The excellent short-term efficacy of the drug was well maintained up to 48 weeks, with only a slight loss of efficacy over time. Abrocitinib is a small molecule. We wouldn't expect a loss of efficacy due to the anti-drug antibodies that we see for large-molecule biologic drugs. I suspect that the slight loss of efficacy over time is a form of tachyphylaxis that is, to my thinking, probably due to poor adherence. Shocking, I know! Patients may not be fully adherent to treatment, even in a clinical trial. I think we should encourage patients to use 7-day pill boxes to aid better long-term adherence and outcomes.

Long-term safety is a critical issue with any new drug, certainly with a Janus kinase (JAK) inhibitor. Reich and colleagues concluded, "The long-term safety profile was manageable and consistent with previous reports." That conclusion seems reasonable to me. The most common side effects were upper respiratory tract infections. There may be a slight signal for increased risk for oral herpes infection, particularly at the higher dose. If this safety profile endures with longer-term data in larger numbers of people, it will be very reassuring.

The study by Wan and colleagues is another extremely well-done, important study by the premier dermatoepidemiology research team at the University of Pennsylvania. The study used an outstanding database from the United Kingdom that encompassed the clinical care experience of hundreds of thousands of children and adults with atopic dermatitis and millions of control patients without atopic dermatitis. With this many patients, the study has tremendous power to detect risk differences between groups.

With all that power, this study’s findings are very reassuring that there is no meaningful overall increased risk for malignancy in children or adults with atopic dermatitis. And while there was a statistically significant increased risk for lymphoma in children with severe atopic dermatitis, that risk is small … very small. Similarly, adults with severe AD had a twofold higher risk for noncutaneous T-cell lymphoma (CTCL), but since non-CTCL is rare, patients with severe AD shouldn't lose any sleep over it..

Simpson and colleagues' study of the effect of dupilumab on Staphylococcus aureus surprised me. Of course, we could expect that S aureus counts would be reduced with dupilumab; as barrier function is restored, surely S aureus counts would go down too. But, fascinatingly, with dupilumab treatment, S aureus counts decreased almost immediately, at both 3 and 7 days, before there was apparent clinical improvement in the skin rash. Simpson and colleagues suggest that the drop in S aureus counts could be due to improvement in immune function when interleukins 4 and 13 are blocked. Whether or not that is true, it is striking how fast S aureus counts improved, long before normal skin barrier function is restored.

Here's a fun fact: Atopic dermatitis is a little less common, about 10% less common, in people born second or later in the birth order. Lisik and colleagues did a meta-analysis of 114 studies and found this marginally lower rate in those born second or later compared with those born first. I'm not sure that there is any clinically meaningful significance to this, but I found it interesting (even though I was born first, and my younger brother had atopic dermatitis).

The excellent short-term efficacy of the drug was well maintained up to 48 weeks, with only a slight loss of efficacy over time. Abrocitinib is a small molecule. We wouldn't expect a loss of efficacy due to the anti-drug antibodies that we see for large-molecule biologic drugs. I suspect that the slight loss of efficacy over time is a form of tachyphylaxis that is, to my thinking, probably due to poor adherence. Shocking, I know! Patients may not be fully adherent to treatment, even in a clinical trial. I think we should encourage patients to use 7-day pill boxes to aid better long-term adherence and outcomes.

Long-term safety is a critical issue with any new drug, certainly with a Janus kinase (JAK) inhibitor. Reich and colleagues concluded, "The long-term safety profile was manageable and consistent with previous reports." That conclusion seems reasonable to me. The most common side effects were upper respiratory tract infections. There may be a slight signal for increased risk for oral herpes infection, particularly at the higher dose. If this safety profile endures with longer-term data in larger numbers of people, it will be very reassuring.

The study by Wan and colleagues is another extremely well-done, important study by the premier dermatoepidemiology research team at the University of Pennsylvania. The study used an outstanding database from the United Kingdom that encompassed the clinical care experience of hundreds of thousands of children and adults with atopic dermatitis and millions of control patients without atopic dermatitis. With this many patients, the study has tremendous power to detect risk differences between groups.

With all that power, this study’s findings are very reassuring that there is no meaningful overall increased risk for malignancy in children or adults with atopic dermatitis. And while there was a statistically significant increased risk for lymphoma in children with severe atopic dermatitis, that risk is small … very small. Similarly, adults with severe AD had a twofold higher risk for noncutaneous T-cell lymphoma (CTCL), but since non-CTCL is rare, patients with severe AD shouldn't lose any sleep over it..

Simpson and colleagues' study of the effect of dupilumab on Staphylococcus aureus surprised me. Of course, we could expect that S aureus counts would be reduced with dupilumab; as barrier function is restored, surely S aureus counts would go down too. But, fascinatingly, with dupilumab treatment, S aureus counts decreased almost immediately, at both 3 and 7 days, before there was apparent clinical improvement in the skin rash. Simpson and colleagues suggest that the drop in S aureus counts could be due to improvement in immune function when interleukins 4 and 13 are blocked. Whether or not that is true, it is striking how fast S aureus counts improved, long before normal skin barrier function is restored.

Here's a fun fact: Atopic dermatitis is a little less common, about 10% less common, in people born second or later in the birth order. Lisik and colleagues did a meta-analysis of 114 studies and found this marginally lower rate in those born second or later compared with those born first. I'm not sure that there is any clinically meaningful significance to this, but I found it interesting (even though I was born first, and my younger brother had atopic dermatitis).

The excellent short-term efficacy of the drug was well maintained up to 48 weeks, with only a slight loss of efficacy over time. Abrocitinib is a small molecule. We wouldn't expect a loss of efficacy due to the anti-drug antibodies that we see for large-molecule biologic drugs. I suspect that the slight loss of efficacy over time is a form of tachyphylaxis that is, to my thinking, probably due to poor adherence. Shocking, I know! Patients may not be fully adherent to treatment, even in a clinical trial. I think we should encourage patients to use 7-day pill boxes to aid better long-term adherence and outcomes.

Long-term safety is a critical issue with any new drug, certainly with a Janus kinase (JAK) inhibitor. Reich and colleagues concluded, "The long-term safety profile was manageable and consistent with previous reports." That conclusion seems reasonable to me. The most common side effects were upper respiratory tract infections. There may be a slight signal for increased risk for oral herpes infection, particularly at the higher dose. If this safety profile endures with longer-term data in larger numbers of people, it will be very reassuring.

The study by Wan and colleagues is another extremely well-done, important study by the premier dermatoepidemiology research team at the University of Pennsylvania. The study used an outstanding database from the United Kingdom that encompassed the clinical care experience of hundreds of thousands of children and adults with atopic dermatitis and millions of control patients without atopic dermatitis. With this many patients, the study has tremendous power to detect risk differences between groups.

With all that power, this study’s findings are very reassuring that there is no meaningful overall increased risk for malignancy in children or adults with atopic dermatitis. And while there was a statistically significant increased risk for lymphoma in children with severe atopic dermatitis, that risk is small … very small. Similarly, adults with severe AD had a twofold higher risk for noncutaneous T-cell lymphoma (CTCL), but since non-CTCL is rare, patients with severe AD shouldn't lose any sleep over it..

Simpson and colleagues' study of the effect of dupilumab on Staphylococcus aureus surprised me. Of course, we could expect that S aureus counts would be reduced with dupilumab; as barrier function is restored, surely S aureus counts would go down too. But, fascinatingly, with dupilumab treatment, S aureus counts decreased almost immediately, at both 3 and 7 days, before there was apparent clinical improvement in the skin rash. Simpson and colleagues suggest that the drop in S aureus counts could be due to improvement in immune function when interleukins 4 and 13 are blocked. Whether or not that is true, it is striking how fast S aureus counts improved, long before normal skin barrier function is restored.

Here's a fun fact: Atopic dermatitis is a little less common, about 10% less common, in people born second or later in the birth order. Lisik and colleagues did a meta-analysis of 114 studies and found this marginally lower rate in those born second or later compared with those born first. I'm not sure that there is any clinically meaningful significance to this, but I found it interesting (even though I was born first, and my younger brother had atopic dermatitis).

GE HealthCare is recalling 7,559 TruSignal arterial oxygen saturation (SpO₂) sensors because of problems that may reduce defibrillation energy, expose patients to unintended voltage, or give inaccurate readings.

The Food and Drug Administration has identified this as a class I recall, the most serious type. The company has not received any reports of patient injury or deaths as a result of these issues.*

The recall includes the TruSignal Adult Pediatric Sensor, TruSignal AllFit Sensor, TruSignal Sensitive Skin Sensor, TruSignal Wrap Sensor, TruSignal Ear Sensor, TruSignal Integrated Ear Sensor with GE Connector, TruSignal Integrated Ear Sensor With Datex Connector, TruSignal Integrated Ear Sensor With Datex Connector, and TruSignal Integrated Ear Sensor With Ohmeda Connector.

The sensors were distributed in the United States from Jan. 1, 2021, to March 4, 2023.

According to the recall notice, the malfunctioning sensors “may reduce the amount of energy sent to the heart during defibrillation without any notification to the care provider, which could prevent delivery of lifesaving therapy in a critical situation.

“This issue is most hazardous to hospitalized patients who may need defibrillation for cardiac arrest. Affected sensors may also unintentionally expose patients to electrical currents from other sources or may provide inaccurate measurements of SpO₂, which can impact treatment decisions,” the notice warns.

In an urgent device correction letter sent to health care professionals in May, GE HealthCare recommends that health care professionals do the following:

• Use an alternate method for SpO₂ monitoring, including TruSignal sensors not impacted or an alternate SpO₂ device.
• If alternate methods are not available, use affected TruSignal SpO₂ sensors as long as they have not been saturated with fluids.
• If defibrillation is necessary when affected TruSignal SpO₂ sensors are being used, remove the affected TruSignal SpO₂ sensor, defibrillate per hospital protocol, and reattach the affected TruSignal SpO₂ sensor after defibrillation is no longer needed.
• For Adult/Pediatric SpO₂ sensors, confirm that material does not cover the emitter or detector before using.
• Discard the sensor and use another sensor if any additional material is present.
• Make sure all potential users are made aware of this safety notification and the recommended actions, and retain this notice.

Customers are also asked to complete and return the acknowledgment form attached to the notice to [email protected].

For questions or concerns about this recall, contact GE HealthCare Service at 1-800-437-1171 or a local service representative.

Health care professionals can report adverse reactions or quality problems they experience using these devices to the FDA’s MedWatch program.

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

*Correction, 8/3/23: An earlier version of this article mischaracterized the reports received by the company.

GE HealthCare is recalling 7,559 TruSignal arterial oxygen saturation (SpO₂) sensors because of problems that may reduce defibrillation energy, expose patients to unintended voltage, or give inaccurate readings.

The Food and Drug Administration has identified this as a class I recall, the most serious type. The company has not received any reports of patient injury or deaths as a result of these issues.*

The recall includes the TruSignal Adult Pediatric Sensor, TruSignal AllFit Sensor, TruSignal Sensitive Skin Sensor, TruSignal Wrap Sensor, TruSignal Ear Sensor, TruSignal Integrated Ear Sensor with GE Connector, TruSignal Integrated Ear Sensor With Datex Connector, TruSignal Integrated Ear Sensor With Datex Connector, and TruSignal Integrated Ear Sensor With Ohmeda Connector.

The sensors were distributed in the United States from Jan. 1, 2021, to March 4, 2023.

According to the recall notice, the malfunctioning sensors “may reduce the amount of energy sent to the heart during defibrillation without any notification to the care provider, which could prevent delivery of lifesaving therapy in a critical situation.

“This issue is most hazardous to hospitalized patients who may need defibrillation for cardiac arrest. Affected sensors may also unintentionally expose patients to electrical currents from other sources or may provide inaccurate measurements of SpO₂, which can impact treatment decisions,” the notice warns.

In an urgent device correction letter sent to health care professionals in May, GE HealthCare recommends that health care professionals do the following:

• Use an alternate method for SpO₂ monitoring, including TruSignal sensors not impacted or an alternate SpO₂ device.
• If alternate methods are not available, use affected TruSignal SpO₂ sensors as long as they have not been saturated with fluids.
• If defibrillation is necessary when affected TruSignal SpO₂ sensors are being used, remove the affected TruSignal SpO₂ sensor, defibrillate per hospital protocol, and reattach the affected TruSignal SpO₂ sensor after defibrillation is no longer needed.
• For Adult/Pediatric SpO₂ sensors, confirm that material does not cover the emitter or detector before using.
• Discard the sensor and use another sensor if any additional material is present.
• Make sure all potential users are made aware of this safety notification and the recommended actions, and retain this notice.

Customers are also asked to complete and return the acknowledgment form attached to the notice to [email protected].

For questions or concerns about this recall, contact GE HealthCare Service at 1-800-437-1171 or a local service representative.

Health care professionals can report adverse reactions or quality problems they experience using these devices to the FDA’s MedWatch program.

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

*Correction, 8/3/23: An earlier version of this article mischaracterized the reports received by the company.

GE HealthCare is recalling 7,559 TruSignal arterial oxygen saturation (SpO₂) sensors because of problems that may reduce defibrillation energy, expose patients to unintended voltage, or give inaccurate readings.

