Conference Coverage

CHICAGO – Oncologists need to learn how to set boundaries in their professional lives and how to address their fear of saying “no” to sometimes illusory career opportunities in order to protect their well-being and reduce their risk of burnout.

This was the message from speakers at a special session on “Setting Boundaries” during the annual meeting of the American Society of Clinical Oncology (ASCO).

Monica Sheila Chatwal, MD, a medical oncologist at Moffitt Cancer Center and Research Institute, Tampa, Fla., suggested that, like a painting in a museum, physicians should have “some level of guardrail” to protect their knowledge and expertise, and also their ability to be able to continue to care for patients.

Having set boundaries “provides more emotional and cognitive flexibility, and less uncertainty, in the relationships that we have with our colleagues, with our patients, with everyone around us,” she argued.

“More importantly, boundaries acknowledge that, as humans, we are multifaceted, multidimensional people,” and that “we have lives outside of medicine, much as we may or may not want to admit that.

“It’s great to be devoted to what we do, but there are so many other aspects of ourselves that make us who we are, and that is wonderful,” she said.
 

A calling, not a job

However, the idea of demarcating one’s professional and personal life can go against the still-persistent idea that being a doctor is a calling rather than a job.

“I don’t think it matters whether you call it a job or a calling,” commented another speaker at the session, Jonathan M. Marron, MD, MPH, Dana-Farber/Boston Children’s Cancer.

But even if it is a calling, which implies that “you are supposed to devote all of yourself to the work and not to anything else,” there is still a need for setting boundaries, he argued. Saying “no” and allowing “yourself to be yourself” are important measures, Dr. Marron emphasized, as taking time out can make you a better clinician.

Crucial to that is being able to communicate with colleagues and share a degree of “vulnerability,” added Dr. Chatwal. “Showing that you’re vulnerable not only to your trainees, but also to your staff and to your patients really normalizes everything.”

“I have nurses who are feeling like they have to work 24/7 and manage their inbox to answer all of their messages, because they feel like they have to keep up.

“But it’s nice for me to be able to model that and say: ‘Listen, I want you to know it’s not urgent, please take 24 hours and we’ll come back to it.’ ”
 

Communicating with patients

Dr. Chatwal noted that, while there are clear boundaries related to sexual or physical relationships between doctors and patients and around not treating family members or friends, the boundaries pertaining to communication, and “how frequently [patients] have access to us ... are not so clearly defined.”

The advent of telemedicine has added to that, she believes, as it offers a “patient portal that can allow access 24/7.”

“Does that mean we as physicians or providers also give that level of access? Are we supposed to check messages at all periods of time?”

“More and more people are becoming more cognizant of this,” she commented, noting that the issue has taken on greater import with the rise of social media and the “ability for our patients to request us as friends.”

She pointed out that former president of the American College of Physicians Wayne J. Riley, MD, MPH, MBA, suggested doctors should maintain an air of detachment with their patients, as “it allows us to protect ourselves and continue to provide that great level of care.”

On the other hand, she noted that there has been a sea change in how patients see doctors. Whereas in the past, medicine “was very paternalistic” with doctors seen as the “be all and end all,” now patients tend to be more knowledgeable and Dr. Google “makes them much more engaged in their care.”

But this can also cause problems when patients become “demanding for certain treatments,” she said.
 

Limits to ethical care?

Dr. Marron posed the question: “Is there a limit to my ethical obligations to ethical care?”

He described a hypothetical scenario where a patient has found their doctor’s email address online and they now sends “frequent emails, despite very clear instructions to use the on-call paging system for something that’s urgent, and the electronic health record messaging system otherwise.”

This patient’s behavior is “causing a huge amount of stress” for the doctor, and this is affecting their care of other patients, as well as their academic work and home life.

Dr. Marron asked the audience: Would it be ethically acceptable to stop seeing such a patient?

Taking a quick straw poll of the audience, Dr. Marron noted that there were “not a lot of hands” raised in favor.

He suggested this is because the notion of nonabandonment comes into play, in which there is an obligation to not let patients go without providing adequate time for them to find an alternative clinician.

In this scenario, for example, the doctor could find “several local oncologists who are willing to accept the patient,” as well as talk the situation through with a trusted colleagues, and only then “compassionately but resolutely” tell the patient that they will be transferred.

Dr. Marron acknowledged that this may seem at odds with the theme of this year’s ASCO annual meeting, which emphasizes “partnering with patients.” But he argued that “it doesn’t have to be.”

When thoughtfully done, setting boundaries “can ethically allow us to give more to, and partner more with, our patients, while supporting our well-being, sense of purpose, and job satisfaction,” he argued.
 

Goldilocks situation

Speaking more broadly, Dr. Marron said that boundaries might be considered on a spectrum.

Too few boundaries can lead to conflicts of interest, loss of balance in the patient-physician relationship, and overengagement, while too many boundaries may result in insufficient connection with patients, thus reducing the “human element” and increasing a sense of disengagement.

Either way, “we run the risk of having decreased satisfaction what with what we’re doing, and decreasing the quality of patient care.”

“It’s a little bit of a Goldilocks situation: You want to find just the right balance, somewhere in the middle,” he said.

In the past, issues around having too few boundaries related to conflicts of interest. This reduced trust in the medical profession, he commented, which may have affected patient outcomes, and certainly increased the risk of reduced well-being and burnout.

“Today, we probably still lie on the end of the spectrum with too few boundaries,” Dr. Marron said, “but in a very different way, as we worry about limited work-life balance, and always being connected.”

“I don’t think there’s anybody in the room who doesn’t have some kind of electronic device, either in their hand or not too far from their hand,” he continued.

Moreover, “the patients that we’re taking care of have a greater amount of complexity than they’ve ever had before ... [with] greater numbers of needs than ever before,” and as a result, they require “a greater amount of our time as clinicians.”

Just as with the lack of boundaries in the past, this “runs the risk of us having decreased well-being and an increased risk of burnout,” he suggested.
 

Wearing several hats

The third speaker, Arif Kamal, MD, MBA, MHS, associate professor of medicine and population health, Duke University, Durham, N.C., and chief patient officer at the American Cancer Society, said that every oncologist wears several “hats” in addition to being a clinician.

These may include, in his case, being “a father, a husband, and a brother, and a soccer coach, and a lot of different things.”

Dr. Kamal underlined that recognizing these various roles is “really important,” especially when it comes to the “moment of comparison with others,” as there is a temptation to see one’s own complexity but not that of a colleague.

“The question is: What are all the other competing priorities that a person faces?”

For example, a person’s tally of publications is “just one of many metrics” when it comes to measuring the “success of a career, and, frankly, I’m not sure that’s one of the good ones,” Dr. Kamal said.

He recalled how a mentor of his when he was at the Mayo Clinic had a “remarkable dip” in the number of publications at a certain point in his career, and he explained to Dr. Kamal that this was the time “when my kids needed me the most.”

“That was really important,” Dr. Kamal said, “because it taught me a lesson about having mentors in your life that are not only focused on your career and academic success, but also those who are very interested in the other hats that you wear.”
 

Fear of saying no

One way of setting boundaries is saying no to certain requests, Dr. Kamal commented.

He gave an example from his own life – when he was at a soccer game and received  a call on his cell from a patient who has seen test results before he has had a chance to review them.

Dr. Kamal also painted a hypothetical scenario, where a doctor on junior faculty, staffing a GI oncology clinic 4 days a week, is also volunteering to collect and organize new cases for the tumor board, and is writing several letters of intent for pharmaceutical trials. They are saying “yes” to 90% of the requests for their time, he said, and the result is they go home “most days feeling like their tank is on empty.”

“Then this person gets asked by the division chief to serve on the hospital’s pain committee,” he said, “regardless of the fact that this is not necessarily in their clinical or research interests.”

“So this is really a bit of an [out of] left field request, and how does this person address this?”

Dr. Kamal said that a useful concept to consider is something commonly ascribed to teenagers, that of the fear of missing out, or FOMO.

The problem is that, “due to this concept of FOMO, when opportunities come your way, saying ‘no’ to them gives rise to the question: What if the opportunity never comes back?”

But Dr. Kamal also reminded the audience that “without being able to say no to things ... your capacity will go down.”

“That’s really important to recognize, because for a long time, healing professions have been thought of as [having] people that can continue to expand and expand and expand, without calling out this concept of inflation.”

This is really about “being true to yourself,” and acknowledging that “no one is going to set boundaries for you.”

“That was a tough lesson I learned in my career,” Dr. Kamal commented, and when he looked for guidance, he found that “everyone is struggling with this.”

Setting boundaries, he emphasized, requires “a certain amount of looking inward ... and it requires some bravery.”

“You just have to ask yourself: Is the only reason you’re going to do something because of FOMO?” Dr. Kamal commented. “Maybe that’s okay, but you have to acknowledge that’s the case.”

Dr. Chatwal reported a relationship with Merck. Dr. Marron reported relationships with Genzyme, Partner Therapeutics, ROM Technologies, Arnett, Draper, & Hagood, and Trentalange & Kelley. Dr. Kamal reported relationships with Acclivity Health, Prepped Health, Private Diagnostic Clinic, AstraZeneca, Care4ward, Compassus, HERON, Janssen Oncology, Medtronic, New Century Health, UnitedHealth Group, and Janssen Oncology.

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

CHICAGO – Oncologists need to learn how to set boundaries in their professional lives and how to address their fear of saying “no” to sometimes illusory career opportunities in order to protect their well-being and reduce their risk of burnout.

This was the message from speakers at a special session on “Setting Boundaries” during the annual meeting of the American Society of Clinical Oncology (ASCO).

Monica Sheila Chatwal, MD, a medical oncologist at Moffitt Cancer Center and Research Institute, Tampa, Fla., suggested that, like a painting in a museum, physicians should have “some level of guardrail” to protect their knowledge and expertise, and also their ability to be able to continue to care for patients.

Having set boundaries “provides more emotional and cognitive flexibility, and less uncertainty, in the relationships that we have with our colleagues, with our patients, with everyone around us,” she argued.

“More importantly, boundaries acknowledge that, as humans, we are multifaceted, multidimensional people,” and that “we have lives outside of medicine, much as we may or may not want to admit that.

“It’s great to be devoted to what we do, but there are so many other aspects of ourselves that make us who we are, and that is wonderful,” she said.
 

A calling, not a job

However, the idea of demarcating one’s professional and personal life can go against the still-persistent idea that being a doctor is a calling rather than a job.

“I don’t think it matters whether you call it a job or a calling,” commented another speaker at the session, Jonathan M. Marron, MD, MPH, Dana-Farber/Boston Children’s Cancer.

But even if it is a calling, which implies that “you are supposed to devote all of yourself to the work and not to anything else,” there is still a need for setting boundaries, he argued. Saying “no” and allowing “yourself to be yourself” are important measures, Dr. Marron emphasized, as taking time out can make you a better clinician.

Crucial to that is being able to communicate with colleagues and share a degree of “vulnerability,” added Dr. Chatwal. “Showing that you’re vulnerable not only to your trainees, but also to your staff and to your patients really normalizes everything.”

“I have nurses who are feeling like they have to work 24/7 and manage their inbox to answer all of their messages, because they feel like they have to keep up.

“But it’s nice for me to be able to model that and say: ‘Listen, I want you to know it’s not urgent, please take 24 hours and we’ll come back to it.’ ”
 

Communicating with patients

Dr. Chatwal noted that, while there are clear boundaries related to sexual or physical relationships between doctors and patients and around not treating family members or friends, the boundaries pertaining to communication, and “how frequently [patients] have access to us ... are not so clearly defined.”

The advent of telemedicine has added to that, she believes, as it offers a “patient portal that can allow access 24/7.”

“Does that mean we as physicians or providers also give that level of access? Are we supposed to check messages at all periods of time?”

“More and more people are becoming more cognizant of this,” she commented, noting that the issue has taken on greater import with the rise of social media and the “ability for our patients to request us as friends.”

She pointed out that former president of the American College of Physicians Wayne J. Riley, MD, MPH, MBA, suggested doctors should maintain an air of detachment with their patients, as “it allows us to protect ourselves and continue to provide that great level of care.”

On the other hand, she noted that there has been a sea change in how patients see doctors. Whereas in the past, medicine “was very paternalistic” with doctors seen as the “be all and end all,” now patients tend to be more knowledgeable and Dr. Google “makes them much more engaged in their care.”

But this can also cause problems when patients become “demanding for certain treatments,” she said.
 

Limits to ethical care?

Dr. Marron posed the question: “Is there a limit to my ethical obligations to ethical care?”

He described a hypothetical scenario where a patient has found their doctor’s email address online and they now sends “frequent emails, despite very clear instructions to use the on-call paging system for something that’s urgent, and the electronic health record messaging system otherwise.”

This patient’s behavior is “causing a huge amount of stress” for the doctor, and this is affecting their care of other patients, as well as their academic work and home life.

Dr. Marron asked the audience: Would it be ethically acceptable to stop seeing such a patient?

Taking a quick straw poll of the audience, Dr. Marron noted that there were “not a lot of hands” raised in favor.

He suggested this is because the notion of nonabandonment comes into play, in which there is an obligation to not let patients go without providing adequate time for them to find an alternative clinician.

In this scenario, for example, the doctor could find “several local oncologists who are willing to accept the patient,” as well as talk the situation through with a trusted colleagues, and only then “compassionately but resolutely” tell the patient that they will be transferred.

Dr. Marron acknowledged that this may seem at odds with the theme of this year’s ASCO annual meeting, which emphasizes “partnering with patients.” But he argued that “it doesn’t have to be.”

When thoughtfully done, setting boundaries “can ethically allow us to give more to, and partner more with, our patients, while supporting our well-being, sense of purpose, and job satisfaction,” he argued.
 

Goldilocks situation

Speaking more broadly, Dr. Marron said that boundaries might be considered on a spectrum.

Too few boundaries can lead to conflicts of interest, loss of balance in the patient-physician relationship, and overengagement, while too many boundaries may result in insufficient connection with patients, thus reducing the “human element” and increasing a sense of disengagement.

Either way, “we run the risk of having decreased satisfaction what with what we’re doing, and decreasing the quality of patient care.”

“It’s a little bit of a Goldilocks situation: You want to find just the right balance, somewhere in the middle,” he said.

In the past, issues around having too few boundaries related to conflicts of interest. This reduced trust in the medical profession, he commented, which may have affected patient outcomes, and certainly increased the risk of reduced well-being and burnout.

“Today, we probably still lie on the end of the spectrum with too few boundaries,” Dr. Marron said, “but in a very different way, as we worry about limited work-life balance, and always being connected.”

“I don’t think there’s anybody in the room who doesn’t have some kind of electronic device, either in their hand or not too far from their hand,” he continued.

Moreover, “the patients that we’re taking care of have a greater amount of complexity than they’ve ever had before ... [with] greater numbers of needs than ever before,” and as a result, they require “a greater amount of our time as clinicians.”

Just as with the lack of boundaries in the past, this “runs the risk of us having decreased well-being and an increased risk of burnout,” he suggested.
 

Wearing several hats

The third speaker, Arif Kamal, MD, MBA, MHS, associate professor of medicine and population health, Duke University, Durham, N.C., and chief patient officer at the American Cancer Society, said that every oncologist wears several “hats” in addition to being a clinician.

These may include, in his case, being “a father, a husband, and a brother, and a soccer coach, and a lot of different things.”

Dr. Kamal underlined that recognizing these various roles is “really important,” especially when it comes to the “moment of comparison with others,” as there is a temptation to see one’s own complexity but not that of a colleague.

“The question is: What are all the other competing priorities that a person faces?”

For example, a person’s tally of publications is “just one of many metrics” when it comes to measuring the “success of a career, and, frankly, I’m not sure that’s one of the good ones,” Dr. Kamal said.

He recalled how a mentor of his when he was at the Mayo Clinic had a “remarkable dip” in the number of publications at a certain point in his career, and he explained to Dr. Kamal that this was the time “when my kids needed me the most.”

“That was really important,” Dr. Kamal said, “because it taught me a lesson about having mentors in your life that are not only focused on your career and academic success, but also those who are very interested in the other hats that you wear.”
 

Fear of saying no

One way of setting boundaries is saying no to certain requests, Dr. Kamal commented.

He gave an example from his own life – when he was at a soccer game and received  a call on his cell from a patient who has seen test results before he has had a chance to review them.

Dr. Kamal also painted a hypothetical scenario, where a doctor on junior faculty, staffing a GI oncology clinic 4 days a week, is also volunteering to collect and organize new cases for the tumor board, and is writing several letters of intent for pharmaceutical trials. They are saying “yes” to 90% of the requests for their time, he said, and the result is they go home “most days feeling like their tank is on empty.”

“Then this person gets asked by the division chief to serve on the hospital’s pain committee,” he said, “regardless of the fact that this is not necessarily in their clinical or research interests.”

“So this is really a bit of an [out of] left field request, and how does this person address this?”

Dr. Kamal said that a useful concept to consider is something commonly ascribed to teenagers, that of the fear of missing out, or FOMO.

The problem is that, “due to this concept of FOMO, when opportunities come your way, saying ‘no’ to them gives rise to the question: What if the opportunity never comes back?”

But Dr. Kamal also reminded the audience that “without being able to say no to things ... your capacity will go down.”

“That’s really important to recognize, because for a long time, healing professions have been thought of as [having] people that can continue to expand and expand and expand, without calling out this concept of inflation.”

This is really about “being true to yourself,” and acknowledging that “no one is going to set boundaries for you.”

“That was a tough lesson I learned in my career,” Dr. Kamal commented, and when he looked for guidance, he found that “everyone is struggling with this.”

Setting boundaries, he emphasized, requires “a certain amount of looking inward ... and it requires some bravery.”

“You just have to ask yourself: Is the only reason you’re going to do something because of FOMO?” Dr. Kamal commented. “Maybe that’s okay, but you have to acknowledge that’s the case.”

Dr. Chatwal reported a relationship with Merck. Dr. Marron reported relationships with Genzyme, Partner Therapeutics, ROM Technologies, Arnett, Draper, & Hagood, and Trentalange & Kelley. Dr. Kamal reported relationships with Acclivity Health, Prepped Health, Private Diagnostic Clinic, AstraZeneca, Care4ward, Compassus, HERON, Janssen Oncology, Medtronic, New Century Health, UnitedHealth Group, and Janssen Oncology.

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

CHICAGO – Oncologists need to learn how to set boundaries in their professional lives and how to address their fear of saying “no” to sometimes illusory career opportunities in order to protect their well-being and reduce their risk of burnout.

This was the message from speakers at a special session on “Setting Boundaries” during the annual meeting of the American Society of Clinical Oncology (ASCO).

Monica Sheila Chatwal, MD, a medical oncologist at Moffitt Cancer Center and Research Institute, Tampa, Fla., suggested that, like a painting in a museum, physicians should have “some level of guardrail” to protect their knowledge and expertise, and also their ability to be able to continue to care for patients.

Having set boundaries “provides more emotional and cognitive flexibility, and less uncertainty, in the relationships that we have with our colleagues, with our patients, with everyone around us,” she argued.

“More importantly, boundaries acknowledge that, as humans, we are multifaceted, multidimensional people,” and that “we have lives outside of medicine, much as we may or may not want to admit that.

“It’s great to be devoted to what we do, but there are so many other aspects of ourselves that make us who we are, and that is wonderful,” she said.
 

A calling, not a job

However, the idea of demarcating one’s professional and personal life can go against the still-persistent idea that being a doctor is a calling rather than a job.

“I don’t think it matters whether you call it a job or a calling,” commented another speaker at the session, Jonathan M. Marron, MD, MPH, Dana-Farber/Boston Children’s Cancer.

But even if it is a calling, which implies that “you are supposed to devote all of yourself to the work and not to anything else,” there is still a need for setting boundaries, he argued. Saying “no” and allowing “yourself to be yourself” are important measures, Dr. Marron emphasized, as taking time out can make you a better clinician.

Crucial to that is being able to communicate with colleagues and share a degree of “vulnerability,” added Dr. Chatwal. “Showing that you’re vulnerable not only to your trainees, but also to your staff and to your patients really normalizes everything.”

“I have nurses who are feeling like they have to work 24/7 and manage their inbox to answer all of their messages, because they feel like they have to keep up.

“But it’s nice for me to be able to model that and say: ‘Listen, I want you to know it’s not urgent, please take 24 hours and we’ll come back to it.’ ”
 

Communicating with patients

Dr. Chatwal noted that, while there are clear boundaries related to sexual or physical relationships between doctors and patients and around not treating family members or friends, the boundaries pertaining to communication, and “how frequently [patients] have access to us ... are not so clearly defined.”

The advent of telemedicine has added to that, she believes, as it offers a “patient portal that can allow access 24/7.”

“Does that mean we as physicians or providers also give that level of access? Are we supposed to check messages at all periods of time?”

“More and more people are becoming more cognizant of this,” she commented, noting that the issue has taken on greater import with the rise of social media and the “ability for our patients to request us as friends.”

