8 to take effect on September 1, issuing its decision on the “Shadow Docket.” As such, a decision was handed down on an expedited timeline in response to an emergency appeal without any oral arguments or a lengthy opinion explaining the ruling.^11,12 The majority delivered a brief, one-paragraph order summarizing their decision, explaining that their refusal to grant the injunction was not a commentary on the law’s constitutionality. The High Court stated that they could not initially comment on the law’s constitutionality before it went into effect, citing that per the law, the state had no role in enforcement, and at the time, no private actions had yet been brought under the law. Justice Sonia Sotomayor dissented, stating, “The Court’s order is stunning. Presented with an application to enjoin a flagrantly unconstitutional law engineered to prohibit women from exercising their constitutional rights and evade judicial scrutiny, a majority of Justices have opted to bury their heads in the sand.”¹³

Following the Supreme Court’s refusal to act, US Attorney General Merrick Garland commented that “the Justice Department was evaluating all options to protect the constitutional rights of women and other persons.” Just one week later, the US Department of Justice filed a lawsuit against the State of Texas, arguing that SB8 was unconstitutional under the Supremacy Clause (federal law takes precedence over state law) and the Fourteenth Amendment.^14,15

On October 6, in response to the Department of Justice’s challenge, District Judge Robert Pitman issued an injunction to prevent enforcement of SB8. In a 113-page ruling, Judge Pitman explained that “a person’s right under the Constitution to choose to obtain an abortion prior to fetal viability is well established.” Judge Pittman held SB8 unconstitutional, stating, “Women have been unlawfully prevented from exercising control over their lives in ways that are protected by the Constitution... Fully aware that depriving its citizens of this right by direct state action would be flagrantly unconstitutional, the State contrived an unprecedented and transparent statutory scheme to do just that.”¹⁶

Just 48 hours after the injunction issued by Judge Pitman, the Fifth Circuit Court of Appeals overturned the injunction, and SB8 went back into effect while litigation on its constitutionality proceeded.^2,17 The Fifth Circuit Court of Appeals is widely considered to be one of the most conservative courts in the country.¹⁸

On October 15, 2021, the Department of Justice appealed the Fifth Circuit Court’s decision and asked the US Supreme Court to intervene, requesting that the Court issue an emergency halt to the law.^19,20 On October 22, 2021, the Court declined to halt the law but scheduled oral arguments on the case for November 1, 2021. This is a stunningly fast briefing schedule for a case of such constitutional importance.

Given the legal back-and-forth, many clinicians are not providing abortion care in Texas as the litigation unfolds. SB8 permits retroactive enforcement, mandating that those “aiding and abetting” of abortion care may be civilly liable for up to 4 years after providing the care.⁵

Continue to: Potential outcomes, and what comes next...

Potential outcomes, and what comes next

Since the ascension of Justice Amy Coney Barrett to the High Court, there has been a nationwide increase in antiabortion legislation. Between January and July 2021, more than 90 abortion restrictions were passed, more restrictions in any single year since Roe v Wade was decided in 1973.⁸ In the past decade, more than 500 laws that restrict abortion have been passed across the United States, and studies indicate that 87% to 90% of American counties today are without a single abortion provider.^21,22 Abortion supporters are particularly concerned about the future of Roe v Wade, with a conservative Supreme Court set to hear the challenge to SB8 on November 1, 2021, followed by a second case from Mississippi challenging the constitutionality of a 15-week ban on abortion in Dobbs v Jackson Women’s Health Organization (read about this case in “Supreme Court Case: Dobbs v Jackson Women’s Health Organization: What you need to know,” at https://www.mdedge.com/obgyn/article/245853/practice-management/supreme-court-case-dobbs-v-jackson-womens-health).^23,24

At the time of this article writing, we do not know how the Supreme Court will rule on the variety of challenges to the right to privacy. That said, advocates believe it is safe to assume that the landscape of abortion access is likely to change dramatically in the coming year.

Action items: What can you do?

It is important to remember that not only does SB8 severely limit access to safe and legal abortion but also it makes pregnancy dangerous for all pregnant people in Texas and places doubt in providers’ minds on how to manage medical care for their patients.

On the federal level, many advocates are focusing on codifying the right to choose and protecting abortion care from medically unnecessary restrictions. The Women’s Health Protection Act of 2021 (WHPA) was introduced in the House of Representatives by Rep. Judy Chu (D-CA), Lois Frankel (D-FL), Ayanna Pressley (D-MA), and Veronica Escobar (D-TX), and it passed in the US House of Representatives in a 218-211 vote.²⁵ WHPA now awaits a vote in a deeply divided US Senate. Although WHPA has wide popular support—an estimated 61% of Americans support the legislation—its future is unclear in the Senate.²⁶ Currently, WHPA has 48 supporters, all Democrats. You can contact your legislators via the links below to encourage them to pass WHPA. If you have friends and colleagues in states in which the Senator does not support WHPA, forward these links and encourage them to sign on: 

• Equal Access to Abortion, Everywhere: https://actforwomen.org/take-action/
• Physicians for Reproductive Rights: https://secure.everyaction.com/p/MOuAyW7F3Ua-FmaGtGD4Kw2
• Center for Reproductive Rights: https://reproductiverights.org/whpa-take-action/

Many also are organizing a crowdfunding campaign to support abortion providers as well as legislative resources. Additional groups to donate specifically to SB8 efforts include²⁷:

• Equal Access to Abortion, Everywhere: https://actforwomen.org/whpa-faqs/
• Planned Parenthood of Greater Texas, Inc: https://www.plannedparenthood.org/planned-parenthood-greater-texas/senate-bill-8
• Texas Equal Access Fund: https://secure.everyaction.com/ztEh8Qeh80-k2k1Yuo5gTw2
• ActBlue Charities: https://secure.actblue.com/donate/txfunds

Furthermore, it is more important than ever to support work within states to support abortion rights. State-specific abortion advocacy groups and their efforts include:

• Avow Foundation for Abortion Access: https://avowtexas.org/support/
• Planned Parenthood of Greater Texas, Inc: https://www.plannedparenthood.org/planned-parenthood-greater-texas
• NARAL Pro-Choice Texas: https://prochoicetexas.org/
• Texas Abortion Access Network: https://txabortionaccessnetwork.org/

Texas Senate Bill 8 (SB8) is the most extreme antiabortion legislation currently in effect in the United States. SB8 was introduced by the Texas legislature on March 11, 2021, and signed into law by Governor Greg Abbott on May 19, 2021.¹ The law went into effect on September 1, 2021, despite an appeal to the US Supreme Court to block the law until the courts could weigh in on its constitutionality. The bill prohibits all abortion care in the state of Texas after cardiac activity has been identified, typically at 6 weeks’ gestational age. The majority of pregnant people may be unaware at that point that they are pregnant, particularly if their menstrual cycles are irregular.² An estimated 85% of abortions in Texas occur after the 6-week mark, leaving millions of Texans without the constitutionally protected rights assured to them in Roe v Wade.^3,4 This has and will disproportionately impact communities of color and low-income people seeking abortion care.

SB8 does not contain exceptions in case of a pregnancy that results from rape, sexual assault, or incest, but it does contain an exemption for abortion care because of a medical emergency, as approved by a physician. The physician is required to note the medical emergency in the patient’s chart, stating that the “medical emergency necessitated the abortion” and “prevented compliance” with SB8.⁵ In practice, this exception is so vague as to leave clinicians concerned that routine management of medical conditions and complications, as in ectopic pregnancy, places them at risk of legal action against them and their colleagues should they authorize abortion care.

In Texas, abortion restrictions are nothing new. Texas patients are already subject to a 2-trip requirement: Since 2011 they have been required to have a mandatory ultrasound in one visit and schedule a second visit, 24 hours later, for the procedure.⁶ As of 2003, Texas law also mandates that providers discuss with patients the medical risks, adoption alternatives, and developmental stages of the pregnancy.⁶ There are no medical indications for either of these laws, and their impact is to delay patient care. Unfortunately, laws such as these have been increasingly common in the past decade, with 106 abortion restrictions enacted in 2021 alone.^7,8

What is different about SB8?

SB8 is unique in that it deputizes private citizens to enforce the law. This represents a major change in the antichoice movement’s tactics, as previous bills have made violations a criminal offense. SB8 allows a citizen to sue anyone associated with abortion care, with a minimum penalty of $10,000. In practice, a citizen of another state, who has no connection to the patient receiving care, can sue under this Texas law.⁹ Anyone “aiding and abetting a violation” can be found liable for up to 4 years after the date of care, including, for example, a ride-hailing driver called to ferry the patient to the appointment, the health care team providing abortion care, or insurance companies covering the costs of care. In addition, anyone found guilty of “aiding and abetting” a violation of the bill is responsible for all costs and attorney fees associated with the civil case.^5,10

Furthermore, SB8 outlines defenses that cannot be used to preempt a finding of civil liability, including “ignorance or mistake of the law,” “belief of the law’s unconstitutionality,” and “consent of the [patient] to the abortion.”⁵ This additional layer of restriction makes it difficult to appeal the bill and convolutes an individual’s ability to challenge the law. The law also forbids the state (Texas), a state official, a court, or a district attorney from intervening on behalf of the law—upending typical courses of appeal. This legislation also complicates both federal and state intervention regarding SB8’s constitutionality, as the state has no role in enforcing the law as it is written.⁵

Continue to: What has been the response?...

What has been the response?

As expected, abortion foes reacted positively to SB8, while abortion advocates expressed outrage that the law went into effect. Many were additionally confused that the Supreme Court chose not to intervene to stay the law while the courts adjudicate its constitutionality, as is typical in other cases concerning abortion restrictions.¹¹

In a 5-4 ruling, the US Supreme Court allowed SB8 to take effect on September 1, issuing its decision on the “Shadow Docket.” As such, a decision was handed down on an expedited timeline in response to an emergency appeal without any oral arguments or a lengthy opinion explaining the ruling.^11,12 The majority delivered a brief, one-paragraph order summarizing their decision, explaining that their refusal to grant the injunction was not a commentary on the law’s constitutionality. The High Court stated that they could not initially comment on the law’s constitutionality before it went into effect, citing that per the law, the state had no role in enforcement, and at the time, no private actions had yet been brought under the law. Justice Sonia Sotomayor dissented, stating, “The Court’s order is stunning. Presented with an application to enjoin a flagrantly unconstitutional law engineered to prohibit women from exercising their constitutional rights and evade judicial scrutiny, a majority of Justices have opted to bury their heads in the sand.”¹³

Following the Supreme Court’s refusal to act, US Attorney General Merrick Garland commented that “the Justice Department was evaluating all options to protect the constitutional rights of women and other persons.” Just one week later, the US Department of Justice filed a lawsuit against the State of Texas, arguing that SB8 was unconstitutional under the Supremacy Clause (federal law takes precedence over state law) and the Fourteenth Amendment.^14,15

On October 6, in response to the Department of Justice’s challenge, District Judge Robert Pitman issued an injunction to prevent enforcement of SB8. In a 113-page ruling, Judge Pitman explained that “a person’s right under the Constitution to choose to obtain an abortion prior to fetal viability is well established.” Judge Pittman held SB8 unconstitutional, stating, “Women have been unlawfully prevented from exercising control over their lives in ways that are protected by the Constitution... Fully aware that depriving its citizens of this right by direct state action would be flagrantly unconstitutional, the State contrived an unprecedented and transparent statutory scheme to do just that.”¹⁶

Just 48 hours after the injunction issued by Judge Pitman, the Fifth Circuit Court of Appeals overturned the injunction, and SB8 went back into effect while litigation on its constitutionality proceeded.^2,17 The Fifth Circuit Court of Appeals is widely considered to be one of the most conservative courts in the country.¹⁸

On October 15, 2021, the Department of Justice appealed the Fifth Circuit Court’s decision and asked the US Supreme Court to intervene, requesting that the Court issue an emergency halt to the law.^19,20 On October 22, 2021, the Court declined to halt the law but scheduled oral arguments on the case for November 1, 2021. This is a stunningly fast briefing schedule for a case of such constitutional importance.

Given the legal back-and-forth, many clinicians are not providing abortion care in Texas as the litigation unfolds. SB8 permits retroactive enforcement, mandating that those “aiding and abetting” of abortion care may be civilly liable for up to 4 years after providing the care.⁵

Continue to: Potential outcomes, and what comes next...

Potential outcomes, and what comes next

Since the ascension of Justice Amy Coney Barrett to the High Court, there has been a nationwide increase in antiabortion legislation. Between January and July 2021, more than 90 abortion restrictions were passed, more restrictions in any single year since Roe v Wade was decided in 1973.⁸ In the past decade, more than 500 laws that restrict abortion have been passed across the United States, and studies indicate that 87% to 90% of American counties today are without a single abortion provider.^21,22 Abortion supporters are particularly concerned about the future of Roe v Wade, with a conservative Supreme Court set to hear the challenge to SB8 on November 1, 2021, followed by a second case from Mississippi challenging the constitutionality of a 15-week ban on abortion in Dobbs v Jackson Women’s Health Organization (read about this case in “Supreme Court Case: Dobbs v Jackson Women’s Health Organization: What you need to know,” at https://www.mdedge.com/obgyn/article/245853/practice-management/supreme-court-case-dobbs-v-jackson-womens-health).^23,24

At the time of this article writing, we do not know how the Supreme Court will rule on the variety of challenges to the right to privacy. That said, advocates believe it is safe to assume that the landscape of abortion access is likely to change dramatically in the coming year.

Action items: What can you do?

It is important to remember that not only does SB8 severely limit access to safe and legal abortion but also it makes pregnancy dangerous for all pregnant people in Texas and places doubt in providers’ minds on how to manage medical care for their patients.

On the federal level, many advocates are focusing on codifying the right to choose and protecting abortion care from medically unnecessary restrictions. The Women’s Health Protection Act of 2021 (WHPA) was introduced in the House of Representatives by Rep. Judy Chu (D-CA), Lois Frankel (D-FL), Ayanna Pressley (D-MA), and Veronica Escobar (D-TX), and it passed in the US House of Representatives in a 218-211 vote.²⁵ WHPA now awaits a vote in a deeply divided US Senate. Although WHPA has wide popular support—an estimated 61% of Americans support the legislation—its future is unclear in the Senate.²⁶ Currently, WHPA has 48 supporters, all Democrats. You can contact your legislators via the links below to encourage them to pass WHPA. If you have friends and colleagues in states in which the Senator does not support WHPA, forward these links and encourage them to sign on: 

• Equal Access to Abortion, Everywhere: https://actforwomen.org/take-action/
• Physicians for Reproductive Rights: https://secure.everyaction.com/p/MOuAyW7F3Ua-FmaGtGD4Kw2
• Center for Reproductive Rights: https://reproductiverights.org/whpa-take-action/

Many also are organizing a crowdfunding campaign to support abortion providers as well as legislative resources. Additional groups to donate specifically to SB8 efforts include²⁷:

• Equal Access to Abortion, Everywhere: https://actforwomen.org/whpa-faqs/
• Planned Parenthood of Greater Texas, Inc: https://www.plannedparenthood.org/planned-parenthood-greater-texas/senate-bill-8
• Texas Equal Access Fund: https://secure.everyaction.com/ztEh8Qeh80-k2k1Yuo5gTw2
• ActBlue Charities: https://secure.actblue.com/donate/txfunds

Furthermore, it is more important than ever to support work within states to support abortion rights. State-specific abortion advocacy groups and their efforts include:

• Avow Foundation for Abortion Access: https://avowtexas.org/support/
• Planned Parenthood of Greater Texas, Inc: https://www.plannedparenthood.org/planned-parenthood-greater-texas
• NARAL Pro-Choice Texas: https://prochoicetexas.org/
• Texas Abortion Access Network: https://txabortionaccessnetwork.org/

Texas Senate Bill 8 (SB8) is the most extreme antiabortion legislation currently in effect in the United States. SB8 was introduced by the Texas legislature on March 11, 2021, and signed into law by Governor Greg Abbott on May 19, 2021.¹ The law went into effect on September 1, 2021, despite an appeal to the US Supreme Court to block the law until the courts could weigh in on its constitutionality. The bill prohibits all abortion care in the state of Texas after cardiac activity has been identified, typically at 6 weeks’ gestational age. The majority of pregnant people may be unaware at that point that they are pregnant, particularly if their menstrual cycles are irregular.² An estimated 85% of abortions in Texas occur after the 6-week mark, leaving millions of Texans without the constitutionally protected rights assured to them in Roe v Wade.^3,4 This has and will disproportionately impact communities of color and low-income people seeking abortion care.