The Food and Drug Administration has identified this as a class I recall, the most serious type. The company has not received any reports of patient injury or deaths as a result of these issues.*

The recall includes the TruSignal Adult Pediatric Sensor, TruSignal AllFit Sensor, TruSignal Sensitive Skin Sensor, TruSignal Wrap Sensor, TruSignal Ear Sensor, TruSignal Integrated Ear Sensor with GE Connector, TruSignal Integrated Ear Sensor With Datex Connector, TruSignal Integrated Ear Sensor With Datex Connector, and TruSignal Integrated Ear Sensor With Ohmeda Connector.

The sensors were distributed in the United States from Jan. 1, 2021, to March 4, 2023.

According to the recall notice, the malfunctioning sensors “may reduce the amount of energy sent to the heart during defibrillation without any notification to the care provider, which could prevent delivery of lifesaving therapy in a critical situation.

“This issue is most hazardous to hospitalized patients who may need defibrillation for cardiac arrest. Affected sensors may also unintentionally expose patients to electrical currents from other sources or may provide inaccurate measurements of SpO₂, which can impact treatment decisions,” the notice warns.

In an urgent device correction letter sent to health care professionals in May, GE HealthCare recommends that health care professionals do the following:

• Use an alternate method for SpO₂ monitoring, including TruSignal sensors not impacted or an alternate SpO₂ device.
• If alternate methods are not available, use affected TruSignal SpO₂ sensors as long as they have not been saturated with fluids.
• If defibrillation is necessary when affected TruSignal SpO₂ sensors are being used, remove the affected TruSignal SpO₂ sensor, defibrillate per hospital protocol, and reattach the affected TruSignal SpO₂ sensor after defibrillation is no longer needed.
• For Adult/Pediatric SpO₂ sensors, confirm that material does not cover the emitter or detector before using.
• Discard the sensor and use another sensor if any additional material is present.
• Make sure all potential users are made aware of this safety notification and the recommended actions, and retain this notice.

Customers are also asked to complete and return the acknowledgment form attached to the notice to [email protected].

For questions or concerns about this recall, contact GE HealthCare Service at 1-800-437-1171 or a local service representative.

Health care professionals can report adverse reactions or quality problems they experience using these devices to the FDA’s MedWatch program.

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

*Correction, 8/3/23: An earlier version of this article mischaracterized the reports received by the company.

Progression-free survival (PFS) is now the dominant endpoint in cancer clinical trials, but simply prolonging time to progression without extending overall survival or quality of life does not justify additional therapy for many patients, new research indicates.
 

“The results of our study demonstrate that more than half of patients with advanced cancer would not want a treatment that delays time to progression on imaging without any improvement in survival or quality of life,” Christopher Booth, MD, an oncologist and professor at Queen’s University, Kingston, Ont., said in an interview.

Even with an overall survival benefit of 6 months, one in five patients said they would decline additional treatment, which indicates the limited value of extra months of life with better quality of life.

“This has very important implications for our field – how we design trials, how we write guidelines, and how we make treatment recommendations to our patients,” said Booth.

The findings highlight the importance of “making sure that we incorporate patient perspectives into what we do and the research around it,” agreed Richard Lee, MD, with City of Hope Comprehensive Cancer Center, Duarte, Calif., who wasn’t involved in the study.

“It’s easy for us to pick outcome measures that are important to us as researchers but really have very little value to the patient,” said Dr. Lee, associate editor (palliative care) for Cancer.Net, the American Society of Clinical Oncology patient information website.

The study was published online in the Journal of the National Cancer Institute.

Although PFS is often used as a primary endpoint in cancer drug trials, evidence indicates that PFS is typically a poor surrogate both for overall survival and quality of life. It’s also unclear how much patients value additional time with no progression, especially if it means extra toxicity with no overall survival or quality of life gains.

In the current study, Dr. Booth and colleagues wanted to better understand patients’ attitudes toward a treatment that offers PFS but does not improve overall survival.

The study involved 100 patients who had received at least 3 months of systemic therapy for incurable solid tumors. Nearly two-thirds of the patients were older than 60. They were asked about their preferences and goals for additional therapy. A variety of primary cancer sites were represented, most commonly gastrointestinal, breast, lung, genitourinary, and brain.

Among the patients interviewed, 80 were currently receiving palliative systemic treatment. Only one patient described the intent as curative; 45% described it as intending to prolong life, and 5% described it as intending to improve quality of life. The remainder had a combination of goals.

Overall, patients expressed a variety of preferences about additional treatment.

More than half (52%) said they would decline additional treatment that only offered PFS gains, while 26% said they would accept more treatment in the absence of an overall survival benefit if it meant delaying disease progression by 3-9 months.

About one in six patients (17%) said they would prefer additional treatment, even without any gain in PFS. These patients expressed “wanting to fight or hoping that they would defy the survival statistics” – an attitude that is “not irrational,” the researchers noted, but rather reflects the “more must be better” line of thinking.

Compared with the 26% of patients willing to undergo additional treatment for a PFS benefit but no overall survival benefit, 71% of patients said they would undergo more treatment for a 6-month gain in overall survival.
 

Weighing the benefits of more treatment

Overall, the findings suggest that while some patients are willing to undergo more toxic treatment regardless of PFS outcomes, most prefer to explicitly weigh the benefits of PFS, overall survival, and quality of life, Dr. Booth and colleagues said.

The findings also make clear the need to design randomized clinical trials that focus on endpoints and the gains that are of greatest value to patients.

“While there are a handful of circumstances in which PFS is a valid surrogate for overall survival, this is the exception and not the rule,” said Dr. Booth, who, along with colleagues, recently launched a global movement called Common Sense Oncology to help make cancer care and clinical trials more patient centered.

Drug companies like the PFS measure because it gives an answer quickly. “They don’t have to wait for the overall survival surrogate,” but in many cases, PFS is not a good primary endpoint, said Dr. Lee.

The exception, he noted, would be for some slow-growing cancers, such as low-grade prostate cancer, in which overall survival takes 10 years to gauge. “But outside of those few cancers, we need to stick to overall survival as the gold standard, and patients are basically telling us the same,” Dr. Lee explained.

What about a treatment that might not extend overall survival but could improve quality of life?

“It is easy to measure a year in life, but what about the life within a year,” Rachel Koven, MSc, author and patient advocate, Queen’s University Cancer Research Institute, said in an interview. “Beyond the potential for an extended number of days, what constitutes a ‘good’ day or a day well lived, and are the treatment decisions impacting that? While this may be different for each person, regardless of the definition used, it will still be of the utmost importance for all.”

Overall, Dr. Lee stressed, it’s important for oncologists to inform patients about what trial results show.

“We have to talk to patients and tell them a drug has shown progression-free improvement but not an overall survival benefit. That absolutely needs to be included in the discussion so that patients can give full, informed consent to what the treatment options are,” he said.

Ms. Koven agreed. “We must continuously strive to improve doctor-patient communication to ensure that patients facing incurable cancer can make evidence-based choices that match their unique goals, preferences, and needs,” she said.

“It is essential that care plans be created with outcomes that matter,” Ms. Koven said. “Treatments with small benefits lead to lost time for patients spent at the cancer center rather than with family and friends.”

The study was supported by the Canadian Institutes of Health Research. Dr. Booth, Ms. Koven, and Dr. Lee reported no relevant disclosures.

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

Progression-free survival (PFS) is now the dominant endpoint in cancer clinical trials, but simply prolonging time to progression without extending overall survival or quality of life does not justify additional therapy for many patients, new research indicates.
 

“The results of our study demonstrate that more than half of patients with advanced cancer would not want a treatment that delays time to progression on imaging without any improvement in survival or quality of life,” Christopher Booth, MD, an oncologist and professor at Queen’s University, Kingston, Ont., said in an interview.

Even with an overall survival benefit of 6 months, one in five patients said they would decline additional treatment, which indicates the limited value of extra months of life with better quality of life.

“This has very important implications for our field – how we design trials, how we write guidelines, and how we make treatment recommendations to our patients,” said Booth.

The findings highlight the importance of “making sure that we incorporate patient perspectives into what we do and the research around it,” agreed Richard Lee, MD, with City of Hope Comprehensive Cancer Center, Duarte, Calif., who wasn’t involved in the study.

“It’s easy for us to pick outcome measures that are important to us as researchers but really have very little value to the patient,” said Dr. Lee, associate editor (palliative care) for Cancer.Net, the American Society of Clinical Oncology patient information website.

The study was published online in the Journal of the National Cancer Institute.

Although PFS is often used as a primary endpoint in cancer drug trials, evidence indicates that PFS is typically a poor surrogate both for overall survival and quality of life. It’s also unclear how much patients value additional time with no progression, especially if it means extra toxicity with no overall survival or quality of life gains.

In the current study, Dr. Booth and colleagues wanted to better understand patients’ attitudes toward a treatment that offers PFS but does not improve overall survival.

The study involved 100 patients who had received at least 3 months of systemic therapy for incurable solid tumors. Nearly two-thirds of the patients were older than 60. They were asked about their preferences and goals for additional therapy. A variety of primary cancer sites were represented, most commonly gastrointestinal, breast, lung, genitourinary, and brain.

Among the patients interviewed, 80 were currently receiving palliative systemic treatment. Only one patient described the intent as curative; 45% described it as intending to prolong life, and 5% described it as intending to improve quality of life. The remainder had a combination of goals.

Overall, patients expressed a variety of preferences about additional treatment.

More than half (52%) said they would decline additional treatment that only offered PFS gains, while 26% said they would accept more treatment in the absence of an overall survival benefit if it meant delaying disease progression by 3-9 months.

About one in six patients (17%) said they would prefer additional treatment, even without any gain in PFS. These patients expressed “wanting to fight or hoping that they would defy the survival statistics” – an attitude that is “not irrational,” the researchers noted, but rather reflects the “more must be better” line of thinking.

Compared with the 26% of patients willing to undergo additional treatment for a PFS benefit but no overall survival benefit, 71% of patients said they would undergo more treatment for a 6-month gain in overall survival.
 

Weighing the benefits of more treatment

Overall, the findings suggest that while some patients are willing to undergo more toxic treatment regardless of PFS outcomes, most prefer to explicitly weigh the benefits of PFS, overall survival, and quality of life, Dr. Booth and colleagues said.

The findings also make clear the need to design randomized clinical trials that focus on endpoints and the gains that are of greatest value to patients.

“While there are a handful of circumstances in which PFS is a valid surrogate for overall survival, this is the exception and not the rule,” said Dr. Booth, who, along with colleagues, recently launched a global movement called Common Sense Oncology to help make cancer care and clinical trials more patient centered.

Drug companies like the PFS measure because it gives an answer quickly. “They don’t have to wait for the overall survival surrogate,” but in many cases, PFS is not a good primary endpoint, said Dr. Lee.

The exception, he noted, would be for some slow-growing cancers, such as low-grade prostate cancer, in which overall survival takes 10 years to gauge. “But outside of those few cancers, we need to stick to overall survival as the gold standard, and patients are basically telling us the same,” Dr. Lee explained.

What about a treatment that might not extend overall survival but could improve quality of life?

“It is easy to measure a year in life, but what about the life within a year,” Rachel Koven, MSc, author and patient advocate, Queen’s University Cancer Research Institute, said in an interview. “Beyond the potential for an extended number of days, what constitutes a ‘good’ day or a day well lived, and are the treatment decisions impacting that? While this may be different for each person, regardless of the definition used, it will still be of the utmost importance for all.”

Overall, Dr. Lee stressed, it’s important for oncologists to inform patients about what trial results show.

“We have to talk to patients and tell them a drug has shown progression-free improvement but not an overall survival benefit. That absolutely needs to be included in the discussion so that patients can give full, informed consent to what the treatment options are,” he said.

Ms. Koven agreed. “We must continuously strive to improve doctor-patient communication to ensure that patients facing incurable cancer can make evidence-based choices that match their unique goals, preferences, and needs,” she said.

“It is essential that care plans be created with outcomes that matter,” Ms. Koven said. “Treatments with small benefits lead to lost time for patients spent at the cancer center rather than with family and friends.”

The study was supported by the Canadian Institutes of Health Research. Dr. Booth, Ms. Koven, and Dr. Lee reported no relevant disclosures.

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

Progression-free survival (PFS) is now the dominant endpoint in cancer clinical trials, but simply prolonging time to progression without extending overall survival or quality of life does not justify additional therapy for many patients, new research indicates.
 

“The results of our study demonstrate that more than half of patients with advanced cancer would not want a treatment that delays time to progression on imaging without any improvement in survival or quality of life,” Christopher Booth, MD, an oncologist and professor at Queen’s University, Kingston, Ont., said in an interview.

Even with an overall survival benefit of 6 months, one in five patients said they would decline additional treatment, which indicates the limited value of extra months of life with better quality of life.

“This has very important implications for our field – how we design trials, how we write guidelines, and how we make treatment recommendations to our patients,” said Booth.

The findings highlight the importance of “making sure that we incorporate patient perspectives into what we do and the research around it,” agreed Richard Lee, MD, with City of Hope Comprehensive Cancer Center, Duarte, Calif., who wasn’t involved in the study.

“It’s easy for us to pick outcome measures that are important to us as researchers but really have very little value to the patient,” said Dr. Lee, associate editor (palliative care) for Cancer.Net, the American Society of Clinical Oncology patient information website.

The study was published online in the Journal of the National Cancer Institute.

Although PFS is often used as a primary endpoint in cancer drug trials, evidence indicates that PFS is typically a poor surrogate both for overall survival and quality of life. It’s also unclear how much patients value additional time with no progression, especially if it means extra toxicity with no overall survival or quality of life gains.