She pointed out that former president of the American College of Physicians Wayne J. Riley, MD, MPH, MBA, suggested doctors should maintain an air of detachment with their patients, as “it allows us to protect ourselves and continue to provide that great level of care.”

On the other hand, she noted that there has been a sea change in how patients see doctors. Whereas in the past, medicine “was very paternalistic” with doctors seen as the “be all and end all,” now patients tend to be more knowledgeable and Dr. Google “makes them much more engaged in their care.”

But this can also cause problems when patients become “demanding for certain treatments,” she said.
 

Limits to ethical care?

Dr. Marron posed the question: “Is there a limit to my ethical obligations to ethical care?”

He described a hypothetical scenario where a patient has found their doctor’s email address online and they now sends “frequent emails, despite very clear instructions to use the on-call paging system for something that’s urgent, and the electronic health record messaging system otherwise.”

This patient’s behavior is “causing a huge amount of stress” for the doctor, and this is affecting their care of other patients, as well as their academic work and home life.

Dr. Marron asked the audience: Would it be ethically acceptable to stop seeing such a patient?

Taking a quick straw poll of the audience, Dr. Marron noted that there were “not a lot of hands” raised in favor.

He suggested this is because the notion of nonabandonment comes into play, in which there is an obligation to not let patients go without providing adequate time for them to find an alternative clinician.

In this scenario, for example, the doctor could find “several local oncologists who are willing to accept the patient,” as well as talk the situation through with a trusted colleagues, and only then “compassionately but resolutely” tell the patient that they will be transferred.

Dr. Marron acknowledged that this may seem at odds with the theme of this year’s ASCO annual meeting, which emphasizes “partnering with patients.” But he argued that “it doesn’t have to be.”

When thoughtfully done, setting boundaries “can ethically allow us to give more to, and partner more with, our patients, while supporting our well-being, sense of purpose, and job satisfaction,” he argued.
 

Goldilocks situation

Speaking more broadly, Dr. Marron said that boundaries might be considered on a spectrum.

Too few boundaries can lead to conflicts of interest, loss of balance in the patient-physician relationship, and overengagement, while too many boundaries may result in insufficient connection with patients, thus reducing the “human element” and increasing a sense of disengagement.

Either way, “we run the risk of having decreased satisfaction what with what we’re doing, and decreasing the quality of patient care.”

“It’s a little bit of a Goldilocks situation: You want to find just the right balance, somewhere in the middle,” he said.

In the past, issues around having too few boundaries related to conflicts of interest. This reduced trust in the medical profession, he commented, which may have affected patient outcomes, and certainly increased the risk of reduced well-being and burnout.

“Today, we probably still lie on the end of the spectrum with too few boundaries,” Dr. Marron said, “but in a very different way, as we worry about limited work-life balance, and always being connected.”

“I don’t think there’s anybody in the room who doesn’t have some kind of electronic device, either in their hand or not too far from their hand,” he continued.

Moreover, “the patients that we’re taking care of have a greater amount of complexity than they’ve ever had before ... [with] greater numbers of needs than ever before,” and as a result, they require “a greater amount of our time as clinicians.”

Just as with the lack of boundaries in the past, this “runs the risk of us having decreased well-being and an increased risk of burnout,” he suggested.
 

Wearing several hats

The third speaker, Arif Kamal, MD, MBA, MHS, associate professor of medicine and population health, Duke University, Durham, N.C., and chief patient officer at the American Cancer Society, said that every oncologist wears several “hats” in addition to being a clinician.

These may include, in his case, being “a father, a husband, and a brother, and a soccer coach, and a lot of different things.”

Dr. Kamal underlined that recognizing these various roles is “really important,” especially when it comes to the “moment of comparison with others,” as there is a temptation to see one’s own complexity but not that of a colleague.

“The question is: What are all the other competing priorities that a person faces?”

For example, a person’s tally of publications is “just one of many metrics” when it comes to measuring the “success of a career, and, frankly, I’m not sure that’s one of the good ones,” Dr. Kamal said.

He recalled how a mentor of his when he was at the Mayo Clinic had a “remarkable dip” in the number of publications at a certain point in his career, and he explained to Dr. Kamal that this was the time “when my kids needed me the most.”

“That was really important,” Dr. Kamal said, “because it taught me a lesson about having mentors in your life that are not only focused on your career and academic success, but also those who are very interested in the other hats that you wear.”
 

Fear of saying no

One way of setting boundaries is saying no to certain requests, Dr. Kamal commented.

He gave an example from his own life – when he was at a soccer game and received  a call on his cell from a patient who has seen test results before he has had a chance to review them.

Dr. Kamal also painted a hypothetical scenario, where a doctor on junior faculty, staffing a GI oncology clinic 4 days a week, is also volunteering to collect and organize new cases for the tumor board, and is writing several letters of intent for pharmaceutical trials. They are saying “yes” to 90% of the requests for their time, he said, and the result is they go home “most days feeling like their tank is on empty.”

“Then this person gets asked by the division chief to serve on the hospital’s pain committee,” he said, “regardless of the fact that this is not necessarily in their clinical or research interests.”

“So this is really a bit of an [out of] left field request, and how does this person address this?”

Dr. Kamal said that a useful concept to consider is something commonly ascribed to teenagers, that of the fear of missing out, or FOMO.

The problem is that, “due to this concept of FOMO, when opportunities come your way, saying ‘no’ to them gives rise to the question: What if the opportunity never comes back?”

But Dr. Kamal also reminded the audience that “without being able to say no to things ... your capacity will go down.”

“That’s really important to recognize, because for a long time, healing professions have been thought of as [having] people that can continue to expand and expand and expand, without calling out this concept of inflation.”

This is really about “being true to yourself,” and acknowledging that “no one is going to set boundaries for you.”

“That was a tough lesson I learned in my career,” Dr. Kamal commented, and when he looked for guidance, he found that “everyone is struggling with this.”

Setting boundaries, he emphasized, requires “a certain amount of looking inward ... and it requires some bravery.”

“You just have to ask yourself: Is the only reason you’re going to do something because of FOMO?” Dr. Kamal commented. “Maybe that’s okay, but you have to acknowledge that’s the case.”

Dr. Chatwal reported a relationship with Merck. Dr. Marron reported relationships with Genzyme, Partner Therapeutics, ROM Technologies, Arnett, Draper, & Hagood, and Trentalange & Kelley. Dr. Kamal reported relationships with Acclivity Health, Prepped Health, Private Diagnostic Clinic, AstraZeneca, Care4ward, Compassus, HERON, Janssen Oncology, Medtronic, New Century Health, UnitedHealth Group, and Janssen Oncology.

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

CHICAGO – By definition, all clinical care is – or should be – patient-centered care, and that is especially true for older women with early stage breast cancer.

“Older women need to be informed of the benefits and risks of their treatment options, including the option of omitting a treatment,” said Mara Schonberg, MD, MPH, of the division of general medicine and primary care at Beth Israel Deaconess Medical Center in Boston.

“High quality shared decision-making considers a woman’s risk of recurrence, her tumor characteristics, her overall prognosis based on her general health, the lag-time to benefit from the treatment – how long will it take for this treatment to likely have an effect or a real chance of having any benefit for her – and her values and preferences,” she explained. Dr. Schonberg was speaking at a session on the management of care for older women with breast cancer held during the recent American Society of Clinical Oncology (ASCO) annual meeting.

Care for older women with a new diagnosis of early stage breast cancer is not one-size-fits all, and patients are faced with many decisions that may depend as much on personal preference as on clinical necessity, Dr. Schonberg said.

For example, patients may need to choose between mastectomy or breast conserving surgery (BCS), whether to have radiotherapy after BCS, what type of radiotherapy (e.g., whole breast, partial breast, accelerated partial breast irradiation, boost dose) to have, whether to undergo a lymph node biopsy, and whether to opt for primary endocrine therapy instead of surgery or radiation.

“It is really important that we think about all these decisions that older women face in their preference-sensitive decisions and that we include them in the decision-making, probably even starting at the time of mammography,” Dr. Schonberg said.
 

Decision-making partnership

Doctor–patient shared decision making improves patient care by helping the patients understand the best available evidence on the risks and benefits of specific choices and their alternatives, Dr. Schonberg said. Discussing and considering all the available options allows the doctor and patient to arrive together at an informed decision based on the individual patient’s needs and preferences, she emphasized.

“It’s particularly useful when there are multiple treatment options, when there’s uncertainty regarding the evidence or uncertainty regarding which patients may benefit or on the outcome, when there are both treatment advantages and disadvantages that patients must weigh, and when the decision is high impact, like for breast cancer treatment,” she said.

Shared decision-making can be complicated by barriers of time, how care is organized, lack of clinician training in patient-centered communication, and mistaken assumptions on the part of clinicians about a particular patient’s preferences or willingness to participate in the process.

Dr. Schonberg and colleagues created the website ePrognosis to consolidate prognostic indices designed to aid clinical decision-making for older adults who do not have a dominant terminal diagnosis. The site contains links to prognostic calculators, information about time to benefit for various cancer screening programs based on life expectancy, and helpful information about communicating information about prognosis, risks, and benefits to patients.
 

De-escalating surgery

Also at the session, Jennifer Tseng, MD, medical director of breast surgery at City of Hope Orange County Cancer Center, Irvine, Calif., discussed de-escalation of locoregional therapy. For some patients, this may mean skipping surgery or radiation.

“How do we de-escalate the extent of surgery, the extent of morbidity that we are imparting on our patients with surgery but still maximizing and preserving oncological outcomes?” she asked.

Currently more than 30% of new breast cancer diagnoses are in women age 70 and older, and estrogen receptor positive, HER2-negative disease is the majority biomarker profile.

At present, more than 70% of women with breast cancer in this older population will receive axillary surgery and/or radiation.

But for many patients with early, node-negative breast cancers with favorable tumor characteristics, less extensive surgery may be an appropriate option, especially for patients who have other significant comorbidities, Dr. Tseng said.

“Just at baseline, we know that mastectomy is a harder operation, it’s a harder recovery. You may be incorporating additional surgery such as reconstructive surgery, so breast-conserving surgery is always considered less invasive, less morbid,” she said.

“Do we absolutely have to do a mastectomy for a patient who has a second episode of cancer in the same breast? The answer is no,” she said, adding that omitting axillary surgery in early-stage disease may also be safe for some older patients.
 

De-escalating radiotherapy

Options for de-escalating radiation therapy include shortening the course of treatment with hypofractionation or ultra hypofractionation, reduction of treatment volumes with partial breast radiation, reducing radiation dose to normal tissues, or even in appropriate cases eliminating radiation entirely, Dr. Tseng said.

“My radiation oncologist turned to me and said, ‘This patient is now eligible for 3 days [or radiation] based on the latest trial we have open at City of Hope.’ I was like, wow, we went from 6 weeks to 3 days of radiation, but that is in the appropriate patient population with those early stage, really more favorable tumor characteristics,” she said.

Moving forward, the debate in radiation oncology is likely to focus on the option of ultra hypofractionation vs no radiation, she added.

Regarding reducing radiation volume, Dr. Tseng noted that most in-breast tumor recurrences happen within 1 cm of the original tumor bed, and partial breast irradiation targets the tumor bed with a 1- to 2-cm margin and provides excellent clinical outcomes with minimal adverse events, allowing for rapid recovery.

Deep inspiration breath holds and prone-positioning of patients with left-side tumors during beam delivery can also significantly decrease the dose to normal tissues, an especially important consideration for patients with cardiopulmonary comorbidities, she said.

Radiation may also be deferred in many older patients who may benefit from endocrine therapy alone and in those who have a very early stage and less aggressive tumor type.
 

Systemic therapy in the older patient

Etienne GC Brain, PhD, of the department of medical oncology at the Curie Institute in Paris and Saint-Cloud, France, reviewed evidence regarding systemic therapy in older patients with high-risk breast cancers.

For patients with triple-negative breast cancer pathologic stage T1b or greater he usually advises adjuvant chemotherapy with the option of neoadjuvant chemotherapy if breast-conserving surgery is a goal; for patients with HER2-positive disease, he advises 1 year of therapy with an anti-HER2 agent.

Shorter HER2 regimens may be possible for older patients, and frail older adults may have good outcomes with HER2 therapy alone, as shown recently by Japanese investigators, Dr. Brain noted.

“For lumimal disease, endocrine therapy remains the standard of treatment for me, and chemo, of course can be considered in higher risk, but the problem is we don’t know how to define this high risk, given the poor guidance provided by gene expression profiles,” he said.

For older patients, longer follow-up is needed to assess treatment benefit vs. life expectancy, Dr. Brain said, warning that the standard of care established in younger patients cannot be easily extrapolated to the care of older patients.

Dr. Schonberg disclosed authorship of review pages on preventive health for older adults for UpToDate. Dr. Tseng disclosed that she is a breast surgeon and that her discussion of radiation therapy may reflect personal bias. Dr. Brain disclosed honoraria from Lilly, Pfizer, and Seagen, consulting/advising for Daiichi Sankyo, AstraZeneca, Pfizer, and Sandoz-Novartis, and travel expenses from Pfizer.

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

CHICAGO – By definition, all clinical care is – or should be – patient-centered care, and that is especially true for older women with early stage breast cancer.

“Older women need to be informed of the benefits and risks of their treatment options, including the option of omitting a treatment,” said Mara Schonberg, MD, MPH, of the division of general medicine and primary care at Beth Israel Deaconess Medical Center in Boston.

“High quality shared decision-making considers a woman’s risk of recurrence, her tumor characteristics, her overall prognosis based on her general health, the lag-time to benefit from the treatment – how long will it take for this treatment to likely have an effect or a real chance of having any benefit for her – and her values and preferences,” she explained. Dr. Schonberg was speaking at a session on the management of care for older women with breast cancer held during the recent American Society of Clinical Oncology (ASCO) annual meeting.

Care for older women with a new diagnosis of early stage breast cancer is not one-size-fits all, and patients are faced with many decisions that may depend as much on personal preference as on clinical necessity, Dr. Schonberg said.

For example, patients may need to choose between mastectomy or breast conserving surgery (BCS), whether to have radiotherapy after BCS, what type of radiotherapy (e.g., whole breast, partial breast, accelerated partial breast irradiation, boost dose) to have, whether to undergo a lymph node biopsy, and whether to opt for primary endocrine therapy instead of surgery or radiation.

“It is really important that we think about all these decisions that older women face in their preference-sensitive decisions and that we include them in the decision-making, probably even starting at the time of mammography,” Dr. Schonberg said.
 

Decision-making partnership

Doctor–patient shared decision making improves patient care by helping the patients understand the best available evidence on the risks and benefits of specific choices and their alternatives, Dr. Schonberg said. Discussing and considering all the available options allows the doctor and patient to arrive together at an informed decision based on the individual patient’s needs and preferences, she emphasized.

“It’s particularly useful when there are multiple treatment options, when there’s uncertainty regarding the evidence or uncertainty regarding which patients may benefit or on the outcome, when there are both treatment advantages and disadvantages that patients must weigh, and when the decision is high impact, like for breast cancer treatment,” she said.

Shared decision-making can be complicated by barriers of time, how care is organized, lack of clinician training in patient-centered communication, and mistaken assumptions on the part of clinicians about a particular patient’s preferences or willingness to participate in the process.

Dr. Schonberg and colleagues created the website ePrognosis to consolidate prognostic indices designed to aid clinical decision-making for older adults who do not have a dominant terminal diagnosis. The site contains links to prognostic calculators, information about time to benefit for various cancer screening programs based on life expectancy, and helpful information about communicating information about prognosis, risks, and benefits to patients.
 

De-escalating surgery

Also at the session, Jennifer Tseng, MD, medical director of breast surgery at City of Hope Orange County Cancer Center, Irvine, Calif., discussed de-escalation of locoregional therapy. For some patients, this may mean skipping surgery or radiation.

“How do we de-escalate the extent of surgery, the extent of morbidity that we are imparting on our patients with surgery but still maximizing and preserving oncological outcomes?” she asked.

Currently more than 30% of new breast cancer diagnoses are in women age 70 and older, and estrogen receptor positive, HER2-negative disease is the majority biomarker profile.

At present, more than 70% of women with breast cancer in this older population will receive axillary surgery and/or radiation.

But for many patients with early, node-negative breast cancers with favorable tumor characteristics, less extensive surgery may be an appropriate option, especially for patients who have other significant comorbidities, Dr. Tseng said.

“Just at baseline, we know that mastectomy is a harder operation, it’s a harder recovery. You may be incorporating additional surgery such as reconstructive surgery, so breast-conserving surgery is always considered less invasive, less morbid,” she said.

“Do we absolutely have to do a mastectomy for a patient who has a second episode of cancer in the same breast? The answer is no,” she said, adding that omitting axillary surgery in early-stage disease may also be safe for some older patients.
 

De-escalating radiotherapy

Options for de-escalating radiation therapy include shortening the course of treatment with hypofractionation or ultra hypofractionation, reduction of treatment volumes with partial breast radiation, reducing radiation dose to normal tissues, or even in appropriate cases eliminating radiation entirely, Dr. Tseng said.

“My radiation oncologist turned to me and said, ‘This patient is now eligible for 3 days [or radiation] based on the latest trial we have open at City of Hope.’ I was like, wow, we went from 6 weeks to 3 days of radiation, but that is in the appropriate patient population with those early stage, really more favorable tumor characteristics,” she said.

Moving forward, the debate in radiation oncology is likely to focus on the option of ultra hypofractionation vs no radiation, she added.

Regarding reducing radiation volume, Dr. Tseng noted that most in-breast tumor recurrences happen within 1 cm of the original tumor bed, and partial breast irradiation targets the tumor bed with a 1- to 2-cm margin and provides excellent clinical outcomes with minimal adverse events, allowing for rapid recovery.

Deep inspiration breath holds and prone-positioning of patients with left-side tumors during beam delivery can also significantly decrease the dose to normal tissues, an especially important consideration for patients with cardiopulmonary comorbidities, she said.

Radiation may also be deferred in many older patients who may benefit from endocrine therapy alone and in those who have a very early stage and less aggressive tumor type.
 

Systemic therapy in the older patient

Etienne GC Brain, PhD, of the department of medical oncology at the Curie Institute in Paris and Saint-Cloud, France, reviewed evidence regarding systemic therapy in older patients with high-risk breast cancers.

For patients with triple-negative breast cancer pathologic stage T1b or greater he usually advises adjuvant chemotherapy with the option of neoadjuvant chemotherapy if breast-conserving surgery is a goal; for patients with HER2-positive disease, he advises 1 year of therapy with an anti-HER2 agent.

Shorter HER2 regimens may be possible for older patients, and frail older adults may have good outcomes with HER2 therapy alone, as shown recently by Japanese investigators, Dr. Brain noted.

“For lumimal disease, endocrine therapy remains the standard of treatment for me, and chemo, of course can be considered in higher risk, but the problem is we don’t know how to define this high risk, given the poor guidance provided by gene expression profiles,” he said.

For older patients, longer follow-up is needed to assess treatment benefit vs. life expectancy, Dr. Brain said, warning that the standard of care established in younger patients cannot be easily extrapolated to the care of older patients.

Dr. Schonberg disclosed authorship of review pages on preventive health for older adults for UpToDate. Dr. Tseng disclosed that she is a breast surgeon and that her discussion of radiation therapy may reflect personal bias. Dr. Brain disclosed honoraria from Lilly, Pfizer, and Seagen, consulting/advising for Daiichi Sankyo, AstraZeneca, Pfizer, and Sandoz-Novartis, and travel expenses from Pfizer.

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

CHICAGO – By definition, all clinical care is – or should be – patient-centered care, and that is especially true for older women with early stage breast cancer.

“Older women need to be informed of the benefits and risks of their treatment options, including the option of omitting a treatment,” said Mara Schonberg, MD, MPH, of the division of general medicine and primary care at Beth Israel Deaconess Medical Center in Boston.

“High quality shared decision-making considers a woman’s risk of recurrence, her tumor characteristics, her overall prognosis based on her general health, the lag-time to benefit from the treatment – how long will it take for this treatment to likely have an effect or a real chance of having any benefit for her – and her values and preferences,” she explained. Dr. Schonberg was speaking at a session on the management of care for older women with breast cancer held during the recent American Society of Clinical Oncology (ASCO) annual meeting.

Care for older women with a new diagnosis of early stage breast cancer is not one-size-fits all, and patients are faced with many decisions that may depend as much on personal preference as on clinical necessity, Dr. Schonberg said.

For example, patients may need to choose between mastectomy or breast conserving surgery (BCS), whether to have radiotherapy after BCS, what type of radiotherapy (e.g., whole breast, partial breast, accelerated partial breast irradiation, boost dose) to have, whether to undergo a lymph node biopsy, and whether to opt for primary endocrine therapy instead of surgery or radiation.

“It is really important that we think about all these decisions that older women face in their preference-sensitive decisions and that we include them in the decision-making, probably even starting at the time of mammography,” Dr. Schonberg said.
 