SB8 does not contain exceptions in case of a pregnancy that results from rape, sexual assault, or incest, but it does contain an exemption for abortion care because of a medical emergency, as approved by a physician. The physician is required to note the medical emergency in the patient’s chart, stating that the “medical emergency necessitated the abortion” and “prevented compliance” with SB8.⁵ In practice, this exception is so vague as to leave clinicians concerned that routine management of medical conditions and complications, as in ectopic pregnancy, places them at risk of legal action against them and their colleagues should they authorize abortion care.

In Texas, abortion restrictions are nothing new. Texas patients are already subject to a 2-trip requirement: Since 2011 they have been required to have a mandatory ultrasound in one visit and schedule a second visit, 24 hours later, for the procedure.⁶ As of 2003, Texas law also mandates that providers discuss with patients the medical risks, adoption alternatives, and developmental stages of the pregnancy.⁶ There are no medical indications for either of these laws, and their impact is to delay patient care. Unfortunately, laws such as these have been increasingly common in the past decade, with 106 abortion restrictions enacted in 2021 alone.^7,8

What is different about SB8?

SB8 is unique in that it deputizes private citizens to enforce the law. This represents a major change in the antichoice movement’s tactics, as previous bills have made violations a criminal offense. SB8 allows a citizen to sue anyone associated with abortion care, with a minimum penalty of $10,000. In practice, a citizen of another state, who has no connection to the patient receiving care, can sue under this Texas law.⁹ Anyone “aiding and abetting a violation” can be found liable for up to 4 years after the date of care, including, for example, a ride-hailing driver called to ferry the patient to the appointment, the health care team providing abortion care, or insurance companies covering the costs of care. In addition, anyone found guilty of “aiding and abetting” a violation of the bill is responsible for all costs and attorney fees associated with the civil case.^5,10

Furthermore, SB8 outlines defenses that cannot be used to preempt a finding of civil liability, including “ignorance or mistake of the law,” “belief of the law’s unconstitutionality,” and “consent of the [patient] to the abortion.”⁵ This additional layer of restriction makes it difficult to appeal the bill and convolutes an individual’s ability to challenge the law. The law also forbids the state (Texas), a state official, a court, or a district attorney from intervening on behalf of the law—upending typical courses of appeal. This legislation also complicates both federal and state intervention regarding SB8’s constitutionality, as the state has no role in enforcing the law as it is written.⁵

Continue to: What has been the response?...

What has been the response?

As expected, abortion foes reacted positively to SB8, while abortion advocates expressed outrage that the law went into effect. Many were additionally confused that the Supreme Court chose not to intervene to stay the law while the courts adjudicate its constitutionality, as is typical in other cases concerning abortion restrictions.¹¹

In a 5-4 ruling, the US Supreme Court allowed SB8 to take effect on September 1, issuing its decision on the “Shadow Docket.” As such, a decision was handed down on an expedited timeline in response to an emergency appeal without any oral arguments or a lengthy opinion explaining the ruling.^11,12 The majority delivered a brief, one-paragraph order summarizing their decision, explaining that their refusal to grant the injunction was not a commentary on the law’s constitutionality. The High Court stated that they could not initially comment on the law’s constitutionality before it went into effect, citing that per the law, the state had no role in enforcement, and at the time, no private actions had yet been brought under the law. Justice Sonia Sotomayor dissented, stating, “The Court’s order is stunning. Presented with an application to enjoin a flagrantly unconstitutional law engineered to prohibit women from exercising their constitutional rights and evade judicial scrutiny, a majority of Justices have opted to bury their heads in the sand.”¹³

Following the Supreme Court’s refusal to act, US Attorney General Merrick Garland commented that “the Justice Department was evaluating all options to protect the constitutional rights of women and other persons.” Just one week later, the US Department of Justice filed a lawsuit against the State of Texas, arguing that SB8 was unconstitutional under the Supremacy Clause (federal law takes precedence over state law) and the Fourteenth Amendment.^14,15

On October 6, in response to the Department of Justice’s challenge, District Judge Robert Pitman issued an injunction to prevent enforcement of SB8. In a 113-page ruling, Judge Pitman explained that “a person’s right under the Constitution to choose to obtain an abortion prior to fetal viability is well established.” Judge Pittman held SB8 unconstitutional, stating, “Women have been unlawfully prevented from exercising control over their lives in ways that are protected by the Constitution... Fully aware that depriving its citizens of this right by direct state action would be flagrantly unconstitutional, the State contrived an unprecedented and transparent statutory scheme to do just that.”¹⁶

Just 48 hours after the injunction issued by Judge Pitman, the Fifth Circuit Court of Appeals overturned the injunction, and SB8 went back into effect while litigation on its constitutionality proceeded.^2,17 The Fifth Circuit Court of Appeals is widely considered to be one of the most conservative courts in the country.¹⁸

On October 15, 2021, the Department of Justice appealed the Fifth Circuit Court’s decision and asked the US Supreme Court to intervene, requesting that the Court issue an emergency halt to the law.^19,20 On October 22, 2021, the Court declined to halt the law but scheduled oral arguments on the case for November 1, 2021. This is a stunningly fast briefing schedule for a case of such constitutional importance.

Given the legal back-and-forth, many clinicians are not providing abortion care in Texas as the litigation unfolds. SB8 permits retroactive enforcement, mandating that those “aiding and abetting” of abortion care may be civilly liable for up to 4 years after providing the care.⁵

Continue to: Potential outcomes, and what comes next...

Potential outcomes, and what comes next

Since the ascension of Justice Amy Coney Barrett to the High Court, there has been a nationwide increase in antiabortion legislation. Between January and July 2021, more than 90 abortion restrictions were passed, more restrictions in any single year since Roe v Wade was decided in 1973.⁸ In the past decade, more than 500 laws that restrict abortion have been passed across the United States, and studies indicate that 87% to 90% of American counties today are without a single abortion provider.^21,22 Abortion supporters are particularly concerned about the future of Roe v Wade, with a conservative Supreme Court set to hear the challenge to SB8 on November 1, 2021, followed by a second case from Mississippi challenging the constitutionality of a 15-week ban on abortion in Dobbs v Jackson Women’s Health Organization (read about this case in “Supreme Court Case: Dobbs v Jackson Women’s Health Organization: What you need to know,” at https://www.mdedge.com/obgyn/article/245853/practice-management/supreme-court-case-dobbs-v-jackson-womens-health).^23,24

At the time of this article writing, we do not know how the Supreme Court will rule on the variety of challenges to the right to privacy. That said, advocates believe it is safe to assume that the landscape of abortion access is likely to change dramatically in the coming year.

Action items: What can you do?

It is important to remember that not only does SB8 severely limit access to safe and legal abortion but also it makes pregnancy dangerous for all pregnant people in Texas and places doubt in providers’ minds on how to manage medical care for their patients.

On the federal level, many advocates are focusing on codifying the right to choose and protecting abortion care from medically unnecessary restrictions. The Women’s Health Protection Act of 2021 (WHPA) was introduced in the House of Representatives by Rep. Judy Chu (D-CA), Lois Frankel (D-FL), Ayanna Pressley (D-MA), and Veronica Escobar (D-TX), and it passed in the US House of Representatives in a 218-211 vote.²⁵ WHPA now awaits a vote in a deeply divided US Senate. Although WHPA has wide popular support—an estimated 61% of Americans support the legislation—its future is unclear in the Senate.²⁶ Currently, WHPA has 48 supporters, all Democrats. You can contact your legislators via the links below to encourage them to pass WHPA. If you have friends and colleagues in states in which the Senator does not support WHPA, forward these links and encourage them to sign on: 

• Equal Access to Abortion, Everywhere: https://actforwomen.org/take-action/
• Physicians for Reproductive Rights: https://secure.everyaction.com/p/MOuAyW7F3Ua-FmaGtGD4Kw2
• Center for Reproductive Rights: https://reproductiverights.org/whpa-take-action/

Many also are organizing a crowdfunding campaign to support abortion providers as well as legislative resources. Additional groups to donate specifically to SB8 efforts include²⁷:

• Equal Access to Abortion, Everywhere: https://actforwomen.org/whpa-faqs/
• Planned Parenthood of Greater Texas, Inc: https://www.plannedparenthood.org/planned-parenthood-greater-texas/senate-bill-8
• Texas Equal Access Fund: https://secure.everyaction.com/ztEh8Qeh80-k2k1Yuo5gTw2
• ActBlue Charities: https://secure.actblue.com/donate/txfunds

Furthermore, it is more important than ever to support work within states to support abortion rights. State-specific abortion advocacy groups and their efforts include:

• Avow Foundation for Abortion Access: https://avowtexas.org/support/
• Planned Parenthood of Greater Texas, Inc: https://www.plannedparenthood.org/planned-parenthood-greater-texas
• NARAL Pro-Choice Texas: https://prochoicetexas.org/
• Texas Abortion Access Network: https://txabortionaccessnetwork.org/

Treatment of antineutrophil cytoplasmic autoantibody (ANCA)–associated vasculitis and renal disease with the oral C5a receptor inhibitor avacopan (Tavneos, ChemoCentryx) provides significant recovery of kidney function, compared with prednisone, particularly in patients with severe kidney disease, novel research indicates.

The new analysis underscores that “the real value of avacopan is that we can now expect to get our patients steroid free,” said first author David R.W. Jayne, MD, a professor of clinical autoimmunity at the University of Cambridge (England), when presenting the findings at the American Society of Nephrology’s Kidney Week 2021.

“Whether or not we’re brave enough to initiate treatment without steroids, I think that will perhaps come with some patient experience,” he added.

The findings are from a subanalysis of renal effects in the phase 3 ADVOCATE trial, which was published in February 2021 in the New England Journal of Medicine and included 330 patients with ANCA-associated vasculitis.

The trial in large part led to the U.S. approval of avacopan by the Food and Drug Administration in October as an adjunctive treatment for adults with severe active ANCA-associated vasculitis in combination with standard therapy including glucocorticoids.

The approval was greeted with enthusiasm as suggesting a much-needed option to help reduce, or even potentially eliminate, the need for glucocorticoids and their side effects. Other agents included in treatment regimens for ANCA-associated vasculitis include cyclophosphamide and rituximab.

Dr. Jayne emphasized that, before avacopan, treatment options had been limited.

“There is nothing else new in the clinic apart from rituximab, which we have now been using for almost 20 years,” he said in an interview. “Avacopan is new, the mode of action is different from any drugs in use at the moment, and the speed of action is very quick.”

The need to more closely investigate the trial’s renal outcomes in this new analysis was important because the high mortality rates in ANCA-associated vasculitis – a rare systemic autoimmune disease causing overactivation of complement resulting in inflammation of small blood vessels – is largely driven by those with MPO and PR3 autoantibody renal vasculitis, Dr. Jayne explained.

Commenting on the study, J. Charles Jennette, MD, a professor of pathology and laboratory medicine and professor of medicine at the University of North Carolina at Chapel Hill, said the new findings on renal outcomes, such as proteinuria, may offer key insights on avacopan’s efficacy.

“To me, the most impressive outcome of the ADVOCATE Phase 3 trial was the more rapid reduction in hematuria and proteinuria with avacopan compared to conventional prednisone therapy,” he said in an interview.
 

Recovery of eGFR with avacopan best in those with severe renal disease

In the trial, patients with ANCA-associated vasculitis were randomized 1:1 to treatment with oral avacopan 30 mg twice daily or oral prednisone on a tapering schedule.

All patients also received background immunosuppression – about two-thirds received rituximab and a third received cyclophosphamide – followed by azathioprine.

The main study results showed similar rates of remission in both groups at week 26 and a superior remission rate with avacopan, in terms of sustained remission, at week 52 (65.7% vs. 54.9%; P < .001).

Approximately 80% of patients in the trial had renal involvement of ANCA vasculitis, the focus of the new analysis, and they had a baseline mean estimated glomerular filtration rate (eGFR) of 45 mL/min per 1.73 m2.

Among those with renal involvement, patients treated with avacopan had a significantly greater eGFR recovery, compared with the prednisone group at week 26 (P = .046) and week 52 (P < .029).

The strongest improvements were observed among patients with moderate to severe kidney damage, who had a mean eGFR of 21 mL/min per 1.73 m2 at baseline. Among those patients, the mean increase in eGFR was 13.7 mL/min per 1.73 m² in the avacopan-treated group (n = 52) versus 8.2 mL/min per 1.73 m² in the prednisone group (n = 48; P < .01) by week 52.

Improvements in urinary albumin:creatinine ratios (UACR) of as much as 40% were also observed in the avacopan group within the first 4 weeks of treatment, while no changes were observed in the same period in the prednisone group.

In other findings, the study also showed more rapid declines in proteinuria within 4 weeks in the avacopan group, and fewer patients had hematuria and there were greater reductions in MCP-1 in avacopan-treated patients at week 52, Dr. Jayne reported.

In terms of safety, there were no differences between the groups, with trends of fewer deaths and severe adverse events in the avacopan group.

“We found that the improved recovery of eGFR with avacopan was accentuated among those with more severe renal disease,” Dr. Jayne said.

He noted that, while the study’s aim was for the avacopan group to be steroid free, the patients received brief, reduced doses of about a third of the normal oral steroid dose early in the trial. However, using a Glucocorticoid Toxicity Index, the authors found those in the avacopan group did have fewer glucocorticoid-related adverse events.

Future issues to be examined include what happens when avacopan is discontinued and whether there will be a high relapse rate, Dr. Jayne noted.

Overall, however, “we anticipate that with longer-term follow-up, this better eGFR recovery will have a [favorable] effect on kidney failure and potentially mortality risk in these patients,” he concluded.

Targeted therapy is good for patients and doctors

Expanding upon his comments regarding the new drug, Dr. Jennette said it implies “that the C5a receptor inhibitor was targeting an event that blocks injury more quickly and effectively than prednisone.”

“This may be because prednisone has more complex pharmacodynamics and less targeted effects than a C5a receptor inhibitor,” he said.

Overall, the findings bode well for a potentially beneficial therapy, he added. “We have entered a new era of more targeted therapies, for example, targeted B-cell therapy using an anti-CD20 antibody, and targeted complement-mediated injury therapy using C5a receptor inhibitor.”

“The validation of this targeted therapy to block complement-mediated autoimmune inflammatory injury is another advance toward targeted precision therapy versus empirical therapy. This will be good for the doctors and good for the patients,” Dr. Jennette concluded.

The study was funded by ChemoCentryx. Dr. Jayne has reported receiving grants and/or consulting for AstraZeneca, ChemoCentryx, GlaxoSmithKline, MiroBio, Vifor, and Roche/Genentech. Dr. Jennette has received funding from ChemoCentryx for preclinical validation studies of avacopan in a mouse model of ANCA glomerulonephritis.

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

Treatment of antineutrophil cytoplasmic autoantibody (ANCA)–associated vasculitis and renal disease with the oral C5a receptor inhibitor avacopan (Tavneos, ChemoCentryx) provides significant recovery of kidney function, compared with prednisone, particularly in patients with severe kidney disease, novel research indicates.