In the current study, Dr. Booth and colleagues wanted to better understand patients’ attitudes toward a treatment that offers PFS but does not improve overall survival.

The study involved 100 patients who had received at least 3 months of systemic therapy for incurable solid tumors. Nearly two-thirds of the patients were older than 60. They were asked about their preferences and goals for additional therapy. A variety of primary cancer sites were represented, most commonly gastrointestinal, breast, lung, genitourinary, and brain.

Among the patients interviewed, 80 were currently receiving palliative systemic treatment. Only one patient described the intent as curative; 45% described it as intending to prolong life, and 5% described it as intending to improve quality of life. The remainder had a combination of goals.

Overall, patients expressed a variety of preferences about additional treatment.

More than half (52%) said they would decline additional treatment that only offered PFS gains, while 26% said they would accept more treatment in the absence of an overall survival benefit if it meant delaying disease progression by 3-9 months.

About one in six patients (17%) said they would prefer additional treatment, even without any gain in PFS. These patients expressed “wanting to fight or hoping that they would defy the survival statistics” – an attitude that is “not irrational,” the researchers noted, but rather reflects the “more must be better” line of thinking.

Compared with the 26% of patients willing to undergo additional treatment for a PFS benefit but no overall survival benefit, 71% of patients said they would undergo more treatment for a 6-month gain in overall survival.
 

Weighing the benefits of more treatment

Overall, the findings suggest that while some patients are willing to undergo more toxic treatment regardless of PFS outcomes, most prefer to explicitly weigh the benefits of PFS, overall survival, and quality of life, Dr. Booth and colleagues said.

The findings also make clear the need to design randomized clinical trials that focus on endpoints and the gains that are of greatest value to patients.

“While there are a handful of circumstances in which PFS is a valid surrogate for overall survival, this is the exception and not the rule,” said Dr. Booth, who, along with colleagues, recently launched a global movement called Common Sense Oncology to help make cancer care and clinical trials more patient centered.

Drug companies like the PFS measure because it gives an answer quickly. “They don’t have to wait for the overall survival surrogate,” but in many cases, PFS is not a good primary endpoint, said Dr. Lee.

The exception, he noted, would be for some slow-growing cancers, such as low-grade prostate cancer, in which overall survival takes 10 years to gauge. “But outside of those few cancers, we need to stick to overall survival as the gold standard, and patients are basically telling us the same,” Dr. Lee explained.

What about a treatment that might not extend overall survival but could improve quality of life?

“It is easy to measure a year in life, but what about the life within a year,” Rachel Koven, MSc, author and patient advocate, Queen’s University Cancer Research Institute, said in an interview. “Beyond the potential for an extended number of days, what constitutes a ‘good’ day or a day well lived, and are the treatment decisions impacting that? While this may be different for each person, regardless of the definition used, it will still be of the utmost importance for all.”

Overall, Dr. Lee stressed, it’s important for oncologists to inform patients about what trial results show.

“We have to talk to patients and tell them a drug has shown progression-free improvement but not an overall survival benefit. That absolutely needs to be included in the discussion so that patients can give full, informed consent to what the treatment options are,” he said.

Ms. Koven agreed. “We must continuously strive to improve doctor-patient communication to ensure that patients facing incurable cancer can make evidence-based choices that match their unique goals, preferences, and needs,” she said.

“It is essential that care plans be created with outcomes that matter,” Ms. Koven said. “Treatments with small benefits lead to lost time for patients spent at the cancer center rather than with family and friends.”

The study was supported by the Canadian Institutes of Health Research. Dr. Booth, Ms. Koven, and Dr. Lee reported no relevant disclosures.

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

The Advisory Committee on Immunization Practices (ACIP) recently issued new recommendations on polio vaccine for adults. The ACIP decided to update its previous recommendations (from 2000) in response to a case in New York that demonstrated the United States is at risk for poliovirus importation as long as the disease has not been eliminated worldwide.¹

What happened in New York? In July 2022, a case of paralytic polio was confirmed in an unvaccinated adult in Rockland County, New York, an area that has low polio vaccine coverage. Subsequent testing of wastewater systems detected poliovirus in a total of 5 New York counties (including 2 in New York City).¹

The Centers for Disease Control and Prevention estimates that this region of the state probably experienced 1000 to 2000 nonparalytic, mostly asymptomatic poliovirus infections. The virus detected in wastewater in New York is genetically linked to polioviruses collected in wastewater in Israel, the United Kingdom, and Canada. No poliovirus has been detected in these wastewater systems since late 2022.^1,2

Why there’s reason for concern. Routine immunization against polio has been part of the immunization schedule for infants and children since the mid-1950s. As a result, endemic polio was eliminated in the United States in 1979 and in the Western Hemisphere in 1994.

However, adult vaccination until now has been recommended only for those at risk for exposure to poliovirus by way of travel or occupation. And while most adults in the United States are immune to polio due to childhood vaccination, unvaccinated adults remain susceptible if exposed to poliovirus—as demonstrated in the New York case.

What does the ACIP now recommend? Two recommendations were adopted by the ACIP this June to address this problem²:

1. Adults who are known or suspected to be unvaccinated or incompletely vaccinated against polio should complete a primary vaccination series with inactivated polio vaccine (IPV).
2. Adults who have received a primary series of oral polio vaccine (OPV) or IPV in any combination and who are at increased risk for poliovirus exposure may receive another dose of IPV. Available data do not indicate a need for > 1 lifetime booster.

A few details: To be considered fully vaccinated, a patient must have received a primary series of ≥ 3 doses of OPV or IPV (in any combination) given at least 4 weeks apart, with the last dose given on or after the 4th birthday and at least 6 months from the previous dose. Most adults who were born and raised in the United States can assume they were vaccinated against polio as children, unless there are specific reasons to suspect otherwise.²

Individuals considered to be at increased risk include: travelers who are going to countries where polio is epidemic or endemic; laboratory and health care workers who handle specimens that might contain polioviruses; and health care workers or other caregivers who have close contact with a person who could be infected with poliovirus.²

Take-home message. Be prepared to discuss and offer IPV (the only form of the vaccine currently in use in the United States) to adults, as either a one-time booster for those at increased risk for exposure to poliovirus or a complete series for those you know or suspect to be unvaccinated or incompletely vaccinated.

The Advisory Committee on Immunization Practices (ACIP) recently issued new recommendations on polio vaccine for adults. The ACIP decided to update its previous recommendations (from 2000) in response to a case in New York that demonstrated the United States is at risk for poliovirus importation as long as the disease has not been eliminated worldwide.¹

What happened in New York? In July 2022, a case of paralytic polio was confirmed in an unvaccinated adult in Rockland County, New York, an area that has low polio vaccine coverage. Subsequent testing of wastewater systems detected poliovirus in a total of 5 New York counties (including 2 in New York City).¹

The Centers for Disease Control and Prevention estimates that this region of the state probably experienced 1000 to 2000 nonparalytic, mostly asymptomatic poliovirus infections. The virus detected in wastewater in New York is genetically linked to polioviruses collected in wastewater in Israel, the United Kingdom, and Canada. No poliovirus has been detected in these wastewater systems since late 2022.^1,2

Why there’s reason for concern. Routine immunization against polio has been part of the immunization schedule for infants and children since the mid-1950s. As a result, endemic polio was eliminated in the United States in 1979 and in the Western Hemisphere in 1994.

However, adult vaccination until now has been recommended only for those at risk for exposure to poliovirus by way of travel or occupation. And while most adults in the United States are immune to polio due to childhood vaccination, unvaccinated adults remain susceptible if exposed to poliovirus—as demonstrated in the New York case.

What does the ACIP now recommend? Two recommendations were adopted by the ACIP this June to address this problem²:

1. Adults who are known or suspected to be unvaccinated or incompletely vaccinated against polio should complete a primary vaccination series with inactivated polio vaccine (IPV).
2. Adults who have received a primary series of oral polio vaccine (OPV) or IPV in any combination and who are at increased risk for poliovirus exposure may receive another dose of IPV. Available data do not indicate a need for > 1 lifetime booster.

A few details: To be considered fully vaccinated, a patient must have received a primary series of ≥ 3 doses of OPV or IPV (in any combination) given at least 4 weeks apart, with the last dose given on or after the 4th birthday and at least 6 months from the previous dose. Most adults who were born and raised in the United States can assume they were vaccinated against polio as children, unless there are specific reasons to suspect otherwise.²

Individuals considered to be at increased risk include: travelers who are going to countries where polio is epidemic or endemic; laboratory and health care workers who handle specimens that might contain polioviruses; and health care workers or other caregivers who have close contact with a person who could be infected with poliovirus.²

Take-home message. Be prepared to discuss and offer IPV (the only form of the vaccine currently in use in the United States) to adults, as either a one-time booster for those at increased risk for exposure to poliovirus or a complete series for those you know or suspect to be unvaccinated or incompletely vaccinated.

The Advisory Committee on Immunization Practices (ACIP) recently issued new recommendations on polio vaccine for adults. The ACIP decided to update its previous recommendations (from 2000) in response to a case in New York that demonstrated the United States is at risk for poliovirus importation as long as the disease has not been eliminated worldwide.¹

What happened in New York? In July 2022, a case of paralytic polio was confirmed in an unvaccinated adult in Rockland County, New York, an area that has low polio vaccine coverage. Subsequent testing of wastewater systems detected poliovirus in a total of 5 New York counties (including 2 in New York City).¹

The Centers for Disease Control and Prevention estimates that this region of the state probably experienced 1000 to 2000 nonparalytic, mostly asymptomatic poliovirus infections. The virus detected in wastewater in New York is genetically linked to polioviruses collected in wastewater in Israel, the United Kingdom, and Canada. No poliovirus has been detected in these wastewater systems since late 2022.^1,2

Why there’s reason for concern. Routine immunization against polio has been part of the immunization schedule for infants and children since the mid-1950s. As a result, endemic polio was eliminated in the United States in 1979 and in the Western Hemisphere in 1994.

However, adult vaccination until now has been recommended only for those at risk for exposure to poliovirus by way of travel or occupation. And while most adults in the United States are immune to polio due to childhood vaccination, unvaccinated adults remain susceptible if exposed to poliovirus—as demonstrated in the New York case.

What does the ACIP now recommend? Two recommendations were adopted by the ACIP this June to address this problem²:

1. Adults who are known or suspected to be unvaccinated or incompletely vaccinated against polio should complete a primary vaccination series with inactivated polio vaccine (IPV).
2. Adults who have received a primary series of oral polio vaccine (OPV) or IPV in any combination and who are at increased risk for poliovirus exposure may receive another dose of IPV. Available data do not indicate a need for > 1 lifetime booster.

A few details: To be considered fully vaccinated, a patient must have received a primary series of ≥ 3 doses of OPV or IPV (in any combination) given at least 4 weeks apart, with the last dose given on or after the 4th birthday and at least 6 months from the previous dose. Most adults who were born and raised in the United States can assume they were vaccinated against polio as children, unless there are specific reasons to suspect otherwise.²

Individuals considered to be at increased risk include: travelers who are going to countries where polio is epidemic or endemic; laboratory and health care workers who handle specimens that might contain polioviruses; and health care workers or other caregivers who have close contact with a person who could be infected with poliovirus.²

Take-home message. Be prepared to discuss and offer IPV (the only form of the vaccine currently in use in the United States) to adults, as either a one-time booster for those at increased risk for exposure to poliovirus or a complete series for those you know or suspect to be unvaccinated or incompletely vaccinated.

Although there are several treatment options for PsA, there have been few head-to-head studies conducted to determine comparative efficacy. Ustekinumab, a biologic agent targeting IL-p40, and therefore both IL-12 and IL-23, has proven efficacy in PsA, but the impression is that this drug is less effective than are TNF inhibitors for the treatment of the peripheral arthritis domain. However, in a prospective, observational study, Gossec and colleagues report that the improvements in patient-reported outcomes were generally comparable between ustekinumab and TNF inhibitor treatments. This study evaluated 437 patients with PsA from the PsABio study who initiated first- to third-line ustekinumab (n = 219) or TNF inhibitors (n = 218) and continued the initial treatment for 3 years. At 3 years, ustekinumab and TNF inhibitors were associated with comparable improvements in the EuroQol-5 dimensions health state visual analog scale scores, Psoriatic Arthritis Impact of Disease 12-item scores, and work productivity, although the improvements were generally greater in the TNF inhibitor–treated group. A randomized trial comparing ustekinumab to TNF inhibitors in PsA is warranted to confirm these findings and inform treatment decisions.

Targeted therapies, such as biologics, are proven to be more efficacious than are conventional therapies; however, only about 60% of patients initiating targeted therapies demonstrate treatment response. Identifying the predictors of treatment response is an active area of research. Linde and colleagues looked at data from 13,369 biologic-naive patients registered with a PsA diagnosis from 13 European registries who initiated a first TNF inhibitor treatment. The study demonstrated that sex, disease duration, C-reactive protein level, age at treatment initiation, and fatigue predicted the achievement of the Disease Activity in Psoriatic Arthritis in 28 joints remission at 6 months.