Decision-making partnership

Doctor–patient shared decision making improves patient care by helping the patients understand the best available evidence on the risks and benefits of specific choices and their alternatives, Dr. Schonberg said. Discussing and considering all the available options allows the doctor and patient to arrive together at an informed decision based on the individual patient’s needs and preferences, she emphasized.

“It’s particularly useful when there are multiple treatment options, when there’s uncertainty regarding the evidence or uncertainty regarding which patients may benefit or on the outcome, when there are both treatment advantages and disadvantages that patients must weigh, and when the decision is high impact, like for breast cancer treatment,” she said.

Shared decision-making can be complicated by barriers of time, how care is organized, lack of clinician training in patient-centered communication, and mistaken assumptions on the part of clinicians about a particular patient’s preferences or willingness to participate in the process.

Dr. Schonberg and colleagues created the website ePrognosis to consolidate prognostic indices designed to aid clinical decision-making for older adults who do not have a dominant terminal diagnosis. The site contains links to prognostic calculators, information about time to benefit for various cancer screening programs based on life expectancy, and helpful information about communicating information about prognosis, risks, and benefits to patients.
 

De-escalating surgery

Also at the session, Jennifer Tseng, MD, medical director of breast surgery at City of Hope Orange County Cancer Center, Irvine, Calif., discussed de-escalation of locoregional therapy. For some patients, this may mean skipping surgery or radiation.

“How do we de-escalate the extent of surgery, the extent of morbidity that we are imparting on our patients with surgery but still maximizing and preserving oncological outcomes?” she asked.

Currently more than 30% of new breast cancer diagnoses are in women age 70 and older, and estrogen receptor positive, HER2-negative disease is the majority biomarker profile.

At present, more than 70% of women with breast cancer in this older population will receive axillary surgery and/or radiation.

But for many patients with early, node-negative breast cancers with favorable tumor characteristics, less extensive surgery may be an appropriate option, especially for patients who have other significant comorbidities, Dr. Tseng said.

“Just at baseline, we know that mastectomy is a harder operation, it’s a harder recovery. You may be incorporating additional surgery such as reconstructive surgery, so breast-conserving surgery is always considered less invasive, less morbid,” she said.

“Do we absolutely have to do a mastectomy for a patient who has a second episode of cancer in the same breast? The answer is no,” she said, adding that omitting axillary surgery in early-stage disease may also be safe for some older patients.
 

De-escalating radiotherapy

Options for de-escalating radiation therapy include shortening the course of treatment with hypofractionation or ultra hypofractionation, reduction of treatment volumes with partial breast radiation, reducing radiation dose to normal tissues, or even in appropriate cases eliminating radiation entirely, Dr. Tseng said.

“My radiation oncologist turned to me and said, ‘This patient is now eligible for 3 days [or radiation] based on the latest trial we have open at City of Hope.’ I was like, wow, we went from 6 weeks to 3 days of radiation, but that is in the appropriate patient population with those early stage, really more favorable tumor characteristics,” she said.

Moving forward, the debate in radiation oncology is likely to focus on the option of ultra hypofractionation vs no radiation, she added.

Regarding reducing radiation volume, Dr. Tseng noted that most in-breast tumor recurrences happen within 1 cm of the original tumor bed, and partial breast irradiation targets the tumor bed with a 1- to 2-cm margin and provides excellent clinical outcomes with minimal adverse events, allowing for rapid recovery.

Deep inspiration breath holds and prone-positioning of patients with left-side tumors during beam delivery can also significantly decrease the dose to normal tissues, an especially important consideration for patients with cardiopulmonary comorbidities, she said.

Radiation may also be deferred in many older patients who may benefit from endocrine therapy alone and in those who have a very early stage and less aggressive tumor type.
 

Systemic therapy in the older patient

Etienne GC Brain, PhD, of the department of medical oncology at the Curie Institute in Paris and Saint-Cloud, France, reviewed evidence regarding systemic therapy in older patients with high-risk breast cancers.

For patients with triple-negative breast cancer pathologic stage T1b or greater he usually advises adjuvant chemotherapy with the option of neoadjuvant chemotherapy if breast-conserving surgery is a goal; for patients with HER2-positive disease, he advises 1 year of therapy with an anti-HER2 agent.

Shorter HER2 regimens may be possible for older patients, and frail older adults may have good outcomes with HER2 therapy alone, as shown recently by Japanese investigators, Dr. Brain noted.

“For lumimal disease, endocrine therapy remains the standard of treatment for me, and chemo, of course can be considered in higher risk, but the problem is we don’t know how to define this high risk, given the poor guidance provided by gene expression profiles,” he said.

For older patients, longer follow-up is needed to assess treatment benefit vs. life expectancy, Dr. Brain said, warning that the standard of care established in younger patients cannot be easily extrapolated to the care of older patients.

Dr. Schonberg disclosed authorship of review pages on preventive health for older adults for UpToDate. Dr. Tseng disclosed that she is a breast surgeon and that her discussion of radiation therapy may reflect personal bias. Dr. Brain disclosed honoraria from Lilly, Pfizer, and Seagen, consulting/advising for Daiichi Sankyo, AstraZeneca, Pfizer, and Sandoz-Novartis, and travel expenses from Pfizer.

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

CHICAGO – Several key updates in esophagology were presented during the esophagus session (Sp75) at the AGA Postgraduate Course 2023 that was held in May during Digestive Disease Week®. These include novel care approaches for esophageal diseases that were published in recent AGA best practice updates on gastroesophageal reflux disease (GERD), extraesophageal reflux, and Barrett’s esophagus, as well as randomized clinical trial data examining therapeutic approaches for erosive esophagitis and eosinophilic esophagitis.

@UCSD

Here are a few highlights: Complications of chronic gastroesophageal reflux include erosive esophagitis for which healing and maintenance of healing is crucial to reduce further erosive sequelae. Healing is typically achieved with pump inhibitor (PPI) therapy. Potassium competitive acid blockers are active prodrugs that bind to the H+/K+ ATPase and have been demonstrated to have a more potent and faster onset in suppressing gastric acid secretion, compared with PPIs.

In a recent phase 3 randomized trial of more than 1,000 adults with erosive esophagitis, the potassium competitive acid blocker vonoprazan was found to be noninferior to lansoprazole in inducing and maintaining healing of erosive esophagitis. Overall, the proportions of subjects that achieved healing by week 8 and maintained healing up to 24 weeks were higher with vonoprazan, when compared with lansoprazole, with a greater treatment effect seen in subjects with severe erosive esophagitis (Los Angeles grade C or D) (Laine L et al. Gastroenterology. Jan 2023;164[1]:61-71).

Screening patients at risk of Barrett’s esophagus (BE), another erosive sequelae of chronic GERD, is critical for early detection and prevention of esophageal cancer. Upper GI endoscopy is standard for Barrett’s screening; however, screening rates of at-risk populations are suboptimal.

In a recent retrospective analysis of a multipractice health care network, only 39% of a screen-eligible population were noted to have undergone upper GI endoscopy. These findings highlight the critical need to improve screening for Barrett’s, including potential of the newer nonendoscopic screening modalities such as swallowable capsule devices combined with a biomarker or cell-collection devices, as well as the need for risk stratification/prediction tools and collaboration with primary care physicians (Eluri S et al. Am J Gastroenterol. Nov 2022;117[11]:1764-71).

Therapeutic options for eosinophilic esophagitis (EoE) have expanded over the past year. Randomized trials demonstrate the efficacy of varied therapeutic approaches including the monoclonal antibody dupilumab as well as topical corticosteroids such as fluticasone propionate orally disintegrated tablet and budesonide oral suspension.

In terms of food elimination diets, a recent multicenter randomized open-label trial identified comparable rates of partial histologic remission with both a traditional six-food elimination diet and a one-food animal milk elimination diet in patients with EoE, though those treated with a six-food elimination were more likely to achieve complete remission (< 1 eosinophil/high power field). Results suggest elimination of animal milk alone is an acceptable initial dietary therapy for EoE, with potential to convert to six-food elimination or alternative therapy when histologic response is not achieved (Kliewer K. Lancet Gastroenterol Hepatol. [published online Feb 2023]).

Dr. Yadlapati is an associate professor in gastroenterology at the University of California, San Diego. She disclosed relationships with Medtronic (Institutional), Ironwood Pharmaceuticals (Institutional), Phathom Pharmaceuticals, and Ironwood Pharmaceuticals. She serves on the advisory board with stock options for RJS Mediagnostix.

These remarks were made during one of the AGA Postgraduate Course sessions held at DDW 2023.

DDW is sponsored by the American Association for the Study of Liver Diseases (AASLD), the American Gastroenterological Association (AGA), the American Society for Gastrointestinal Endoscopy (ASGE) and The Society for Surgery of the Alimentary Tract (SSAT).

CHICAGO – Several key updates in esophagology were presented during the esophagus session (Sp75) at the AGA Postgraduate Course 2023 that was held in May during Digestive Disease Week®. These include novel care approaches for esophageal diseases that were published in recent AGA best practice updates on gastroesophageal reflux disease (GERD), extraesophageal reflux, and Barrett’s esophagus, as well as randomized clinical trial data examining therapeutic approaches for erosive esophagitis and eosinophilic esophagitis.

@UCSD

Here are a few highlights: Complications of chronic gastroesophageal reflux include erosive esophagitis for which healing and maintenance of healing is crucial to reduce further erosive sequelae. Healing is typically achieved with pump inhibitor (PPI) therapy. Potassium competitive acid blockers are active prodrugs that bind to the H+/K+ ATPase and have been demonstrated to have a more potent and faster onset in suppressing gastric acid secretion, compared with PPIs.

In a recent phase 3 randomized trial of more than 1,000 adults with erosive esophagitis, the potassium competitive acid blocker vonoprazan was found to be noninferior to lansoprazole in inducing and maintaining healing of erosive esophagitis. Overall, the proportions of subjects that achieved healing by week 8 and maintained healing up to 24 weeks were higher with vonoprazan, when compared with lansoprazole, with a greater treatment effect seen in subjects with severe erosive esophagitis (Los Angeles grade C or D) (Laine L et al. Gastroenterology. Jan 2023;164[1]:61-71).

Screening patients at risk of Barrett’s esophagus (BE), another erosive sequelae of chronic GERD, is critical for early detection and prevention of esophageal cancer. Upper GI endoscopy is standard for Barrett’s screening; however, screening rates of at-risk populations are suboptimal.

In a recent retrospective analysis of a multipractice health care network, only 39% of a screen-eligible population were noted to have undergone upper GI endoscopy. These findings highlight the critical need to improve screening for Barrett’s, including potential of the newer nonendoscopic screening modalities such as swallowable capsule devices combined with a biomarker or cell-collection devices, as well as the need for risk stratification/prediction tools and collaboration with primary care physicians (Eluri S et al. Am J Gastroenterol. Nov 2022;117[11]:1764-71).

Therapeutic options for eosinophilic esophagitis (EoE) have expanded over the past year. Randomized trials demonstrate the efficacy of varied therapeutic approaches including the monoclonal antibody dupilumab as well as topical corticosteroids such as fluticasone propionate orally disintegrated tablet and budesonide oral suspension.

In terms of food elimination diets, a recent multicenter randomized open-label trial identified comparable rates of partial histologic remission with both a traditional six-food elimination diet and a one-food animal milk elimination diet in patients with EoE, though those treated with a six-food elimination were more likely to achieve complete remission (< 1 eosinophil/high power field). Results suggest elimination of animal milk alone is an acceptable initial dietary therapy for EoE, with potential to convert to six-food elimination or alternative therapy when histologic response is not achieved (Kliewer K. Lancet Gastroenterol Hepatol. [published online Feb 2023]).

Dr. Yadlapati is an associate professor in gastroenterology at the University of California, San Diego. She disclosed relationships with Medtronic (Institutional), Ironwood Pharmaceuticals (Institutional), Phathom Pharmaceuticals, and Ironwood Pharmaceuticals. She serves on the advisory board with stock options for RJS Mediagnostix.

These remarks were made during one of the AGA Postgraduate Course sessions held at DDW 2023.

DDW is sponsored by the American Association for the Study of Liver Diseases (AASLD), the American Gastroenterological Association (AGA), the American Society for Gastrointestinal Endoscopy (ASGE) and The Society for Surgery of the Alimentary Tract (SSAT).

CHICAGO – Several key updates in esophagology were presented during the esophagus session (Sp75) at the AGA Postgraduate Course 2023 that was held in May during Digestive Disease Week®. These include novel care approaches for esophageal diseases that were published in recent AGA best practice updates on gastroesophageal reflux disease (GERD), extraesophageal reflux, and Barrett’s esophagus, as well as randomized clinical trial data examining therapeutic approaches for erosive esophagitis and eosinophilic esophagitis.

@UCSD

Here are a few highlights: Complications of chronic gastroesophageal reflux include erosive esophagitis for which healing and maintenance of healing is crucial to reduce further erosive sequelae. Healing is typically achieved with pump inhibitor (PPI) therapy. Potassium competitive acid blockers are active prodrugs that bind to the H+/K+ ATPase and have been demonstrated to have a more potent and faster onset in suppressing gastric acid secretion, compared with PPIs.

In a recent phase 3 randomized trial of more than 1,000 adults with erosive esophagitis, the potassium competitive acid blocker vonoprazan was found to be noninferior to lansoprazole in inducing and maintaining healing of erosive esophagitis. Overall, the proportions of subjects that achieved healing by week 8 and maintained healing up to 24 weeks were higher with vonoprazan, when compared with lansoprazole, with a greater treatment effect seen in subjects with severe erosive esophagitis (Los Angeles grade C or D) (Laine L et al. Gastroenterology. Jan 2023;164[1]:61-71).

Screening patients at risk of Barrett’s esophagus (BE), another erosive sequelae of chronic GERD, is critical for early detection and prevention of esophageal cancer. Upper GI endoscopy is standard for Barrett’s screening; however, screening rates of at-risk populations are suboptimal.

In a recent retrospective analysis of a multipractice health care network, only 39% of a screen-eligible population were noted to have undergone upper GI endoscopy. These findings highlight the critical need to improve screening for Barrett’s, including potential of the newer nonendoscopic screening modalities such as swallowable capsule devices combined with a biomarker or cell-collection devices, as well as the need for risk stratification/prediction tools and collaboration with primary care physicians (Eluri S et al. Am J Gastroenterol. Nov 2022;117[11]:1764-71).

Therapeutic options for eosinophilic esophagitis (EoE) have expanded over the past year. Randomized trials demonstrate the efficacy of varied therapeutic approaches including the monoclonal antibody dupilumab as well as topical corticosteroids such as fluticasone propionate orally disintegrated tablet and budesonide oral suspension.

In terms of food elimination diets, a recent multicenter randomized open-label trial identified comparable rates of partial histologic remission with both a traditional six-food elimination diet and a one-food animal milk elimination diet in patients with EoE, though those treated with a six-food elimination were more likely to achieve complete remission (< 1 eosinophil/high power field). Results suggest elimination of animal milk alone is an acceptable initial dietary therapy for EoE, with potential to convert to six-food elimination or alternative therapy when histologic response is not achieved (Kliewer K. Lancet Gastroenterol Hepatol. [published online Feb 2023]).

Dr. Yadlapati is an associate professor in gastroenterology at the University of California, San Diego. She disclosed relationships with Medtronic (Institutional), Ironwood Pharmaceuticals (Institutional), Phathom Pharmaceuticals, and Ironwood Pharmaceuticals. She serves on the advisory board with stock options for RJS Mediagnostix.

These remarks were made during one of the AGA Postgraduate Course sessions held at DDW 2023.

DDW is sponsored by the American Association for the Study of Liver Diseases (AASLD), the American Gastroenterological Association (AGA), the American Society for Gastrointestinal Endoscopy (ASGE) and The Society for Surgery of the Alimentary Tract (SSAT).

Insomnia may increase vulnerability to influenza-like illness, a novel finding that was revealed by the passive collection of biometric data from a smart bed.

The study of smart-bed sleepers found that there was a statistically significant correlation between a higher number of episodes of influenza-like illnesses (ILI) per year with longer duration compared to people without insomnia.

However, more research is needed to determine causality and whether insomnia may predispose to ILI or whether ILI affects long-term sleep behavior, the researchers noted. 

“Several lines of evidence make me think that it’s more likely that insomnia makes one more vulnerable to influenza through pathways that involve decreased immune function,” study investigator Gary Garcia-Molina, PhD, with Sleep Number Labs, San Jose, Calif., said in an interview.

Sleep disorders, including insomnia, can dampen immune function and an individual’s ability to fight off illness, he noted.

The findings were presented at the annual meeting of the Associated Professional Sleep Societies.
 

Smart, connected devices

Pathophysiological responses to respiratory viral infection affect sleep duration and quality in addition to breathing function. “Smart” and “connected” devices that monitor biosignals over time have shown promise for monitoring infectious disease.

In an earlier study presented at SLEEP 2021, Dr. Garcia-Molina and colleagues found that real-world biometric data obtained from a smart bed can help predict and track symptoms of COVID-19 and other respiratory infections. They showed that worsening of COVID-19 symptoms correlated with an increase in sleep duration, breathing rate, and heart rate and a decrease in sleep quality.

In the new study, the researchers evaluated vulnerability to ILI in people with insomnia.

They quantified insomnia over time using the insomnia severity index (ISI). They quantified ILI vulnerability using an established artificial intelligence model they developed that estimates the daily probability of ILI symptoms from a Sleep Number smart bed using ballistocardiograph sensors.

Smart bed data – including daily and restful sleep duration, sleep latency, sleep quality, heart rate, breathing rate and motion level – were queried from 2019 (pre-COVID) and 2021.

A total of 1,680 smart sleepers had nearly constant ISI scores over the study period, with 249 having insomnia and 1,431 not having insomnia.

Data from both 2019 and 2021 show that smart sleepers with insomnia had significantly more and longer ILI episodes per year, compared with peers without insomnia.

For 2019, individuals without insomnia had 1.2 ILI episodes on average, which was significantly less (P < .01) than individuals with insomnia, at 1.5 episodes. The average ILI episode duration for those without insomnia was 4.3 days, which was significantly lower (P < .01) in those with insomnia group, at 6.1 days.

The data for 2021 show similar results, with the no-insomnia group having significantly fewer (P < .01) ILI episodes (about 1.2), compared with the insomnia group (about 1.5).

The average ILI episode duration for the no-insomnia group was 5 days, which was significantly less (P < .01) than the insomnia group, at 6.1 days.

The researchers said their study adds to other data on the relationship between sleep and overall health and well-being. It also highlights the potential health risk of insomnia and the importance of identifying and treating sleep disorders.

“Sleep has such a profound influence on health and wellness and the ability to capture these data unobtrusively in such an easy way and with such a large number of participants paves the way to investigate different aspects of health and disease,” Dr. Garcia-Molina said.
 

Rich data source

In a comment, Adam C. Powell, PhD, president of Payer+Provider Syndicate, a management advisory and operational consulting firm, said “smart beds provide a new data source for passively monitoring the health of individuals.”

“Unlike active monitoring methods requiring self-report, passive monitoring enables data to be captured without an individual taking any action. This data can be potentially integrated with data from other sources, such as pedometers, smart scales, and smart blood pressure cuffs, to gain a more holistic understanding of how an individual’s activities and behaviors impact their well-being,” said Dr. Powell, who wasn’t involved in the study.

There are some methodological limitations to the study, he noted.

“While the dependent variables examined were the duration and presence of episodes of influenza-like illness, they did not directly measure these episodes. Instead, they calculated the daily probability of influenza-like illness symptoms using a model that received input from the ballistocardiograph sensors in the smart beds,” Dr. Powell noted.

“The model used to calculate daily probability of influenza-like illness was created by examining associations between individuals’ smart-bed sensor data and population-level trends in influenza-like illness reported by the Centers for Disease Control and Prevention,” he explained.

Nonetheless, the findings are “consistent with the literature. It has been established by other researchers that impaired sleep is associated with greater risk of influenza, as well as other illnesses,” Dr. Powell said.

Funding for the study was provided by Sleep Number. Dr. Garcia-Molina and five coauthors are employed by Sleep Number. Dr. Powell reported no relevant financial relationships.

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

Insomnia may increase vulnerability to influenza-like illness, a novel finding that was revealed by the passive collection of biometric data from a smart bed.

The study of smart-bed sleepers found that there was a statistically significant correlation between a higher number of episodes of influenza-like illnesses (ILI) per year with longer duration compared to people without insomnia.

However, more research is needed to determine causality and whether insomnia may predispose to ILI or whether ILI affects long-term sleep behavior, the researchers noted. 

“Several lines of evidence make me think that it’s more likely that insomnia makes one more vulnerable to influenza through pathways that involve decreased immune function,” study investigator Gary Garcia-Molina, PhD, with Sleep Number Labs, San Jose, Calif., said in an interview.

Sleep disorders, including insomnia, can dampen immune function and an individual’s ability to fight off illness, he noted.

The findings were presented at the annual meeting of the Associated Professional Sleep Societies.
 