The new analysis underscores that “the real value of avacopan is that we can now expect to get our patients steroid free,” said first author David R.W. Jayne, MD, a professor of clinical autoimmunity at the University of Cambridge (England), when presenting the findings at the American Society of Nephrology’s Kidney Week 2021.

“Whether or not we’re brave enough to initiate treatment without steroids, I think that will perhaps come with some patient experience,” he added.

The findings are from a subanalysis of renal effects in the phase 3 ADVOCATE trial, which was published in February 2021 in the New England Journal of Medicine and included 330 patients with ANCA-associated vasculitis.

The trial in large part led to the U.S. approval of avacopan by the Food and Drug Administration in October as an adjunctive treatment for adults with severe active ANCA-associated vasculitis in combination with standard therapy including glucocorticoids.

The approval was greeted with enthusiasm as suggesting a much-needed option to help reduce, or even potentially eliminate, the need for glucocorticoids and their side effects. Other agents included in treatment regimens for ANCA-associated vasculitis include cyclophosphamide and rituximab.

Dr. Jayne emphasized that, before avacopan, treatment options had been limited.

“There is nothing else new in the clinic apart from rituximab, which we have now been using for almost 20 years,” he said in an interview. “Avacopan is new, the mode of action is different from any drugs in use at the moment, and the speed of action is very quick.”

The need to more closely investigate the trial’s renal outcomes in this new analysis was important because the high mortality rates in ANCA-associated vasculitis – a rare systemic autoimmune disease causing overactivation of complement resulting in inflammation of small blood vessels – is largely driven by those with MPO and PR3 autoantibody renal vasculitis, Dr. Jayne explained.

Commenting on the study, J. Charles Jennette, MD, a professor of pathology and laboratory medicine and professor of medicine at the University of North Carolina at Chapel Hill, said the new findings on renal outcomes, such as proteinuria, may offer key insights on avacopan’s efficacy.

“To me, the most impressive outcome of the ADVOCATE Phase 3 trial was the more rapid reduction in hematuria and proteinuria with avacopan compared to conventional prednisone therapy,” he said in an interview.
 

Recovery of eGFR with avacopan best in those with severe renal disease

In the trial, patients with ANCA-associated vasculitis were randomized 1:1 to treatment with oral avacopan 30 mg twice daily or oral prednisone on a tapering schedule.

All patients also received background immunosuppression – about two-thirds received rituximab and a third received cyclophosphamide – followed by azathioprine.

The main study results showed similar rates of remission in both groups at week 26 and a superior remission rate with avacopan, in terms of sustained remission, at week 52 (65.7% vs. 54.9%; P < .001).

Approximately 80% of patients in the trial had renal involvement of ANCA vasculitis, the focus of the new analysis, and they had a baseline mean estimated glomerular filtration rate (eGFR) of 45 mL/min per 1.73 m2.

Among those with renal involvement, patients treated with avacopan had a significantly greater eGFR recovery, compared with the prednisone group at week 26 (P = .046) and week 52 (P < .029).

The strongest improvements were observed among patients with moderate to severe kidney damage, who had a mean eGFR of 21 mL/min per 1.73 m2 at baseline. Among those patients, the mean increase in eGFR was 13.7 mL/min per 1.73 m² in the avacopan-treated group (n = 52) versus 8.2 mL/min per 1.73 m² in the prednisone group (n = 48; P < .01) by week 52.

Improvements in urinary albumin:creatinine ratios (UACR) of as much as 40% were also observed in the avacopan group within the first 4 weeks of treatment, while no changes were observed in the same period in the prednisone group.

In other findings, the study also showed more rapid declines in proteinuria within 4 weeks in the avacopan group, and fewer patients had hematuria and there were greater reductions in MCP-1 in avacopan-treated patients at week 52, Dr. Jayne reported.

In terms of safety, there were no differences between the groups, with trends of fewer deaths and severe adverse events in the avacopan group.

“We found that the improved recovery of eGFR with avacopan was accentuated among those with more severe renal disease,” Dr. Jayne said.

He noted that, while the study’s aim was for the avacopan group to be steroid free, the patients received brief, reduced doses of about a third of the normal oral steroid dose early in the trial. However, using a Glucocorticoid Toxicity Index, the authors found those in the avacopan group did have fewer glucocorticoid-related adverse events.

Future issues to be examined include what happens when avacopan is discontinued and whether there will be a high relapse rate, Dr. Jayne noted.

Overall, however, “we anticipate that with longer-term follow-up, this better eGFR recovery will have a [favorable] effect on kidney failure and potentially mortality risk in these patients,” he concluded.

Targeted therapy is good for patients and doctors

Expanding upon his comments regarding the new drug, Dr. Jennette said it implies “that the C5a receptor inhibitor was targeting an event that blocks injury more quickly and effectively than prednisone.”

“This may be because prednisone has more complex pharmacodynamics and less targeted effects than a C5a receptor inhibitor,” he said.

Overall, the findings bode well for a potentially beneficial therapy, he added. “We have entered a new era of more targeted therapies, for example, targeted B-cell therapy using an anti-CD20 antibody, and targeted complement-mediated injury therapy using C5a receptor inhibitor.”

“The validation of this targeted therapy to block complement-mediated autoimmune inflammatory injury is another advance toward targeted precision therapy versus empirical therapy. This will be good for the doctors and good for the patients,” Dr. Jennette concluded.

The study was funded by ChemoCentryx. Dr. Jayne has reported receiving grants and/or consulting for AstraZeneca, ChemoCentryx, GlaxoSmithKline, MiroBio, Vifor, and Roche/Genentech. Dr. Jennette has received funding from ChemoCentryx for preclinical validation studies of avacopan in a mouse model of ANCA glomerulonephritis.

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

Treatment of antineutrophil cytoplasmic autoantibody (ANCA)–associated vasculitis and renal disease with the oral C5a receptor inhibitor avacopan (Tavneos, ChemoCentryx) provides significant recovery of kidney function, compared with prednisone, particularly in patients with severe kidney disease, novel research indicates.

The new analysis underscores that “the real value of avacopan is that we can now expect to get our patients steroid free,” said first author David R.W. Jayne, MD, a professor of clinical autoimmunity at the University of Cambridge (England), when presenting the findings at the American Society of Nephrology’s Kidney Week 2021.

“Whether or not we’re brave enough to initiate treatment without steroids, I think that will perhaps come with some patient experience,” he added.

The findings are from a subanalysis of renal effects in the phase 3 ADVOCATE trial, which was published in February 2021 in the New England Journal of Medicine and included 330 patients with ANCA-associated vasculitis.

The trial in large part led to the U.S. approval of avacopan by the Food and Drug Administration in October as an adjunctive treatment for adults with severe active ANCA-associated vasculitis in combination with standard therapy including glucocorticoids.

The approval was greeted with enthusiasm as suggesting a much-needed option to help reduce, or even potentially eliminate, the need for glucocorticoids and their side effects. Other agents included in treatment regimens for ANCA-associated vasculitis include cyclophosphamide and rituximab.

Dr. Jayne emphasized that, before avacopan, treatment options had been limited.

“There is nothing else new in the clinic apart from rituximab, which we have now been using for almost 20 years,” he said in an interview. “Avacopan is new, the mode of action is different from any drugs in use at the moment, and the speed of action is very quick.”

The need to more closely investigate the trial’s renal outcomes in this new analysis was important because the high mortality rates in ANCA-associated vasculitis – a rare systemic autoimmune disease causing overactivation of complement resulting in inflammation of small blood vessels – is largely driven by those with MPO and PR3 autoantibody renal vasculitis, Dr. Jayne explained.

Commenting on the study, J. Charles Jennette, MD, a professor of pathology and laboratory medicine and professor of medicine at the University of North Carolina at Chapel Hill, said the new findings on renal outcomes, such as proteinuria, may offer key insights on avacopan’s efficacy.

“To me, the most impressive outcome of the ADVOCATE Phase 3 trial was the more rapid reduction in hematuria and proteinuria with avacopan compared to conventional prednisone therapy,” he said in an interview.
 

Recovery of eGFR with avacopan best in those with severe renal disease

In the trial, patients with ANCA-associated vasculitis were randomized 1:1 to treatment with oral avacopan 30 mg twice daily or oral prednisone on a tapering schedule.

All patients also received background immunosuppression – about two-thirds received rituximab and a third received cyclophosphamide – followed by azathioprine.

The main study results showed similar rates of remission in both groups at week 26 and a superior remission rate with avacopan, in terms of sustained remission, at week 52 (65.7% vs. 54.9%; P < .001).

Approximately 80% of patients in the trial had renal involvement of ANCA vasculitis, the focus of the new analysis, and they had a baseline mean estimated glomerular filtration rate (eGFR) of 45 mL/min per 1.73 m2.

Among those with renal involvement, patients treated with avacopan had a significantly greater eGFR recovery, compared with the prednisone group at week 26 (P = .046) and week 52 (P < .029).

The strongest improvements were observed among patients with moderate to severe kidney damage, who had a mean eGFR of 21 mL/min per 1.73 m2 at baseline. Among those patients, the mean increase in eGFR was 13.7 mL/min per 1.73 m² in the avacopan-treated group (n = 52) versus 8.2 mL/min per 1.73 m² in the prednisone group (n = 48; P < .01) by week 52.

Improvements in urinary albumin:creatinine ratios (UACR) of as much as 40% were also observed in the avacopan group within the first 4 weeks of treatment, while no changes were observed in the same period in the prednisone group.

In other findings, the study also showed more rapid declines in proteinuria within 4 weeks in the avacopan group, and fewer patients had hematuria and there were greater reductions in MCP-1 in avacopan-treated patients at week 52, Dr. Jayne reported.

In terms of safety, there were no differences between the groups, with trends of fewer deaths and severe adverse events in the avacopan group.

“We found that the improved recovery of eGFR with avacopan was accentuated among those with more severe renal disease,” Dr. Jayne said.

He noted that, while the study’s aim was for the avacopan group to be steroid free, the patients received brief, reduced doses of about a third of the normal oral steroid dose early in the trial. However, using a Glucocorticoid Toxicity Index, the authors found those in the avacopan group did have fewer glucocorticoid-related adverse events.

Future issues to be examined include what happens when avacopan is discontinued and whether there will be a high relapse rate, Dr. Jayne noted.

Overall, however, “we anticipate that with longer-term follow-up, this better eGFR recovery will have a [favorable] effect on kidney failure and potentially mortality risk in these patients,” he concluded.

Targeted therapy is good for patients and doctors

Expanding upon his comments regarding the new drug, Dr. Jennette said it implies “that the C5a receptor inhibitor was targeting an event that blocks injury more quickly and effectively than prednisone.”

“This may be because prednisone has more complex pharmacodynamics and less targeted effects than a C5a receptor inhibitor,” he said.

Overall, the findings bode well for a potentially beneficial therapy, he added. “We have entered a new era of more targeted therapies, for example, targeted B-cell therapy using an anti-CD20 antibody, and targeted complement-mediated injury therapy using C5a receptor inhibitor.”

“The validation of this targeted therapy to block complement-mediated autoimmune inflammatory injury is another advance toward targeted precision therapy versus empirical therapy. This will be good for the doctors and good for the patients,” Dr. Jennette concluded.

The study was funded by ChemoCentryx. Dr. Jayne has reported receiving grants and/or consulting for AstraZeneca, ChemoCentryx, GlaxoSmithKline, MiroBio, Vifor, and Roche/Genentech. Dr. Jennette has received funding from ChemoCentryx for preclinical validation studies of avacopan in a mouse model of ANCA glomerulonephritis.

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

In men with a normal waist circumference, obstructive sleep apnea (OSA) metrics were positively associated with serum triglycerides, according to results of a study published in Nature and Science of Sleep (2021:13 1771-82).

Layla B. Guscoth, MD, of the South Australian Health and Medical Research Institute and Faculty of Health and Medical Sciences, University of Adelaide, Australia, and colleagues assessed unselected male community-dwelling participants in the Men Androgen Inflammation Lifestyle Environment and Stress (MAILES) and the Florey Adelaide Male Aging Study (FAMAS) studies.

They examined the association of OSA and nocturnal hypoxemia with serum lipid profiles, and suggested that the cardiometabolic risk profiles of healthy weight individuals with OSA require clinical attention, according to the researchers.

The partial or complete obstruction of upper airways found in the OSA syndrome results in intermittent hypoxia, accompanied variably by sleep fragmentation and daytime sleepiness. While the prevalence of moderate to severe OSA was 49.7% in the Swiss HypnoLaus cohort, it was 74.7% in men aged 40 or older (or having OSA syndrome according to ICD-3 criteria). Dr. Guscoth and colleagues point out, however, that OSA is frequently underdiagnosed or unrecognized in clinical settings, and that OSA has been implicated in development of cardiovascular conditions. Furthermore, the nocturnal hypoxemia resulting from OSA during rapid eye movement (REM) sleep is longitudinally associated with cardiovascular disease and its risk factors (hypertension, insulin resistance, metabolic syndrome and carotid atherosclerosis).
 

Study details

Prior research suggests that intermittent hypoxemia activates the sympathetic nervous system, increases oxidative stress and systemic inflammation, and that when chronic, reduces clearance of triglyceride-rich lipoproteins and inhibits adipose tissue lipoprotein lipase activity. To clarify inconsistent results in studies investigating potential OSA-dyslipidemia associations, and to confirm research suggesting an independent association with severe OSA (apnea-hypopnea index [AHI] ≥ 30/h), the authors conducted analyses stratified by waist circumference to observe an obesity-independent association between OSA metrics and dyslipidemia.

The investigators assessed 753 MAILES participants (mean age 60.8 years) who underwent full in-home polysomnography (Embletta X100). They looked at triglycerides, high- (HDL) and low-density lipoprotein (LDL), total cholesterol, associations between lipids and continuous measures of nocturnal hypoxemia (oxygen desaturation index [ODI], AHI, and REM-AHI), and adjusted for chronic conditions, risk behavior, and sociodemographic factors.

Mean waist circumference was 99.3 cm and OSA (AHI ≥ 10) prevalence was 52.6%. No significant associations were found between OSA metrics and lipid measures in an overall analysis, nor in a sensitivity analysis excluding lipid-lowering therapies.

In a covariate adjusted analysis stratified according to waist circumference (< 95 cm, 95-100 cm, > 100 cm) to minimize the contribution of obesity to hypertriglyceridemia, triglyceride levels were positively associated with AHI, ODI and REM-AHI in the participants with a waist circumference < 95 cm (P < .05), but not in participants with waist circumferences of 95-100 cm or > 100 cm.
 

Worse during REM

The authors observed also that OSA during REM sleep is marked by longer obstructive events with greater oxygen desaturations. Obstructive events during REM sleep, research has shown, may be more harmful than obstructive events during non-REM sleep with respect to hypertension, cardiovascular disease, and glycemic control in type 2 diabetes.

Looking at clinical categories of OSA, Dr. Guscoth and colleagues found that severe OSA was significantly associated with higher likelihood of triglyceride levels ≥ 1.7 mmol/L (odds ratio, 4.1, 95% confidence interval, 1.1-15.5, P = .039). Analysis according to waist circumference confirmed the relationship only among men with waist circumference < 95 cm.
 

Clinical concern

“We therefore suggest that with our data unstratified by weight circumference, metabolic derangements associated with insulin resistance induced by intermittent hypoxia due to OSA cannot be separated from the predominant effect of visceral obesity. When stratified by weight circumference, our data show that these derangements in triglycerides are observed only in lean participants where obesity does not have a dominant effect,” the researchers concluded.

“These findings of high prevalence of metabolic risk in lean patients with OSA, I find very worrying,” coauthor Sarah Appleton, PhD, Flinders Medical Center, Adelaide, Australia, said in an interview. She cited a study showing a 61% risk of dyslipidemia in lean patients with OSA (AHI > 5/hr, body mass index < 25 kg/m², and waist < 80 cm in women, < 90 cm in men), and two of three metabolic syndrome components in 64%. “Annual fasting blood tests would identify metabolic problems such as elevated fasting glucose and triglyceride levels,” she noted.