Could biomarkers help predict response beyond clinical predictors? An interesting study indicates that beta–defensin 2 (BD-2) may serve as a predictive biomarker for clinical response to secukinumab in PsA. BD-2 is an antimicrobial peptide and an important protein in innate immune response. Cardner and colleagues analyzed protein expression data in serum samples from the phase 3 FUTURE 1-5 trials that included 1989 patients with PsA who received secukinumab or placebo. Baseline BD-2 levels were associated with early as well as sustained PsA treatment response to secukinumab, independent of psoriasis severity. BD-2 levels did not predict response to adalimumab in PsA nor was it associated with treatment response to secukinumab in RA. The addition of BD-2 to the clinical prediction model significantly improved the prediction of the 16-week American College of Rheumatology 20 response. Thus, BD-2 seems to be a secukinumab treatment response biomarker and requires further evaluation.

Although there are several treatment options for PsA, there have been few head-to-head studies conducted to determine comparative efficacy. Ustekinumab, a biologic agent targeting IL-p40, and therefore both IL-12 and IL-23, has proven efficacy in PsA, but the impression is that this drug is less effective than are TNF inhibitors for the treatment of the peripheral arthritis domain. However, in a prospective, observational study, Gossec and colleagues report that the improvements in patient-reported outcomes were generally comparable between ustekinumab and TNF inhibitor treatments. This study evaluated 437 patients with PsA from the PsABio study who initiated first- to third-line ustekinumab (n = 219) or TNF inhibitors (n = 218) and continued the initial treatment for 3 years. At 3 years, ustekinumab and TNF inhibitors were associated with comparable improvements in the EuroQol-5 dimensions health state visual analog scale scores, Psoriatic Arthritis Impact of Disease 12-item scores, and work productivity, although the improvements were generally greater in the TNF inhibitor–treated group. A randomized trial comparing ustekinumab to TNF inhibitors in PsA is warranted to confirm these findings and inform treatment decisions.

Targeted therapies, such as biologics, are proven to be more efficacious than are conventional therapies; however, only about 60% of patients initiating targeted therapies demonstrate treatment response. Identifying the predictors of treatment response is an active area of research. Linde and colleagues looked at data from 13,369 biologic-naive patients registered with a PsA diagnosis from 13 European registries who initiated a first TNF inhibitor treatment. The study demonstrated that sex, disease duration, C-reactive protein level, age at treatment initiation, and fatigue predicted the achievement of the Disease Activity in Psoriatic Arthritis in 28 joints remission at 6 months.

Could biomarkers help predict response beyond clinical predictors? An interesting study indicates that beta–defensin 2 (BD-2) may serve as a predictive biomarker for clinical response to secukinumab in PsA. BD-2 is an antimicrobial peptide and an important protein in innate immune response. Cardner and colleagues analyzed protein expression data in serum samples from the phase 3 FUTURE 1-5 trials that included 1989 patients with PsA who received secukinumab or placebo. Baseline BD-2 levels were associated with early as well as sustained PsA treatment response to secukinumab, independent of psoriasis severity. BD-2 levels did not predict response to adalimumab in PsA nor was it associated with treatment response to secukinumab in RA. The addition of BD-2 to the clinical prediction model significantly improved the prediction of the 16-week American College of Rheumatology 20 response. Thus, BD-2 seems to be a secukinumab treatment response biomarker and requires further evaluation.

Although there are several treatment options for PsA, there have been few head-to-head studies conducted to determine comparative efficacy. Ustekinumab, a biologic agent targeting IL-p40, and therefore both IL-12 and IL-23, has proven efficacy in PsA, but the impression is that this drug is less effective than are TNF inhibitors for the treatment of the peripheral arthritis domain. However, in a prospective, observational study, Gossec and colleagues report that the improvements in patient-reported outcomes were generally comparable between ustekinumab and TNF inhibitor treatments. This study evaluated 437 patients with PsA from the PsABio study who initiated first- to third-line ustekinumab (n = 219) or TNF inhibitors (n = 218) and continued the initial treatment for 3 years. At 3 years, ustekinumab and TNF inhibitors were associated with comparable improvements in the EuroQol-5 dimensions health state visual analog scale scores, Psoriatic Arthritis Impact of Disease 12-item scores, and work productivity, although the improvements were generally greater in the TNF inhibitor–treated group. A randomized trial comparing ustekinumab to TNF inhibitors in PsA is warranted to confirm these findings and inform treatment decisions.

Targeted therapies, such as biologics, are proven to be more efficacious than are conventional therapies; however, only about 60% of patients initiating targeted therapies demonstrate treatment response. Identifying the predictors of treatment response is an active area of research. Linde and colleagues looked at data from 13,369 biologic-naive patients registered with a PsA diagnosis from 13 European registries who initiated a first TNF inhibitor treatment. The study demonstrated that sex, disease duration, C-reactive protein level, age at treatment initiation, and fatigue predicted the achievement of the Disease Activity in Psoriatic Arthritis in 28 joints remission at 6 months.

Could biomarkers help predict response beyond clinical predictors? An interesting study indicates that beta–defensin 2 (BD-2) may serve as a predictive biomarker for clinical response to secukinumab in PsA. BD-2 is an antimicrobial peptide and an important protein in innate immune response. Cardner and colleagues analyzed protein expression data in serum samples from the phase 3 FUTURE 1-5 trials that included 1989 patients with PsA who received secukinumab or placebo. Baseline BD-2 levels were associated with early as well as sustained PsA treatment response to secukinumab, independent of psoriasis severity. BD-2 levels did not predict response to adalimumab in PsA nor was it associated with treatment response to secukinumab in RA. The addition of BD-2 to the clinical prediction model significantly improved the prediction of the 16-week American College of Rheumatology 20 response. Thus, BD-2 seems to be a secukinumab treatment response biomarker and requires further evaluation.

On May 24, the news outlet ProPublica published a scathing investigation of Jeffery Dormu, DO, said to have performed hundreds of “medically unnecessary and invasive vascular procedures” in his Laurel, Md. office, putting patients’ limbs and lives at risk.

On July 15, The New York Times published a broader-based investigation of several vascular specialists said to have performed “risky” procedures on patients with peripheral artery disease (PAD) who subsequently had to have amputations, or died. The focus was mainly on Michigan-based interventional cardiologist Jihad Mustapha, MD.

This follows a 2019 analysis of Medicare claims data that identified outlier physicians with a high early intervention rate for patients newly diagnosed with claudication. According to the American Heart Association statistics, PAD affects approximately 8.5 million U.S. adults age 40 and older (some claim that’s an underestimate); most cases don’t require invasive treatment.

Are the ProPublica and Times stories emblematic of the field at large or a case of a few rogue doctors, and did changes in reimbursement and support from device manufacturers exacerbate the problem?

Responding to the Times’ revelations, Joseph L. Mills, MD, president of the Society for Vascular Surgery, wrote on the society’s website: “The overwhelming majority of vascular surgeons, and a vast majority of other specialists that receive some training and play a role in the care of vascular patients, including those trained in vascular medicine, interventional cardiology, and interventional radiology are providing high-quality, evidence-based care with safety and the best patient outcomes in mind.

“This is a complex issue that requires the examination not only of the events detailed in this story ... but of the underlying health care economic, legal and regulatory policies that created fertile soil for this behavior to germinate and take root.”
 

‘A few bad apples’

“I think it’s a case of a few bad apples,” Sunil V. Rao, MD, director of interventional cardiology at NYU Langone Health, New York, said in an interview. “In general, I think physicians who take care of patients with vascular issues are trying to do the right thing. I think all of us who take care of patients with vascular disease see patients who are very, very complex, and there are going to be some procedures that have complications.

“Without knowing the clinical details, it’s hard to know whether the procedures described in the articles were overuse or unnecessary, or exactly what led to the amputations,” he said. “All we know is that these physicians are outliers in terms of the number of procedures they were billing for.

“But although correlation is not causation, it certainly is cause for concern because you would expect that the use of procedures for specific indications would fall within a certain range,” he added.
 

Lifestyle changes first

PAD is often asymptomatic or mild, making it difficult to diagnose. Revascularization procedures usually are reserved for the 5%-8% of patients at risk for chronic limb-threatening ischemia (CLTI) or those in whom the cornerstones of PAD treatment – lifestyle changes and, if needed, medication – fail.

Revascularization options include balloon angioplasty or stent placement; atherectomy to remove plaques from the artery; or bypass surgery if a long portion of a leg artery is completely blocked. All carry a risk of long-term adverse outcomes, but the rates are highest for atherectomy.

Lifestyle changes include regular exercise, following a healthy diet, quitting smoking, and controlling diabetes and high blood pressure. When PAD continues or progresses despite these modifications, medications such as antiplatelet agents, antihypertensives, and/or lipid-lowering drugs may be prescribed.
 

‘Medically unnecessary’

According to the latest American Heart Association/American College of Cardiology guideline on managing patients with lower-extremity PAD, patients should be selected for revascularization based on symptom severity.

Factors to consider include a significant disability as assessed by the patient, and adequacy of response to medical and structured exercise therapy.

There’s the rub regarding the clinicians investigated in the Times and ProPublica. Many patients, apparently, were not encouraged to make lifestyle changes, nor did they receive medication. Instead, they were advised from the get-go to undergo invasive procedures, and often multiple times. Underuse of prevention and lifestyle counseling n the management of PAD has long been a concern.

Furthermore, in at least some cases, patients without any symptoms were encouraged to be screened for blockages that were then treated invasively, according to the Times.

Dr. Dormu, as highlighted in ProPublica, positioned his practice as “life and limb saving.” Yet, in investigative findings that led to a suspension of Dr. Dormu’s license to practice medicine in Maryland, peer reviewers expressed concern regarding his repeated use of invasive and medically unnecessary procedures, exposing patients to “potential risks such as bleeding, infection, blood vessel injuries which could acutely or chronically worsen the patient’s circulation, and limb loss.”

The peer reviewers concurred that Dr. Dormu failed to use conservative management techniques to address the patients’ vascular complaints before resorting to invasive procedures.

Dr. Mustapha is described in the Times as a “high-volume” atherectomy provider. From 2017 to 2021, about half of Medicare’s atherectomy payments – $1.4 billion – went to 200 high-volume providers, with Dr. Mustapha near the top of the list.

Some of Dr. Mustapha’s patients underwent multiple procedures said to help prevent leg amputation, but their legs were amputated anyway, possibly because of the multiple atherectomies, according to the Times.

Judith Lin, MD, MBA, who treated some of Dr. Mustapha’s former patients, was among those who complained about his practice to Michigan’s licensing board. Some of the patients she treated needed amputations; others needed to have leftover wires extracted from their legs.

In 2020, the board investigated Dr. Lin’s complaint and referred it to Michigan’s attorney general, who brought a disciplinary action against Dr. Mustapha. An expert hired by the state to review eight patient cases concluded that Dr. Mustapha’s practice “was characterized by overtreatment and poor documentation.” In some cases, the expert wrote, “unnecessary procedures hastened amputations.”

The statement issued by Dr. Mills, the president of SVS, noted that the society’s practice guideline proposes a threshold of at least 2 years of likely durability for an intervention performed for claudication.

“The growing frequency of multiple, repeated procedures [is] emblematic of poor patient selection and inadequate durability of the chosen procedure, leading to a vicious cycle of repetitive interventions that is not only costly, but also dangerous,” he wrote.
 

Financial incentives to blame?

In 2008, Medicare created incentives for physicians to perform vascular procedures in offices rather than hospitals, in an effort to reduce medical costs, according to both investigative articles. But the effort backfired.

Before the changes, an office provider inserting a stent could make about $1,700 from Medicare; deploying a balloon could bring in roughly $3,800. By 2011, the payments rose to about $6,400 and $4,800, respectively.

Office-based atherectomies soared when, in 2011, the Centers for Medicare & Medicaid Services started reimbursing $13,500 per procedure, as opposed to roughly $11,450 in a hospital. Atherectomies increased by 60% from 2011 to 2014, and Medicare’s overall costs for peripheral vascular treatments climbed by nearly half a billion dollars.

“The government is really to blame for setting these tremendously high reimbursement values without looking into whether these procedures are helping people or are just worthless procedures or, in fact, are hurting people,” Dipankar Mukherjee, MD, a vascular surgeon and chief of vascular surgery at Inova Fairfax (Va.) Hospital, said in ProPublica.

The result, noted Dr. Rao, is that “there can be perverse or nefarious incentives for doing these procedures. People are incentivized by reimbursement to do something that really falls in the area of clinical judgment and guidelines.”

Major incentives also come from device manufacturers, who often reward physicians who do the most vascular procedures with payments for consulting and other services, according to the Times. In addition, these companies lend money to help physicians or their clinics to finance the purchase of equipment used to perform the procedures.

“Vascular medicine now is the frontier of the Wild West,” Marty Makary, MD, MPH, a professor of surgery and health care quality researcher at Johns Hopkins University, Baltimore, told ProPublica. “People are flying blind walking into the clinics of these doctors with egregious practice patterns, and we know that their pattern is indefensible.”

Recognizing that the situation posed a threat to patients and also damaged the credibility of his specialty, Kim J. Hodgson, MD, a former SVS president, told attendees at the 2021 annual meeting of the SVS, “Somebody has to address what should never have been allowed to get to this level of threat to us and our patients in the first place. We can play whack-a-mole every time the bad actors surface until the cows come home, but that leaves a trail of harmed patients and wasted resources.”

Dr. Hodgson described atherectomy as “a procedure that many believe provides no demonstrable value whatsoever to the patient” and challenged those who disagree to prove it.
 