Smart, connected devices

Pathophysiological responses to respiratory viral infection affect sleep duration and quality in addition to breathing function. “Smart” and “connected” devices that monitor biosignals over time have shown promise for monitoring infectious disease.

In an earlier study presented at SLEEP 2021, Dr. Garcia-Molina and colleagues found that real-world biometric data obtained from a smart bed can help predict and track symptoms of COVID-19 and other respiratory infections. They showed that worsening of COVID-19 symptoms correlated with an increase in sleep duration, breathing rate, and heart rate and a decrease in sleep quality.

In the new study, the researchers evaluated vulnerability to ILI in people with insomnia.

They quantified insomnia over time using the insomnia severity index (ISI). They quantified ILI vulnerability using an established artificial intelligence model they developed that estimates the daily probability of ILI symptoms from a Sleep Number smart bed using ballistocardiograph sensors.

Smart bed data – including daily and restful sleep duration, sleep latency, sleep quality, heart rate, breathing rate and motion level – were queried from 2019 (pre-COVID) and 2021.

A total of 1,680 smart sleepers had nearly constant ISI scores over the study period, with 249 having insomnia and 1,431 not having insomnia.

Data from both 2019 and 2021 show that smart sleepers with insomnia had significantly more and longer ILI episodes per year, compared with peers without insomnia.

For 2019, individuals without insomnia had 1.2 ILI episodes on average, which was significantly less (P < .01) than individuals with insomnia, at 1.5 episodes. The average ILI episode duration for those without insomnia was 4.3 days, which was significantly lower (P < .01) in those with insomnia group, at 6.1 days.

The data for 2021 show similar results, with the no-insomnia group having significantly fewer (P < .01) ILI episodes (about 1.2), compared with the insomnia group (about 1.5).

The average ILI episode duration for the no-insomnia group was 5 days, which was significantly less (P < .01) than the insomnia group, at 6.1 days.

The researchers said their study adds to other data on the relationship between sleep and overall health and well-being. It also highlights the potential health risk of insomnia and the importance of identifying and treating sleep disorders.

“Sleep has such a profound influence on health and wellness and the ability to capture these data unobtrusively in such an easy way and with such a large number of participants paves the way to investigate different aspects of health and disease,” Dr. Garcia-Molina said.
 

Rich data source

In a comment, Adam C. Powell, PhD, president of Payer+Provider Syndicate, a management advisory and operational consulting firm, said “smart beds provide a new data source for passively monitoring the health of individuals.”

“Unlike active monitoring methods requiring self-report, passive monitoring enables data to be captured without an individual taking any action. This data can be potentially integrated with data from other sources, such as pedometers, smart scales, and smart blood pressure cuffs, to gain a more holistic understanding of how an individual’s activities and behaviors impact their well-being,” said Dr. Powell, who wasn’t involved in the study.

There are some methodological limitations to the study, he noted.

“While the dependent variables examined were the duration and presence of episodes of influenza-like illness, they did not directly measure these episodes. Instead, they calculated the daily probability of influenza-like illness symptoms using a model that received input from the ballistocardiograph sensors in the smart beds,” Dr. Powell noted.

“The model used to calculate daily probability of influenza-like illness was created by examining associations between individuals’ smart-bed sensor data and population-level trends in influenza-like illness reported by the Centers for Disease Control and Prevention,” he explained.

Nonetheless, the findings are “consistent with the literature. It has been established by other researchers that impaired sleep is associated with greater risk of influenza, as well as other illnesses,” Dr. Powell said.

Funding for the study was provided by Sleep Number. Dr. Garcia-Molina and five coauthors are employed by Sleep Number. Dr. Powell reported no relevant financial relationships.

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

Insomnia may increase vulnerability to influenza-like illness, a novel finding that was revealed by the passive collection of biometric data from a smart bed.

The study of smart-bed sleepers found that there was a statistically significant correlation between a higher number of episodes of influenza-like illnesses (ILI) per year with longer duration compared to people without insomnia.

However, more research is needed to determine causality and whether insomnia may predispose to ILI or whether ILI affects long-term sleep behavior, the researchers noted. 

“Several lines of evidence make me think that it’s more likely that insomnia makes one more vulnerable to influenza through pathways that involve decreased immune function,” study investigator Gary Garcia-Molina, PhD, with Sleep Number Labs, San Jose, Calif., said in an interview.

Sleep disorders, including insomnia, can dampen immune function and an individual’s ability to fight off illness, he noted.

The findings were presented at the annual meeting of the Associated Professional Sleep Societies.
 

Smart, connected devices

Pathophysiological responses to respiratory viral infection affect sleep duration and quality in addition to breathing function. “Smart” and “connected” devices that monitor biosignals over time have shown promise for monitoring infectious disease.

In an earlier study presented at SLEEP 2021, Dr. Garcia-Molina and colleagues found that real-world biometric data obtained from a smart bed can help predict and track symptoms of COVID-19 and other respiratory infections. They showed that worsening of COVID-19 symptoms correlated with an increase in sleep duration, breathing rate, and heart rate and a decrease in sleep quality.

In the new study, the researchers evaluated vulnerability to ILI in people with insomnia.

They quantified insomnia over time using the insomnia severity index (ISI). They quantified ILI vulnerability using an established artificial intelligence model they developed that estimates the daily probability of ILI symptoms from a Sleep Number smart bed using ballistocardiograph sensors.

Smart bed data – including daily and restful sleep duration, sleep latency, sleep quality, heart rate, breathing rate and motion level – were queried from 2019 (pre-COVID) and 2021.

A total of 1,680 smart sleepers had nearly constant ISI scores over the study period, with 249 having insomnia and 1,431 not having insomnia.

Data from both 2019 and 2021 show that smart sleepers with insomnia had significantly more and longer ILI episodes per year, compared with peers without insomnia.

For 2019, individuals without insomnia had 1.2 ILI episodes on average, which was significantly less (P < .01) than individuals with insomnia, at 1.5 episodes. The average ILI episode duration for those without insomnia was 4.3 days, which was significantly lower (P < .01) in those with insomnia group, at 6.1 days.

The data for 2021 show similar results, with the no-insomnia group having significantly fewer (P < .01) ILI episodes (about 1.2), compared with the insomnia group (about 1.5).

The average ILI episode duration for the no-insomnia group was 5 days, which was significantly less (P < .01) than the insomnia group, at 6.1 days.

The researchers said their study adds to other data on the relationship between sleep and overall health and well-being. It also highlights the potential health risk of insomnia and the importance of identifying and treating sleep disorders.

“Sleep has such a profound influence on health and wellness and the ability to capture these data unobtrusively in such an easy way and with such a large number of participants paves the way to investigate different aspects of health and disease,” Dr. Garcia-Molina said.
 

Rich data source

In a comment, Adam C. Powell, PhD, president of Payer+Provider Syndicate, a management advisory and operational consulting firm, said “smart beds provide a new data source for passively monitoring the health of individuals.”

“Unlike active monitoring methods requiring self-report, passive monitoring enables data to be captured without an individual taking any action. This data can be potentially integrated with data from other sources, such as pedometers, smart scales, and smart blood pressure cuffs, to gain a more holistic understanding of how an individual’s activities and behaviors impact their well-being,” said Dr. Powell, who wasn’t involved in the study.

There are some methodological limitations to the study, he noted.

“While the dependent variables examined were the duration and presence of episodes of influenza-like illness, they did not directly measure these episodes. Instead, they calculated the daily probability of influenza-like illness symptoms using a model that received input from the ballistocardiograph sensors in the smart beds,” Dr. Powell noted.

“The model used to calculate daily probability of influenza-like illness was created by examining associations between individuals’ smart-bed sensor data and population-level trends in influenza-like illness reported by the Centers for Disease Control and Prevention,” he explained.

Nonetheless, the findings are “consistent with the literature. It has been established by other researchers that impaired sleep is associated with greater risk of influenza, as well as other illnesses,” Dr. Powell said.

Funding for the study was provided by Sleep Number. Dr. Garcia-Molina and five coauthors are employed by Sleep Number. Dr. Powell reported no relevant financial relationships.

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

CHICAGO – It has been a busy year for hepatology with major developments in the detection, management, and prevention of chronic liver disease. Two landmark phase 2 trials of the glucagon-like peptide 1 (GLP-1) receptor agonist, semaglutide, Food and Drug Administration–approved for type 2 diabetes or obesity, demonstrated improvements in nonalcoholic steatohepatitis (NASH) activity and resolution in stage 2 or 3 fibrosis (F2/F3), but not F4 fibrosis.^1,2 The first randomized trial to compare the efficacy and safety of bariatric surgery with lifestyle intervention plus best medical care for histologically confirmed NASH demonstrated the superiority of bariatric surgery.³

There has been a paradigm shift in risk stratification of cirrhosis and targets for prevention and treatment of decompensation. A newer term, advanced chronic liver disease (ACLD), represents a shift away from needing a histologic or radiologic diagnosis of cirrhosis while reduction in portal pressure is a therapeutic goal. Evidence supports noninvasive liver stiffness measurement (LSM) using transient elastography to identify those with clinically significant portal hypertension (CSPH) (e.g., hepatic venous pressure gradient ≥ 10 mm Hg) who may benefit from therapy to lower portal pressure. Accordingly, based on landmark studies, the American Association for the Study of Liver Diseases (AASLD) recommends early utilization of nonselective beta-blocker therapy, with carvedilol as a preferred agent, in CSPH to decrease the risk of decompensation and mortality.⁴

University of Miami

Surveillance and treatment approaches for hepatocellular carcinoma (HCC) continue to evolve as reflected in new AASLD guidance in June 2023. Screening among high-risk patients should include ultrasound and serum alpha-fetoprotein every 6 months and novel screening approaches including imaging and blood-based biomarkers are on the horizon. There also have been significant advances in systemic therapies for HCC. First-line therapy for advanced HCC with CTP A cirrhosis now includes either atezolizumab/bevacizumab or durvalumab/tremelimumab. There is an evolving role for systemic therapy in the adjuvant setting as well, with emerging data supporting checkpoint inhibitors after resection or ablation among patients at high risk of recurrence.

Allocation policies continue to evolve for liver transplantation as waitlist prioritization transitions to MELD 3.0. The new score improves predictive accuracy for short-term mortality and addresses sex disparity in waitlist outcomes by lowering the prioritization of creatinine (and its threshold) and adding albumin to the current MELD-Na formula. MELD 3.0 will be adopted by the United Network for Organ Sharing in July 2023.

It has been a whirlwind 2023 for the liver community and we are excited and hopeful for new breakthroughs to come.

Dr. VanWagner is with the division of digestive and liver diseases, University of Texas Southwestern Medical Center; Dr. Serper is with the division of gastroenterology and hepatology, University of Pennsylvania; Dr. Goldberg is with the division of digestive health and liver diseases, University of Miami; and Dr. Verna is with the division of digestive and liver diseases, Columbia University. Dr. VanWagner is an adviser for Numares and Novo Nordisk and received a research grant from W.L. Gore & Associates. Dr. Serper disclosed research funding from Grifols. Dr. Verna disclosed research support from Salix. Dr. Goldberg had no disclosures. These remarks were made during one of the AGA Postgraduate Course sessions held at DDW 2023. DDW is sponsored by the American Association for the Study of Liver Diseases (AASLD), the American Gastroenterological Association (AGA), the American Society for Gastrointestinal Endoscopy (ASGE) and The Society for Surgery of the Alimentary Tract (SSAT).

References

1. Loomba R et al. Semaglutide 2.4 mg once weekly in patients with non-alcoholic steatohepatitis-related cirrhosis: A randomised, placebo-controlled phase 2 trial. Lancet Gastroenterol Hepatol. 2023;8:511-22.

2. Newsome PN et al. A placebo-controlled trial of subcutaneous semaglutide in nonalcoholic steatohepatitis. N Engl J Med. 2021;384:1113-24.

3. Verrastro O et al. Bariatric-metabolic surgery versus lifestyle intervention plus best medical care in non-alcoholic steatohepatitis (BRAVES): A multicentre, open-label, randomised trial. Lancet 2023;401:1786-97.

4. Rowe IA et al. Quantifying the benefit of nonselective beta-blockers in the prevention of hepatic decompensation: A Bayesian reanalysis of the PREDESCI trial. Hepatology 2023 Mar 13. doi: 10.1097/HEP.0000000000000342.

5. Nadim MK and Garcia-Tsao G. Acute kidney injury in patients with cirrhosis. N Engl J Med. 2023;388:733-45.

6. Bureau C et al. The use of rifaximin in the prevention of overt hepatic encephalopathy after transjugular intrahepatic portosystemic shunt: A randomized controlled trial. Ann Intern Med. 2021;174:633-40.

CHICAGO – It has been a busy year for hepatology with major developments in the detection, management, and prevention of chronic liver disease. Two landmark phase 2 trials of the glucagon-like peptide 1 (GLP-1) receptor agonist, semaglutide, Food and Drug Administration–approved for type 2 diabetes or obesity, demonstrated improvements in nonalcoholic steatohepatitis (NASH) activity and resolution in stage 2 or 3 fibrosis (F2/F3), but not F4 fibrosis.^1,2 The first randomized trial to compare the efficacy and safety of bariatric surgery with lifestyle intervention plus best medical care for histologically confirmed NASH demonstrated the superiority of bariatric surgery.³

There has been a paradigm shift in risk stratification of cirrhosis and targets for prevention and treatment of decompensation. A newer term, advanced chronic liver disease (ACLD), represents a shift away from needing a histologic or radiologic diagnosis of cirrhosis while reduction in portal pressure is a therapeutic goal. Evidence supports noninvasive liver stiffness measurement (LSM) using transient elastography to identify those with clinically significant portal hypertension (CSPH) (e.g., hepatic venous pressure gradient ≥ 10 mm Hg) who may benefit from therapy to lower portal pressure. Accordingly, based on landmark studies, the American Association for the Study of Liver Diseases (AASLD) recommends early utilization of nonselective beta-blocker therapy, with carvedilol as a preferred agent, in CSPH to decrease the risk of decompensation and mortality.⁴

University of Miami

Surveillance and treatment approaches for hepatocellular carcinoma (HCC) continue to evolve as reflected in new AASLD guidance in June 2023. Screening among high-risk patients should include ultrasound and serum alpha-fetoprotein every 6 months and novel screening approaches including imaging and blood-based biomarkers are on the horizon. There also have been significant advances in systemic therapies for HCC. First-line therapy for advanced HCC with CTP A cirrhosis now includes either atezolizumab/bevacizumab or durvalumab/tremelimumab. There is an evolving role for systemic therapy in the adjuvant setting as well, with emerging data supporting checkpoint inhibitors after resection or ablation among patients at high risk of recurrence.

Allocation policies continue to evolve for liver transplantation as waitlist prioritization transitions to MELD 3.0. The new score improves predictive accuracy for short-term mortality and addresses sex disparity in waitlist outcomes by lowering the prioritization of creatinine (and its threshold) and adding albumin to the current MELD-Na formula. MELD 3.0 will be adopted by the United Network for Organ Sharing in July 2023.

It has been a whirlwind 2023 for the liver community and we are excited and hopeful for new breakthroughs to come.

Dr. VanWagner is with the division of digestive and liver diseases, University of Texas Southwestern Medical Center; Dr. Serper is with the division of gastroenterology and hepatology, University of Pennsylvania; Dr. Goldberg is with the division of digestive health and liver diseases, University of Miami; and Dr. Verna is with the division of digestive and liver diseases, Columbia University. Dr. VanWagner is an adviser for Numares and Novo Nordisk and received a research grant from W.L. Gore & Associates. Dr. Serper disclosed research funding from Grifols. Dr. Verna disclosed research support from Salix. Dr. Goldberg had no disclosures. These remarks were made during one of the AGA Postgraduate Course sessions held at DDW 2023. DDW is sponsored by the American Association for the Study of Liver Diseases (AASLD), the American Gastroenterological Association (AGA), the American Society for Gastrointestinal Endoscopy (ASGE) and The Society for Surgery of the Alimentary Tract (SSAT).

References

1. Loomba R et al. Semaglutide 2.4 mg once weekly in patients with non-alcoholic steatohepatitis-related cirrhosis: A randomised, placebo-controlled phase 2 trial. Lancet Gastroenterol Hepatol. 2023;8:511-22.

2. Newsome PN et al. A placebo-controlled trial of subcutaneous semaglutide in nonalcoholic steatohepatitis. N Engl J Med. 2021;384:1113-24.

3. Verrastro O et al. Bariatric-metabolic surgery versus lifestyle intervention plus best medical care in non-alcoholic steatohepatitis (BRAVES): A multicentre, open-label, randomised trial. Lancet 2023;401:1786-97.

4. Rowe IA et al. Quantifying the benefit of nonselective beta-blockers in the prevention of hepatic decompensation: A Bayesian reanalysis of the PREDESCI trial. Hepatology 2023 Mar 13. doi: 10.1097/HEP.0000000000000342.

5. Nadim MK and Garcia-Tsao G. Acute kidney injury in patients with cirrhosis. N Engl J Med. 2023;388:733-45.

6. Bureau C et al. The use of rifaximin in the prevention of overt hepatic encephalopathy after transjugular intrahepatic portosystemic shunt: A randomized controlled trial. Ann Intern Med. 2021;174:633-40.

CHICAGO – It has been a busy year for hepatology with major developments in the detection, management, and prevention of chronic liver disease. Two landmark phase 2 trials of the glucagon-like peptide 1 (GLP-1) receptor agonist, semaglutide, Food and Drug Administration–approved for type 2 diabetes or obesity, demonstrated improvements in nonalcoholic steatohepatitis (NASH) activity and resolution in stage 2 or 3 fibrosis (F2/F3), but not F4 fibrosis.^1,2 The first randomized trial to compare the efficacy and safety of bariatric surgery with lifestyle intervention plus best medical care for histologically confirmed NASH demonstrated the superiority of bariatric surgery.³

There has been a paradigm shift in risk stratification of cirrhosis and targets for prevention and treatment of decompensation. A newer term, advanced chronic liver disease (ACLD), represents a shift away from needing a histologic or radiologic diagnosis of cirrhosis while reduction in portal pressure is a therapeutic goal. Evidence supports noninvasive liver stiffness measurement (LSM) using transient elastography to identify those with clinically significant portal hypertension (CSPH) (e.g., hepatic venous pressure gradient ≥ 10 mm Hg) who may benefit from therapy to lower portal pressure. Accordingly, based on landmark studies, the American Association for the Study of Liver Diseases (AASLD) recommends early utilization of nonselective beta-blocker therapy, with carvedilol as a preferred agent, in CSPH to decrease the risk of decompensation and mortality.⁴

University of Miami

Surveillance and treatment approaches for hepatocellular carcinoma (HCC) continue to evolve as reflected in new AASLD guidance in June 2023. Screening among high-risk patients should include ultrasound and serum alpha-fetoprotein every 6 months and novel screening approaches including imaging and blood-based biomarkers are on the horizon. There also have been significant advances in systemic therapies for HCC. First-line therapy for advanced HCC with CTP A cirrhosis now includes either atezolizumab/bevacizumab or durvalumab/tremelimumab. There is an evolving role for systemic therapy in the adjuvant setting as well, with emerging data supporting checkpoint inhibitors after resection or ablation among patients at high risk of recurrence.

Allocation policies continue to evolve for liver transplantation as waitlist prioritization transitions to MELD 3.0. The new score improves predictive accuracy for short-term mortality and addresses sex disparity in waitlist outcomes by lowering the prioritization of creatinine (and its threshold) and adding albumin to the current MELD-Na formula. MELD 3.0 will be adopted by the United Network for Organ Sharing in July 2023.

It has been a whirlwind 2023 for the liver community and we are excited and hopeful for new breakthroughs to come.

Dr. VanWagner is with the division of digestive and liver diseases, University of Texas Southwestern Medical Center; Dr. Serper is with the division of gastroenterology and hepatology, University of Pennsylvania; Dr. Goldberg is with the division of digestive health and liver diseases, University of Miami; and Dr. Verna is with the division of digestive and liver diseases, Columbia University. Dr. VanWagner is an adviser for Numares and Novo Nordisk and received a research grant from W.L. Gore & Associates. Dr. Serper disclosed research funding from Grifols. Dr. Verna disclosed research support from Salix. Dr. Goldberg had no disclosures. These remarks were made during one of the AGA Postgraduate Course sessions held at DDW 2023. DDW is sponsored by the American Association for the Study of Liver Diseases (AASLD), the American Gastroenterological Association (AGA), the American Society for Gastrointestinal Endoscopy (ASGE) and The Society for Surgery of the Alimentary Tract (SSAT).

References

1. Loomba R et al. Semaglutide 2.4 mg once weekly in patients with non-alcoholic steatohepatitis-related cirrhosis: A randomised, placebo-controlled phase 2 trial. Lancet Gastroenterol Hepatol. 2023;8:511-22.

2. Newsome PN et al. A placebo-controlled trial of subcutaneous semaglutide in nonalcoholic steatohepatitis. N Engl J Med. 2021;384:1113-24.