This work was supported by a National Health and Medical Research Council of Australia Project Grant (627227), the Hospital Research Foundation and ResMed Foundation. There were no relevant conflicts reported.

In men with a normal waist circumference, obstructive sleep apnea (OSA) metrics were positively associated with serum triglycerides, according to results of a study published in Nature and Science of Sleep (2021:13 1771-82).

Layla B. Guscoth, MD, of the South Australian Health and Medical Research Institute and Faculty of Health and Medical Sciences, University of Adelaide, Australia, and colleagues assessed unselected male community-dwelling participants in the Men Androgen Inflammation Lifestyle Environment and Stress (MAILES) and the Florey Adelaide Male Aging Study (FAMAS) studies.

They examined the association of OSA and nocturnal hypoxemia with serum lipid profiles, and suggested that the cardiometabolic risk profiles of healthy weight individuals with OSA require clinical attention, according to the researchers.

The partial or complete obstruction of upper airways found in the OSA syndrome results in intermittent hypoxia, accompanied variably by sleep fragmentation and daytime sleepiness. While the prevalence of moderate to severe OSA was 49.7% in the Swiss HypnoLaus cohort, it was 74.7% in men aged 40 or older (or having OSA syndrome according to ICD-3 criteria). Dr. Guscoth and colleagues point out, however, that OSA is frequently underdiagnosed or unrecognized in clinical settings, and that OSA has been implicated in development of cardiovascular conditions. Furthermore, the nocturnal hypoxemia resulting from OSA during rapid eye movement (REM) sleep is longitudinally associated with cardiovascular disease and its risk factors (hypertension, insulin resistance, metabolic syndrome and carotid atherosclerosis).
 

Study details

Prior research suggests that intermittent hypoxemia activates the sympathetic nervous system, increases oxidative stress and systemic inflammation, and that when chronic, reduces clearance of triglyceride-rich lipoproteins and inhibits adipose tissue lipoprotein lipase activity. To clarify inconsistent results in studies investigating potential OSA-dyslipidemia associations, and to confirm research suggesting an independent association with severe OSA (apnea-hypopnea index [AHI] ≥ 30/h), the authors conducted analyses stratified by waist circumference to observe an obesity-independent association between OSA metrics and dyslipidemia.

The investigators assessed 753 MAILES participants (mean age 60.8 years) who underwent full in-home polysomnography (Embletta X100). They looked at triglycerides, high- (HDL) and low-density lipoprotein (LDL), total cholesterol, associations between lipids and continuous measures of nocturnal hypoxemia (oxygen desaturation index [ODI], AHI, and REM-AHI), and adjusted for chronic conditions, risk behavior, and sociodemographic factors.

Mean waist circumference was 99.3 cm and OSA (AHI ≥ 10) prevalence was 52.6%. No significant associations were found between OSA metrics and lipid measures in an overall analysis, nor in a sensitivity analysis excluding lipid-lowering therapies.

In a covariate adjusted analysis stratified according to waist circumference (< 95 cm, 95-100 cm, > 100 cm) to minimize the contribution of obesity to hypertriglyceridemia, triglyceride levels were positively associated with AHI, ODI and REM-AHI in the participants with a waist circumference < 95 cm (P < .05), but not in participants with waist circumferences of 95-100 cm or > 100 cm.
 

Worse during REM

The authors observed also that OSA during REM sleep is marked by longer obstructive events with greater oxygen desaturations. Obstructive events during REM sleep, research has shown, may be more harmful than obstructive events during non-REM sleep with respect to hypertension, cardiovascular disease, and glycemic control in type 2 diabetes.

Looking at clinical categories of OSA, Dr. Guscoth and colleagues found that severe OSA was significantly associated with higher likelihood of triglyceride levels ≥ 1.7 mmol/L (odds ratio, 4.1, 95% confidence interval, 1.1-15.5, P = .039). Analysis according to waist circumference confirmed the relationship only among men with waist circumference < 95 cm.
 

Clinical concern

“We therefore suggest that with our data unstratified by weight circumference, metabolic derangements associated with insulin resistance induced by intermittent hypoxia due to OSA cannot be separated from the predominant effect of visceral obesity. When stratified by weight circumference, our data show that these derangements in triglycerides are observed only in lean participants where obesity does not have a dominant effect,” the researchers concluded.

“These findings of high prevalence of metabolic risk in lean patients with OSA, I find very worrying,” coauthor Sarah Appleton, PhD, Flinders Medical Center, Adelaide, Australia, said in an interview. She cited a study showing a 61% risk of dyslipidemia in lean patients with OSA (AHI > 5/hr, body mass index < 25 kg/m², and waist < 80 cm in women, < 90 cm in men), and two of three metabolic syndrome components in 64%. “Annual fasting blood tests would identify metabolic problems such as elevated fasting glucose and triglyceride levels,” she noted.

This work was supported by a National Health and Medical Research Council of Australia Project Grant (627227), the Hospital Research Foundation and ResMed Foundation. There were no relevant conflicts reported.

In men with a normal waist circumference, obstructive sleep apnea (OSA) metrics were positively associated with serum triglycerides, according to results of a study published in Nature and Science of Sleep (2021:13 1771-82).

Layla B. Guscoth, MD, of the South Australian Health and Medical Research Institute and Faculty of Health and Medical Sciences, University of Adelaide, Australia, and colleagues assessed unselected male community-dwelling participants in the Men Androgen Inflammation Lifestyle Environment and Stress (MAILES) and the Florey Adelaide Male Aging Study (FAMAS) studies.

They examined the association of OSA and nocturnal hypoxemia with serum lipid profiles, and suggested that the cardiometabolic risk profiles of healthy weight individuals with OSA require clinical attention, according to the researchers.

The partial or complete obstruction of upper airways found in the OSA syndrome results in intermittent hypoxia, accompanied variably by sleep fragmentation and daytime sleepiness. While the prevalence of moderate to severe OSA was 49.7% in the Swiss HypnoLaus cohort, it was 74.7% in men aged 40 or older (or having OSA syndrome according to ICD-3 criteria). Dr. Guscoth and colleagues point out, however, that OSA is frequently underdiagnosed or unrecognized in clinical settings, and that OSA has been implicated in development of cardiovascular conditions. Furthermore, the nocturnal hypoxemia resulting from OSA during rapid eye movement (REM) sleep is longitudinally associated with cardiovascular disease and its risk factors (hypertension, insulin resistance, metabolic syndrome and carotid atherosclerosis).
 

Study details

Prior research suggests that intermittent hypoxemia activates the sympathetic nervous system, increases oxidative stress and systemic inflammation, and that when chronic, reduces clearance of triglyceride-rich lipoproteins and inhibits adipose tissue lipoprotein lipase activity. To clarify inconsistent results in studies investigating potential OSA-dyslipidemia associations, and to confirm research suggesting an independent association with severe OSA (apnea-hypopnea index [AHI] ≥ 30/h), the authors conducted analyses stratified by waist circumference to observe an obesity-independent association between OSA metrics and dyslipidemia.

The investigators assessed 753 MAILES participants (mean age 60.8 years) who underwent full in-home polysomnography (Embletta X100). They looked at triglycerides, high- (HDL) and low-density lipoprotein (LDL), total cholesterol, associations between lipids and continuous measures of nocturnal hypoxemia (oxygen desaturation index [ODI], AHI, and REM-AHI), and adjusted for chronic conditions, risk behavior, and sociodemographic factors.

Mean waist circumference was 99.3 cm and OSA (AHI ≥ 10) prevalence was 52.6%. No significant associations were found between OSA metrics and lipid measures in an overall analysis, nor in a sensitivity analysis excluding lipid-lowering therapies.

In a covariate adjusted analysis stratified according to waist circumference (< 95 cm, 95-100 cm, > 100 cm) to minimize the contribution of obesity to hypertriglyceridemia, triglyceride levels were positively associated with AHI, ODI and REM-AHI in the participants with a waist circumference < 95 cm (P < .05), but not in participants with waist circumferences of 95-100 cm or > 100 cm.
 

Worse during REM

The authors observed also that OSA during REM sleep is marked by longer obstructive events with greater oxygen desaturations. Obstructive events during REM sleep, research has shown, may be more harmful than obstructive events during non-REM sleep with respect to hypertension, cardiovascular disease, and glycemic control in type 2 diabetes.

Looking at clinical categories of OSA, Dr. Guscoth and colleagues found that severe OSA was significantly associated with higher likelihood of triglyceride levels ≥ 1.7 mmol/L (odds ratio, 4.1, 95% confidence interval, 1.1-15.5, P = .039). Analysis according to waist circumference confirmed the relationship only among men with waist circumference < 95 cm.
 

Clinical concern

“We therefore suggest that with our data unstratified by weight circumference, metabolic derangements associated with insulin resistance induced by intermittent hypoxia due to OSA cannot be separated from the predominant effect of visceral obesity. When stratified by weight circumference, our data show that these derangements in triglycerides are observed only in lean participants where obesity does not have a dominant effect,” the researchers concluded.

“These findings of high prevalence of metabolic risk in lean patients with OSA, I find very worrying,” coauthor Sarah Appleton, PhD, Flinders Medical Center, Adelaide, Australia, said in an interview. She cited a study showing a 61% risk of dyslipidemia in lean patients with OSA (AHI > 5/hr, body mass index < 25 kg/m², and waist < 80 cm in women, < 90 cm in men), and two of three metabolic syndrome components in 64%. “Annual fasting blood tests would identify metabolic problems such as elevated fasting glucose and triglyceride levels,” she noted.

This work was supported by a National Health and Medical Research Council of Australia Project Grant (627227), the Hospital Research Foundation and ResMed Foundation. There were no relevant conflicts reported.

Background: Despite advances in AFib management, up to 5% of patients will have a major complication each year. Current guidelines favor rate control based on prior studies that did not show mortality benefit with rhythm control. By expanding the rhythm strategy to include catheter ablation in early AFib, this trial re-examines if implementing rhythm control leads to improved clinical outcomes. 

Dr. Korovaichuk is a hospitalist at Northwestern Memorial Hospital and assistant professor of medicine, Feinberg School of Medicine, both in Chicago.

Background: Despite advances in AFib management, up to 5% of patients will have a major complication each year. Current guidelines favor rate control based on prior studies that did not show mortality benefit with rhythm control. By expanding the rhythm strategy to include catheter ablation in early AFib, this trial re-examines if implementing rhythm control leads to improved clinical outcomes. 

Dr. Korovaichuk is a hospitalist at Northwestern Memorial Hospital and assistant professor of medicine, Feinberg School of Medicine, both in Chicago.

Background: Despite advances in AFib management, up to 5% of patients will have a major complication each year. Current guidelines favor rate control based on prior studies that did not show mortality benefit with rhythm control. By expanding the rhythm strategy to include catheter ablation in early AFib, this trial re-examines if implementing rhythm control leads to improved clinical outcomes. 

Dr. Korovaichuk is a hospitalist at Northwestern Memorial Hospital and assistant professor of medicine, Feinberg School of Medicine, both in Chicago.

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Each month of glucocorticoid use in middle-aged patients with rheumatoid arthritis increases their odds of a major adverse cardiac event by 14%, independent of their baseline cardiovascular risk, according to a Veterans Administration study presented at the virtual annual meeting of the American College of Rheumatology. A similar study of Medicare and insurance claims data also presented at the meeting similarly found a dose-dependent increase in cardiovascular risk with long-term glucocorticoid use among patients with RA.

Up to half of patients with RA use long-term glucocorticoids, Beth Wallace, MD, an assistant professor of internal medicine at the University of Michigan, Ann Arbor, and a staff rheumatologist at the VA Ann Arbor Healthcare Center, told attendees in her presentation.

“Despite previous work suggesting they increase major [adverse] cardiovascular events, or MACE, in a dose-dependent way, prior work suggests long-term glucocorticoid use is common among RA patients with traditional basic risk factors like hyperlipidemia, diabetes, hypertension, and smoking,” Dr. Wallace said. “But we know little about the incremental effects of ongoing glucocorticoid use on MACE risk in RA, particularly as traditional predisposing comorbidities might confound its assessment.”

VA study details

The retrospective cohort study relied on VA administrative data for 26,239 patients with RA who had at least one rheumatology visit during 2013-2017. Only adults aged 40-90 were included (85% men), and none had other rheumatologic conditions, a previous MACE, or congestive heart failure in the preceding 5 years.

The researchers used pharmacy dispensing data to determine exposure to glucocorticoids, based on the number of days’ supply per 6 months and claims data to identify the primary outcome of MACE, defined as acute myocardial infarction, stroke, transient ischemic attack, cardiac arrest, or coronary revascularization, in the following 6 months. After a first MACE, a patient was removed from subsequent analysis so that only a participant’s initial event was considered.

The researchers adjusted their analysis for demographics, health care utilization, long-term glucocorticoid use (over 90 days), use of methotrexate or biologics, and baseline cardiac risk based on the Veterans Affairs Risk Score for Cardiovascular Disease (VARS-CVD). The VARS-CVD uses age, sex, race, tobacco use, systolic blood pressure, cholesterol, diabetes diagnosis, and use of antihypertensives to estimate the risk of a MACE in the next 5 years. A 5-year risk of less than 3% was considered low, 3%-9% medium, and above 9% high.

The population’s median 5-year MACE risk based on VARS-CVD was 5.7%, with nearly a quarter of participants (23%) having a high risk. During the first year of follow-up, 23% of patients overall, including 24% of those with high risk, received at least 90 days of glucocorticoids. An incident MACE occurred in 3.2% of overall patients and in 4.9% of high-risk patients. Median time until an incident MACE was 25 months.

After adjusting for confounders, the researchers calculated that each additional 30 days of glucocorticoid use per 6-month period was linked to a 14% increase in odds of a MACE in the subsequent 6-month period (odds ratio, 1.14). This finding remained independent of baseline cardiovascular risk, previous long-term exposure to glucocorticoids, baseline office visits, methotrexate or biologic use, and baseline Elixhauser Cormobidity Index (except rheumatoid arthritis, diabetes, hypertension, and congestive heart failure).

Dr. Wallace noted that the observational study could still include residual confounding because of factors such as rheumatic disease activity, glucocorticoid dose, and care outside the VA. They also did not distinguish between existing and incident RA and were missing some VARS-CVD data, and they did not adjust for hydroxychloroquine use, which can reduce cardiovascular risk.
 

Details of Medicare and private insurance claims study

In the second study, Brian Coburn, MD, a fourth-year internal medicine resident at the University of Pennsylvania, Philadelphia, presented findings on long-term glucocorticoid use and cardiovascular outcomes in patients with RA based on 2006-2015 claims data from Medicare and the Optum Clinformatics Data Mart. That study similarly found a dose-dependent increase in cardiovascular risk with increasing dosage of long-term glucocorticoids.

All the patients in the two databases had an RA diagnosis and remained on disease-modifying antirheumatic drugs (DMARDs) for at least 180 days without adding a new DMARD or stopping therapy for more than 90 days. Patients were not included if they had a history of myocardial infarction, stroke, coronary artery bypass grafting, or percutaneous coronary intervention.

Using the 180 days before and after starting DMARDs as baseline, the researchers assessed average dose of glucocorticoids during the last 90 days of the baseline period. Participants included 135,583 patients with Medicare, contributing 158,839 years at risk, and 39,272 patients in the Optum database, contributing 36,876 years at risk. The researchers then assessed composite cardiovascular events as a combination of strokes and myocardial infarctions.

A total of 2,067 cardiovascular events occurred among the Medicare patients, for a incidence of 1.3 events per 100 people per year, and 313 cardiovascular events occurred among Optum patients, for an incidence of 0.8 events per 100 people per year.