Multidisciplinary teams needed

Other experts believe there are times that revascularization procedures, including atherectomy, are appropriate. However, the majority of patients with PAD do not require a procedure, Soo Hyun (Esther) Kim, MD, MPH, director of the Center for Women’s Cardiovascular Health at Atrium Health Sanger Heart and Vascular Institute in Charlotte, N.C., said in an interview. In fact, “many patients do not even know they have leg artery blockages.”

Invasive procedures may well be appropriate for patients with severe PAD, especially those with CLTI, and disparities may be keeping those who truly need such interventions – or for whom they may be at least considered – from accessing them. If PAD is not diagnosed and treated in a timely way, Dr. Kim said, those individuals “do indeed lose their limbs.”

Multidisciplinary teams can help, Dr. Kim said. “Specialists from multiple different training backgrounds [can] take good care of patients with PAD,” she said. This is important when access to a particular type of specialist is limited, and because patients with PAD often have complex medical problems that can benefit from a team approach.

Transcatheter aortic valve replacement heart teams and complex coronary disease heart teams are two examples, Dr. Kim noted. “When a high-stakes procedure is being considered, the patient’s case is reviewed by multiple stakeholders to ensure appropriateness of the procedure and collaboratively evaluate risk.”

Dr. Rao also emphasized a team approach. “PAD does not belong to a single specialty,” he said. The revelations from the Times, ProPublica, and other sources “point to the fact that we all – cardiologists, vascular surgeons, interventional radiologists – should start thinking about how best to police ourselves and also account for the variation in clinical judgment.”

Use of a multidisciplinary team is a “guideline-recommended approach” for coronary artery revascularization, he said, “I think the same should apply for PAD.”

PAD is a sign of systemic atherosclerosis, Dr. Kim noted. “The treatment of PAD includes addressing leg pain and wounds with procedures, but the interventions that will keep people alive are the medications we use to prevent heart attack and stroke. Patients with PAD need to understand that treatment is much more than opening up a blockage in the leg.”

Dr. Rao and Dr. Kim disclosed no relevant conflicts of interest.

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

On May 24, the news outlet ProPublica published a scathing investigation of Jeffery Dormu, DO, said to have performed hundreds of “medically unnecessary and invasive vascular procedures” in his Laurel, Md. office, putting patients’ limbs and lives at risk.

On July 15, The New York Times published a broader-based investigation of several vascular specialists said to have performed “risky” procedures on patients with peripheral artery disease (PAD) who subsequently had to have amputations, or died. The focus was mainly on Michigan-based interventional cardiologist Jihad Mustapha, MD.

This follows a 2019 analysis of Medicare claims data that identified outlier physicians with a high early intervention rate for patients newly diagnosed with claudication. According to the American Heart Association statistics, PAD affects approximately 8.5 million U.S. adults age 40 and older (some claim that’s an underestimate); most cases don’t require invasive treatment.

Are the ProPublica and Times stories emblematic of the field at large or a case of a few rogue doctors, and did changes in reimbursement and support from device manufacturers exacerbate the problem?

Responding to the Times’ revelations, Joseph L. Mills, MD, president of the Society for Vascular Surgery, wrote on the society’s website: “The overwhelming majority of vascular surgeons, and a vast majority of other specialists that receive some training and play a role in the care of vascular patients, including those trained in vascular medicine, interventional cardiology, and interventional radiology are providing high-quality, evidence-based care with safety and the best patient outcomes in mind.

“This is a complex issue that requires the examination not only of the events detailed in this story ... but of the underlying health care economic, legal and regulatory policies that created fertile soil for this behavior to germinate and take root.”
 

‘A few bad apples’

“I think it’s a case of a few bad apples,” Sunil V. Rao, MD, director of interventional cardiology at NYU Langone Health, New York, said in an interview. “In general, I think physicians who take care of patients with vascular issues are trying to do the right thing. I think all of us who take care of patients with vascular disease see patients who are very, very complex, and there are going to be some procedures that have complications.

“Without knowing the clinical details, it’s hard to know whether the procedures described in the articles were overuse or unnecessary, or exactly what led to the amputations,” he said. “All we know is that these physicians are outliers in terms of the number of procedures they were billing for.

“But although correlation is not causation, it certainly is cause for concern because you would expect that the use of procedures for specific indications would fall within a certain range,” he added.
 

Lifestyle changes first

PAD is often asymptomatic or mild, making it difficult to diagnose. Revascularization procedures usually are reserved for the 5%-8% of patients at risk for chronic limb-threatening ischemia (CLTI) or those in whom the cornerstones of PAD treatment – lifestyle changes and, if needed, medication – fail.

Revascularization options include balloon angioplasty or stent placement; atherectomy to remove plaques from the artery; or bypass surgery if a long portion of a leg artery is completely blocked. All carry a risk of long-term adverse outcomes, but the rates are highest for atherectomy.

Lifestyle changes include regular exercise, following a healthy diet, quitting smoking, and controlling diabetes and high blood pressure. When PAD continues or progresses despite these modifications, medications such as antiplatelet agents, antihypertensives, and/or lipid-lowering drugs may be prescribed.
 

‘Medically unnecessary’

According to the latest American Heart Association/American College of Cardiology guideline on managing patients with lower-extremity PAD, patients should be selected for revascularization based on symptom severity.

Factors to consider include a significant disability as assessed by the patient, and adequacy of response to medical and structured exercise therapy.

There’s the rub regarding the clinicians investigated in the Times and ProPublica. Many patients, apparently, were not encouraged to make lifestyle changes, nor did they receive medication. Instead, they were advised from the get-go to undergo invasive procedures, and often multiple times. Underuse of prevention and lifestyle counseling n the management of PAD has long been a concern.

Furthermore, in at least some cases, patients without any symptoms were encouraged to be screened for blockages that were then treated invasively, according to the Times.

Dr. Dormu, as highlighted in ProPublica, positioned his practice as “life and limb saving.” Yet, in investigative findings that led to a suspension of Dr. Dormu’s license to practice medicine in Maryland, peer reviewers expressed concern regarding his repeated use of invasive and medically unnecessary procedures, exposing patients to “potential risks such as bleeding, infection, blood vessel injuries which could acutely or chronically worsen the patient’s circulation, and limb loss.”

The peer reviewers concurred that Dr. Dormu failed to use conservative management techniques to address the patients’ vascular complaints before resorting to invasive procedures.

Dr. Mustapha is described in the Times as a “high-volume” atherectomy provider. From 2017 to 2021, about half of Medicare’s atherectomy payments – $1.4 billion – went to 200 high-volume providers, with Dr. Mustapha near the top of the list.

Some of Dr. Mustapha’s patients underwent multiple procedures said to help prevent leg amputation, but their legs were amputated anyway, possibly because of the multiple atherectomies, according to the Times.

Judith Lin, MD, MBA, who treated some of Dr. Mustapha’s former patients, was among those who complained about his practice to Michigan’s licensing board. Some of the patients she treated needed amputations; others needed to have leftover wires extracted from their legs.

In 2020, the board investigated Dr. Lin’s complaint and referred it to Michigan’s attorney general, who brought a disciplinary action against Dr. Mustapha. An expert hired by the state to review eight patient cases concluded that Dr. Mustapha’s practice “was characterized by overtreatment and poor documentation.” In some cases, the expert wrote, “unnecessary procedures hastened amputations.”

The statement issued by Dr. Mills, the president of SVS, noted that the society’s practice guideline proposes a threshold of at least 2 years of likely durability for an intervention performed for claudication.

“The growing frequency of multiple, repeated procedures [is] emblematic of poor patient selection and inadequate durability of the chosen procedure, leading to a vicious cycle of repetitive interventions that is not only costly, but also dangerous,” he wrote.
 

Financial incentives to blame?

In 2008, Medicare created incentives for physicians to perform vascular procedures in offices rather than hospitals, in an effort to reduce medical costs, according to both investigative articles. But the effort backfired.

Before the changes, an office provider inserting a stent could make about $1,700 from Medicare; deploying a balloon could bring in roughly $3,800. By 2011, the payments rose to about $6,400 and $4,800, respectively.

Office-based atherectomies soared when, in 2011, the Centers for Medicare & Medicaid Services started reimbursing $13,500 per procedure, as opposed to roughly $11,450 in a hospital. Atherectomies increased by 60% from 2011 to 2014, and Medicare’s overall costs for peripheral vascular treatments climbed by nearly half a billion dollars.

“The government is really to blame for setting these tremendously high reimbursement values without looking into whether these procedures are helping people or are just worthless procedures or, in fact, are hurting people,” Dipankar Mukherjee, MD, a vascular surgeon and chief of vascular surgery at Inova Fairfax (Va.) Hospital, said in ProPublica.

The result, noted Dr. Rao, is that “there can be perverse or nefarious incentives for doing these procedures. People are incentivized by reimbursement to do something that really falls in the area of clinical judgment and guidelines.”

Major incentives also come from device manufacturers, who often reward physicians who do the most vascular procedures with payments for consulting and other services, according to the Times. In addition, these companies lend money to help physicians or their clinics to finance the purchase of equipment used to perform the procedures.

“Vascular medicine now is the frontier of the Wild West,” Marty Makary, MD, MPH, a professor of surgery and health care quality researcher at Johns Hopkins University, Baltimore, told ProPublica. “People are flying blind walking into the clinics of these doctors with egregious practice patterns, and we know that their pattern is indefensible.”

Recognizing that the situation posed a threat to patients and also damaged the credibility of his specialty, Kim J. Hodgson, MD, a former SVS president, told attendees at the 2021 annual meeting of the SVS, “Somebody has to address what should never have been allowed to get to this level of threat to us and our patients in the first place. We can play whack-a-mole every time the bad actors surface until the cows come home, but that leaves a trail of harmed patients and wasted resources.”

Dr. Hodgson described atherectomy as “a procedure that many believe provides no demonstrable value whatsoever to the patient” and challenged those who disagree to prove it.
 

Multidisciplinary teams needed

Other experts believe there are times that revascularization procedures, including atherectomy, are appropriate. However, the majority of patients with PAD do not require a procedure, Soo Hyun (Esther) Kim, MD, MPH, director of the Center for Women’s Cardiovascular Health at Atrium Health Sanger Heart and Vascular Institute in Charlotte, N.C., said in an interview. In fact, “many patients do not even know they have leg artery blockages.”

Invasive procedures may well be appropriate for patients with severe PAD, especially those with CLTI, and disparities may be keeping those who truly need such interventions – or for whom they may be at least considered – from accessing them. If PAD is not diagnosed and treated in a timely way, Dr. Kim said, those individuals “do indeed lose their limbs.”

Multidisciplinary teams can help, Dr. Kim said. “Specialists from multiple different training backgrounds [can] take good care of patients with PAD,” she said. This is important when access to a particular type of specialist is limited, and because patients with PAD often have complex medical problems that can benefit from a team approach.

Transcatheter aortic valve replacement heart teams and complex coronary disease heart teams are two examples, Dr. Kim noted. “When a high-stakes procedure is being considered, the patient’s case is reviewed by multiple stakeholders to ensure appropriateness of the procedure and collaboratively evaluate risk.”

Dr. Rao also emphasized a team approach. “PAD does not belong to a single specialty,” he said. The revelations from the Times, ProPublica, and other sources “point to the fact that we all – cardiologists, vascular surgeons, interventional radiologists – should start thinking about how best to police ourselves and also account for the variation in clinical judgment.”

Use of a multidisciplinary team is a “guideline-recommended approach” for coronary artery revascularization, he said, “I think the same should apply for PAD.”

PAD is a sign of systemic atherosclerosis, Dr. Kim noted. “The treatment of PAD includes addressing leg pain and wounds with procedures, but the interventions that will keep people alive are the medications we use to prevent heart attack and stroke. Patients with PAD need to understand that treatment is much more than opening up a blockage in the leg.”

Dr. Rao and Dr. Kim disclosed no relevant conflicts of interest.

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

On May 24, the news outlet ProPublica published a scathing investigation of Jeffery Dormu, DO, said to have performed hundreds of “medically unnecessary and invasive vascular procedures” in his Laurel, Md. office, putting patients’ limbs and lives at risk.

On July 15, The New York Times published a broader-based investigation of several vascular specialists said to have performed “risky” procedures on patients with peripheral artery disease (PAD) who subsequently had to have amputations, or died. The focus was mainly on Michigan-based interventional cardiologist Jihad Mustapha, MD.

This follows a 2019 analysis of Medicare claims data that identified outlier physicians with a high early intervention rate for patients newly diagnosed with claudication. According to the American Heart Association statistics, PAD affects approximately 8.5 million U.S. adults age 40 and older (some claim that’s an underestimate); most cases don’t require invasive treatment.

Are the ProPublica and Times stories emblematic of the field at large or a case of a few rogue doctors, and did changes in reimbursement and support from device manufacturers exacerbate the problem?

Responding to the Times’ revelations, Joseph L. Mills, MD, president of the Society for Vascular Surgery, wrote on the society’s website: “The overwhelming majority of vascular surgeons, and a vast majority of other specialists that receive some training and play a role in the care of vascular patients, including those trained in vascular medicine, interventional cardiology, and interventional radiology are providing high-quality, evidence-based care with safety and the best patient outcomes in mind.

“This is a complex issue that requires the examination not only of the events detailed in this story ... but of the underlying health care economic, legal and regulatory policies that created fertile soil for this behavior to germinate and take root.”
 