3. Verrastro O et al. Bariatric-metabolic surgery versus lifestyle intervention plus best medical care in non-alcoholic steatohepatitis (BRAVES): A multicentre, open-label, randomised trial. Lancet 2023;401:1786-97.

4. Rowe IA et al. Quantifying the benefit of nonselective beta-blockers in the prevention of hepatic decompensation: A Bayesian reanalysis of the PREDESCI trial. Hepatology 2023 Mar 13. doi: 10.1097/HEP.0000000000000342.

5. Nadim MK and Garcia-Tsao G. Acute kidney injury in patients with cirrhosis. N Engl J Med. 2023;388:733-45.

6. Bureau C et al. The use of rifaximin in the prevention of overt hepatic encephalopathy after transjugular intrahepatic portosystemic shunt: A randomized controlled trial. Ann Intern Med. 2021;174:633-40.

In metastatic breast cancer, a fixed dose of capecitabine given on a 7-day-on, 7-day-off schedule had similar efficacy and reduced adverse events compared with the standard 14-day-on, 7-day-off schedule, in a new study.

Both progression-free survival (PFS) and overall survival (OS) were similar between the two groups, but patients on the alternative schedule experienced fewer cases of hand-foot syndrome (HFS), diarrhea, and stomatitis, and also had fewer discontinuations and dose modifications.

The Food and Drug Administration–approved dose of capecitabine is 1,250 mg/m², but 14 days of treatment can lead to significant toxicity, said Qamar Khan, MD, during a presentation of the study at the annual meeting of the American Society of Clinical Oncology. “Mathematical models applied to xenograft [animal model] data suggest that the maximum cytotoxic effect of capecitabine occurs after about 7 days of treatment, beyond which time only toxicity increases,” Dr. Khan said during his talk on the randomized control trial.

The researchers randomized 153 patients to receive a fixed 1,500-mg capecitabine dose twice per day on a 7-day-on, 7-day-off schedule (7/7), or the 1,250–mg/m² dose twice per day for 14 days followed by 7 days off (14/7). The median age was 60 years, and 85.6% were White, 8.5% were African American, 3.3% were Hispanic, 0.7% were American Indian or Alaskan Native, and 2.0% were other. With respect to disease characteristics, 44% had visceral metastasis, 78% were hormone receptor positive/HER2 negative, and 11% had triple-negative breast cancer. About two-thirds (65%) had received no prior chemotherapy.

Restricted mean survival time (RMST) at 36 months for PFS was 13.9 months in the 7/7 group and 14.6 months in the 14/7 group (difference, 0.7 months; 95.5% CI, –3.14 to 4.57 months). The objective response rate was 8.9% in the 7/7 group and 19.6% in the 14/7 group (P = .11). Median OS was 19.8 months in the 7/7 group and 17.5 months in the 14/7 group (hazard ratio, 0.76; P = .17). The RMST at 47 months for OS was 24.5 months in the 7/7 group and 20.9 months in the 14/7 group (difference, –3.6 months; 95% CI, –8.89 to 1.54 months).

The researchers found no differences in subgroup analyses by visceral metastasis, breast cancer subtype, or number of lines of previous therapy.

The toxicity profile of 7/7 was better with respect to grade 2-4 diarrhea (2.5% vs. 20.5%, P = .0008), grade 2-4 HFS (3.8% vs. 15.1%; P = .0019), and grade 2-4 mucositis (0% vs. 5.5%; P =.0001).
 

Findings back up clinical practice

“The fixed-dose capecitabine dosing is something that’s been done a lot in practice, because a lot of practitioners recognize that giving the drug for two weeks in a row with a week break is overly toxic, so it’s something we’ve been doing in the community for quite a while,” said Michael Danso, MD, who comoderated the session.

Still, the safety and efficacy data back up that general clinical practice. “There was a randomized trial and colon cancer that didn’t show [equivalent outcomes with the alternate dosing schedule]. So to see that it’s safe and effective in breast cancer is an important [finding],” said Dr. Danso, who is the Research Director at Virginia Oncology Associates, Norfolk.

During the question-and-answer following the talk, Jeffrey Kirshner, MD, a medical oncologist at Hematology-Oncology Associates of Central New York, East Syracuse, noted that his practice has used a similar schedule for years. “I really commend you for doing that study. It really supports what many of us in the real world have been doing for many years. We figured this out empirically, both upfront and when patients can’t tolerate [the 14/7 schedule].”
 

Fixed dose versus body surface area

Dr. Kirshner also said his practice uses a dose of 1 g/m² of body surface area on a 7/7 schedule rather than a fixed dose as was done in Dr. Khan’s study. “If you use the higher dose, you might have seen a higher response rate because many of our patients, as you know, have a body surface [BSA] area much greater than 1.5 g/m².”

Dr. Khan responded that there is little data available on BSA dosing. “We selected 1,500 mg because a lot of people are practicing that, and for convenience, and that most patients who started at a higher dose eventually wound up on a dose of 1,500 mg twice daily.”

Dr. Kirshner also pointed out that the study was conducted in a population with metastatic disease. “I think we need to emphasize that we do not use the 7/7 regimen in a potentially curative setting, such as the CREATE-X regimen for triple-negative [breast cancer].”

Dr. Khan agreed. “I would use the same dose as the CREATE-X trial in the adjuvant setting,” he responded.

Dr. Danso has received honoraria from Amgen and has consulted or advised Immunomedics, Novartis, Pfizer, and Seagen. Dr. Khan and Dr. Kirshner have no relevant financial disclosures.

In metastatic breast cancer, a fixed dose of capecitabine given on a 7-day-on, 7-day-off schedule had similar efficacy and reduced adverse events compared with the standard 14-day-on, 7-day-off schedule, in a new study.

Both progression-free survival (PFS) and overall survival (OS) were similar between the two groups, but patients on the alternative schedule experienced fewer cases of hand-foot syndrome (HFS), diarrhea, and stomatitis, and also had fewer discontinuations and dose modifications.

The Food and Drug Administration–approved dose of capecitabine is 1,250 mg/m², but 14 days of treatment can lead to significant toxicity, said Qamar Khan, MD, during a presentation of the study at the annual meeting of the American Society of Clinical Oncology. “Mathematical models applied to xenograft [animal model] data suggest that the maximum cytotoxic effect of capecitabine occurs after about 7 days of treatment, beyond which time only toxicity increases,” Dr. Khan said during his talk on the randomized control trial.

The researchers randomized 153 patients to receive a fixed 1,500-mg capecitabine dose twice per day on a 7-day-on, 7-day-off schedule (7/7), or the 1,250–mg/m² dose twice per day for 14 days followed by 7 days off (14/7). The median age was 60 years, and 85.6% were White, 8.5% were African American, 3.3% were Hispanic, 0.7% were American Indian or Alaskan Native, and 2.0% were other. With respect to disease characteristics, 44% had visceral metastasis, 78% were hormone receptor positive/HER2 negative, and 11% had triple-negative breast cancer. About two-thirds (65%) had received no prior chemotherapy.

Restricted mean survival time (RMST) at 36 months for PFS was 13.9 months in the 7/7 group and 14.6 months in the 14/7 group (difference, 0.7 months; 95.5% CI, –3.14 to 4.57 months). The objective response rate was 8.9% in the 7/7 group and 19.6% in the 14/7 group (P = .11). Median OS was 19.8 months in the 7/7 group and 17.5 months in the 14/7 group (hazard ratio, 0.76; P = .17). The RMST at 47 months for OS was 24.5 months in the 7/7 group and 20.9 months in the 14/7 group (difference, –3.6 months; 95% CI, –8.89 to 1.54 months).

The researchers found no differences in subgroup analyses by visceral metastasis, breast cancer subtype, or number of lines of previous therapy.

The toxicity profile of 7/7 was better with respect to grade 2-4 diarrhea (2.5% vs. 20.5%, P = .0008), grade 2-4 HFS (3.8% vs. 15.1%; P = .0019), and grade 2-4 mucositis (0% vs. 5.5%; P =.0001).
 

Findings back up clinical practice

“The fixed-dose capecitabine dosing is something that’s been done a lot in practice, because a lot of practitioners recognize that giving the drug for two weeks in a row with a week break is overly toxic, so it’s something we’ve been doing in the community for quite a while,” said Michael Danso, MD, who comoderated the session.

Still, the safety and efficacy data back up that general clinical practice. “There was a randomized trial and colon cancer that didn’t show [equivalent outcomes with the alternate dosing schedule]. So to see that it’s safe and effective in breast cancer is an important [finding],” said Dr. Danso, who is the Research Director at Virginia Oncology Associates, Norfolk.

During the question-and-answer following the talk, Jeffrey Kirshner, MD, a medical oncologist at Hematology-Oncology Associates of Central New York, East Syracuse, noted that his practice has used a similar schedule for years. “I really commend you for doing that study. It really supports what many of us in the real world have been doing for many years. We figured this out empirically, both upfront and when patients can’t tolerate [the 14/7 schedule].”
 

Fixed dose versus body surface area

Dr. Kirshner also said his practice uses a dose of 1 g/m² of body surface area on a 7/7 schedule rather than a fixed dose as was done in Dr. Khan’s study. “If you use the higher dose, you might have seen a higher response rate because many of our patients, as you know, have a body surface [BSA] area much greater than 1.5 g/m².”

Dr. Khan responded that there is little data available on BSA dosing. “We selected 1,500 mg because a lot of people are practicing that, and for convenience, and that most patients who started at a higher dose eventually wound up on a dose of 1,500 mg twice daily.”

Dr. Kirshner also pointed out that the study was conducted in a population with metastatic disease. “I think we need to emphasize that we do not use the 7/7 regimen in a potentially curative setting, such as the CREATE-X regimen for triple-negative [breast cancer].”

Dr. Khan agreed. “I would use the same dose as the CREATE-X trial in the adjuvant setting,” he responded.

Dr. Danso has received honoraria from Amgen and has consulted or advised Immunomedics, Novartis, Pfizer, and Seagen. Dr. Khan and Dr. Kirshner have no relevant financial disclosures.

In metastatic breast cancer, a fixed dose of capecitabine given on a 7-day-on, 7-day-off schedule had similar efficacy and reduced adverse events compared with the standard 14-day-on, 7-day-off schedule, in a new study.

Both progression-free survival (PFS) and overall survival (OS) were similar between the two groups, but patients on the alternative schedule experienced fewer cases of hand-foot syndrome (HFS), diarrhea, and stomatitis, and also had fewer discontinuations and dose modifications.

The Food and Drug Administration–approved dose of capecitabine is 1,250 mg/m², but 14 days of treatment can lead to significant toxicity, said Qamar Khan, MD, during a presentation of the study at the annual meeting of the American Society of Clinical Oncology. “Mathematical models applied to xenograft [animal model] data suggest that the maximum cytotoxic effect of capecitabine occurs after about 7 days of treatment, beyond which time only toxicity increases,” Dr. Khan said during his talk on the randomized control trial.

The researchers randomized 153 patients to receive a fixed 1,500-mg capecitabine dose twice per day on a 7-day-on, 7-day-off schedule (7/7), or the 1,250–mg/m² dose twice per day for 14 days followed by 7 days off (14/7). The median age was 60 years, and 85.6% were White, 8.5% were African American, 3.3% were Hispanic, 0.7% were American Indian or Alaskan Native, and 2.0% were other. With respect to disease characteristics, 44% had visceral metastasis, 78% were hormone receptor positive/HER2 negative, and 11% had triple-negative breast cancer. About two-thirds (65%) had received no prior chemotherapy.

Restricted mean survival time (RMST) at 36 months for PFS was 13.9 months in the 7/7 group and 14.6 months in the 14/7 group (difference, 0.7 months; 95.5% CI, –3.14 to 4.57 months). The objective response rate was 8.9% in the 7/7 group and 19.6% in the 14/7 group (P = .11). Median OS was 19.8 months in the 7/7 group and 17.5 months in the 14/7 group (hazard ratio, 0.76; P = .17). The RMST at 47 months for OS was 24.5 months in the 7/7 group and 20.9 months in the 14/7 group (difference, –3.6 months; 95% CI, –8.89 to 1.54 months).

The researchers found no differences in subgroup analyses by visceral metastasis, breast cancer subtype, or number of lines of previous therapy.

The toxicity profile of 7/7 was better with respect to grade 2-4 diarrhea (2.5% vs. 20.5%, P = .0008), grade 2-4 HFS (3.8% vs. 15.1%; P = .0019), and grade 2-4 mucositis (0% vs. 5.5%; P =.0001).
 

Findings back up clinical practice

“The fixed-dose capecitabine dosing is something that’s been done a lot in practice, because a lot of practitioners recognize that giving the drug for two weeks in a row with a week break is overly toxic, so it’s something we’ve been doing in the community for quite a while,” said Michael Danso, MD, who comoderated the session.

Still, the safety and efficacy data back up that general clinical practice. “There was a randomized trial and colon cancer that didn’t show [equivalent outcomes with the alternate dosing schedule]. So to see that it’s safe and effective in breast cancer is an important [finding],” said Dr. Danso, who is the Research Director at Virginia Oncology Associates, Norfolk.

During the question-and-answer following the talk, Jeffrey Kirshner, MD, a medical oncologist at Hematology-Oncology Associates of Central New York, East Syracuse, noted that his practice has used a similar schedule for years. “I really commend you for doing that study. It really supports what many of us in the real world have been doing for many years. We figured this out empirically, both upfront and when patients can’t tolerate [the 14/7 schedule].”
 

Fixed dose versus body surface area

Dr. Kirshner also said his practice uses a dose of 1 g/m² of body surface area on a 7/7 schedule rather than a fixed dose as was done in Dr. Khan’s study. “If you use the higher dose, you might have seen a higher response rate because many of our patients, as you know, have a body surface [BSA] area much greater than 1.5 g/m².”

Dr. Khan responded that there is little data available on BSA dosing. “We selected 1,500 mg because a lot of people are practicing that, and for convenience, and that most patients who started at a higher dose eventually wound up on a dose of 1,500 mg twice daily.”

Dr. Kirshner also pointed out that the study was conducted in a population with metastatic disease. “I think we need to emphasize that we do not use the 7/7 regimen in a potentially curative setting, such as the CREATE-X regimen for triple-negative [breast cancer].”

Dr. Khan agreed. “I would use the same dose as the CREATE-X trial in the adjuvant setting,” he responded.

Dr. Danso has received honoraria from Amgen and has consulted or advised Immunomedics, Novartis, Pfizer, and Seagen. Dr. Khan and Dr. Kirshner have no relevant financial disclosures.

MUNICH – Patients undergoing carotid artery stenting (CAS) may have fewer ischemic lesions and a lower lesion burden if they are given the reversible P2Y12 receptor antagonist ticagrelor rather than clopidogrel, another P2Y12 inhibitor, prior to the procedure, secondary endpoint results of the PRECISE-MRI trial suggest.

More than 200 patients with carotid artery stenosis underwent MRI and were randomized to ticagrelor or clopidogrel before undergoing CAS. They then had two follow-up MRIs to assess the presence of emergent ischemic lesions.

Although the trial, which was stopped early, failed to show a difference between the two treatments in the primary endpoint – occurrence of at least one ischemic lesion – it did show that ticagrelor was associated with significant reductions in secondary endpoints including the total number and total volume of new lesions.

There were also significantly fewer cases of a composite of adverse clinical events with ticagrelor versus clopidogrel, but no difference in rates of hemorrhagic bleeds.

The research was presented at the annual European Stroke Organisation Conference .

Highlighting the failure of the trial to meet its primary endpoint, study presenter Leo Bonati, MD, head of the Stroke Center, Rena Rheinfelden, University Hospital Basel (Switzerland), pointed out that the proportion of patients with one or more ischemic brain lesions was “much higher than expected.”

Based on the secondary outcomes, the study nevertheless indicates that, “compared with clopidogrel, ticagrelor reduces the total burden of ischemic brain lesions occurring during CAS,” he said.

Ticagrelor is therefore a “safe alternative to clopidogrel as an add-on to aspirin to cover carotid artery stent procedures.”

Dr. Bonati cautioned, however, that the findings are preliminary.
 

‘Promising’ results

Session cochair Else Charlotte Sandset, MD, PhD, a consultant neurologist in the stroke unit, department of neurology, Oslo University Hospital, called the results “interesting” and “promising.”

She said in an interview that they “also provide us with an additional option” in the management of patients undergoing CAS.

Dr. Sandset suggested that “it may have been a little bit hard to prove the primary endpoint” chosen for the trial, but believes that the secondary endpoint results “are very interesting.”

“Of course, we would need more data and further trials to provide some reassurance that we can use ticagrelor in this fashion,” she said.
 

Major complication

Dr. Bonati began by noting that the major procedural complication of CAS is embolic stroke, but this may be prevented with optimized antiplatelet therapy.

Previous studies have shown that ticagrelor is superior to clopidogrel as an add-on to aspirin in reducing rates of major adverse cardiovascular events in acute coronary syndrome patients undergoing percutaneous coronary intervention.

Adding the drug to aspirin is also superior to aspirin alone in preventing recurrent stroke in patients with minor stroke or transient ischemic attack, Dr. Bonati said.

To examine whether ticagrelor is superior to clopidogrel as an add-on to aspirin in preventing ischemic brain lesions during CAS, the team conducted a randomized, open, active-controlled trial.

They recruited patients with ≥ 50% symptomatic or asymptomatic carotid stenosis undergoing CAS in line with local guidelines and performed a baseline MRI scan and clinical examination.

The patients were then randomized to ticagrelor or clopidogrel plus aspirin 1-3 days before undergoing CAS. A second MRI and clinical examination, as well as an ultrasound scan, was performed at 1 to 3 days post-CAS, with a third set of examinations performed at 28-32 days after the procedure.

The study included 14 sites in Belgium, Germany, Italy, the Netherlands, Switzerland, and the United Kingdom. Enrollment was stopped after 209 of the originally planned 370 patients, “due to slow recruitment and a lack of further funding,” Dr. Bonati said.

Of those, 207 patients were included in the intention-to-treat safety analysis, and 172 in the per-protocol efficacy analysis.

The mean age of the patients was 69.0-69.5 years in the two treatment groups, and 67%-71% were male. Dr. Bonati noted that 52%-55% of the patients had symptomatic stenosis, and that in 83%-88% the stenosis was severe.

The majority (79%-82%) of patients had hypertension, alongside hypercholesterolemia, at 76% in both treatment groups.

Dr. Bonati showed that there was no significant difference in the primary efficacy outcome of the presence of at least new ischemic brain lesion on the second or third MRI, at 74.7% for patients given ticagrelor versus 79.8% with clopidogrel, or a relative risk of 0.94 (95% confidence interval, 0.79-1.10; P = .43).

However, there was a significant reduction in the number of new ischemic lesions, at a median of 2 (interquartile range, 0.5-5.5) with ticagrelor versus 3 with clopidogrel (IQR, 1-8), or an exponential beta value of 0.63 (95% CI, 0.42-0.95; P = .027).

Ticagrelor was also associated with a significant reduction in the total volume of lesions, at a median of 66 mcL (IQR, 2.5-2.19) versus 91 mcL (IQR, 25-394) for clopidogrel, or an exponential beta value of 0.30 (95% CI, 0.10-0.92; P = .030).

Patients assigned to ticagrelor also had a significantly lower rate of the primary clinical safety outcome, a composite of stroke, myocardial infarction, major bleeding, or cardiovascular death, at 2.9% versus 7.8% (relative risk, 0.36; 95% CI, 0.08-1.20). This was driven by a reduction in rates of post-CAS stroke.

Dr. Bonati noted that there was no significant difference in the presence of at least one hemorrhagic lesion after CAS, at 42.7% with ticagrelor and 47.6% in the clopidogrel group (RR, 0.90; 95% CI, 0.63-1.26).

There was also a similar rate of microbleeds between the two treatment groups, at 36.6% in patients given ticagrelor and 47.6% in those assigned to clopidogrel.

The study was investigator initiated and funded by an unrestricted research grant from AstraZeneca. No relevant financial relationships were declared.

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

MUNICH – Patients undergoing carotid artery stenting (CAS) may have fewer ischemic lesions and a lower lesion burden if they are given the reversible P2Y12 receptor antagonist ticagrelor rather than clopidogrel, another P2Y12 inhibitor, prior to the procedure, secondary endpoint results of the PRECISE-MRI trial suggest.

More than 200 patients with carotid artery stenosis underwent MRI and were randomized to ticagrelor or clopidogrel before undergoing CAS. They then had two follow-up MRIs to assess the presence of emergent ischemic lesions.

Although the trial, which was stopped early, failed to show a difference between the two treatments in the primary endpoint – occurrence of at least one ischemic lesion – it did show that ticagrelor was associated with significant reductions in secondary endpoints including the total number and total volume of new lesions.

There were also significantly fewer cases of a composite of adverse clinical events with ticagrelor versus clopidogrel, but no difference in rates of hemorrhagic bleeds.

The research was presented at the annual European Stroke Organisation Conference .