Over 1 year, a predicted 1.1% of Medicare patients not taking glucocorticoids would experience a stroke or heart attack, compared with 1.4% of those taking up to 5 mg/day of glucocorticoids, 1.7% of those taking 5-10 mg/day glucocorticoids, and 1.9% of those taking more than 10 mg/day glucocorticoids. The number needed to harm was 400 people for up to 5 mg/day, 192 people for 5-10 mg/day, and 137 people for more than 10 mg/day.

Among Optum patients, 0.7% not taking glucocorticoids would experience a stroke or heart attack over 1 year, compared with 0.9% of those taking up to 5 mg/day and 0.8% of those taking either 5-10 mg/day or more than 10 mg/day. The number needed to harm was 714 people for up to 5 mg/day of glucocorticoids, 5,000 people for 5-10 mg/day, and 1,667 for over 10 mg/day.

Dr. Bartels noted that this study “reported unadjusted rates, without controlling for traditional CVD risk factors, for instance, so it will be interesting to see that report after full analysis and peer review as well.” She added that the rates in the VA study may even be higher if there were uncounted cardiovascular events or deaths outside the VA.

“The key take away is that glucocorticoids have dose-related cardiovascular risk shown in both duration and dose of use now in these three large U.S. cohorts,” Dr. Bartels said. “Providers need to counsel patients in judicious use of glucocorticoids, favoring the role of biologic and nonbiologic DMARDs while balancing unique needs and quality-of-life considerations in our patients.”

The VA retrospective cohort study was funded by the National Institutes of Health, the American Autoimmune Related Diseases Association, the U.S. Department of Veterans Affairs, and the Michigan Institute for Clinical & Health Research. Dr. Wallace and seven other authors reported no disclosures. Several coauthors reported financial ties to multiple pharmaceutical companies. The Medicare/Optum retrospective cohort study was funded by the National Institutes of Health, the Patient-Centered Outcomes Research Institute, and the Rheumatology Research Foundation. Dr. Coburn and five coauthors had no disclosures, while several others reported financial ties to a variety of pharmaceutical companies. Dr. Bartels has received institutional grant support from Pfizer for tobacco cessation research

Each month of glucocorticoid use in middle-aged patients with rheumatoid arthritis increases their odds of a major adverse cardiac event by 14%, independent of their baseline cardiovascular risk, according to a Veterans Administration study presented at the virtual annual meeting of the American College of Rheumatology. A similar study of Medicare and insurance claims data also presented at the meeting similarly found a dose-dependent increase in cardiovascular risk with long-term glucocorticoid use among patients with RA.

Up to half of patients with RA use long-term glucocorticoids, Beth Wallace, MD, an assistant professor of internal medicine at the University of Michigan, Ann Arbor, and a staff rheumatologist at the VA Ann Arbor Healthcare Center, told attendees in her presentation.

“Despite previous work suggesting they increase major [adverse] cardiovascular events, or MACE, in a dose-dependent way, prior work suggests long-term glucocorticoid use is common among RA patients with traditional basic risk factors like hyperlipidemia, diabetes, hypertension, and smoking,” Dr. Wallace said. “But we know little about the incremental effects of ongoing glucocorticoid use on MACE risk in RA, particularly as traditional predisposing comorbidities might confound its assessment.”

VA study details

The retrospective cohort study relied on VA administrative data for 26,239 patients with RA who had at least one rheumatology visit during 2013-2017. Only adults aged 40-90 were included (85% men), and none had other rheumatologic conditions, a previous MACE, or congestive heart failure in the preceding 5 years.

The researchers used pharmacy dispensing data to determine exposure to glucocorticoids, based on the number of days’ supply per 6 months and claims data to identify the primary outcome of MACE, defined as acute myocardial infarction, stroke, transient ischemic attack, cardiac arrest, or coronary revascularization, in the following 6 months. After a first MACE, a patient was removed from subsequent analysis so that only a participant’s initial event was considered.

The researchers adjusted their analysis for demographics, health care utilization, long-term glucocorticoid use (over 90 days), use of methotrexate or biologics, and baseline cardiac risk based on the Veterans Affairs Risk Score for Cardiovascular Disease (VARS-CVD). The VARS-CVD uses age, sex, race, tobacco use, systolic blood pressure, cholesterol, diabetes diagnosis, and use of antihypertensives to estimate the risk of a MACE in the next 5 years. A 5-year risk of less than 3% was considered low, 3%-9% medium, and above 9% high.

The population’s median 5-year MACE risk based on VARS-CVD was 5.7%, with nearly a quarter of participants (23%) having a high risk. During the first year of follow-up, 23% of patients overall, including 24% of those with high risk, received at least 90 days of glucocorticoids. An incident MACE occurred in 3.2% of overall patients and in 4.9% of high-risk patients. Median time until an incident MACE was 25 months.

After adjusting for confounders, the researchers calculated that each additional 30 days of glucocorticoid use per 6-month period was linked to a 14% increase in odds of a MACE in the subsequent 6-month period (odds ratio, 1.14). This finding remained independent of baseline cardiovascular risk, previous long-term exposure to glucocorticoids, baseline office visits, methotrexate or biologic use, and baseline Elixhauser Cormobidity Index (except rheumatoid arthritis, diabetes, hypertension, and congestive heart failure).

Dr. Wallace noted that the observational study could still include residual confounding because of factors such as rheumatic disease activity, glucocorticoid dose, and care outside the VA. They also did not distinguish between existing and incident RA and were missing some VARS-CVD data, and they did not adjust for hydroxychloroquine use, which can reduce cardiovascular risk.
 

Details of Medicare and private insurance claims study

In the second study, Brian Coburn, MD, a fourth-year internal medicine resident at the University of Pennsylvania, Philadelphia, presented findings on long-term glucocorticoid use and cardiovascular outcomes in patients with RA based on 2006-2015 claims data from Medicare and the Optum Clinformatics Data Mart. That study similarly found a dose-dependent increase in cardiovascular risk with increasing dosage of long-term glucocorticoids.

All the patients in the two databases had an RA diagnosis and remained on disease-modifying antirheumatic drugs (DMARDs) for at least 180 days without adding a new DMARD or stopping therapy for more than 90 days. Patients were not included if they had a history of myocardial infarction, stroke, coronary artery bypass grafting, or percutaneous coronary intervention.

Using the 180 days before and after starting DMARDs as baseline, the researchers assessed average dose of glucocorticoids during the last 90 days of the baseline period. Participants included 135,583 patients with Medicare, contributing 158,839 years at risk, and 39,272 patients in the Optum database, contributing 36,876 years at risk. The researchers then assessed composite cardiovascular events as a combination of strokes and myocardial infarctions.

A total of 2,067 cardiovascular events occurred among the Medicare patients, for a incidence of 1.3 events per 100 people per year, and 313 cardiovascular events occurred among Optum patients, for an incidence of 0.8 events per 100 people per year.

Over 1 year, a predicted 1.1% of Medicare patients not taking glucocorticoids would experience a stroke or heart attack, compared with 1.4% of those taking up to 5 mg/day of glucocorticoids, 1.7% of those taking 5-10 mg/day glucocorticoids, and 1.9% of those taking more than 10 mg/day glucocorticoids. The number needed to harm was 400 people for up to 5 mg/day, 192 people for 5-10 mg/day, and 137 people for more than 10 mg/day.

Among Optum patients, 0.7% not taking glucocorticoids would experience a stroke or heart attack over 1 year, compared with 0.9% of those taking up to 5 mg/day and 0.8% of those taking either 5-10 mg/day or more than 10 mg/day. The number needed to harm was 714 people for up to 5 mg/day of glucocorticoids, 5,000 people for 5-10 mg/day, and 1,667 for over 10 mg/day.

Dr. Bartels noted that this study “reported unadjusted rates, without controlling for traditional CVD risk factors, for instance, so it will be interesting to see that report after full analysis and peer review as well.” She added that the rates in the VA study may even be higher if there were uncounted cardiovascular events or deaths outside the VA.

“The key take away is that glucocorticoids have dose-related cardiovascular risk shown in both duration and dose of use now in these three large U.S. cohorts,” Dr. Bartels said. “Providers need to counsel patients in judicious use of glucocorticoids, favoring the role of biologic and nonbiologic DMARDs while balancing unique needs and quality-of-life considerations in our patients.”

The VA retrospective cohort study was funded by the National Institutes of Health, the American Autoimmune Related Diseases Association, the U.S. Department of Veterans Affairs, and the Michigan Institute for Clinical & Health Research. Dr. Wallace and seven other authors reported no disclosures. Several coauthors reported financial ties to multiple pharmaceutical companies. The Medicare/Optum retrospective cohort study was funded by the National Institutes of Health, the Patient-Centered Outcomes Research Institute, and the Rheumatology Research Foundation. Dr. Coburn and five coauthors had no disclosures, while several others reported financial ties to a variety of pharmaceutical companies. Dr. Bartels has received institutional grant support from Pfizer for tobacco cessation research

Each month of glucocorticoid use in middle-aged patients with rheumatoid arthritis increases their odds of a major adverse cardiac event by 14%, independent of their baseline cardiovascular risk, according to a Veterans Administration study presented at the virtual annual meeting of the American College of Rheumatology. A similar study of Medicare and insurance claims data also presented at the meeting similarly found a dose-dependent increase in cardiovascular risk with long-term glucocorticoid use among patients with RA.

Up to half of patients with RA use long-term glucocorticoids, Beth Wallace, MD, an assistant professor of internal medicine at the University of Michigan, Ann Arbor, and a staff rheumatologist at the VA Ann Arbor Healthcare Center, told attendees in her presentation.

“Despite previous work suggesting they increase major [adverse] cardiovascular events, or MACE, in a dose-dependent way, prior work suggests long-term glucocorticoid use is common among RA patients with traditional basic risk factors like hyperlipidemia, diabetes, hypertension, and smoking,” Dr. Wallace said. “But we know little about the incremental effects of ongoing glucocorticoid use on MACE risk in RA, particularly as traditional predisposing comorbidities might confound its assessment.”

VA study details

The retrospective cohort study relied on VA administrative data for 26,239 patients with RA who had at least one rheumatology visit during 2013-2017. Only adults aged 40-90 were included (85% men), and none had other rheumatologic conditions, a previous MACE, or congestive heart failure in the preceding 5 years.

The researchers used pharmacy dispensing data to determine exposure to glucocorticoids, based on the number of days’ supply per 6 months and claims data to identify the primary outcome of MACE, defined as acute myocardial infarction, stroke, transient ischemic attack, cardiac arrest, or coronary revascularization, in the following 6 months. After a first MACE, a patient was removed from subsequent analysis so that only a participant’s initial event was considered.

The researchers adjusted their analysis for demographics, health care utilization, long-term glucocorticoid use (over 90 days), use of methotrexate or biologics, and baseline cardiac risk based on the Veterans Affairs Risk Score for Cardiovascular Disease (VARS-CVD). The VARS-CVD uses age, sex, race, tobacco use, systolic blood pressure, cholesterol, diabetes diagnosis, and use of antihypertensives to estimate the risk of a MACE in the next 5 years. A 5-year risk of less than 3% was considered low, 3%-9% medium, and above 9% high.

The population’s median 5-year MACE risk based on VARS-CVD was 5.7%, with nearly a quarter of participants (23%) having a high risk. During the first year of follow-up, 23% of patients overall, including 24% of those with high risk, received at least 90 days of glucocorticoids. An incident MACE occurred in 3.2% of overall patients and in 4.9% of high-risk patients. Median time until an incident MACE was 25 months.

After adjusting for confounders, the researchers calculated that each additional 30 days of glucocorticoid use per 6-month period was linked to a 14% increase in odds of a MACE in the subsequent 6-month period (odds ratio, 1.14). This finding remained independent of baseline cardiovascular risk, previous long-term exposure to glucocorticoids, baseline office visits, methotrexate or biologic use, and baseline Elixhauser Cormobidity Index (except rheumatoid arthritis, diabetes, hypertension, and congestive heart failure).

Dr. Wallace noted that the observational study could still include residual confounding because of factors such as rheumatic disease activity, glucocorticoid dose, and care outside the VA. They also did not distinguish between existing and incident RA and were missing some VARS-CVD data, and they did not adjust for hydroxychloroquine use, which can reduce cardiovascular risk.
 

Details of Medicare and private insurance claims study

In the second study, Brian Coburn, MD, a fourth-year internal medicine resident at the University of Pennsylvania, Philadelphia, presented findings on long-term glucocorticoid use and cardiovascular outcomes in patients with RA based on 2006-2015 claims data from Medicare and the Optum Clinformatics Data Mart. That study similarly found a dose-dependent increase in cardiovascular risk with increasing dosage of long-term glucocorticoids.

All the patients in the two databases had an RA diagnosis and remained on disease-modifying antirheumatic drugs (DMARDs) for at least 180 days without adding a new DMARD or stopping therapy for more than 90 days. Patients were not included if they had a history of myocardial infarction, stroke, coronary artery bypass grafting, or percutaneous coronary intervention.

Using the 180 days before and after starting DMARDs as baseline, the researchers assessed average dose of glucocorticoids during the last 90 days of the baseline period. Participants included 135,583 patients with Medicare, contributing 158,839 years at risk, and 39,272 patients in the Optum database, contributing 36,876 years at risk. The researchers then assessed composite cardiovascular events as a combination of strokes and myocardial infarctions.

A total of 2,067 cardiovascular events occurred among the Medicare patients, for a incidence of 1.3 events per 100 people per year, and 313 cardiovascular events occurred among Optum patients, for an incidence of 0.8 events per 100 people per year.

Over 1 year, a predicted 1.1% of Medicare patients not taking glucocorticoids would experience a stroke or heart attack, compared with 1.4% of those taking up to 5 mg/day of glucocorticoids, 1.7% of those taking 5-10 mg/day glucocorticoids, and 1.9% of those taking more than 10 mg/day glucocorticoids. The number needed to harm was 400 people for up to 5 mg/day, 192 people for 5-10 mg/day, and 137 people for more than 10 mg/day.

Among Optum patients, 0.7% not taking glucocorticoids would experience a stroke or heart attack over 1 year, compared with 0.9% of those taking up to 5 mg/day and 0.8% of those taking either 5-10 mg/day or more than 10 mg/day. The number needed to harm was 714 people for up to 5 mg/day of glucocorticoids, 5,000 people for 5-10 mg/day, and 1,667 for over 10 mg/day.

Dr. Bartels noted that this study “reported unadjusted rates, without controlling for traditional CVD risk factors, for instance, so it will be interesting to see that report after full analysis and peer review as well.” She added that the rates in the VA study may even be higher if there were uncounted cardiovascular events or deaths outside the VA.

“The key take away is that glucocorticoids have dose-related cardiovascular risk shown in both duration and dose of use now in these three large U.S. cohorts,” Dr. Bartels said. “Providers need to counsel patients in judicious use of glucocorticoids, favoring the role of biologic and nonbiologic DMARDs while balancing unique needs and quality-of-life considerations in our patients.”

The VA retrospective cohort study was funded by the National Institutes of Health, the American Autoimmune Related Diseases Association, the U.S. Department of Veterans Affairs, and the Michigan Institute for Clinical & Health Research. Dr. Wallace and seven other authors reported no disclosures. Several coauthors reported financial ties to multiple pharmaceutical companies. The Medicare/Optum retrospective cohort study was funded by the National Institutes of Health, the Patient-Centered Outcomes Research Institute, and the Rheumatology Research Foundation. Dr. Coburn and five coauthors had no disclosures, while several others reported financial ties to a variety of pharmaceutical companies. Dr. Bartels has received institutional grant support from Pfizer for tobacco cessation research

Main results from the landmark EMPEROR-Preserved trial, reported in August, established for the first time that treatment with a drug, the sodium-glucose cotransporter 2 inhibitor empagliflozin, could clearly benefit patients with heart failure with preserved ejection fraction (HFpEF).