‘A few bad apples’

“I think it’s a case of a few bad apples,” Sunil V. Rao, MD, director of interventional cardiology at NYU Langone Health, New York, said in an interview. “In general, I think physicians who take care of patients with vascular issues are trying to do the right thing. I think all of us who take care of patients with vascular disease see patients who are very, very complex, and there are going to be some procedures that have complications.

“Without knowing the clinical details, it’s hard to know whether the procedures described in the articles were overuse or unnecessary, or exactly what led to the amputations,” he said. “All we know is that these physicians are outliers in terms of the number of procedures they were billing for.

“But although correlation is not causation, it certainly is cause for concern because you would expect that the use of procedures for specific indications would fall within a certain range,” he added.
 

Lifestyle changes first

PAD is often asymptomatic or mild, making it difficult to diagnose. Revascularization procedures usually are reserved for the 5%-8% of patients at risk for chronic limb-threatening ischemia (CLTI) or those in whom the cornerstones of PAD treatment – lifestyle changes and, if needed, medication – fail.

Revascularization options include balloon angioplasty or stent placement; atherectomy to remove plaques from the artery; or bypass surgery if a long portion of a leg artery is completely blocked. All carry a risk of long-term adverse outcomes, but the rates are highest for atherectomy.

Lifestyle changes include regular exercise, following a healthy diet, quitting smoking, and controlling diabetes and high blood pressure. When PAD continues or progresses despite these modifications, medications such as antiplatelet agents, antihypertensives, and/or lipid-lowering drugs may be prescribed.
 

‘Medically unnecessary’

According to the latest American Heart Association/American College of Cardiology guideline on managing patients with lower-extremity PAD, patients should be selected for revascularization based on symptom severity.

Factors to consider include a significant disability as assessed by the patient, and adequacy of response to medical and structured exercise therapy.

There’s the rub regarding the clinicians investigated in the Times and ProPublica. Many patients, apparently, were not encouraged to make lifestyle changes, nor did they receive medication. Instead, they were advised from the get-go to undergo invasive procedures, and often multiple times. Underuse of prevention and lifestyle counseling n the management of PAD has long been a concern.

Furthermore, in at least some cases, patients without any symptoms were encouraged to be screened for blockages that were then treated invasively, according to the Times.

Dr. Dormu, as highlighted in ProPublica, positioned his practice as “life and limb saving.” Yet, in investigative findings that led to a suspension of Dr. Dormu’s license to practice medicine in Maryland, peer reviewers expressed concern regarding his repeated use of invasive and medically unnecessary procedures, exposing patients to “potential risks such as bleeding, infection, blood vessel injuries which could acutely or chronically worsen the patient’s circulation, and limb loss.”

The peer reviewers concurred that Dr. Dormu failed to use conservative management techniques to address the patients’ vascular complaints before resorting to invasive procedures.

Dr. Mustapha is described in the Times as a “high-volume” atherectomy provider. From 2017 to 2021, about half of Medicare’s atherectomy payments – $1.4 billion – went to 200 high-volume providers, with Dr. Mustapha near the top of the list.

Some of Dr. Mustapha’s patients underwent multiple procedures said to help prevent leg amputation, but their legs were amputated anyway, possibly because of the multiple atherectomies, according to the Times.

Judith Lin, MD, MBA, who treated some of Dr. Mustapha’s former patients, was among those who complained about his practice to Michigan’s licensing board. Some of the patients she treated needed amputations; others needed to have leftover wires extracted from their legs.

In 2020, the board investigated Dr. Lin’s complaint and referred it to Michigan’s attorney general, who brought a disciplinary action against Dr. Mustapha. An expert hired by the state to review eight patient cases concluded that Dr. Mustapha’s practice “was characterized by overtreatment and poor documentation.” In some cases, the expert wrote, “unnecessary procedures hastened amputations.”

The statement issued by Dr. Mills, the president of SVS, noted that the society’s practice guideline proposes a threshold of at least 2 years of likely durability for an intervention performed for claudication.

“The growing frequency of multiple, repeated procedures [is] emblematic of poor patient selection and inadequate durability of the chosen procedure, leading to a vicious cycle of repetitive interventions that is not only costly, but also dangerous,” he wrote.
 

Financial incentives to blame?

In 2008, Medicare created incentives for physicians to perform vascular procedures in offices rather than hospitals, in an effort to reduce medical costs, according to both investigative articles. But the effort backfired.

Before the changes, an office provider inserting a stent could make about $1,700 from Medicare; deploying a balloon could bring in roughly $3,800. By 2011, the payments rose to about $6,400 and $4,800, respectively.

Office-based atherectomies soared when, in 2011, the Centers for Medicare & Medicaid Services started reimbursing $13,500 per procedure, as opposed to roughly $11,450 in a hospital. Atherectomies increased by 60% from 2011 to 2014, and Medicare’s overall costs for peripheral vascular treatments climbed by nearly half a billion dollars.

“The government is really to blame for setting these tremendously high reimbursement values without looking into whether these procedures are helping people or are just worthless procedures or, in fact, are hurting people,” Dipankar Mukherjee, MD, a vascular surgeon and chief of vascular surgery at Inova Fairfax (Va.) Hospital, said in ProPublica.

The result, noted Dr. Rao, is that “there can be perverse or nefarious incentives for doing these procedures. People are incentivized by reimbursement to do something that really falls in the area of clinical judgment and guidelines.”

Major incentives also come from device manufacturers, who often reward physicians who do the most vascular procedures with payments for consulting and other services, according to the Times. In addition, these companies lend money to help physicians or their clinics to finance the purchase of equipment used to perform the procedures.

“Vascular medicine now is the frontier of the Wild West,” Marty Makary, MD, MPH, a professor of surgery and health care quality researcher at Johns Hopkins University, Baltimore, told ProPublica. “People are flying blind walking into the clinics of these doctors with egregious practice patterns, and we know that their pattern is indefensible.”

Recognizing that the situation posed a threat to patients and also damaged the credibility of his specialty, Kim J. Hodgson, MD, a former SVS president, told attendees at the 2021 annual meeting of the SVS, “Somebody has to address what should never have been allowed to get to this level of threat to us and our patients in the first place. We can play whack-a-mole every time the bad actors surface until the cows come home, but that leaves a trail of harmed patients and wasted resources.”

Dr. Hodgson described atherectomy as “a procedure that many believe provides no demonstrable value whatsoever to the patient” and challenged those who disagree to prove it.
 

Multidisciplinary teams needed

Other experts believe there are times that revascularization procedures, including atherectomy, are appropriate. However, the majority of patients with PAD do not require a procedure, Soo Hyun (Esther) Kim, MD, MPH, director of the Center for Women’s Cardiovascular Health at Atrium Health Sanger Heart and Vascular Institute in Charlotte, N.C., said in an interview. In fact, “many patients do not even know they have leg artery blockages.”

Invasive procedures may well be appropriate for patients with severe PAD, especially those with CLTI, and disparities may be keeping those who truly need such interventions – or for whom they may be at least considered – from accessing them. If PAD is not diagnosed and treated in a timely way, Dr. Kim said, those individuals “do indeed lose their limbs.”

Multidisciplinary teams can help, Dr. Kim said. “Specialists from multiple different training backgrounds [can] take good care of patients with PAD,” she said. This is important when access to a particular type of specialist is limited, and because patients with PAD often have complex medical problems that can benefit from a team approach.

Transcatheter aortic valve replacement heart teams and complex coronary disease heart teams are two examples, Dr. Kim noted. “When a high-stakes procedure is being considered, the patient’s case is reviewed by multiple stakeholders to ensure appropriateness of the procedure and collaboratively evaluate risk.”

Dr. Rao also emphasized a team approach. “PAD does not belong to a single specialty,” he said. The revelations from the Times, ProPublica, and other sources “point to the fact that we all – cardiologists, vascular surgeons, interventional radiologists – should start thinking about how best to police ourselves and also account for the variation in clinical judgment.”

Use of a multidisciplinary team is a “guideline-recommended approach” for coronary artery revascularization, he said, “I think the same should apply for PAD.”

PAD is a sign of systemic atherosclerosis, Dr. Kim noted. “The treatment of PAD includes addressing leg pain and wounds with procedures, but the interventions that will keep people alive are the medications we use to prevent heart attack and stroke. Patients with PAD need to understand that treatment is much more than opening up a blockage in the leg.”

Dr. Rao and Dr. Kim disclosed no relevant conflicts of interest.

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

Higher daily step counts, as measured by actigraphy, were linked to heart failure symptoms and health status, although reductions in step counts were not, in a new study.

Daily step counts between 1,000 and 5,000 were significantly associated with symptoms and physical limitations, as reflected in Kansas City Cardiomyopathy Questionnaire (KCCQ) total symptom (TS) and physical limitation (PL) scores.

Participants whose step counts increased by 2,000 steps per day demonstrated a 5.2-point increase in their KCCQ-TS scores and a 5.33-point increase in their KCCQ-PL scores, with higher scores reflecting improvement.

oneinchpunch/Thinkstock

However, declines in step counts were not associated with significant declines in KCCQ-PL scores.

The findings are not yet ready to be implemented into practice, first author Jessica R. Golbus, MD, of the University of Michigan, Ann Arbor, said in an interview. However, she said, they “suggest that clinicians should interpret improvements in step counts as indicative of improving health status, though they should not necessarily be as concerned with reductions in step count.

“I would certainly, however, still encourage clinicians to discuss decrementing physical activity levels with their patients, though an intervention may not necessarily be warranted,” she added.

The study was published online in JACC: Heart Failure.
 

Nonlinear relationship

The investigators analyzed data from the Canagliflozin: Impact on Health Status, Quality of Life and Functional Status in Heart Failure (CHIEF-HF) trial, a randomized, controlled trial that enrolled participants with heart failure who had a smartphone.

Participants were given a Fitbit Versa 2 and completed serial KCCQs via the smartphone app.

The researchers assessed the relationship between daily step count and KCCQ-TS and KCCQ-PL scores at baseline, as well as changes in the scores between 2 and 12 weeks.

The study included 425 patients. The mean age was 63.5 years, 44.5% were women, and 83.3% were White; 40.9% had reduced ejection fraction, 59.1% had preserved ejection fraction, and 27.5% had type 2 diabetes.

At 2 weeks, the mean KCCQ-TS score was 62.7, and the mean KCCQ-PL score was 55.7.

KCCQ-TS scores increased by 2.5 points on average, and KCCQ-PL scores by 4 points through 12 weeks.

When categorized by 25-point ranges, the step count increased with increasing scores for both KCCQ-TS and KCCQ-PL. Those with KCCQ-TS scores of 0-24 averaged 2,437.6 steps daily, and those with scores of 75-100 averaged 4,870.9 steps daily.

Similarly, participants with KCCQ-PL scores of 0-24 averaged 2301.5 steps daily, and those with scores of 75-100 averaged 5,351.9. The relationship remained significant after adjustment.

There were nonlinear relationships between activity and KCCQ scores: Daily step counts below 5,000 steps were associated with KCCQ scores, but there was little association with counts above 5,000 steps.

Compared with participants who walked 2,000 steps per day, those who walked 1,000 had KCCQ-TS scores that were 3.11 points lower; participants who walked 3,000 had KCCQ-TS scores that were 2.89 points higher.

Similarly, participants who walked 1,000 steps per day had KCCQ-PL scores that were 5.36 points lower than those who walked 2,000 steps, and those who walked 3,000 steps had KCCQ-PL scores that were 4.97 points higher.

After adjustment, change in daily step counts was significantly associated with a change in KCCQ-PL scores from baseline through 12 weeks; for example, participants whose step counts increased by 2,000 steps per day experienced a 5.33 increase in their KCCQ-PL scores relative to participants whose step counts did not change.
 

‘New kid on the block’

Frederick Ho, PhD, a lecturer in public health at the University of Glasgow (Scotland), who is a volunteer spokesperson for the American Heart Association, called the study “promising.”

“The study follow-up is relatively short, so it is not known whether the association is valid longer term,” he said in an interview. “It is also possible that patients with more severe symptoms became physically less active, and at the same time had worse outcomes.

“A study with longer follow-up among patients from a broader background would provide confidence on the generalizability of the findings,” said Dr. Ho, who led a recent study that showed accelerometer-measured physical activity was associated with a lower risk of heart failure. “It’d also be interesting to validate the findings using different types of wearable devices.”

Previous studies have shown that wrist-worn wearables might overestimate light-intensity activities, compared with hip-worn devices, he noted. “I’d imagine that the findings would be slightly different due to different types of devices, but the overall premise should remain.”

In a related editorial, Mitchell Psotka, MD, PhD, writes that Dr. Golbus and colleagues “have thankfully moved our understanding of actigraphy forward, although it is still the new kid on the block and will require substantial further testing and validation before widespread reliable clinical and research use.”

Terminology and reporting features need to be standardized, and preferred methods of implementation need to be established, including how to wear the devices, he suggests.

Further research is needed to validate that “accelerometers and their digitally processed movement ‘counts’ actually measure activity and that this measured activity has clinical relevance.”

The study did not receive commercial funding. Dr. Golbus, Dr. Ho, and Dr. Psotka report no relevant relationships.

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

Higher daily step counts, as measured by actigraphy, were linked to heart failure symptoms and health status, although reductions in step counts were not, in a new study.

Daily step counts between 1,000 and 5,000 were significantly associated with symptoms and physical limitations, as reflected in Kansas City Cardiomyopathy Questionnaire (KCCQ) total symptom (TS) and physical limitation (PL) scores.