Highlighting the failure of the trial to meet its primary endpoint, study presenter Leo Bonati, MD, head of the Stroke Center, Rena Rheinfelden, University Hospital Basel (Switzerland), pointed out that the proportion of patients with one or more ischemic brain lesions was “much higher than expected.”

Based on the secondary outcomes, the study nevertheless indicates that, “compared with clopidogrel, ticagrelor reduces the total burden of ischemic brain lesions occurring during CAS,” he said.

Ticagrelor is therefore a “safe alternative to clopidogrel as an add-on to aspirin to cover carotid artery stent procedures.”

Dr. Bonati cautioned, however, that the findings are preliminary.
 

‘Promising’ results

Session cochair Else Charlotte Sandset, MD, PhD, a consultant neurologist in the stroke unit, department of neurology, Oslo University Hospital, called the results “interesting” and “promising.”

She said in an interview that they “also provide us with an additional option” in the management of patients undergoing CAS.

Dr. Sandset suggested that “it may have been a little bit hard to prove the primary endpoint” chosen for the trial, but believes that the secondary endpoint results “are very interesting.”

“Of course, we would need more data and further trials to provide some reassurance that we can use ticagrelor in this fashion,” she said.
 

Major complication

Dr. Bonati began by noting that the major procedural complication of CAS is embolic stroke, but this may be prevented with optimized antiplatelet therapy.

Previous studies have shown that ticagrelor is superior to clopidogrel as an add-on to aspirin in reducing rates of major adverse cardiovascular events in acute coronary syndrome patients undergoing percutaneous coronary intervention.

Adding the drug to aspirin is also superior to aspirin alone in preventing recurrent stroke in patients with minor stroke or transient ischemic attack, Dr. Bonati said.

To examine whether ticagrelor is superior to clopidogrel as an add-on to aspirin in preventing ischemic brain lesions during CAS, the team conducted a randomized, open, active-controlled trial.

They recruited patients with ≥ 50% symptomatic or asymptomatic carotid stenosis undergoing CAS in line with local guidelines and performed a baseline MRI scan and clinical examination.

The patients were then randomized to ticagrelor or clopidogrel plus aspirin 1-3 days before undergoing CAS. A second MRI and clinical examination, as well as an ultrasound scan, was performed at 1 to 3 days post-CAS, with a third set of examinations performed at 28-32 days after the procedure.

The study included 14 sites in Belgium, Germany, Italy, the Netherlands, Switzerland, and the United Kingdom. Enrollment was stopped after 209 of the originally planned 370 patients, “due to slow recruitment and a lack of further funding,” Dr. Bonati said.

Of those, 207 patients were included in the intention-to-treat safety analysis, and 172 in the per-protocol efficacy analysis.

The mean age of the patients was 69.0-69.5 years in the two treatment groups, and 67%-71% were male. Dr. Bonati noted that 52%-55% of the patients had symptomatic stenosis, and that in 83%-88% the stenosis was severe.

The majority (79%-82%) of patients had hypertension, alongside hypercholesterolemia, at 76% in both treatment groups.

Dr. Bonati showed that there was no significant difference in the primary efficacy outcome of the presence of at least new ischemic brain lesion on the second or third MRI, at 74.7% for patients given ticagrelor versus 79.8% with clopidogrel, or a relative risk of 0.94 (95% confidence interval, 0.79-1.10; P = .43).

However, there was a significant reduction in the number of new ischemic lesions, at a median of 2 (interquartile range, 0.5-5.5) with ticagrelor versus 3 with clopidogrel (IQR, 1-8), or an exponential beta value of 0.63 (95% CI, 0.42-0.95; P = .027).

Ticagrelor was also associated with a significant reduction in the total volume of lesions, at a median of 66 mcL (IQR, 2.5-2.19) versus 91 mcL (IQR, 25-394) for clopidogrel, or an exponential beta value of 0.30 (95% CI, 0.10-0.92; P = .030).

Patients assigned to ticagrelor also had a significantly lower rate of the primary clinical safety outcome, a composite of stroke, myocardial infarction, major bleeding, or cardiovascular death, at 2.9% versus 7.8% (relative risk, 0.36; 95% CI, 0.08-1.20). This was driven by a reduction in rates of post-CAS stroke.

Dr. Bonati noted that there was no significant difference in the presence of at least one hemorrhagic lesion after CAS, at 42.7% with ticagrelor and 47.6% in the clopidogrel group (RR, 0.90; 95% CI, 0.63-1.26).

There was also a similar rate of microbleeds between the two treatment groups, at 36.6% in patients given ticagrelor and 47.6% in those assigned to clopidogrel.

The study was investigator initiated and funded by an unrestricted research grant from AstraZeneca. No relevant financial relationships were declared.

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

MUNICH – Patients undergoing carotid artery stenting (CAS) may have fewer ischemic lesions and a lower lesion burden if they are given the reversible P2Y12 receptor antagonist ticagrelor rather than clopidogrel, another P2Y12 inhibitor, prior to the procedure, secondary endpoint results of the PRECISE-MRI trial suggest.

More than 200 patients with carotid artery stenosis underwent MRI and were randomized to ticagrelor or clopidogrel before undergoing CAS. They then had two follow-up MRIs to assess the presence of emergent ischemic lesions.

Although the trial, which was stopped early, failed to show a difference between the two treatments in the primary endpoint – occurrence of at least one ischemic lesion – it did show that ticagrelor was associated with significant reductions in secondary endpoints including the total number and total volume of new lesions.

There were also significantly fewer cases of a composite of adverse clinical events with ticagrelor versus clopidogrel, but no difference in rates of hemorrhagic bleeds.

The research was presented at the annual European Stroke Organisation Conference .

Highlighting the failure of the trial to meet its primary endpoint, study presenter Leo Bonati, MD, head of the Stroke Center, Rena Rheinfelden, University Hospital Basel (Switzerland), pointed out that the proportion of patients with one or more ischemic brain lesions was “much higher than expected.”

Based on the secondary outcomes, the study nevertheless indicates that, “compared with clopidogrel, ticagrelor reduces the total burden of ischemic brain lesions occurring during CAS,” he said.

Ticagrelor is therefore a “safe alternative to clopidogrel as an add-on to aspirin to cover carotid artery stent procedures.”

Dr. Bonati cautioned, however, that the findings are preliminary.
 

‘Promising’ results

Session cochair Else Charlotte Sandset, MD, PhD, a consultant neurologist in the stroke unit, department of neurology, Oslo University Hospital, called the results “interesting” and “promising.”

She said in an interview that they “also provide us with an additional option” in the management of patients undergoing CAS.

Dr. Sandset suggested that “it may have been a little bit hard to prove the primary endpoint” chosen for the trial, but believes that the secondary endpoint results “are very interesting.”

“Of course, we would need more data and further trials to provide some reassurance that we can use ticagrelor in this fashion,” she said.
 

Major complication

Dr. Bonati began by noting that the major procedural complication of CAS is embolic stroke, but this may be prevented with optimized antiplatelet therapy.

Previous studies have shown that ticagrelor is superior to clopidogrel as an add-on to aspirin in reducing rates of major adverse cardiovascular events in acute coronary syndrome patients undergoing percutaneous coronary intervention.

Adding the drug to aspirin is also superior to aspirin alone in preventing recurrent stroke in patients with minor stroke or transient ischemic attack, Dr. Bonati said.

To examine whether ticagrelor is superior to clopidogrel as an add-on to aspirin in preventing ischemic brain lesions during CAS, the team conducted a randomized, open, active-controlled trial.

They recruited patients with ≥ 50% symptomatic or asymptomatic carotid stenosis undergoing CAS in line with local guidelines and performed a baseline MRI scan and clinical examination.

The patients were then randomized to ticagrelor or clopidogrel plus aspirin 1-3 days before undergoing CAS. A second MRI and clinical examination, as well as an ultrasound scan, was performed at 1 to 3 days post-CAS, with a third set of examinations performed at 28-32 days after the procedure.

The study included 14 sites in Belgium, Germany, Italy, the Netherlands, Switzerland, and the United Kingdom. Enrollment was stopped after 209 of the originally planned 370 patients, “due to slow recruitment and a lack of further funding,” Dr. Bonati said.

Of those, 207 patients were included in the intention-to-treat safety analysis, and 172 in the per-protocol efficacy analysis.

The mean age of the patients was 69.0-69.5 years in the two treatment groups, and 67%-71% were male. Dr. Bonati noted that 52%-55% of the patients had symptomatic stenosis, and that in 83%-88% the stenosis was severe.

The majority (79%-82%) of patients had hypertension, alongside hypercholesterolemia, at 76% in both treatment groups.

Dr. Bonati showed that there was no significant difference in the primary efficacy outcome of the presence of at least new ischemic brain lesion on the second or third MRI, at 74.7% for patients given ticagrelor versus 79.8% with clopidogrel, or a relative risk of 0.94 (95% confidence interval, 0.79-1.10; P = .43).

However, there was a significant reduction in the number of new ischemic lesions, at a median of 2 (interquartile range, 0.5-5.5) with ticagrelor versus 3 with clopidogrel (IQR, 1-8), or an exponential beta value of 0.63 (95% CI, 0.42-0.95; P = .027).

Ticagrelor was also associated with a significant reduction in the total volume of lesions, at a median of 66 mcL (IQR, 2.5-2.19) versus 91 mcL (IQR, 25-394) for clopidogrel, or an exponential beta value of 0.30 (95% CI, 0.10-0.92; P = .030).

Patients assigned to ticagrelor also had a significantly lower rate of the primary clinical safety outcome, a composite of stroke, myocardial infarction, major bleeding, or cardiovascular death, at 2.9% versus 7.8% (relative risk, 0.36; 95% CI, 0.08-1.20). This was driven by a reduction in rates of post-CAS stroke.

Dr. Bonati noted that there was no significant difference in the presence of at least one hemorrhagic lesion after CAS, at 42.7% with ticagrelor and 47.6% in the clopidogrel group (RR, 0.90; 95% CI, 0.63-1.26).

There was also a similar rate of microbleeds between the two treatment groups, at 36.6% in patients given ticagrelor and 47.6% in those assigned to clopidogrel.

The study was investigator initiated and funded by an unrestricted research grant from AstraZeneca. No relevant financial relationships were declared.

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

MILAN – Treatment of systemic lupus erythematosus with biologics may enable steroid tapering while ensuring the achievement of remission or low disease activity in more patients with fewer flares and less organ damage, as well as leading to better responses if used early, according to the latest recommendations on the management of SLE from the European Alliance of Associations for Rheumatology (EULAR).

Dimitrios Boumpas, MD, president of the Athens Medical Society and chair of the European Task force on SLE, presented the recommendations at the annual European Congress of Rheumatology. “Although steroids save lives, it is at the expense of excessive collateral damage. They are better for short-term use as a rescue or bridging therapy but may be used in some patients at 5 mg/day of prednisone or less, rather than the previous 7.5 mg/day,” he emphasized.

The 2023 recommendations cover new treatment strategies with more ambitious goals, new data on adverse effects of chronic glucocorticoid use, and newly approved agents and combination therapies.

“Most importantly, we sourced help from experts from all over the world,” said Dr. Boumpas, describing the task force that included 35 rheumatologists, 5 nephrologists, 2 methodologists, 2 patient representatives, and 2 fellows, all brought together from across Europe, North America, Asia, and Australia.

Over 7,000 papers were reviewed, with 437 included in the systematic literature review to inform the updated recommendations.

Session moderator Robert Landewé, MD, PhD, professor of clinical immunology and rheumatology at the University of Amsterdam, said that “the underlying heterogeneity and multisystem involvement of SLE can make it difficult to demonstrate and know which drugs work in the condition. However, these latest recommendations should encourage greater confidence to taper steroids early on and perhaps consider new biologic drugs, so that more patients can achieve better results sooner to prevent flares and organ damage, improve prognosis, and enhance their quality of life.”

Dr. Boumpas provided a summary of the overarching principles that guide the recommendations. These say that SLE requires multidisciplinary individualized management; disease activity should be assessed at each visit; nonpharmacologic interventions such as sun protection, smoking cessation, and following a healthy diet are all important for improving long-term outcomes; pharmacologic interventions are to be directed by patient characteristics, type and severity of organ involvement, treatment-related harms, and patient preferences, among other factors; and early SLE diagnosis is essential to prevent flares and organ damage, improve prognosis, and enhance quality of life.

Referring to each recommendation statement in turn, Dr. Boumpas provided a detailed description of each, and highlighted any changes since the 2019 recommendations.
 

Hydroxychloroquine, glucocorticoids as bridging therapy, and biologics

Referring to statement 1, Dr. Boumpas reported that hydroxychloroquine should be a first-line therapy at a dose of 5 mg/kg, but this dose should be individualized based on risk of flare and retinal toxicity. “There was some discussion about monitoring blood levels, but this was to ensure adherence only,” said Dr. Boumpas.

Continuing to statement 2, he added, “here is one change. With chronic use of glucocorticoids, the maintenance dose is 5 mg/day or less or prednisone equivalent. This pertains to both new onset and relapsing disease.” Previous recommendations advised a maintenance dose of 7.5 mg/day or less.

But he pointed out that “we are discussing using glucocorticoids in lupus as a bridging therapy only, for short, limited periods of time. We should shy away from chronic use of glucocorticoids and only use them for 3 months, and to do this we need to use glucocorticoid-sparing strategies.”

This led to statement 3, which refers to glucocorticoid-sparing strategies. Dr. Boumpas explained that, in patients who are not responding to hydroxychloroquine or unable to reduce glucocorticoids further during chronic use, add immunosuppressive agents, such as methotrexate and/or biologics (for example, belimumab [Benlysta] or anifrolumab [Saphnelo]).

“To allow flexibility for patients and clinicians, it isn’t necessary to use DMARDs [disease-modifying antirheumatic drugs] first if you prefer biologics,” he continued. “We are becoming more liberal with the use of biologics because there are new data that confirm the efficacy of belimumab in extrarenal SLE, plus good data with 3-year extension with anifrolumab.”

Statement 4 says that for patients with organ- or life-threatening disease, intravenous cyclophosphamide, “our old friend,” should be considered, while in refractory cases, rituximab may be considered, Dr. Boumpas said. “It’s okay to use cyclophosphamide. It isn’t a sin.”

Statement 5 refers to skin disease, and Dr. Boumpas explained that good data suggested that biologics help, including both belimumab and anifrolumab.

Nothing has changed with statement 6 concerning neuropsychiatric lupus, said Dr. Boumpas. “Glucocorticoids, immunosuppressive, and antithrombotic therapies should be considered.”

Regarding hematologic disease (statement 7), he said, “the new kid on the block is MMF [mycophenolate mofetil]. For acute treatment, still use the same drugs, including rituximab, but for maintenance you may use rituximab, azathioprine, MMF, or cyclosporine.”
 

Lupus nephritis

Turning to what Dr. Boumpas described as the “reason you had all come here, and what you had been waiting for ... what’s changing with lupus nephritis?” he said.

Statement 8 describes initial therapy in active lupus nephritis. Dr. Boumpas said that low-dose, intravenous cyclophosphamide or mycophenolate should be considered, but also that belimumab or a calcineurin inhibitor (CNI) should be considered at the start. The changes were based on two successful phase 3 trials of belimumab and voclosporin, with belimumab being associated with a reduced flare rate and estimated glomerular filtration rate (eGFR).

“Changes from 2019 include that there is no distinction between classes III/IV and V, which is heretical,” he stressed. Belimumab and CNIs/voclosporin should be considered in all patents as an add-on therapy from the start. “Lupus nephritis has high morbidity, and it’s difficult to predict outcomes at the beginning, but there are clear benefits of add-on therapies. CNIs, although they can be used for all patients, might be more appropriate for membranous or nephrotic-range proteinuria.”

He went on to announce that the “million-dollar question” was whether to use belimumab or voclosporin (or other CNIs), and that this was “a question of gentle, compared with forceful, power and collateral damage.

“For me, voclosporin works very fast, but you worry about side effects, while belimumab is gentle and the response is sustained, preventing flares and organ damage,” he said, adding that “our expert panel discussions showed that nephrologists were more eager to support steroid-free regimens.”

Moving on to statement 9, Dr. Boumpas explained that after initial therapy and renal response, subsequent therapy should continue for at least 3 years. If treated with MMF alone or in combination with belimumab, then these drugs should continue. However, MMF should replace cyclophosphamide if the latter is used initially.

Regarding treat-to-target in lupus nephritis, he said that EULAR now advises to aim for a 25% drop in urine protein/creatinine ratio by 3 months, a 50% drop by 6 months, and a UPCR of less than 0.5-0.7, plus normal eGFR, by 12 months, Dr. Boumpas said.

Statement 10 advises considering high-dose intravenous cyclophosphamide in combination with pulse intravenous methylprednisolone for patients at high risk of renal failure.
 

Tapering drugs in sustained remission, managing antiphospholipid syndrome, giving immunizations

Statement 11 suggests to consider tapering immunosuppressive agents and glucocorticoids in patients achieving sustained remission, starting with glucocorticoids first.

There was no change to statement 12, which recommends that thrombotic antiphospholipid syndrome associated with SLE be treated with long-term vitamin K antagonists.

Statement 13 addresses immunizations and adjunct therapies. In addition to conventional immunizations, Dr. Boumpas said that renoprotection should receive attention in case of proteinuria and/or hypertension.

“With [sodium-glucose cotransporter 2] inhibitors, it’s a bit early. They’re promising, and you may consider them, although there are no data for patients with eGFR below 60 mL/min per 1.73 m²,” he remarked, completing his detailed discussion of the updated recommendations.

Dr. Boumpas reported no relevant financial relationships. Dr. Landewé served as past chair of EULAR’s Quality of Care Committee, which develops recommendations.

MILAN – Treatment of systemic lupus erythematosus with biologics may enable steroid tapering while ensuring the achievement of remission or low disease activity in more patients with fewer flares and less organ damage, as well as leading to better responses if used early, according to the latest recommendations on the management of SLE from the European Alliance of Associations for Rheumatology (EULAR).

Dimitrios Boumpas, MD, president of the Athens Medical Society and chair of the European Task force on SLE, presented the recommendations at the annual European Congress of Rheumatology. “Although steroids save lives, it is at the expense of excessive collateral damage. They are better for short-term use as a rescue or bridging therapy but may be used in some patients at 5 mg/day of prednisone or less, rather than the previous 7.5 mg/day,” he emphasized.

The 2023 recommendations cover new treatment strategies with more ambitious goals, new data on adverse effects of chronic glucocorticoid use, and newly approved agents and combination therapies.

“Most importantly, we sourced help from experts from all over the world,” said Dr. Boumpas, describing the task force that included 35 rheumatologists, 5 nephrologists, 2 methodologists, 2 patient representatives, and 2 fellows, all brought together from across Europe, North America, Asia, and Australia.

Over 7,000 papers were reviewed, with 437 included in the systematic literature review to inform the updated recommendations.

Session moderator Robert Landewé, MD, PhD, professor of clinical immunology and rheumatology at the University of Amsterdam, said that “the underlying heterogeneity and multisystem involvement of SLE can make it difficult to demonstrate and know which drugs work in the condition. However, these latest recommendations should encourage greater confidence to taper steroids early on and perhaps consider new biologic drugs, so that more patients can achieve better results sooner to prevent flares and organ damage, improve prognosis, and enhance their quality of life.”

Dr. Boumpas provided a summary of the overarching principles that guide the recommendations. These say that SLE requires multidisciplinary individualized management; disease activity should be assessed at each visit; nonpharmacologic interventions such as sun protection, smoking cessation, and following a healthy diet are all important for improving long-term outcomes; pharmacologic interventions are to be directed by patient characteristics, type and severity of organ involvement, treatment-related harms, and patient preferences, among other factors; and early SLE diagnosis is essential to prevent flares and organ damage, improve prognosis, and enhance quality of life.

Referring to each recommendation statement in turn, Dr. Boumpas provided a detailed description of each, and highlighted any changes since the 2019 recommendations.
 

Hydroxychloroquine, glucocorticoids as bridging therapy, and biologics

Referring to statement 1, Dr. Boumpas reported that hydroxychloroquine should be a first-line therapy at a dose of 5 mg/kg, but this dose should be individualized based on risk of flare and retinal toxicity. “There was some discussion about monitoring blood levels, but this was to ensure adherence only,” said Dr. Boumpas.

Continuing to statement 2, he added, “here is one change. With chronic use of glucocorticoids, the maintenance dose is 5 mg/day or less or prednisone equivalent. This pertains to both new onset and relapsing disease.” Previous recommendations advised a maintenance dose of 7.5 mg/day or less.

But he pointed out that “we are discussing using glucocorticoids in lupus as a bridging therapy only, for short, limited periods of time. We should shy away from chronic use of glucocorticoids and only use them for 3 months, and to do this we need to use glucocorticoid-sparing strategies.”

This led to statement 3, which refers to glucocorticoid-sparing strategies. Dr. Boumpas explained that, in patients who are not responding to hydroxychloroquine or unable to reduce glucocorticoids further during chronic use, add immunosuppressive agents, such as methotrexate and/or biologics (for example, belimumab [Benlysta] or anifrolumab [Saphnelo]).