The only caveat was that EMPEROR-Preserved enrolled patients with a left ventricular ejection fraction of at least 41%, while “true” HFpEF means patients with heart failure and an LVEF of at least 50%, according to recent definitions. About one-third of the 5,988 patients enrolled in EMPEROR-Preserved had an LVEF of 41%-49%, heart failure with mildly reduced ejection fraction.

Secondary analysis from the EMPEROR-Preserved trial has now resolved this ambiguity by showing that, among the 4,005 patients (67%) enrolled in the trial with an LVEF of at least 50%, treatment with empagliflozin (Jardiance) reduced the study’s primary endpoint – cardiovascular death or first hospitalization for heart failure – by a significant 17%, relative to patients who received placebo, dismissing any doubt about the relevance of the overall finding to the subgroup of patients with unmitigated HFpEF.

“This is the first large-scale trial to document meaningful and significant improvements associated with drug therapy in patients with ‘true’ HFpEF,” Stefan D. Anker, MD, said in presenting the results at the American Heart Association scientific sessions.

Streamlining heart failure treatment

The demonstration that empagliflozin is an effective – and safe – treatment for patients with HFpEF not only provides a new treatment for a disorder that until now had no evidence-based intervention, but also streamlines the management approach for treating patients with heart failure with an agent from empagliflozin’s class, the SGLT2 inhibitors, commented Mary Norine Walsh, MD, medical director of the heart failure and cardiac transplantation programs at Ascension St. Vincent Heart Center in Indianapolis.

That’s because empagliflozin has shown significant and consistent benefit across essentially the full range of LVEFs seen in patients with heart failure based on its performance in EMPEROR-Preserved as well as in a mirror-image trial, EMPEROR-Reduced, run in patients with heart failure with reduced ejection fraction.

“Clinicians do not need to stop and assess LVEF with echocardiography or other imaging before they decide on how to treat heart failure patients” with an SGLT2 inhibitor, noted Dr. Walsh, a designated discussant for the report. “Clinicians who are busy can now refer less to LVEF than to the patient’s phenotype.”
 

Treatment prevents hospitalization for heart failure

The more-detailed data reported by Dr. Anker also strengthened the case that the benefit from empagliflozin in patients with an LVEF of at least 50% mostly came from a reduction in hospitalizations for heart failure (HHF), which dropped following start of empagliflozin treatment by a relative 22%, compared with placebo for first HHF, a significant decline, and by a relative 17% for total HHF, a reduction that missed significance in this secondary analysis. The other half of the primary endpoint, cardiovascular death, declined by a nonsignificant 11% with empagliflozin treatment, compared with placebo in patients with clear-cut HFpEF.

The significant reduction in first HHF is, by itself, sufficient reason to use empagliflozin (or possibly a different SGLT2 inhibitor) in patients with HFpEF, maintained Clyde W. Yancy, MD, professor and chief of cardiology at Northwestern Medicine in Chicago.

“Attenuated HHF is a meaningful outcome,” stressed Dr. Yancy, also a discussant for the study. “This is the first time we’ve had evidence supporting that we can change the natural history of patients with HFpEF. While we still need to find interventions that save lives, we cannot overlook that this treatment can improve morbidity, and we cannot overlook that patient quality of life is better.”
 

Further benefits in patients with an LVEF of at least 50%

Dr. Anker, professor of cardiology and metabolism at Charité Medical University in Berlin, also reported results from several other analyses that further defined the effect of empagliflozin on clinical outcomes of patients with “true” HFpEF:

• The impact of empagliflozin, compared with placebo, for reducing both the study’s combined, primary outcome as well as total HHF was statistically consistent across all strata of LVEF, from 50% to greater than 70%. However, both outcome measures also showed a puzzling loss of benefit among patients with an LVEF of 65%-69%. In prior reports, a researcher on the EMPEROR-Preserved team, Milton Packer, MD, speculated that some patients in this LVEF stratum might not actually have had heart failure but instead had a different disorder that mimicked heart failure in clinical presentation, such as atrial fibrillation.
• Patients’ quality of life as measured by the Kansas City Cardiomyopathy Questionnaire showed a consistent benefit from empagliflozin treatment, compared with placebo, both in patients with an LVEF of at least 50% as well as in those with an LVEF of 41%-49%. In both subgroups the adjusted mean difference from placebo was significant and about 1.5 points.
• Patients showed a significant improvement in average New York Heart Association functional class while on treatment, and a strong trend toward less deterioration in functional class while on treatment.
• Deterioration of renal function on treatment slowed by an average 1.24 mL/min per 1.73 m² per year in patients on empagliflozin, compared with placebo, in the subgroup with an LVEF of at least 50%.

Dr. Anker also reported the primary outcome and component results for the subgroup of patients with a baseline LVEF of 41%-49%. These patients had what looked like a “bigger magnitude” of effect from treatment, he noted, showing a significant 29% relative decline in the primary endpoint, compared with placebo-treated patients, and a significant 42% relative drop in first HHF and a significant 43% relative decline in total HHF, compared with placebo.

The primary analysis from EMPEROR-Preserved, which included all 5,988 randomized patients with heart failure and an LVEF of 41% or greater, showed a significant reduction in the combined, primary endpoint with empagliflozin treatment of 21%, compared with control patients during a median follow-up of about 26 months. The absolute rate reduction of the combined primary endpoint was 3.3% during 26-months’ follow-up. Statistical tests have shown no heterogeneity of this effect by diabetes status (49% of patients had diabetes), nor by renal function down to an estimated glomerular filtration rate at entry as low as 20 mL/min per 1.73 m².

EMPEROR-Preserved was sponsored by Boehringer Ingelheim and Lilly, the two companies that market empagliflozin (Jardiance). Dr. Anker has been a consultant to Boehringer Ingelheim as well as to Abbott Vascular, Bayer, Brahms, Cardiac Dimensions, Cordio, Novartis, Servier, and Vifor. Dr. Walsh and Dr. Yancy had no disclosures.

mzoler@mdedge.com

Main results from the landmark EMPEROR-Preserved trial, reported in August, established for the first time that treatment with a drug, the sodium-glucose cotransporter 2 inhibitor empagliflozin, could clearly benefit patients with heart failure with preserved ejection fraction (HFpEF).

The only caveat was that EMPEROR-Preserved enrolled patients with a left ventricular ejection fraction of at least 41%, while “true” HFpEF means patients with heart failure and an LVEF of at least 50%, according to recent definitions. About one-third of the 5,988 patients enrolled in EMPEROR-Preserved had an LVEF of 41%-49%, heart failure with mildly reduced ejection fraction.

Secondary analysis from the EMPEROR-Preserved trial has now resolved this ambiguity by showing that, among the 4,005 patients (67%) enrolled in the trial with an LVEF of at least 50%, treatment with empagliflozin (Jardiance) reduced the study’s primary endpoint – cardiovascular death or first hospitalization for heart failure – by a significant 17%, relative to patients who received placebo, dismissing any doubt about the relevance of the overall finding to the subgroup of patients with unmitigated HFpEF.

“This is the first large-scale trial to document meaningful and significant improvements associated with drug therapy in patients with ‘true’ HFpEF,” Stefan D. Anker, MD, said in presenting the results at the American Heart Association scientific sessions.

Streamlining heart failure treatment

The demonstration that empagliflozin is an effective – and safe – treatment for patients with HFpEF not only provides a new treatment for a disorder that until now had no evidence-based intervention, but also streamlines the management approach for treating patients with heart failure with an agent from empagliflozin’s class, the SGLT2 inhibitors, commented Mary Norine Walsh, MD, medical director of the heart failure and cardiac transplantation programs at Ascension St. Vincent Heart Center in Indianapolis.

That’s because empagliflozin has shown significant and consistent benefit across essentially the full range of LVEFs seen in patients with heart failure based on its performance in EMPEROR-Preserved as well as in a mirror-image trial, EMPEROR-Reduced, run in patients with heart failure with reduced ejection fraction.

“Clinicians do not need to stop and assess LVEF with echocardiography or other imaging before they decide on how to treat heart failure patients” with an SGLT2 inhibitor, noted Dr. Walsh, a designated discussant for the report. “Clinicians who are busy can now refer less to LVEF than to the patient’s phenotype.”
 

Treatment prevents hospitalization for heart failure

The more-detailed data reported by Dr. Anker also strengthened the case that the benefit from empagliflozin in patients with an LVEF of at least 50% mostly came from a reduction in hospitalizations for heart failure (HHF), which dropped following start of empagliflozin treatment by a relative 22%, compared with placebo for first HHF, a significant decline, and by a relative 17% for total HHF, a reduction that missed significance in this secondary analysis. The other half of the primary endpoint, cardiovascular death, declined by a nonsignificant 11% with empagliflozin treatment, compared with placebo in patients with clear-cut HFpEF.

The significant reduction in first HHF is, by itself, sufficient reason to use empagliflozin (or possibly a different SGLT2 inhibitor) in patients with HFpEF, maintained Clyde W. Yancy, MD, professor and chief of cardiology at Northwestern Medicine in Chicago.

“Attenuated HHF is a meaningful outcome,” stressed Dr. Yancy, also a discussant for the study. “This is the first time we’ve had evidence supporting that we can change the natural history of patients with HFpEF. While we still need to find interventions that save lives, we cannot overlook that this treatment can improve morbidity, and we cannot overlook that patient quality of life is better.”
 

Further benefits in patients with an LVEF of at least 50%

Dr. Anker, professor of cardiology and metabolism at Charité Medical University in Berlin, also reported results from several other analyses that further defined the effect of empagliflozin on clinical outcomes of patients with “true” HFpEF:

• The impact of empagliflozin, compared with placebo, for reducing both the study’s combined, primary outcome as well as total HHF was statistically consistent across all strata of LVEF, from 50% to greater than 70%. However, both outcome measures also showed a puzzling loss of benefit among patients with an LVEF of 65%-69%. In prior reports, a researcher on the EMPEROR-Preserved team, Milton Packer, MD, speculated that some patients in this LVEF stratum might not actually have had heart failure but instead had a different disorder that mimicked heart failure in clinical presentation, such as atrial fibrillation.
• Patients’ quality of life as measured by the Kansas City Cardiomyopathy Questionnaire showed a consistent benefit from empagliflozin treatment, compared with placebo, both in patients with an LVEF of at least 50% as well as in those with an LVEF of 41%-49%. In both subgroups the adjusted mean difference from placebo was significant and about 1.5 points.
• Patients showed a significant improvement in average New York Heart Association functional class while on treatment, and a strong trend toward less deterioration in functional class while on treatment.
• Deterioration of renal function on treatment slowed by an average 1.24 mL/min per 1.73 m² per year in patients on empagliflozin, compared with placebo, in the subgroup with an LVEF of at least 50%.

Dr. Anker also reported the primary outcome and component results for the subgroup of patients with a baseline LVEF of 41%-49%. These patients had what looked like a “bigger magnitude” of effect from treatment, he noted, showing a significant 29% relative decline in the primary endpoint, compared with placebo-treated patients, and a significant 42% relative drop in first HHF and a significant 43% relative decline in total HHF, compared with placebo.

The primary analysis from EMPEROR-Preserved, which included all 5,988 randomized patients with heart failure and an LVEF of 41% or greater, showed a significant reduction in the combined, primary endpoint with empagliflozin treatment of 21%, compared with control patients during a median follow-up of about 26 months. The absolute rate reduction of the combined primary endpoint was 3.3% during 26-months’ follow-up. Statistical tests have shown no heterogeneity of this effect by diabetes status (49% of patients had diabetes), nor by renal function down to an estimated glomerular filtration rate at entry as low as 20 mL/min per 1.73 m².

EMPEROR-Preserved was sponsored by Boehringer Ingelheim and Lilly, the two companies that market empagliflozin (Jardiance). Dr. Anker has been a consultant to Boehringer Ingelheim as well as to Abbott Vascular, Bayer, Brahms, Cardiac Dimensions, Cordio, Novartis, Servier, and Vifor. Dr. Walsh and Dr. Yancy had no disclosures.

mzoler@mdedge.com

Main results from the landmark EMPEROR-Preserved trial, reported in August, established for the first time that treatment with a drug, the sodium-glucose cotransporter 2 inhibitor empagliflozin, could clearly benefit patients with heart failure with preserved ejection fraction (HFpEF).

The only caveat was that EMPEROR-Preserved enrolled patients with a left ventricular ejection fraction of at least 41%, while “true” HFpEF means patients with heart failure and an LVEF of at least 50%, according to recent definitions. About one-third of the 5,988 patients enrolled in EMPEROR-Preserved had an LVEF of 41%-49%, heart failure with mildly reduced ejection fraction.

Secondary analysis from the EMPEROR-Preserved trial has now resolved this ambiguity by showing that, among the 4,005 patients (67%) enrolled in the trial with an LVEF of at least 50%, treatment with empagliflozin (Jardiance) reduced the study’s primary endpoint – cardiovascular death or first hospitalization for heart failure – by a significant 17%, relative to patients who received placebo, dismissing any doubt about the relevance of the overall finding to the subgroup of patients with unmitigated HFpEF.

“This is the first large-scale trial to document meaningful and significant improvements associated with drug therapy in patients with ‘true’ HFpEF,” Stefan D. Anker, MD, said in presenting the results at the American Heart Association scientific sessions.

Streamlining heart failure treatment

The demonstration that empagliflozin is an effective – and safe – treatment for patients with HFpEF not only provides a new treatment for a disorder that until now had no evidence-based intervention, but also streamlines the management approach for treating patients with heart failure with an agent from empagliflozin’s class, the SGLT2 inhibitors, commented Mary Norine Walsh, MD, medical director of the heart failure and cardiac transplantation programs at Ascension St. Vincent Heart Center in Indianapolis.

That’s because empagliflozin has shown significant and consistent benefit across essentially the full range of LVEFs seen in patients with heart failure based on its performance in EMPEROR-Preserved as well as in a mirror-image trial, EMPEROR-Reduced, run in patients with heart failure with reduced ejection fraction.

“Clinicians do not need to stop and assess LVEF with echocardiography or other imaging before they decide on how to treat heart failure patients” with an SGLT2 inhibitor, noted Dr. Walsh, a designated discussant for the report. “Clinicians who are busy can now refer less to LVEF than to the patient’s phenotype.”
 

Treatment prevents hospitalization for heart failure

The more-detailed data reported by Dr. Anker also strengthened the case that the benefit from empagliflozin in patients with an LVEF of at least 50% mostly came from a reduction in hospitalizations for heart failure (HHF), which dropped following start of empagliflozin treatment by a relative 22%, compared with placebo for first HHF, a significant decline, and by a relative 17% for total HHF, a reduction that missed significance in this secondary analysis. The other half of the primary endpoint, cardiovascular death, declined by a nonsignificant 11% with empagliflozin treatment, compared with placebo in patients with clear-cut HFpEF.

The significant reduction in first HHF is, by itself, sufficient reason to use empagliflozin (or possibly a different SGLT2 inhibitor) in patients with HFpEF, maintained Clyde W. Yancy, MD, professor and chief of cardiology at Northwestern Medicine in Chicago.

“Attenuated HHF is a meaningful outcome,” stressed Dr. Yancy, also a discussant for the study. “This is the first time we’ve had evidence supporting that we can change the natural history of patients with HFpEF. While we still need to find interventions that save lives, we cannot overlook that this treatment can improve morbidity, and we cannot overlook that patient quality of life is better.”
 