Participants whose step counts increased by 2,000 steps per day demonstrated a 5.2-point increase in their KCCQ-TS scores and a 5.33-point increase in their KCCQ-PL scores, with higher scores reflecting improvement.

oneinchpunch/Thinkstock

However, declines in step counts were not associated with significant declines in KCCQ-PL scores.

The findings are not yet ready to be implemented into practice, first author Jessica R. Golbus, MD, of the University of Michigan, Ann Arbor, said in an interview. However, she said, they “suggest that clinicians should interpret improvements in step counts as indicative of improving health status, though they should not necessarily be as concerned with reductions in step count.

“I would certainly, however, still encourage clinicians to discuss decrementing physical activity levels with their patients, though an intervention may not necessarily be warranted,” she added.

The study was published online in JACC: Heart Failure.
 

Nonlinear relationship

The investigators analyzed data from the Canagliflozin: Impact on Health Status, Quality of Life and Functional Status in Heart Failure (CHIEF-HF) trial, a randomized, controlled trial that enrolled participants with heart failure who had a smartphone.

Participants were given a Fitbit Versa 2 and completed serial KCCQs via the smartphone app.

The researchers assessed the relationship between daily step count and KCCQ-TS and KCCQ-PL scores at baseline, as well as changes in the scores between 2 and 12 weeks.

The study included 425 patients. The mean age was 63.5 years, 44.5% were women, and 83.3% were White; 40.9% had reduced ejection fraction, 59.1% had preserved ejection fraction, and 27.5% had type 2 diabetes.

At 2 weeks, the mean KCCQ-TS score was 62.7, and the mean KCCQ-PL score was 55.7.

KCCQ-TS scores increased by 2.5 points on average, and KCCQ-PL scores by 4 points through 12 weeks.

When categorized by 25-point ranges, the step count increased with increasing scores for both KCCQ-TS and KCCQ-PL. Those with KCCQ-TS scores of 0-24 averaged 2,437.6 steps daily, and those with scores of 75-100 averaged 4,870.9 steps daily.

Similarly, participants with KCCQ-PL scores of 0-24 averaged 2301.5 steps daily, and those with scores of 75-100 averaged 5,351.9. The relationship remained significant after adjustment.

There were nonlinear relationships between activity and KCCQ scores: Daily step counts below 5,000 steps were associated with KCCQ scores, but there was little association with counts above 5,000 steps.

Compared with participants who walked 2,000 steps per day, those who walked 1,000 had KCCQ-TS scores that were 3.11 points lower; participants who walked 3,000 had KCCQ-TS scores that were 2.89 points higher.

Similarly, participants who walked 1,000 steps per day had KCCQ-PL scores that were 5.36 points lower than those who walked 2,000 steps, and those who walked 3,000 steps had KCCQ-PL scores that were 4.97 points higher.

After adjustment, change in daily step counts was significantly associated with a change in KCCQ-PL scores from baseline through 12 weeks; for example, participants whose step counts increased by 2,000 steps per day experienced a 5.33 increase in their KCCQ-PL scores relative to participants whose step counts did not change.
 

‘New kid on the block’

Frederick Ho, PhD, a lecturer in public health at the University of Glasgow (Scotland), who is a volunteer spokesperson for the American Heart Association, called the study “promising.”

“The study follow-up is relatively short, so it is not known whether the association is valid longer term,” he said in an interview. “It is also possible that patients with more severe symptoms became physically less active, and at the same time had worse outcomes.

“A study with longer follow-up among patients from a broader background would provide confidence on the generalizability of the findings,” said Dr. Ho, who led a recent study that showed accelerometer-measured physical activity was associated with a lower risk of heart failure. “It’d also be interesting to validate the findings using different types of wearable devices.”

Previous studies have shown that wrist-worn wearables might overestimate light-intensity activities, compared with hip-worn devices, he noted. “I’d imagine that the findings would be slightly different due to different types of devices, but the overall premise should remain.”

In a related editorial, Mitchell Psotka, MD, PhD, writes that Dr. Golbus and colleagues “have thankfully moved our understanding of actigraphy forward, although it is still the new kid on the block and will require substantial further testing and validation before widespread reliable clinical and research use.”

Terminology and reporting features need to be standardized, and preferred methods of implementation need to be established, including how to wear the devices, he suggests.

Further research is needed to validate that “accelerometers and their digitally processed movement ‘counts’ actually measure activity and that this measured activity has clinical relevance.”

The study did not receive commercial funding. Dr. Golbus, Dr. Ho, and Dr. Psotka report no relevant relationships.

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

Higher daily step counts, as measured by actigraphy, were linked to heart failure symptoms and health status, although reductions in step counts were not, in a new study.

Daily step counts between 1,000 and 5,000 were significantly associated with symptoms and physical limitations, as reflected in Kansas City Cardiomyopathy Questionnaire (KCCQ) total symptom (TS) and physical limitation (PL) scores.

Participants whose step counts increased by 2,000 steps per day demonstrated a 5.2-point increase in their KCCQ-TS scores and a 5.33-point increase in their KCCQ-PL scores, with higher scores reflecting improvement.

oneinchpunch/Thinkstock

However, declines in step counts were not associated with significant declines in KCCQ-PL scores.

The findings are not yet ready to be implemented into practice, first author Jessica R. Golbus, MD, of the University of Michigan, Ann Arbor, said in an interview. However, she said, they “suggest that clinicians should interpret improvements in step counts as indicative of improving health status, though they should not necessarily be as concerned with reductions in step count.

“I would certainly, however, still encourage clinicians to discuss decrementing physical activity levels with their patients, though an intervention may not necessarily be warranted,” she added.

The study was published online in JACC: Heart Failure.
 

Nonlinear relationship

The investigators analyzed data from the Canagliflozin: Impact on Health Status, Quality of Life and Functional Status in Heart Failure (CHIEF-HF) trial, a randomized, controlled trial that enrolled participants with heart failure who had a smartphone.

Participants were given a Fitbit Versa 2 and completed serial KCCQs via the smartphone app.

The researchers assessed the relationship between daily step count and KCCQ-TS and KCCQ-PL scores at baseline, as well as changes in the scores between 2 and 12 weeks.

The study included 425 patients. The mean age was 63.5 years, 44.5% were women, and 83.3% were White; 40.9% had reduced ejection fraction, 59.1% had preserved ejection fraction, and 27.5% had type 2 diabetes.

At 2 weeks, the mean KCCQ-TS score was 62.7, and the mean KCCQ-PL score was 55.7.

KCCQ-TS scores increased by 2.5 points on average, and KCCQ-PL scores by 4 points through 12 weeks.

When categorized by 25-point ranges, the step count increased with increasing scores for both KCCQ-TS and KCCQ-PL. Those with KCCQ-TS scores of 0-24 averaged 2,437.6 steps daily, and those with scores of 75-100 averaged 4,870.9 steps daily.

Similarly, participants with KCCQ-PL scores of 0-24 averaged 2301.5 steps daily, and those with scores of 75-100 averaged 5,351.9. The relationship remained significant after adjustment.

There were nonlinear relationships between activity and KCCQ scores: Daily step counts below 5,000 steps were associated with KCCQ scores, but there was little association with counts above 5,000 steps.

Compared with participants who walked 2,000 steps per day, those who walked 1,000 had KCCQ-TS scores that were 3.11 points lower; participants who walked 3,000 had KCCQ-TS scores that were 2.89 points higher.

Similarly, participants who walked 1,000 steps per day had KCCQ-PL scores that were 5.36 points lower than those who walked 2,000 steps, and those who walked 3,000 steps had KCCQ-PL scores that were 4.97 points higher.

After adjustment, change in daily step counts was significantly associated with a change in KCCQ-PL scores from baseline through 12 weeks; for example, participants whose step counts increased by 2,000 steps per day experienced a 5.33 increase in their KCCQ-PL scores relative to participants whose step counts did not change.
 

‘New kid on the block’

Frederick Ho, PhD, a lecturer in public health at the University of Glasgow (Scotland), who is a volunteer spokesperson for the American Heart Association, called the study “promising.”

“The study follow-up is relatively short, so it is not known whether the association is valid longer term,” he said in an interview. “It is also possible that patients with more severe symptoms became physically less active, and at the same time had worse outcomes.

“A study with longer follow-up among patients from a broader background would provide confidence on the generalizability of the findings,” said Dr. Ho, who led a recent study that showed accelerometer-measured physical activity was associated with a lower risk of heart failure. “It’d also be interesting to validate the findings using different types of wearable devices.”

Previous studies have shown that wrist-worn wearables might overestimate light-intensity activities, compared with hip-worn devices, he noted. “I’d imagine that the findings would be slightly different due to different types of devices, but the overall premise should remain.”

In a related editorial, Mitchell Psotka, MD, PhD, writes that Dr. Golbus and colleagues “have thankfully moved our understanding of actigraphy forward, although it is still the new kid on the block and will require substantial further testing and validation before widespread reliable clinical and research use.”

Terminology and reporting features need to be standardized, and preferred methods of implementation need to be established, including how to wear the devices, he suggests.

Further research is needed to validate that “accelerometers and their digitally processed movement ‘counts’ actually measure activity and that this measured activity has clinical relevance.”

The study did not receive commercial funding. Dr. Golbus, Dr. Ho, and Dr. Psotka report no relevant relationships.

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

TOPLINE:

Direct oral anticoagulants (DOACs) are associated with a reduced risk of venous thromboembolism (VTE), major bleeding, and mortality for cancer patients with VTE in comparison with low-molecular-weight heparin (LMWH), according to a recent analysis of U.S. claims data.

METHODOLOGY:

• This retrospective cohort study of electronic records claims data from OptumLabs included adults with an active primary cancer and acute VTE.
• Patients had filled an anticoagulation prescription within 30 days of VTE onset and were categorized on the basis of the anticoagulant prescribed: DOAC, LMWH, or warfarin.
• Patients were followed until the end of treatment. VTE recurrence and all-cause mortality were the main efficacy endpoints, and major bleeding episodes and bleeding sites were the main safety endpoints.
• Overall, 5,100 patients were included (mean age, 66.3 years); a majority (69.8%) were White, 15.7% were Black, and 7.6% were Hispanic. The patients had a range of cancer types, including lung, colorectal, gynecologic, and urologic.
• Nearly half of patients (49.3%) filled prescriptions for DOACs, 29.2% for LMWH, and 28.6% for warfarin.

TAKEAWAY:

• Compared with DOACs, LMWH and warfarin were associated with an increased risk of VTE recurrence (hazard ratio, 1.47 and 1.46, respectively).
• LMWH use was associated with an increased risk of major bleeding (HR, 2.27) and all-cause mortality (HR, 1.61), compared with DOAC use; mortality rates did not differ significantly between warfarin and DOACs (HR, 1.19; 95% confidence interval, 0.85-1.68).
• Patients who received LMWH were at increased risk of hospitalization for major bleeding, GI bleeding, and intracranial bleeding, compared with those who received DOACs (HR, 2.27, 1.72, 2.72, respectively).
• The risks of hospitalization for major bleeding, GI bleeding, and intracranial bleeding among patients who received warfarin and DOACs were similar (HR, 1.12, 1.03, 1.04, respectively).

IN PRACTICE:

Consistent with recent trials, “these data reinforce the general efficacy and safety of DOACs in this patient population” and reveal an association between DOACs and reduced all-cause mortality, the study authors wrote. These data may “help facilitate shared decision-marking and inform clinical guidelines for the treatment of such patients.”

SOURCE:

The study, led by Irbaz Bin Riaz, MD, PhD, of Mayo Clinic, Phoenix, Ariz., was published online in JAMA Network Open on July 24.

LIMITATIONS:

The study is limited by the potential for information bias in the database, the use of ICD codes to identify VTE patients, and the lack of radiologic evidence for VTE, as well as the lack of assessment for clinically relevant nonmajor bleeding.

The use of U.S. claims data limits the applicability of the results to other populations, including the uninsured.
 

DISCLOSURES:

No funding was declared. The authors have disclosed no relevant financial relationships.

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

TOPLINE:

Direct oral anticoagulants (DOACs) are associated with a reduced risk of venous thromboembolism (VTE), major bleeding, and mortality for cancer patients with VTE in comparison with low-molecular-weight heparin (LMWH), according to a recent analysis of U.S. claims data.

METHODOLOGY:

• This retrospective cohort study of electronic records claims data from OptumLabs included adults with an active primary cancer and acute VTE.
• Patients had filled an anticoagulation prescription within 30 days of VTE onset and were categorized on the basis of the anticoagulant prescribed: DOAC, LMWH, or warfarin.
• Patients were followed until the end of treatment. VTE recurrence and all-cause mortality were the main efficacy endpoints, and major bleeding episodes and bleeding sites were the main safety endpoints.
• Overall, 5,100 patients were included (mean age, 66.3 years); a majority (69.8%) were White, 15.7% were Black, and 7.6% were Hispanic. The patients had a range of cancer types, including lung, colorectal, gynecologic, and urologic.
• Nearly half of patients (49.3%) filled prescriptions for DOACs, 29.2% for LMWH, and 28.6% for warfarin.