“To allow flexibility for patients and clinicians, it isn’t necessary to use DMARDs [disease-modifying antirheumatic drugs] first if you prefer biologics,” he continued. “We are becoming more liberal with the use of biologics because there are new data that confirm the efficacy of belimumab in extrarenal SLE, plus good data with 3-year extension with anifrolumab.”

Statement 4 says that for patients with organ- or life-threatening disease, intravenous cyclophosphamide, “our old friend,” should be considered, while in refractory cases, rituximab may be considered, Dr. Boumpas said. “It’s okay to use cyclophosphamide. It isn’t a sin.”

Statement 5 refers to skin disease, and Dr. Boumpas explained that good data suggested that biologics help, including both belimumab and anifrolumab.

Nothing has changed with statement 6 concerning neuropsychiatric lupus, said Dr. Boumpas. “Glucocorticoids, immunosuppressive, and antithrombotic therapies should be considered.”

Regarding hematologic disease (statement 7), he said, “the new kid on the block is MMF [mycophenolate mofetil]. For acute treatment, still use the same drugs, including rituximab, but for maintenance you may use rituximab, azathioprine, MMF, or cyclosporine.”
 

Lupus nephritis

Turning to what Dr. Boumpas described as the “reason you had all come here, and what you had been waiting for ... what’s changing with lupus nephritis?” he said.

Statement 8 describes initial therapy in active lupus nephritis. Dr. Boumpas said that low-dose, intravenous cyclophosphamide or mycophenolate should be considered, but also that belimumab or a calcineurin inhibitor (CNI) should be considered at the start. The changes were based on two successful phase 3 trials of belimumab and voclosporin, with belimumab being associated with a reduced flare rate and estimated glomerular filtration rate (eGFR).

“Changes from 2019 include that there is no distinction between classes III/IV and V, which is heretical,” he stressed. Belimumab and CNIs/voclosporin should be considered in all patents as an add-on therapy from the start. “Lupus nephritis has high morbidity, and it’s difficult to predict outcomes at the beginning, but there are clear benefits of add-on therapies. CNIs, although they can be used for all patients, might be more appropriate for membranous or nephrotic-range proteinuria.”

He went on to announce that the “million-dollar question” was whether to use belimumab or voclosporin (or other CNIs), and that this was “a question of gentle, compared with forceful, power and collateral damage.

“For me, voclosporin works very fast, but you worry about side effects, while belimumab is gentle and the response is sustained, preventing flares and organ damage,” he said, adding that “our expert panel discussions showed that nephrologists were more eager to support steroid-free regimens.”

Moving on to statement 9, Dr. Boumpas explained that after initial therapy and renal response, subsequent therapy should continue for at least 3 years. If treated with MMF alone or in combination with belimumab, then these drugs should continue. However, MMF should replace cyclophosphamide if the latter is used initially.

Regarding treat-to-target in lupus nephritis, he said that EULAR now advises to aim for a 25% drop in urine protein/creatinine ratio by 3 months, a 50% drop by 6 months, and a UPCR of less than 0.5-0.7, plus normal eGFR, by 12 months, Dr. Boumpas said.

Statement 10 advises considering high-dose intravenous cyclophosphamide in combination with pulse intravenous methylprednisolone for patients at high risk of renal failure.
 

Tapering drugs in sustained remission, managing antiphospholipid syndrome, giving immunizations

Statement 11 suggests to consider tapering immunosuppressive agents and glucocorticoids in patients achieving sustained remission, starting with glucocorticoids first.

There was no change to statement 12, which recommends that thrombotic antiphospholipid syndrome associated with SLE be treated with long-term vitamin K antagonists.

Statement 13 addresses immunizations and adjunct therapies. In addition to conventional immunizations, Dr. Boumpas said that renoprotection should receive attention in case of proteinuria and/or hypertension.

“With [sodium-glucose cotransporter 2] inhibitors, it’s a bit early. They’re promising, and you may consider them, although there are no data for patients with eGFR below 60 mL/min per 1.73 m²,” he remarked, completing his detailed discussion of the updated recommendations.

Dr. Boumpas reported no relevant financial relationships. Dr. Landewé served as past chair of EULAR’s Quality of Care Committee, which develops recommendations.

MILAN – Treatment of systemic lupus erythematosus with biologics may enable steroid tapering while ensuring the achievement of remission or low disease activity in more patients with fewer flares and less organ damage, as well as leading to better responses if used early, according to the latest recommendations on the management of SLE from the European Alliance of Associations for Rheumatology (EULAR).

Dimitrios Boumpas, MD, president of the Athens Medical Society and chair of the European Task force on SLE, presented the recommendations at the annual European Congress of Rheumatology. “Although steroids save lives, it is at the expense of excessive collateral damage. They are better for short-term use as a rescue or bridging therapy but may be used in some patients at 5 mg/day of prednisone or less, rather than the previous 7.5 mg/day,” he emphasized.

The 2023 recommendations cover new treatment strategies with more ambitious goals, new data on adverse effects of chronic glucocorticoid use, and newly approved agents and combination therapies.

“Most importantly, we sourced help from experts from all over the world,” said Dr. Boumpas, describing the task force that included 35 rheumatologists, 5 nephrologists, 2 methodologists, 2 patient representatives, and 2 fellows, all brought together from across Europe, North America, Asia, and Australia.

Over 7,000 papers were reviewed, with 437 included in the systematic literature review to inform the updated recommendations.

Session moderator Robert Landewé, MD, PhD, professor of clinical immunology and rheumatology at the University of Amsterdam, said that “the underlying heterogeneity and multisystem involvement of SLE can make it difficult to demonstrate and know which drugs work in the condition. However, these latest recommendations should encourage greater confidence to taper steroids early on and perhaps consider new biologic drugs, so that more patients can achieve better results sooner to prevent flares and organ damage, improve prognosis, and enhance their quality of life.”

Dr. Boumpas provided a summary of the overarching principles that guide the recommendations. These say that SLE requires multidisciplinary individualized management; disease activity should be assessed at each visit; nonpharmacologic interventions such as sun protection, smoking cessation, and following a healthy diet are all important for improving long-term outcomes; pharmacologic interventions are to be directed by patient characteristics, type and severity of organ involvement, treatment-related harms, and patient preferences, among other factors; and early SLE diagnosis is essential to prevent flares and organ damage, improve prognosis, and enhance quality of life.

Referring to each recommendation statement in turn, Dr. Boumpas provided a detailed description of each, and highlighted any changes since the 2019 recommendations.
 

Hydroxychloroquine, glucocorticoids as bridging therapy, and biologics

Referring to statement 1, Dr. Boumpas reported that hydroxychloroquine should be a first-line therapy at a dose of 5 mg/kg, but this dose should be individualized based on risk of flare and retinal toxicity. “There was some discussion about monitoring blood levels, but this was to ensure adherence only,” said Dr. Boumpas.

Continuing to statement 2, he added, “here is one change. With chronic use of glucocorticoids, the maintenance dose is 5 mg/day or less or prednisone equivalent. This pertains to both new onset and relapsing disease.” Previous recommendations advised a maintenance dose of 7.5 mg/day or less.

But he pointed out that “we are discussing using glucocorticoids in lupus as a bridging therapy only, for short, limited periods of time. We should shy away from chronic use of glucocorticoids and only use them for 3 months, and to do this we need to use glucocorticoid-sparing strategies.”

This led to statement 3, which refers to glucocorticoid-sparing strategies. Dr. Boumpas explained that, in patients who are not responding to hydroxychloroquine or unable to reduce glucocorticoids further during chronic use, add immunosuppressive agents, such as methotrexate and/or biologics (for example, belimumab [Benlysta] or anifrolumab [Saphnelo]).

“To allow flexibility for patients and clinicians, it isn’t necessary to use DMARDs [disease-modifying antirheumatic drugs] first if you prefer biologics,” he continued. “We are becoming more liberal with the use of biologics because there are new data that confirm the efficacy of belimumab in extrarenal SLE, plus good data with 3-year extension with anifrolumab.”

Statement 4 says that for patients with organ- or life-threatening disease, intravenous cyclophosphamide, “our old friend,” should be considered, while in refractory cases, rituximab may be considered, Dr. Boumpas said. “It’s okay to use cyclophosphamide. It isn’t a sin.”

Statement 5 refers to skin disease, and Dr. Boumpas explained that good data suggested that biologics help, including both belimumab and anifrolumab.

Nothing has changed with statement 6 concerning neuropsychiatric lupus, said Dr. Boumpas. “Glucocorticoids, immunosuppressive, and antithrombotic therapies should be considered.”

Regarding hematologic disease (statement 7), he said, “the new kid on the block is MMF [mycophenolate mofetil]. For acute treatment, still use the same drugs, including rituximab, but for maintenance you may use rituximab, azathioprine, MMF, or cyclosporine.”
 

Lupus nephritis

Turning to what Dr. Boumpas described as the “reason you had all come here, and what you had been waiting for ... what’s changing with lupus nephritis?” he said.

Statement 8 describes initial therapy in active lupus nephritis. Dr. Boumpas said that low-dose, intravenous cyclophosphamide or mycophenolate should be considered, but also that belimumab or a calcineurin inhibitor (CNI) should be considered at the start. The changes were based on two successful phase 3 trials of belimumab and voclosporin, with belimumab being associated with a reduced flare rate and estimated glomerular filtration rate (eGFR).

“Changes from 2019 include that there is no distinction between classes III/IV and V, which is heretical,” he stressed. Belimumab and CNIs/voclosporin should be considered in all patents as an add-on therapy from the start. “Lupus nephritis has high morbidity, and it’s difficult to predict outcomes at the beginning, but there are clear benefits of add-on therapies. CNIs, although they can be used for all patients, might be more appropriate for membranous or nephrotic-range proteinuria.”

He went on to announce that the “million-dollar question” was whether to use belimumab or voclosporin (or other CNIs), and that this was “a question of gentle, compared with forceful, power and collateral damage.

“For me, voclosporin works very fast, but you worry about side effects, while belimumab is gentle and the response is sustained, preventing flares and organ damage,” he said, adding that “our expert panel discussions showed that nephrologists were more eager to support steroid-free regimens.”

Moving on to statement 9, Dr. Boumpas explained that after initial therapy and renal response, subsequent therapy should continue for at least 3 years. If treated with MMF alone or in combination with belimumab, then these drugs should continue. However, MMF should replace cyclophosphamide if the latter is used initially.

Regarding treat-to-target in lupus nephritis, he said that EULAR now advises to aim for a 25% drop in urine protein/creatinine ratio by 3 months, a 50% drop by 6 months, and a UPCR of less than 0.5-0.7, plus normal eGFR, by 12 months, Dr. Boumpas said.

Statement 10 advises considering high-dose intravenous cyclophosphamide in combination with pulse intravenous methylprednisolone for patients at high risk of renal failure.
 

Tapering drugs in sustained remission, managing antiphospholipid syndrome, giving immunizations

Statement 11 suggests to consider tapering immunosuppressive agents and glucocorticoids in patients achieving sustained remission, starting with glucocorticoids first.

There was no change to statement 12, which recommends that thrombotic antiphospholipid syndrome associated with SLE be treated with long-term vitamin K antagonists.

Statement 13 addresses immunizations and adjunct therapies. In addition to conventional immunizations, Dr. Boumpas said that renoprotection should receive attention in case of proteinuria and/or hypertension.

“With [sodium-glucose cotransporter 2] inhibitors, it’s a bit early. They’re promising, and you may consider them, although there are no data for patients with eGFR below 60 mL/min per 1.73 m²,” he remarked, completing his detailed discussion of the updated recommendations.

Dr. Boumpas reported no relevant financial relationships. Dr. Landewé served as past chair of EULAR’s Quality of Care Committee, which develops recommendations.

SEOUL, SOUTH KOREA – A major challenge for clinical trials in systemic lupus erythematosus (SLE) is how to get the placebo response rate down low enough that the effectiveness of a drug can actually be seen. Better patient selection may be the key.

Speaking at an international congress on SLE, Joan Merrill, MD, professor of medicine at the University of Oklahoma Health Sciences Center, Oklahoma City, presented on how the heterogeneity of lupus is contributing to the ongoing failure of so many potential therapies in clinical trials.

“It’s a miracle that any drug has been successful in clinical trials,” she told the conference, comparing the few drugs approved for the treatment of lupus with the much larger numbers of approved, targeted biologics that are available for rheumatoid arthritis.

Bianca Nogrady/MDedge News

The problem is that placebo response rates in clinical trials for lupus are high – well over 40% – Dr. Merrill said, and trials aren’t showing a big difference in response rates between the treatment and placebo arms. “If the placebo response is 40%, wouldn’t an effective drug help 80%?” she said. “If it also affects only 40%, does that mean it’s a failed drug?”

Dr. Merrill suggested that better patient selection could be key to achieving lower placebo response rates, which could in turn reveal if and in whom a drug might be effective. “If we could get the placebo response rate down, at least we’d be able to see a little bit better whether the drug is effective, even if it only could work in 50% of the patients,” she said.

Data from research done by the Oklahoma Medical Research Foundation suggested that patients with SLE could be loosely categorized into seven different clusters based on patterns of gene expression in areas such as interferon expression and inflammation pathways.

For example, two of those clusters represented patients with high levels of expression for both interferons and inflammation. “Maybe those are the patients who’d want to be put in a trial for interferon inhibition,” Dr. Merrill said.

This was demonstrated in a trial of type 1 interferon inhibitor anifrolumab (Saphnelo), where patients were sorted into groups according to their level of interferon expression – either high or low – based on expression of certain interferon genes. This revealed that patients in the interferon-high group had a much higher treatment effect than patients in the interferon-low group. But the difference lay in the placebo response.

“The efficacy rate was not that different between the interferon-high and the interferon-low patients,” Dr. Merrill said. “The difference was in the placebo response rate – what they had managed to find was a great marker for sicker patients.”

This phenomenon is not limited to interferon-targeted therapies. Dr. Merrill cited another literature review which looked at subset studies within clinical trials that had delivered disappointing results. This showed consistently that patients who were considered more unwell, by virtue of higher SLE Disease Activity Index (SLEDAI) scores, for example, were more likely to show an effect of treatment.

“You begin to see bigger differences between treatment and placebo because the treatment rate might go up, but mostly because the placebo rate goes down,” she said.

Another issue that could be affecting both placebo and treatment response rates is background medication. “Subset analysis of people on less background drugs was showing lower placebo response rates and better differences between treatments and placebo,” Dr. Merrill said. For example, a recent phase 2 study of anifrolumab took the strategy of actively pursuing tapering of glucocorticoids in patients where that could be done safely. That achieved a lowering of the placebo response rate to the point where a greater difference could be seen between the placebo response and the treatment response rates.

The challenge for clinical trials is therefore to identify which patients to include. “If we could figure out which patients would be the most appropriate [to enroll to fit a particular drug’s mechanism of action], then we could really get ahead of the game,” she said.

The unique problem for lupus clinic trials is the heterogeneity of lupus as a disease, Dr. Merrill said in an interview. “We’re going to have to find combinations of treatments that fit right for each patient, and they won’t necessarily be one size fits all,” she said.

Dr. Merrill said that subset analyses at the phase 2 stage could help identify the patients who responded better to the treatment and could therefore be targeted in phase 3 trials. “Once you take that hypothesis, and if you can establish and validate it in phase 3, now you’ve got yourself a biomarker,” she said.

Richard A. Furie, MD, chief of the division of rheumatology at Northwell Health in New York, agreed that the high placebo response rate was a particular nemesis for researchers involved in lupus clinical trials.

Sara Freeman/MDedge News

Dr. Furie said it could be that selecting sicker patients is a solution to this, as had been suggested in the subset analysis of the anifrolumab studies – which he was involved in – that identified differences in the response rates between interferon-high and interferon-low patients.

But if that was the case, the challenge would be recruiting enough of any particular subset of patients. For example, relatively few patients in the anifrolumab trial were classified as interferon low.

If the interferon expression levels are a marker for patients who are sicker, that could serve as a way to better select patients for clinical trials, he said. But it would also make it harder to achieve recruitment targets.

“I think the major problem in SLE trials is that patients have inflated activity scores, so you can gain SLEDAI scores with a little alopecia and an oral ulcer,” he said. “You can start eliminating those parameters from counting towards entry, but then as soon as you do that, you’re going to have trouble recruiting.”

Dr. Merrill reported consulting for and receiving research support from a range of pharmaceutical companies including Genentech/Roche, GlaxoSmithKline, Pfizer, Janssen, Bristol-Myers Squibb, AbbVie, and anifrolumab manufacturer AstraZeneca. Dr. Furie reported financial relationships with Genentech/Roche, GlaxoSmithKline, Kezar Life Sciences, Kyverna Therapeutics, and Takeda.

SEOUL, SOUTH KOREA – A major challenge for clinical trials in systemic lupus erythematosus (SLE) is how to get the placebo response rate down low enough that the effectiveness of a drug can actually be seen. Better patient selection may be the key.

Speaking at an international congress on SLE, Joan Merrill, MD, professor of medicine at the University of Oklahoma Health Sciences Center, Oklahoma City, presented on how the heterogeneity of lupus is contributing to the ongoing failure of so many potential therapies in clinical trials.

“It’s a miracle that any drug has been successful in clinical trials,” she told the conference, comparing the few drugs approved for the treatment of lupus with the much larger numbers of approved, targeted biologics that are available for rheumatoid arthritis.

Bianca Nogrady/MDedge News

The problem is that placebo response rates in clinical trials for lupus are high – well over 40% – Dr. Merrill said, and trials aren’t showing a big difference in response rates between the treatment and placebo arms. “If the placebo response is 40%, wouldn’t an effective drug help 80%?” she said. “If it also affects only 40%, does that mean it’s a failed drug?”

Dr. Merrill suggested that better patient selection could be key to achieving lower placebo response rates, which could in turn reveal if and in whom a drug might be effective. “If we could get the placebo response rate down, at least we’d be able to see a little bit better whether the drug is effective, even if it only could work in 50% of the patients,” she said.

Data from research done by the Oklahoma Medical Research Foundation suggested that patients with SLE could be loosely categorized into seven different clusters based on patterns of gene expression in areas such as interferon expression and inflammation pathways.

For example, two of those clusters represented patients with high levels of expression for both interferons and inflammation. “Maybe those are the patients who’d want to be put in a trial for interferon inhibition,” Dr. Merrill said.

This was demonstrated in a trial of type 1 interferon inhibitor anifrolumab (Saphnelo), where patients were sorted into groups according to their level of interferon expression – either high or low – based on expression of certain interferon genes. This revealed that patients in the interferon-high group had a much higher treatment effect than patients in the interferon-low group. But the difference lay in the placebo response.

“The efficacy rate was not that different between the interferon-high and the interferon-low patients,” Dr. Merrill said. “The difference was in the placebo response rate – what they had managed to find was a great marker for sicker patients.”

This phenomenon is not limited to interferon-targeted therapies. Dr. Merrill cited another literature review which looked at subset studies within clinical trials that had delivered disappointing results. This showed consistently that patients who were considered more unwell, by virtue of higher SLE Disease Activity Index (SLEDAI) scores, for example, were more likely to show an effect of treatment.

“You begin to see bigger differences between treatment and placebo because the treatment rate might go up, but mostly because the placebo rate goes down,” she said.

Another issue that could be affecting both placebo and treatment response rates is background medication. “Subset analysis of people on less background drugs was showing lower placebo response rates and better differences between treatments and placebo,” Dr. Merrill said. For example, a recent phase 2 study of anifrolumab took the strategy of actively pursuing tapering of glucocorticoids in patients where that could be done safely. That achieved a lowering of the placebo response rate to the point where a greater difference could be seen between the placebo response and the treatment response rates.

The challenge for clinical trials is therefore to identify which patients to include. “If we could figure out which patients would be the most appropriate [to enroll to fit a particular drug’s mechanism of action], then we could really get ahead of the game,” she said.

The unique problem for lupus clinic trials is the heterogeneity of lupus as a disease, Dr. Merrill said in an interview. “We’re going to have to find combinations of treatments that fit right for each patient, and they won’t necessarily be one size fits all,” she said.

Dr. Merrill said that subset analyses at the phase 2 stage could help identify the patients who responded better to the treatment and could therefore be targeted in phase 3 trials. “Once you take that hypothesis, and if you can establish and validate it in phase 3, now you’ve got yourself a biomarker,” she said.

Richard A. Furie, MD, chief of the division of rheumatology at Northwell Health in New York, agreed that the high placebo response rate was a particular nemesis for researchers involved in lupus clinical trials.

Sara Freeman/MDedge News

Dr. Furie said it could be that selecting sicker patients is a solution to this, as had been suggested in the subset analysis of the anifrolumab studies – which he was involved in – that identified differences in the response rates between interferon-high and interferon-low patients.

But if that was the case, the challenge would be recruiting enough of any particular subset of patients. For example, relatively few patients in the anifrolumab trial were classified as interferon low.