Further benefits in patients with an LVEF of at least 50%

Dr. Anker, professor of cardiology and metabolism at Charité Medical University in Berlin, also reported results from several other analyses that further defined the effect of empagliflozin on clinical outcomes of patients with “true” HFpEF:

• The impact of empagliflozin, compared with placebo, for reducing both the study’s combined, primary outcome as well as total HHF was statistically consistent across all strata of LVEF, from 50% to greater than 70%. However, both outcome measures also showed a puzzling loss of benefit among patients with an LVEF of 65%-69%. In prior reports, a researcher on the EMPEROR-Preserved team, Milton Packer, MD, speculated that some patients in this LVEF stratum might not actually have had heart failure but instead had a different disorder that mimicked heart failure in clinical presentation, such as atrial fibrillation.
• Patients’ quality of life as measured by the Kansas City Cardiomyopathy Questionnaire showed a consistent benefit from empagliflozin treatment, compared with placebo, both in patients with an LVEF of at least 50% as well as in those with an LVEF of 41%-49%. In both subgroups the adjusted mean difference from placebo was significant and about 1.5 points.
• Patients showed a significant improvement in average New York Heart Association functional class while on treatment, and a strong trend toward less deterioration in functional class while on treatment.
• Deterioration of renal function on treatment slowed by an average 1.24 mL/min per 1.73 m² per year in patients on empagliflozin, compared with placebo, in the subgroup with an LVEF of at least 50%.

Dr. Anker also reported the primary outcome and component results for the subgroup of patients with a baseline LVEF of 41%-49%. These patients had what looked like a “bigger magnitude” of effect from treatment, he noted, showing a significant 29% relative decline in the primary endpoint, compared with placebo-treated patients, and a significant 42% relative drop in first HHF and a significant 43% relative decline in total HHF, compared with placebo.

The primary analysis from EMPEROR-Preserved, which included all 5,988 randomized patients with heart failure and an LVEF of 41% or greater, showed a significant reduction in the combined, primary endpoint with empagliflozin treatment of 21%, compared with control patients during a median follow-up of about 26 months. The absolute rate reduction of the combined primary endpoint was 3.3% during 26-months’ follow-up. Statistical tests have shown no heterogeneity of this effect by diabetes status (49% of patients had diabetes), nor by renal function down to an estimated glomerular filtration rate at entry as low as 20 mL/min per 1.73 m².

EMPEROR-Preserved was sponsored by Boehringer Ingelheim and Lilly, the two companies that market empagliflozin (Jardiance). Dr. Anker has been a consultant to Boehringer Ingelheim as well as to Abbott Vascular, Bayer, Brahms, Cardiac Dimensions, Cordio, Novartis, Servier, and Vifor. Dr. Walsh and Dr. Yancy had no disclosures.

mzoler@mdedge.com

Collaboration between specialized centers and local oncologists could improve equitable access to cellular therapies for patients with diffuse, large B-cell lymphoma (DLBCL), but other “multifaceted and personalized” strategies are also needed, a new study shows.

Fox Chase Cancer Center, Philadelphia

The findings, from a survey focused on patients’ willingness to travel for treatment, offer valuable insights on DLBCL patients’ perspectives and care needs, and on racial and sociodemographic variations among their perspectives and needs, the investigators said.
 

Treatment decision factors

They used a choice-based conjoint analysis to assess the relative value that 302 patients with DLBCL place on clinical factors, continuity of care, and travel time. Patients were asked to select treatment plans, choosing between pairs of hypothetical options that varied in travel time, follow-up arrangement, oncologist continuity, 2-year overall survival, and intensive care unit admission rate, the authors explained.

When all follow-up care in the hypothetical scenario was provided at the treatment center, plans requiring travel time of longer than 30 minutes were less attractive, Zachary A. K. Frosch, MD, and colleagues reported in the Journal of Clinical Oncology.

Importance weights, when compared with 30-minute travel time, were –0.54, –0.57, and –0.17 for 60, 90, and 120 minute travel time, they found.

However, scenarios involving shared follow-up by the treatment center and patients’ local providers mitigated the negative impact of travel on treatment plan choice, they noted (importance weights, 0.63, 0.32, and 0.26 at 60, 90, and 120-minute travel times).

Importantly, an analysis of responses based on sociodemographic factors showed that Black participants were less likely to choose plans requiring longer travel, regardless of follow-up arrangement, the authors said.

“Black patients were also less likely than White patients to choose treatment plans that offered lower continuity with their current oncologist (importance weights, 2.50 to vs. 1.09, respectively),” they wrote.

Further, when making choices that required trade-offs, treatment efficacy was a weaker driver of treatment plan preferences for Black patient than for White patients (importance weights, 0.34 vs. 0.75 per 5% point increase in overall survival, respectively).
 

Why the findings matter

“Certain cancer treatments aren’t offered everywhere. Examples of this are the bone marrow transplants and [chimeric antigen receptor T-cell] therapies used to treat patients with blood cancers such as lymphoma,” Dr. Frosch said in an interview, adding that the limited geographic availability of these treatments means that patients who need them may have to travel farther and also to establish care with a new oncologist.

“These are both things that some patients may be reluctant to do,” added Dr. Frosch, who was with the Perelman School of Medicine at the University of Pennsylvania, Philadelphia, at the time of the study, but is now assistant professor at Fox Chase Cancer Center in Philadelphia.

“We wanted to better understand how patients think about these trade-offs,” he said. “We found that they were less likely to choose treatments requiring more travel, or treatments that required them to transfer care to a new oncologist. This was the case, even if it meant choosing a treatment that might be less effective against their cancer. But when patients were offered a chance to have half of their follow-up appointments locally, travel was less of a barrier.”

Importantly, not all participants valued each aspect of treatments equally, Dr. Frosch noted, referencing the responses of Black versus White patients.

He and his colleagues stressed that while collaborative follow-up may ease access to more distant treatments for some patients, the lesser willingness among Black participants to travel for cancer therapy – regardless of follow-up arrangement – means that attention must be paid to unintended consequences, to avoid worsening the existing disparities in access to cellular therapies.

These data represent a step toward better understanding of how patients considering whether or not to travel for specialized cancer care weigh trade-offs, he said.

“However, we need to dig deeper into the issues we uncovered in future research, he added. “Our findings suggest that collaborative follow-up between the hospitals that offer these treatments and the oncologists in patients’ own communities could improve access to specialized cancer treatments. But I also think it’s important to understand that this may not be the solution for everyone, and so multiple and individualized strategies are going to be needed.”
 

Personalized treatment strategies

The findings provide important perspective on the need to address patients’ concerns and circumstances to improve access to cellular therapies, said Ankit Kansagra, MD, the Eugene P. Frenkel, M.D. Scholar in Clinical Medicine at the University of Texas Southwestern Medical Center, Dallas.

The unique focus by Dr. Frosch and his associates on the patient perspective versus the health care system perspective underscores the need to be patient-focused, and serves as a reminder that different strategies are needed for different patients, Dr. Kansagra, who has also conducted research on access to CAR T therapies, said in an interview.

For some patients, a shared model of care is much more important than a 5% improvement in survival, he said, adding that providers shouldn’t assume that they understand a patient’s perspective.

Devising hybrid solutions that take community and individual needs into consideration would be preferable to seeking one national solution for care access, he added.

“It’s also pretty clear from this that it can be a shared model versus just an academic center or community center doing everything,” he said. “I think that’s going to be the next frontier – [determining] how we can hand over a patient, once CAR T is done, back to the community oncologist so he or she can continue following the patient and knows the survivorship plan – and keeping that model in place.”

Next steps

Further work is needed to determine the mechanisms driving the differences observed between Black and White patients in this study, the authors said, explaining that “[a]lthough the differences observed by race may reflect structural racism-driven access inequities, the relatively small subsample of Black patients and model complexity constraints limited our ability to analyze multiple factors.

“A prospective validation study to demonstrate the association of stated preferences with real-world decisions would further support our findings,” they wrote.

Dr. Frosch reported having no conflicts of interest. Dr. Kansagra is on advisory boards for Alnylam, Bristol Myers Squibb, Cota Healthcare, GSK, Janssen, Oncopeptides, and Takeda.

sworcester@mdedge.com

Collaboration between specialized centers and local oncologists could improve equitable access to cellular therapies for patients with diffuse, large B-cell lymphoma (DLBCL), but other “multifaceted and personalized” strategies are also needed, a new study shows.

Fox Chase Cancer Center, Philadelphia

The findings, from a survey focused on patients’ willingness to travel for treatment, offer valuable insights on DLBCL patients’ perspectives and care needs, and on racial and sociodemographic variations among their perspectives and needs, the investigators said.
 

Treatment decision factors

They used a choice-based conjoint analysis to assess the relative value that 302 patients with DLBCL place on clinical factors, continuity of care, and travel time. Patients were asked to select treatment plans, choosing between pairs of hypothetical options that varied in travel time, follow-up arrangement, oncologist continuity, 2-year overall survival, and intensive care unit admission rate, the authors explained.

When all follow-up care in the hypothetical scenario was provided at the treatment center, plans requiring travel time of longer than 30 minutes were less attractive, Zachary A. K. Frosch, MD, and colleagues reported in the Journal of Clinical Oncology.

Importance weights, when compared with 30-minute travel time, were –0.54, –0.57, and –0.17 for 60, 90, and 120 minute travel time, they found.

However, scenarios involving shared follow-up by the treatment center and patients’ local providers mitigated the negative impact of travel on treatment plan choice, they noted (importance weights, 0.63, 0.32, and 0.26 at 60, 90, and 120-minute travel times).

Importantly, an analysis of responses based on sociodemographic factors showed that Black participants were less likely to choose plans requiring longer travel, regardless of follow-up arrangement, the authors said.

“Black patients were also less likely than White patients to choose treatment plans that offered lower continuity with their current oncologist (importance weights, 2.50 to vs. 1.09, respectively),” they wrote.

Further, when making choices that required trade-offs, treatment efficacy was a weaker driver of treatment plan preferences for Black patient than for White patients (importance weights, 0.34 vs. 0.75 per 5% point increase in overall survival, respectively).
 

Why the findings matter

“Certain cancer treatments aren’t offered everywhere. Examples of this are the bone marrow transplants and [chimeric antigen receptor T-cell] therapies used to treat patients with blood cancers such as lymphoma,” Dr. Frosch said in an interview, adding that the limited geographic availability of these treatments means that patients who need them may have to travel farther and also to establish care with a new oncologist.

“These are both things that some patients may be reluctant to do,” added Dr. Frosch, who was with the Perelman School of Medicine at the University of Pennsylvania, Philadelphia, at the time of the study, but is now assistant professor at Fox Chase Cancer Center in Philadelphia.

“We wanted to better understand how patients think about these trade-offs,” he said. “We found that they were less likely to choose treatments requiring more travel, or treatments that required them to transfer care to a new oncologist. This was the case, even if it meant choosing a treatment that might be less effective against their cancer. But when patients were offered a chance to have half of their follow-up appointments locally, travel was less of a barrier.”

Importantly, not all participants valued each aspect of treatments equally, Dr. Frosch noted, referencing the responses of Black versus White patients.

He and his colleagues stressed that while collaborative follow-up may ease access to more distant treatments for some patients, the lesser willingness among Black participants to travel for cancer therapy – regardless of follow-up arrangement – means that attention must be paid to unintended consequences, to avoid worsening the existing disparities in access to cellular therapies.

These data represent a step toward better understanding of how patients considering whether or not to travel for specialized cancer care weigh trade-offs, he said.

“However, we need to dig deeper into the issues we uncovered in future research, he added. “Our findings suggest that collaborative follow-up between the hospitals that offer these treatments and the oncologists in patients’ own communities could improve access to specialized cancer treatments. But I also think it’s important to understand that this may not be the solution for everyone, and so multiple and individualized strategies are going to be needed.”
 

Personalized treatment strategies

The findings provide important perspective on the need to address patients’ concerns and circumstances to improve access to cellular therapies, said Ankit Kansagra, MD, the Eugene P. Frenkel, M.D. Scholar in Clinical Medicine at the University of Texas Southwestern Medical Center, Dallas.

The unique focus by Dr. Frosch and his associates on the patient perspective versus the health care system perspective underscores the need to be patient-focused, and serves as a reminder that different strategies are needed for different patients, Dr. Kansagra, who has also conducted research on access to CAR T therapies, said in an interview.

For some patients, a shared model of care is much more important than a 5% improvement in survival, he said, adding that providers shouldn’t assume that they understand a patient’s perspective.

Devising hybrid solutions that take community and individual needs into consideration would be preferable to seeking one national solution for care access, he added.

“It’s also pretty clear from this that it can be a shared model versus just an academic center or community center doing everything,” he said. “I think that’s going to be the next frontier – [determining] how we can hand over a patient, once CAR T is done, back to the community oncologist so he or she can continue following the patient and knows the survivorship plan – and keeping that model in place.”

Next steps

Further work is needed to determine the mechanisms driving the differences observed between Black and White patients in this study, the authors said, explaining that “[a]lthough the differences observed by race may reflect structural racism-driven access inequities, the relatively small subsample of Black patients and model complexity constraints limited our ability to analyze multiple factors.

“A prospective validation study to demonstrate the association of stated preferences with real-world decisions would further support our findings,” they wrote.

Dr. Frosch reported having no conflicts of interest. Dr. Kansagra is on advisory boards for Alnylam, Bristol Myers Squibb, Cota Healthcare, GSK, Janssen, Oncopeptides, and Takeda.

sworcester@mdedge.com

Collaboration between specialized centers and local oncologists could improve equitable access to cellular therapies for patients with diffuse, large B-cell lymphoma (DLBCL), but other “multifaceted and personalized” strategies are also needed, a new study shows.

Fox Chase Cancer Center, Philadelphia

The findings, from a survey focused on patients’ willingness to travel for treatment, offer valuable insights on DLBCL patients’ perspectives and care needs, and on racial and sociodemographic variations among their perspectives and needs, the investigators said.
 

Treatment decision factors

They used a choice-based conjoint analysis to assess the relative value that 302 patients with DLBCL place on clinical factors, continuity of care, and travel time. Patients were asked to select treatment plans, choosing between pairs of hypothetical options that varied in travel time, follow-up arrangement, oncologist continuity, 2-year overall survival, and intensive care unit admission rate, the authors explained.

When all follow-up care in the hypothetical scenario was provided at the treatment center, plans requiring travel time of longer than 30 minutes were less attractive, Zachary A. K. Frosch, MD, and colleagues reported in the Journal of Clinical Oncology.

Importance weights, when compared with 30-minute travel time, were –0.54, –0.57, and –0.17 for 60, 90, and 120 minute travel time, they found.

However, scenarios involving shared follow-up by the treatment center and patients’ local providers mitigated the negative impact of travel on treatment plan choice, they noted (importance weights, 0.63, 0.32, and 0.26 at 60, 90, and 120-minute travel times).

Importantly, an analysis of responses based on sociodemographic factors showed that Black participants were less likely to choose plans requiring longer travel, regardless of follow-up arrangement, the authors said.

“Black patients were also less likely than White patients to choose treatment plans that offered lower continuity with their current oncologist (importance weights, 2.50 to vs. 1.09, respectively),” they wrote.

Further, when making choices that required trade-offs, treatment efficacy was a weaker driver of treatment plan preferences for Black patient than for White patients (importance weights, 0.34 vs. 0.75 per 5% point increase in overall survival, respectively).
 

Why the findings matter

“Certain cancer treatments aren’t offered everywhere. Examples of this are the bone marrow transplants and [chimeric antigen receptor T-cell] therapies used to treat patients with blood cancers such as lymphoma,” Dr. Frosch said in an interview, adding that the limited geographic availability of these treatments means that patients who need them may have to travel farther and also to establish care with a new oncologist.

“These are both things that some patients may be reluctant to do,” added Dr. Frosch, who was with the Perelman School of Medicine at the University of Pennsylvania, Philadelphia, at the time of the study, but is now assistant professor at Fox Chase Cancer Center in Philadelphia.

“We wanted to better understand how patients think about these trade-offs,” he said. “We found that they were less likely to choose treatments requiring more travel, or treatments that required them to transfer care to a new oncologist. This was the case, even if it meant choosing a treatment that might be less effective against their cancer. But when patients were offered a chance to have half of their follow-up appointments locally, travel was less of a barrier.”

Importantly, not all participants valued each aspect of treatments equally, Dr. Frosch noted, referencing the responses of Black versus White patients.

He and his colleagues stressed that while collaborative follow-up may ease access to more distant treatments for some patients, the lesser willingness among Black participants to travel for cancer therapy – regardless of follow-up arrangement – means that attention must be paid to unintended consequences, to avoid worsening the existing disparities in access to cellular therapies.

These data represent a step toward better understanding of how patients considering whether or not to travel for specialized cancer care weigh trade-offs, he said.

“However, we need to dig deeper into the issues we uncovered in future research, he added. “Our findings suggest that collaborative follow-up between the hospitals that offer these treatments and the oncologists in patients’ own communities could improve access to specialized cancer treatments. But I also think it’s important to understand that this may not be the solution for everyone, and so multiple and individualized strategies are going to be needed.”
 

Personalized treatment strategies

The findings provide important perspective on the need to address patients’ concerns and circumstances to improve access to cellular therapies, said Ankit Kansagra, MD, the Eugene P. Frenkel, M.D. Scholar in Clinical Medicine at the University of Texas Southwestern Medical Center, Dallas.

The unique focus by Dr. Frosch and his associates on the patient perspective versus the health care system perspective underscores the need to be patient-focused, and serves as a reminder that different strategies are needed for different patients, Dr. Kansagra, who has also conducted research on access to CAR T therapies, said in an interview.

For some patients, a shared model of care is much more important than a 5% improvement in survival, he said, adding that providers shouldn’t assume that they understand a patient’s perspective.

Devising hybrid solutions that take community and individual needs into consideration would be preferable to seeking one national solution for care access, he added.

“It’s also pretty clear from this that it can be a shared model versus just an academic center or community center doing everything,” he said. “I think that’s going to be the next frontier – [determining] how we can hand over a patient, once CAR T is done, back to the community oncologist so he or she can continue following the patient and knows the survivorship plan – and keeping that model in place.”

Next steps

Further work is needed to determine the mechanisms driving the differences observed between Black and White patients in this study, the authors said, explaining that “[a]lthough the differences observed by race may reflect structural racism-driven access inequities, the relatively small subsample of Black patients and model complexity constraints limited our ability to analyze multiple factors.

“A prospective validation study to demonstrate the association of stated preferences with real-world decisions would further support our findings,” they wrote.

Dr. Frosch reported having no conflicts of interest. Dr. Kansagra is on advisory boards for Alnylam, Bristol Myers Squibb, Cota Healthcare, GSK, Janssen, Oncopeptides, and Takeda.

sworcester@mdedge.com

In recent years, the survival rate for patients with lung cancer has increased to the point where now, almost one-quarter of patients with lung cancer are alive 5 years after being diagnosed.

This new statistic is highlighted in the State of Lung Cancer report from the American Lung Association (ALA), published online on Nov. 16.

“If you look back, the 5-year survival rate has been very slowly eking up at about 1% over the years,” Andrea McKee, MD, volunteer spokesperson at the ALA, told this news organization. The report shows that the 5-year survival rate increased by 14.5% over the past 5 years. “To see this big jump is truly remarkable, so that is something we are all celebrating,” she added.

“But we have to change the fatalistic thinking that both patients and primary care physicians still have about lung cancer. Most people say, ‘Everybody I know who had lung cancer died,’ and that was the way it used to be,” she commented, “but that has now changed. Lung cancer is highly curable in its early stages, and even if not early-stage, there are treatments that are making an impact now.”

“So we’ve got to change that perception, as it does exist, even on the part of primary care providers, too,” Dr. McKee emphasized.
 

Lung cancer decreasing but still being diagnosed late

The report notes that the risk of being diagnosed with lung cancer varies considerably across the United States. For example, rates of lung cancer diagnoses are almost 2.5 times higher in Kentucky than in Utah.

Overall, the incidence is decreasing. “Over the last 5 years, the rate of new cases decreased 10% nationally,” the authors point out.

However, in almost half of the cases, the disease is diagnosed in late stages.

When diagnosed at a late stage, the 5-year survival rate for lung cancer drops to only 6%, whereas when the disease is diagnosed early, the 5-year survival rate is 60%.

At present, around 24% of cases of lung cancer are diagnosed at early stages, the report notes, but again, this varies across the United States. The highest rate (30%) is in Massachusetts, and the lowest rate (19%) is in Hawaii.

The percentage of lung cancer cases diagnosed early has been steadily increasing, presumably in part because of the introduction of low-dose CT screening for individuals at highest risk (such as smokers).

However, across the nation, only 5.7% of individuals at high risk for lung cancer underwent annual low-dose CT screening, the report notes.

“CT screening is so powerful at saving lives that even with only 5.7% of people that we’ve been able to screen, I believe it’s making a difference,” Dr. McKee commented. That small national percentage still represents a considerable number of patients, she noted, “so even with what we’ve done so far, I believe that screening is making a difference, at least within my own practice, where I’m definitely seeing it,” Dr. McKee emphasized.

Recent changes to the recommendations as to who should undergo lung cancer screening “have almost doubled the size of the screening population in the U.S.,” Dr. McKee commented. “So there are now about 15 million people who need to get screened, and it again helps that primary care physicians know that screening is very powerful at detecting early-stage lung cancer,” she said.

In her hospital’s own screening program, among the individuals who regularly undergo screening, the majority (88%) of lung cancer cases are detected at stage I or II, for which the cure rate is approximately 90%, she noted.

Another misconception of primary care physicians is that lung cancer screening has an unacceptably high false positive rate. Previous reports in the medical literature suggested the rate could be as high as 96%. “This is absolutely, positively wrong. That is not the false positive rate; the false positive rate for lung cancer screening is less than 10%,” Dr. McKee emphasized.

“So we have to change that in the minds of primary care providers as well,” she underscored.
 

Report highlights racial disparities

The report also highlights the racial disparities that persist in all aspects of lung cancer management – early diagnosis, surgical treatment, lack of treatment, and survival.

For example, Black Americans are 18% less likely to be diagnosed with early-stage disease and are 23% less likely to receive surgical treatment than their White counterparts. They are also 9% more likely to receive no treatment at all, and mortality from lung cancer among Black patients is 21% worse than it is for White patients.

The same trend is seen among Latinx persons, although they are just as likely as White patients to undergo surgical treatment.

First and foremost, “we have to make sure that the [Black and Latinx persons] are screened in an equal fashion,” Dr. McKee said. Providing screening for communities of color is one strategy that might improve screening rates, she suggested.

So, too, can outreach programs in which lung cancer experts work with leaders within these communities, because people are more likely to listen to their leaders regarding the importance of screening for early detection of lung cancer.

Physicians also need to emphasize that even for people who quit smoking decades ago, once those persons are in their 70s, “there is a spike again in lung cancer diagnoses, and that is true for both Black and White patients,” Dr. McKee stressed.

“Again, this is something that many doctors are not aware of,” she emphasized.

Dr. McKee has disclosed no relevant financial relationships.

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

In recent years, the survival rate for patients with lung cancer has increased to the point where now, almost one-quarter of patients with lung cancer are alive 5 years after being diagnosed.

This new statistic is highlighted in the State of Lung Cancer report from the American Lung Association (ALA), published online on Nov. 16.

“If you look back, the 5-year survival rate has been very slowly eking up at about 1% over the years,” Andrea McKee, MD, volunteer spokesperson at the ALA, told this news organization. The report shows that the 5-year survival rate increased by 14.5% over the past 5 years. “To see this big jump is truly remarkable, so that is something we are all celebrating,” she added.

“But we have to change the fatalistic thinking that both patients and primary care physicians still have about lung cancer. Most people say, ‘Everybody I know who had lung cancer died,’ and that was the way it used to be,” she commented, “but that has now changed. Lung cancer is highly curable in its early stages, and even if not early-stage, there are treatments that are making an impact now.”

“So we’ve got to change that perception, as it does exist, even on the part of primary care providers, too,” Dr. McKee emphasized.
 

Lung cancer decreasing but still being diagnosed late

The report notes that the risk of being diagnosed with lung cancer varies considerably across the United States. For example, rates of lung cancer diagnoses are almost 2.5 times higher in Kentucky than in Utah.

Overall, the incidence is decreasing. “Over the last 5 years, the rate of new cases decreased 10% nationally,” the authors point out.

However, in almost half of the cases, the disease is diagnosed in late stages.

When diagnosed at a late stage, the 5-year survival rate for lung cancer drops to only 6%, whereas when the disease is diagnosed early, the 5-year survival rate is 60%.

At present, around 24% of cases of lung cancer are diagnosed at early stages, the report notes, but again, this varies across the United States. The highest rate (30%) is in Massachusetts, and the lowest rate (19%) is in Hawaii.

The percentage of lung cancer cases diagnosed early has been steadily increasing, presumably in part because of the introduction of low-dose CT screening for individuals at highest risk (such as smokers).

However, across the nation, only 5.7% of individuals at high risk for lung cancer underwent annual low-dose CT screening, the report notes.

“CT screening is so powerful at saving lives that even with only 5.7% of people that we’ve been able to screen, I believe it’s making a difference,” Dr. McKee commented. That small national percentage still represents a considerable number of patients, she noted, “so even with what we’ve done so far, I believe that screening is making a difference, at least within my own practice, where I’m definitely seeing it,” Dr. McKee emphasized.

Recent changes to the recommendations as to who should undergo lung cancer screening “have almost doubled the size of the screening population in the U.S.,” Dr. McKee commented. “So there are now about 15 million people who need to get screened, and it again helps that primary care physicians know that screening is very powerful at detecting early-stage lung cancer,” she said.

In her hospital’s own screening program, among the individuals who regularly undergo screening, the majority (88%) of lung cancer cases are detected at stage I or II, for which the cure rate is approximately 90%, she noted.

Another misconception of primary care physicians is that lung cancer screening has an unacceptably high false positive rate. Previous reports in the medical literature suggested the rate could be as high as 96%. “This is absolutely, positively wrong. That is not the false positive rate; the false positive rate for lung cancer screening is less than 10%,” Dr. McKee emphasized.

“So we have to change that in the minds of primary care providers as well,” she underscored.
 

Report highlights racial disparities

The report also highlights the racial disparities that persist in all aspects of lung cancer management – early diagnosis, surgical treatment, lack of treatment, and survival.

For example, Black Americans are 18% less likely to be diagnosed with early-stage disease and are 23% less likely to receive surgical treatment than their White counterparts. They are also 9% more likely to receive no treatment at all, and mortality from lung cancer among Black patients is 21% worse than it is for White patients.

The same trend is seen among Latinx persons, although they are just as likely as White patients to undergo surgical treatment.

First and foremost, “we have to make sure that the [Black and Latinx persons] are screened in an equal fashion,” Dr. McKee said. Providing screening for communities of color is one strategy that might improve screening rates, she suggested.

So, too, can outreach programs in which lung cancer experts work with leaders within these communities, because people are more likely to listen to their leaders regarding the importance of screening for early detection of lung cancer.

Physicians also need to emphasize that even for people who quit smoking decades ago, once those persons are in their 70s, “there is a spike again in lung cancer diagnoses, and that is true for both Black and White patients,” Dr. McKee stressed.

“Again, this is something that many doctors are not aware of,” she emphasized.

Dr. McKee has disclosed no relevant financial relationships.

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

In recent years, the survival rate for patients with lung cancer has increased to the point where now, almost one-quarter of patients with lung cancer are alive 5 years after being diagnosed.

This new statistic is highlighted in the State of Lung Cancer report from the American Lung Association (ALA), published online on Nov. 16.

“If you look back, the 5-year survival rate has been very slowly eking up at about 1% over the years,” Andrea McKee, MD, volunteer spokesperson at the ALA, told this news organization. The report shows that the 5-year survival rate increased by 14.5% over the past 5 years. “To see this big jump is truly remarkable, so that is something we are all celebrating,” she added.

“But we have to change the fatalistic thinking that both patients and primary care physicians still have about lung cancer. Most people say, ‘Everybody I know who had lung cancer died,’ and that was the way it used to be,” she commented, “but that has now changed. Lung cancer is highly curable in its early stages, and even if not early-stage, there are treatments that are making an impact now.”

“So we’ve got to change that perception, as it does exist, even on the part of primary care providers, too,” Dr. McKee emphasized.
 

Lung cancer decreasing but still being diagnosed late

The report notes that the risk of being diagnosed with lung cancer varies considerably across the United States. For example, rates of lung cancer diagnoses are almost 2.5 times higher in Kentucky than in Utah.

Overall, the incidence is decreasing. “Over the last 5 years, the rate of new cases decreased 10% nationally,” the authors point out.

However, in almost half of the cases, the disease is diagnosed in late stages.

When diagnosed at a late stage, the 5-year survival rate for lung cancer drops to only 6%, whereas when the disease is diagnosed early, the 5-year survival rate is 60%.

At present, around 24% of cases of lung cancer are diagnosed at early stages, the report notes, but again, this varies across the United States. The highest rate (30%) is in Massachusetts, and the lowest rate (19%) is in Hawaii.

The percentage of lung cancer cases diagnosed early has been steadily increasing, presumably in part because of the introduction of low-dose CT screening for individuals at highest risk (such as smokers).

However, across the nation, only 5.7% of individuals at high risk for lung cancer underwent annual low-dose CT screening, the report notes.

“CT screening is so powerful at saving lives that even with only 5.7% of people that we’ve been able to screen, I believe it’s making a difference,” Dr. McKee commented. That small national percentage still represents a considerable number of patients, she noted, “so even with what we’ve done so far, I believe that screening is making a difference, at least within my own practice, where I’m definitely seeing it,” Dr. McKee emphasized.

Recent changes to the recommendations as to who should undergo lung cancer screening “have almost doubled the size of the screening population in the U.S.,” Dr. McKee commented. “So there are now about 15 million people who need to get screened, and it again helps that primary care physicians know that screening is very powerful at detecting early-stage lung cancer,” she said.

In her hospital’s own screening program, among the individuals who regularly undergo screening, the majority (88%) of lung cancer cases are detected at stage I or II, for which the cure rate is approximately 90%, she noted.

Another misconception of primary care physicians is that lung cancer screening has an unacceptably high false positive rate. Previous reports in the medical literature suggested the rate could be as high as 96%. “This is absolutely, positively wrong. That is not the false positive rate; the false positive rate for lung cancer screening is less than 10%,” Dr. McKee emphasized.

“So we have to change that in the minds of primary care providers as well,” she underscored.
 

Report highlights racial disparities

The report also highlights the racial disparities that persist in all aspects of lung cancer management – early diagnosis, surgical treatment, lack of treatment, and survival.

For example, Black Americans are 18% less likely to be diagnosed with early-stage disease and are 23% less likely to receive surgical treatment than their White counterparts. They are also 9% more likely to receive no treatment at all, and mortality from lung cancer among Black patients is 21% worse than it is for White patients.

The same trend is seen among Latinx persons, although they are just as likely as White patients to undergo surgical treatment.

First and foremost, “we have to make sure that the [Black and Latinx persons] are screened in an equal fashion,” Dr. McKee said. Providing screening for communities of color is one strategy that might improve screening rates, she suggested.

So, too, can outreach programs in which lung cancer experts work with leaders within these communities, because people are more likely to listen to their leaders regarding the importance of screening for early detection of lung cancer.

Physicians also need to emphasize that even for people who quit smoking decades ago, once those persons are in their 70s, “there is a spike again in lung cancer diagnoses, and that is true for both Black and White patients,” Dr. McKee stressed.

“Again, this is something that many doctors are not aware of,” she emphasized.

Dr. McKee has disclosed no relevant financial relationships.

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