If the interferon expression levels are a marker for patients who are sicker, that could serve as a way to better select patients for clinical trials, he said. But it would also make it harder to achieve recruitment targets.

“I think the major problem in SLE trials is that patients have inflated activity scores, so you can gain SLEDAI scores with a little alopecia and an oral ulcer,” he said. “You can start eliminating those parameters from counting towards entry, but then as soon as you do that, you’re going to have trouble recruiting.”

Dr. Merrill reported consulting for and receiving research support from a range of pharmaceutical companies including Genentech/Roche, GlaxoSmithKline, Pfizer, Janssen, Bristol-Myers Squibb, AbbVie, and anifrolumab manufacturer AstraZeneca. Dr. Furie reported financial relationships with Genentech/Roche, GlaxoSmithKline, Kezar Life Sciences, Kyverna Therapeutics, and Takeda.

SEOUL, SOUTH KOREA – A major challenge for clinical trials in systemic lupus erythematosus (SLE) is how to get the placebo response rate down low enough that the effectiveness of a drug can actually be seen. Better patient selection may be the key.

Speaking at an international congress on SLE, Joan Merrill, MD, professor of medicine at the University of Oklahoma Health Sciences Center, Oklahoma City, presented on how the heterogeneity of lupus is contributing to the ongoing failure of so many potential therapies in clinical trials.

“It’s a miracle that any drug has been successful in clinical trials,” she told the conference, comparing the few drugs approved for the treatment of lupus with the much larger numbers of approved, targeted biologics that are available for rheumatoid arthritis.

Bianca Nogrady/MDedge News

The problem is that placebo response rates in clinical trials for lupus are high – well over 40% – Dr. Merrill said, and trials aren’t showing a big difference in response rates between the treatment and placebo arms. “If the placebo response is 40%, wouldn’t an effective drug help 80%?” she said. “If it also affects only 40%, does that mean it’s a failed drug?”

Dr. Merrill suggested that better patient selection could be key to achieving lower placebo response rates, which could in turn reveal if and in whom a drug might be effective. “If we could get the placebo response rate down, at least we’d be able to see a little bit better whether the drug is effective, even if it only could work in 50% of the patients,” she said.

Data from research done by the Oklahoma Medical Research Foundation suggested that patients with SLE could be loosely categorized into seven different clusters based on patterns of gene expression in areas such as interferon expression and inflammation pathways.

For example, two of those clusters represented patients with high levels of expression for both interferons and inflammation. “Maybe those are the patients who’d want to be put in a trial for interferon inhibition,” Dr. Merrill said.

This was demonstrated in a trial of type 1 interferon inhibitor anifrolumab (Saphnelo), where patients were sorted into groups according to their level of interferon expression – either high or low – based on expression of certain interferon genes. This revealed that patients in the interferon-high group had a much higher treatment effect than patients in the interferon-low group. But the difference lay in the placebo response.

“The efficacy rate was not that different between the interferon-high and the interferon-low patients,” Dr. Merrill said. “The difference was in the placebo response rate – what they had managed to find was a great marker for sicker patients.”

This phenomenon is not limited to interferon-targeted therapies. Dr. Merrill cited another literature review which looked at subset studies within clinical trials that had delivered disappointing results. This showed consistently that patients who were considered more unwell, by virtue of higher SLE Disease Activity Index (SLEDAI) scores, for example, were more likely to show an effect of treatment.

“You begin to see bigger differences between treatment and placebo because the treatment rate might go up, but mostly because the placebo rate goes down,” she said.

Another issue that could be affecting both placebo and treatment response rates is background medication. “Subset analysis of people on less background drugs was showing lower placebo response rates and better differences between treatments and placebo,” Dr. Merrill said. For example, a recent phase 2 study of anifrolumab took the strategy of actively pursuing tapering of glucocorticoids in patients where that could be done safely. That achieved a lowering of the placebo response rate to the point where a greater difference could be seen between the placebo response and the treatment response rates.

The challenge for clinical trials is therefore to identify which patients to include. “If we could figure out which patients would be the most appropriate [to enroll to fit a particular drug’s mechanism of action], then we could really get ahead of the game,” she said.

The unique problem for lupus clinic trials is the heterogeneity of lupus as a disease, Dr. Merrill said in an interview. “We’re going to have to find combinations of treatments that fit right for each patient, and they won’t necessarily be one size fits all,” she said.

Dr. Merrill said that subset analyses at the phase 2 stage could help identify the patients who responded better to the treatment and could therefore be targeted in phase 3 trials. “Once you take that hypothesis, and if you can establish and validate it in phase 3, now you’ve got yourself a biomarker,” she said.

Richard A. Furie, MD, chief of the division of rheumatology at Northwell Health in New York, agreed that the high placebo response rate was a particular nemesis for researchers involved in lupus clinical trials.

Sara Freeman/MDedge News

Dr. Furie said it could be that selecting sicker patients is a solution to this, as had been suggested in the subset analysis of the anifrolumab studies – which he was involved in – that identified differences in the response rates between interferon-high and interferon-low patients.

But if that was the case, the challenge would be recruiting enough of any particular subset of patients. For example, relatively few patients in the anifrolumab trial were classified as interferon low.

If the interferon expression levels are a marker for patients who are sicker, that could serve as a way to better select patients for clinical trials, he said. But it would also make it harder to achieve recruitment targets.

“I think the major problem in SLE trials is that patients have inflated activity scores, so you can gain SLEDAI scores with a little alopecia and an oral ulcer,” he said. “You can start eliminating those parameters from counting towards entry, but then as soon as you do that, you’re going to have trouble recruiting.”

Dr. Merrill reported consulting for and receiving research support from a range of pharmaceutical companies including Genentech/Roche, GlaxoSmithKline, Pfizer, Janssen, Bristol-Myers Squibb, AbbVie, and anifrolumab manufacturer AstraZeneca. Dr. Furie reported financial relationships with Genentech/Roche, GlaxoSmithKline, Kezar Life Sciences, Kyverna Therapeutics, and Takeda.

SEOUL, SOUTH KOREA – B cell–depleting therapies in patients with lupus nephritis have a higher likelihood of complete response if B cells are almost completely depleted, and strategies for achieving more complete B-cell depletion continue to be tested, according to evidence presented by Richard A. Furie, MD, at an international congress on systemic lupus erythematosus (SLE).

“If you go back about 20 years ago or so, when we designed the LUNAR and EXPLORER trials, we were scared to death of rituximab [Rituxan and biosimilars], about what would happen when you deplete B cells,” said Dr. Furie, chief of the division of rheumatology at Northwell Health in New York.

Sara Freeman/MDedge News

The LUNAR trial, which compared rituximab with placebo in patients with lupus nephritis, did not show a statistically significant difference in renal outcomes at 1 year. However, a post hoc analysis done several years later told a different story. It looked at patients who achieved complete peripheral depletion of B cells, defined as zero cells per microliter in peripheral blood. “You can see about a fourfold increase in complete response rates in those who were complete B-cell depleters at 1 year,” Dr. Furie told the conference.

It therefore raises the question of how to achieve greater B-cell depletion rates in patients. Dr. Furie said one strategy might be to first mobilize memory B cells and neutralize B cell–activating factor using belimumab (Benlysta), and then treat with rituximab to eliminate B cells. This strategy of sequential belimumab-rituximab treatment has been taken in several clinical trials.
 

More potent B-cell depletion with obinutuzumab

Another approach is to choose more potent B cell–depleting therapies, such as obinutuzumab (Gazyva), which is an anti-CD20 monoclonal antibody that was approved in 2013 for the treatment of chronic lymphocytic leukemia.

The NOBILITY trial compared obinutuzumab with placebo in 125 patients with lupus nephritis who were on background treatment with mycophenolate and corticosteroids. At 1 year, significantly more patients achieved B-cell thresholds either below 5 cells per microliter or even zero cells per microliter than had been seen previously with rituximab.

That also translated into clinical benefit, Dr. Furie said. By week 76, half the patients who had sustained depletion of B cells below 0.4 cells per microliter had a complete response, compared with 35% of those who still had detectable B cells and 18% of the placebo group. Treatment with obinutuzumab did not show any link to higher rates of serious adverse events, serious infections, or deaths.

“I think we’re all pretty much convinced more is better, without introducing safety issues,” Dr. Furie said in an interview.

Bianca Nogrady/MDedge News

Joan Merrill, MD, professor of medicine at the University of Oklahoma Health Sciences Center, Oklahoma City, said the data did suggest that renal outcomes were better with more complete depletion, but raised the question of whether this might increase the risk of infections or infectious severity.

Dr. Furie noted that complete response not only required improvement in proteinuria, complement levels, and anti–double-stranded DNA antibodies, but also in serum creatinine, “because maintenance of eGFR [estimated glomerular filtration rate] is the name of the game with lupus nephritis.”

However, he also pointed out that there may be a ceiling for response rates in patients with lupus nephritis when using stricter endpoints for serum creatinine. The NOBILITY trial required patients to achieve a serum creatinine that did not increase by more than 15% from baseline. But when researchers did an analysis that instead only required patients to achieve a reduction in proteinuria and maintain normal creatinine, the complete response rate in complete B-cell depleters increased to 72%, compared with 50% in partial depleters and 37% in the placebo group.
 

Newer strategies for greater B-cell depletion

A third strategy for achieving greater B-cell depletion is bispecific T-cell engagers, or BiTEs. “I called it a ‘frenemy,’ where it’s taking the activated T cell and introducing it to the B cell, and it can kill it via direct T-cell killing,” Dr. Furie said in an interview. Mosunetuzumab (Lunsumio) is one example, and is currently in a phase 1 clinical trial of patients with SLE.

And the fourth strategy, which has proved so successful in lymphoma, is chimeric antigen receptor T-cell therapy (CAR T). Dr. Furie cited the recent publication of data from a CAR T clinical trial in five patients with refractory SLE. He said the data were impressive but the question for this treatment approach will be which patients are most likely to benefit and whether CAR T will experience the same ceiling effect because of pre-existing kidney damage.

“We won’t be seeing 100% response rates,” he said. “What we’ll be seeing, as a maximum, might be about 70%.” The big question for B-cell depletion in lupus was therefore how best to achieve it. “Is the future a potent monoclonal antibody, or is it in fact CAR T?”

Dr. Merrill said the analyses from B-cell depletion trials, showing greater response rates among more complete depleters, highlighted the importance of a personalized approach to treating lupus.

“One size fits all is never optimal in any disease, but it will prove a nonstarter in lupus, where we ought to be trying to find the optimal treatment regimen for each patient guided by biomarkers,” she said in an interview.

Dr. Furie reported having financial relationships with Genentech/Roche, which manufactures obinutuzumab and rituximab, as well as GlaxoSmithKline, Kezar Life Sciences, Kyverna Therapeutics, and Takeda. Dr. Merrill reported consulting for and receiving research support from a range of pharmaceutical companies including Genentech/Roche, GlaxoSmithKline, Pfizer, Janssen, Bristol-Myers Squibb, AbbVie, and AstraZeneca.

SEOUL, SOUTH KOREA – B cell–depleting therapies in patients with lupus nephritis have a higher likelihood of complete response if B cells are almost completely depleted, and strategies for achieving more complete B-cell depletion continue to be tested, according to evidence presented by Richard A. Furie, MD, at an international congress on systemic lupus erythematosus (SLE).

“If you go back about 20 years ago or so, when we designed the LUNAR and EXPLORER trials, we were scared to death of rituximab [Rituxan and biosimilars], about what would happen when you deplete B cells,” said Dr. Furie, chief of the division of rheumatology at Northwell Health in New York.

Sara Freeman/MDedge News

The LUNAR trial, which compared rituximab with placebo in patients with lupus nephritis, did not show a statistically significant difference in renal outcomes at 1 year. However, a post hoc analysis done several years later told a different story. It looked at patients who achieved complete peripheral depletion of B cells, defined as zero cells per microliter in peripheral blood. “You can see about a fourfold increase in complete response rates in those who were complete B-cell depleters at 1 year,” Dr. Furie told the conference.

It therefore raises the question of how to achieve greater B-cell depletion rates in patients. Dr. Furie said one strategy might be to first mobilize memory B cells and neutralize B cell–activating factor using belimumab (Benlysta), and then treat with rituximab to eliminate B cells. This strategy of sequential belimumab-rituximab treatment has been taken in several clinical trials.
 

More potent B-cell depletion with obinutuzumab

Another approach is to choose more potent B cell–depleting therapies, such as obinutuzumab (Gazyva), which is an anti-CD20 monoclonal antibody that was approved in 2013 for the treatment of chronic lymphocytic leukemia.

The NOBILITY trial compared obinutuzumab with placebo in 125 patients with lupus nephritis who were on background treatment with mycophenolate and corticosteroids. At 1 year, significantly more patients achieved B-cell thresholds either below 5 cells per microliter or even zero cells per microliter than had been seen previously with rituximab.

That also translated into clinical benefit, Dr. Furie said. By week 76, half the patients who had sustained depletion of B cells below 0.4 cells per microliter had a complete response, compared with 35% of those who still had detectable B cells and 18% of the placebo group. Treatment with obinutuzumab did not show any link to higher rates of serious adverse events, serious infections, or deaths.

“I think we’re all pretty much convinced more is better, without introducing safety issues,” Dr. Furie said in an interview.

Bianca Nogrady/MDedge News

Joan Merrill, MD, professor of medicine at the University of Oklahoma Health Sciences Center, Oklahoma City, said the data did suggest that renal outcomes were better with more complete depletion, but raised the question of whether this might increase the risk of infections or infectious severity.

Dr. Furie noted that complete response not only required improvement in proteinuria, complement levels, and anti–double-stranded DNA antibodies, but also in serum creatinine, “because maintenance of eGFR [estimated glomerular filtration rate] is the name of the game with lupus nephritis.”

However, he also pointed out that there may be a ceiling for response rates in patients with lupus nephritis when using stricter endpoints for serum creatinine. The NOBILITY trial required patients to achieve a serum creatinine that did not increase by more than 15% from baseline. But when researchers did an analysis that instead only required patients to achieve a reduction in proteinuria and maintain normal creatinine, the complete response rate in complete B-cell depleters increased to 72%, compared with 50% in partial depleters and 37% in the placebo group.
 

Newer strategies for greater B-cell depletion

A third strategy for achieving greater B-cell depletion is bispecific T-cell engagers, or BiTEs. “I called it a ‘frenemy,’ where it’s taking the activated T cell and introducing it to the B cell, and it can kill it via direct T-cell killing,” Dr. Furie said in an interview. Mosunetuzumab (Lunsumio) is one example, and is currently in a phase 1 clinical trial of patients with SLE.

And the fourth strategy, which has proved so successful in lymphoma, is chimeric antigen receptor T-cell therapy (CAR T). Dr. Furie cited the recent publication of data from a CAR T clinical trial in five patients with refractory SLE. He said the data were impressive but the question for this treatment approach will be which patients are most likely to benefit and whether CAR T will experience the same ceiling effect because of pre-existing kidney damage.

“We won’t be seeing 100% response rates,” he said. “What we’ll be seeing, as a maximum, might be about 70%.” The big question for B-cell depletion in lupus was therefore how best to achieve it. “Is the future a potent monoclonal antibody, or is it in fact CAR T?”

Dr. Merrill said the analyses from B-cell depletion trials, showing greater response rates among more complete depleters, highlighted the importance of a personalized approach to treating lupus.

“One size fits all is never optimal in any disease, but it will prove a nonstarter in lupus, where we ought to be trying to find the optimal treatment regimen for each patient guided by biomarkers,” she said in an interview.

Dr. Furie reported having financial relationships with Genentech/Roche, which manufactures obinutuzumab and rituximab, as well as GlaxoSmithKline, Kezar Life Sciences, Kyverna Therapeutics, and Takeda. Dr. Merrill reported consulting for and receiving research support from a range of pharmaceutical companies including Genentech/Roche, GlaxoSmithKline, Pfizer, Janssen, Bristol-Myers Squibb, AbbVie, and AstraZeneca.

SEOUL, SOUTH KOREA – B cell–depleting therapies in patients with lupus nephritis have a higher likelihood of complete response if B cells are almost completely depleted, and strategies for achieving more complete B-cell depletion continue to be tested, according to evidence presented by Richard A. Furie, MD, at an international congress on systemic lupus erythematosus (SLE).

“If you go back about 20 years ago or so, when we designed the LUNAR and EXPLORER trials, we were scared to death of rituximab [Rituxan and biosimilars], about what would happen when you deplete B cells,” said Dr. Furie, chief of the division of rheumatology at Northwell Health in New York.

Sara Freeman/MDedge News

The LUNAR trial, which compared rituximab with placebo in patients with lupus nephritis, did not show a statistically significant difference in renal outcomes at 1 year. However, a post hoc analysis done several years later told a different story. It looked at patients who achieved complete peripheral depletion of B cells, defined as zero cells per microliter in peripheral blood. “You can see about a fourfold increase in complete response rates in those who were complete B-cell depleters at 1 year,” Dr. Furie told the conference.

It therefore raises the question of how to achieve greater B-cell depletion rates in patients. Dr. Furie said one strategy might be to first mobilize memory B cells and neutralize B cell–activating factor using belimumab (Benlysta), and then treat with rituximab to eliminate B cells. This strategy of sequential belimumab-rituximab treatment has been taken in several clinical trials.
 

More potent B-cell depletion with obinutuzumab

Another approach is to choose more potent B cell–depleting therapies, such as obinutuzumab (Gazyva), which is an anti-CD20 monoclonal antibody that was approved in 2013 for the treatment of chronic lymphocytic leukemia.

The NOBILITY trial compared obinutuzumab with placebo in 125 patients with lupus nephritis who were on background treatment with mycophenolate and corticosteroids. At 1 year, significantly more patients achieved B-cell thresholds either below 5 cells per microliter or even zero cells per microliter than had been seen previously with rituximab.

That also translated into clinical benefit, Dr. Furie said. By week 76, half the patients who had sustained depletion of B cells below 0.4 cells per microliter had a complete response, compared with 35% of those who still had detectable B cells and 18% of the placebo group. Treatment with obinutuzumab did not show any link to higher rates of serious adverse events, serious infections, or deaths.

“I think we’re all pretty much convinced more is better, without introducing safety issues,” Dr. Furie said in an interview.

Bianca Nogrady/MDedge News

Joan Merrill, MD, professor of medicine at the University of Oklahoma Health Sciences Center, Oklahoma City, said the data did suggest that renal outcomes were better with more complete depletion, but raised the question of whether this might increase the risk of infections or infectious severity.

Dr. Furie noted that complete response not only required improvement in proteinuria, complement levels, and anti–double-stranded DNA antibodies, but also in serum creatinine, “because maintenance of eGFR [estimated glomerular filtration rate] is the name of the game with lupus nephritis.”

However, he also pointed out that there may be a ceiling for response rates in patients with lupus nephritis when using stricter endpoints for serum creatinine. The NOBILITY trial required patients to achieve a serum creatinine that did not increase by more than 15% from baseline. But when researchers did an analysis that instead only required patients to achieve a reduction in proteinuria and maintain normal creatinine, the complete response rate in complete B-cell depleters increased to 72%, compared with 50% in partial depleters and 37% in the placebo group.
 

Newer strategies for greater B-cell depletion

A third strategy for achieving greater B-cell depletion is bispecific T-cell engagers, or BiTEs. “I called it a ‘frenemy,’ where it’s taking the activated T cell and introducing it to the B cell, and it can kill it via direct T-cell killing,” Dr. Furie said in an interview. Mosunetuzumab (Lunsumio) is one example, and is currently in a phase 1 clinical trial of patients with SLE.

And the fourth strategy, which has proved so successful in lymphoma, is chimeric antigen receptor T-cell therapy (CAR T). Dr. Furie cited the recent publication of data from a CAR T clinical trial in five patients with refractory SLE. He said the data were impressive but the question for this treatment approach will be which patients are most likely to benefit and whether CAR T will experience the same ceiling effect because of pre-existing kidney damage.

“We won’t be seeing 100% response rates,” he said. “What we’ll be seeing, as a maximum, might be about 70%.” The big question for B-cell depletion in lupus was therefore how best to achieve it. “Is the future a potent monoclonal antibody, or is it in fact CAR T?”

Dr. Merrill said the analyses from B-cell depletion trials, showing greater response rates among more complete depleters, highlighted the importance of a personalized approach to treating lupus.

“One size fits all is never optimal in any disease, but it will prove a nonstarter in lupus, where we ought to be trying to find the optimal treatment regimen for each patient guided by biomarkers,” she said in an interview.

Dr. Furie reported having financial relationships with Genentech/Roche, which manufactures obinutuzumab and rituximab, as well as GlaxoSmithKline, Kezar Life Sciences, Kyverna Therapeutics, and Takeda. Dr. Merrill reported consulting for and receiving research support from a range of pharmaceutical companies including Genentech/Roche, GlaxoSmithKline, Pfizer, Janssen, Bristol-Myers Squibb, AbbVie, and AstraZeneca.