TAKEAWAY:

• Compared with DOACs, LMWH and warfarin were associated with an increased risk of VTE recurrence (hazard ratio, 1.47 and 1.46, respectively).
• LMWH use was associated with an increased risk of major bleeding (HR, 2.27) and all-cause mortality (HR, 1.61), compared with DOAC use; mortality rates did not differ significantly between warfarin and DOACs (HR, 1.19; 95% confidence interval, 0.85-1.68).
• Patients who received LMWH were at increased risk of hospitalization for major bleeding, GI bleeding, and intracranial bleeding, compared with those who received DOACs (HR, 2.27, 1.72, 2.72, respectively).
• The risks of hospitalization for major bleeding, GI bleeding, and intracranial bleeding among patients who received warfarin and DOACs were similar (HR, 1.12, 1.03, 1.04, respectively).

IN PRACTICE:

Consistent with recent trials, “these data reinforce the general efficacy and safety of DOACs in this patient population” and reveal an association between DOACs and reduced all-cause mortality, the study authors wrote. These data may “help facilitate shared decision-marking and inform clinical guidelines for the treatment of such patients.”

SOURCE:

The study, led by Irbaz Bin Riaz, MD, PhD, of Mayo Clinic, Phoenix, Ariz., was published online in JAMA Network Open on July 24.

LIMITATIONS:

The study is limited by the potential for information bias in the database, the use of ICD codes to identify VTE patients, and the lack of radiologic evidence for VTE, as well as the lack of assessment for clinically relevant nonmajor bleeding.

The use of U.S. claims data limits the applicability of the results to other populations, including the uninsured.
 

DISCLOSURES:

No funding was declared. The authors have disclosed no relevant financial relationships.

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

TOPLINE:

Direct oral anticoagulants (DOACs) are associated with a reduced risk of venous thromboembolism (VTE), major bleeding, and mortality for cancer patients with VTE in comparison with low-molecular-weight heparin (LMWH), according to a recent analysis of U.S. claims data.

METHODOLOGY:

• This retrospective cohort study of electronic records claims data from OptumLabs included adults with an active primary cancer and acute VTE.
• Patients had filled an anticoagulation prescription within 30 days of VTE onset and were categorized on the basis of the anticoagulant prescribed: DOAC, LMWH, or warfarin.
• Patients were followed until the end of treatment. VTE recurrence and all-cause mortality were the main efficacy endpoints, and major bleeding episodes and bleeding sites were the main safety endpoints.
• Overall, 5,100 patients were included (mean age, 66.3 years); a majority (69.8%) were White, 15.7% were Black, and 7.6% were Hispanic. The patients had a range of cancer types, including lung, colorectal, gynecologic, and urologic.
• Nearly half of patients (49.3%) filled prescriptions for DOACs, 29.2% for LMWH, and 28.6% for warfarin.

TAKEAWAY:

• Compared with DOACs, LMWH and warfarin were associated with an increased risk of VTE recurrence (hazard ratio, 1.47 and 1.46, respectively).
• LMWH use was associated with an increased risk of major bleeding (HR, 2.27) and all-cause mortality (HR, 1.61), compared with DOAC use; mortality rates did not differ significantly between warfarin and DOACs (HR, 1.19; 95% confidence interval, 0.85-1.68).
• Patients who received LMWH were at increased risk of hospitalization for major bleeding, GI bleeding, and intracranial bleeding, compared with those who received DOACs (HR, 2.27, 1.72, 2.72, respectively).
• The risks of hospitalization for major bleeding, GI bleeding, and intracranial bleeding among patients who received warfarin and DOACs were similar (HR, 1.12, 1.03, 1.04, respectively).

IN PRACTICE:

Consistent with recent trials, “these data reinforce the general efficacy and safety of DOACs in this patient population” and reveal an association between DOACs and reduced all-cause mortality, the study authors wrote. These data may “help facilitate shared decision-marking and inform clinical guidelines for the treatment of such patients.”

SOURCE:

The study, led by Irbaz Bin Riaz, MD, PhD, of Mayo Clinic, Phoenix, Ariz., was published online in JAMA Network Open on July 24.

LIMITATIONS:

The study is limited by the potential for information bias in the database, the use of ICD codes to identify VTE patients, and the lack of radiologic evidence for VTE, as well as the lack of assessment for clinically relevant nonmajor bleeding.

The use of U.S. claims data limits the applicability of the results to other populations, including the uninsured.
 

DISCLOSURES:

No funding was declared. The authors have disclosed no relevant financial relationships.

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

The artificial intelligence chatbot ChatGPT can potentially be used as source of information for patients, as well as an aid to clinicians managing gastroesophageal reflux disease (GERD), investigators have found.

The researchers say the tool’s conversational format could improve clinical efficiency and reduce the volume of patient messages and calls, potentially diminishing clinician burnout.

However, inconsistencies and content errors observed require a certain level of clinical oversight, caution the researchers, led by Jacqueline Henson, MD, with the division of gastroenterology, Duke University, Durham, N.C.

The study was published online in the American Journal of Gastroenterology.
 

Putting ChatGPT to the GERD test

Affecting nearly 30% of U.S. adults, GERD is a common and increasingly complex condition to manage. AI technologies like ChatGPT (Open AI/Microsoft) have demonstrated an increasing role in medicine, although the ability of ChatGPT to provide guidance for GERD management is uncertain.

Dr. Henson and colleagues assessed ChatGPT’s ability to provide accurate and specific responses to questions regarding GERD care.

They generated 23 GERD management prompts based on published clinical guidelines and expert consensus recommendations. Five questions were about diagnosis, eleven on treatment, and seven on both diagnosis and treatment.

Each prompt was submitted to ChatGPT 3.5 (version 3/14/2023) three times on separate occasions without feedback to assess the consistency of the answer. Responses were rated by three board-certified gastroenterologists for appropriateness and specificity.

ChatGPT returned appropriate responses to 63 of 69 (91.3%) queries, with 29% considered completely appropriate and 62.3% mostly appropriate.

However, responses to the same prompt were often inconsistent, with 16 of 23 (70%) prompts yielding varying appropriateness, including three (13%) with both inappropriate and appropriate responses.

Prompts regarding treatment received the highest proportion of completely appropriate responses (39.4%), while prompts for diagnosis and management had the highest proportion of mostly inappropriate responses (14.3%).

For example, the chatbot failed to recommend consideration of Roux-en-Y gastric bypass for ongoing GERD symptoms with pathologic acid exposure in the setting of obesity, and some potential risks associated with proton pump inhibitor therapy were stated as fact.

However, the majority (78.3%) of responses contained at least some specific guidance, especially for prompts assessing diagnosis (93.3%). In all responses, ChatGPT suggested contacting a health care professional for further advice.

Eight patients from a range of educational backgrounds who provided feedback on the responses generally felt that the ChatGPT responses were both understandable and useful.

Overall, ChatGPT “provided largely appropriate and at least some specific guidance for GERD management, highlighting the potential for this technology to serve as a source of information for patients, as well as an aid for clinicians,” Dr. Henson and colleagues write.

However, “the presence of inappropriate responses with inconsistencies to the same prompt largely preclude its application within health care in its present state, at least for GERD,” they add.

The study had no commercial funding. Dr. Henson has served as a consultant for Medtronic.

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

The artificial intelligence chatbot ChatGPT can potentially be used as source of information for patients, as well as an aid to clinicians managing gastroesophageal reflux disease (GERD), investigators have found.

The researchers say the tool’s conversational format could improve clinical efficiency and reduce the volume of patient messages and calls, potentially diminishing clinician burnout.

However, inconsistencies and content errors observed require a certain level of clinical oversight, caution the researchers, led by Jacqueline Henson, MD, with the division of gastroenterology, Duke University, Durham, N.C.

The study was published online in the American Journal of Gastroenterology.
 

Putting ChatGPT to the GERD test

Affecting nearly 30% of U.S. adults, GERD is a common and increasingly complex condition to manage. AI technologies like ChatGPT (Open AI/Microsoft) have demonstrated an increasing role in medicine, although the ability of ChatGPT to provide guidance for GERD management is uncertain.

Dr. Henson and colleagues assessed ChatGPT’s ability to provide accurate and specific responses to questions regarding GERD care.

They generated 23 GERD management prompts based on published clinical guidelines and expert consensus recommendations. Five questions were about diagnosis, eleven on treatment, and seven on both diagnosis and treatment.

Each prompt was submitted to ChatGPT 3.5 (version 3/14/2023) three times on separate occasions without feedback to assess the consistency of the answer. Responses were rated by three board-certified gastroenterologists for appropriateness and specificity.

ChatGPT returned appropriate responses to 63 of 69 (91.3%) queries, with 29% considered completely appropriate and 62.3% mostly appropriate.

However, responses to the same prompt were often inconsistent, with 16 of 23 (70%) prompts yielding varying appropriateness, including three (13%) with both inappropriate and appropriate responses.

Prompts regarding treatment received the highest proportion of completely appropriate responses (39.4%), while prompts for diagnosis and management had the highest proportion of mostly inappropriate responses (14.3%).

For example, the chatbot failed to recommend consideration of Roux-en-Y gastric bypass for ongoing GERD symptoms with pathologic acid exposure in the setting of obesity, and some potential risks associated with proton pump inhibitor therapy were stated as fact.

However, the majority (78.3%) of responses contained at least some specific guidance, especially for prompts assessing diagnosis (93.3%). In all responses, ChatGPT suggested contacting a health care professional for further advice.

Eight patients from a range of educational backgrounds who provided feedback on the responses generally felt that the ChatGPT responses were both understandable and useful.

Overall, ChatGPT “provided largely appropriate and at least some specific guidance for GERD management, highlighting the potential for this technology to serve as a source of information for patients, as well as an aid for clinicians,” Dr. Henson and colleagues write.

However, “the presence of inappropriate responses with inconsistencies to the same prompt largely preclude its application within health care in its present state, at least for GERD,” they add.

The study had no commercial funding. Dr. Henson has served as a consultant for Medtronic.

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

The artificial intelligence chatbot ChatGPT can potentially be used as source of information for patients, as well as an aid to clinicians managing gastroesophageal reflux disease (GERD), investigators have found.

The researchers say the tool’s conversational format could improve clinical efficiency and reduce the volume of patient messages and calls, potentially diminishing clinician burnout.

However, inconsistencies and content errors observed require a certain level of clinical oversight, caution the researchers, led by Jacqueline Henson, MD, with the division of gastroenterology, Duke University, Durham, N.C.

The study was published online in the American Journal of Gastroenterology.
 

Putting ChatGPT to the GERD test

Affecting nearly 30% of U.S. adults, GERD is a common and increasingly complex condition to manage. AI technologies like ChatGPT (Open AI/Microsoft) have demonstrated an increasing role in medicine, although the ability of ChatGPT to provide guidance for GERD management is uncertain.

Dr. Henson and colleagues assessed ChatGPT’s ability to provide accurate and specific responses to questions regarding GERD care.

They generated 23 GERD management prompts based on published clinical guidelines and expert consensus recommendations. Five questions were about diagnosis, eleven on treatment, and seven on both diagnosis and treatment.

Each prompt was submitted to ChatGPT 3.5 (version 3/14/2023) three times on separate occasions without feedback to assess the consistency of the answer. Responses were rated by three board-certified gastroenterologists for appropriateness and specificity.

ChatGPT returned appropriate responses to 63 of 69 (91.3%) queries, with 29% considered completely appropriate and 62.3% mostly appropriate.

However, responses to the same prompt were often inconsistent, with 16 of 23 (70%) prompts yielding varying appropriateness, including three (13%) with both inappropriate and appropriate responses.

Prompts regarding treatment received the highest proportion of completely appropriate responses (39.4%), while prompts for diagnosis and management had the highest proportion of mostly inappropriate responses (14.3%).

For example, the chatbot failed to recommend consideration of Roux-en-Y gastric bypass for ongoing GERD symptoms with pathologic acid exposure in the setting of obesity, and some potential risks associated with proton pump inhibitor therapy were stated as fact.

However, the majority (78.3%) of responses contained at least some specific guidance, especially for prompts assessing diagnosis (93.3%). In all responses, ChatGPT suggested contacting a health care professional for further advice.

Eight patients from a range of educational backgrounds who provided feedback on the responses generally felt that the ChatGPT responses were both understandable and useful.

Overall, ChatGPT “provided largely appropriate and at least some specific guidance for GERD management, highlighting the potential for this technology to serve as a source of information for patients, as well as an aid for clinicians,” Dr. Henson and colleagues write.

However, “the presence of inappropriate responses with inconsistencies to the same prompt largely preclude its application within health care in its present state, at least for GERD,” they add.

The study had no commercial funding. Dr. Henson has served as a consultant for Medtronic.

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

Janus kinase inhibitors (JAKi) are a novel class of oral, targeted small-molecule inhibitors that are increasingly used to treat several different autoimmune conditions. In terms of rheumatologic indications, the FDA first approved tofacitinib (TOF) for use in moderate to severe rheumatoid arthritis (RA) unresponsive to methotrexate therapy. Eleven years later, the indications for JAKi use have expanded to include ulcerative colitis, ankylosing spondylitis, and psoriatic arthritis (PsA), among other diseases. As with any new therapeutic mechanism, there are questions as to how JAKi should be incorporated into the treatment paradigm of PsA. In this article, we briefly review the efficacy and safety data of these agents and discuss our approach to their use in PsA.

Two JAKi are currently FDA approved for the treatment of PsA: tofacitinib (TOF) and upadacitinib (UPA). Other JAKi, such as filgotinib and peficitinib, are only approved outside the United States and will not be discussed here. 

TOF was originally studied in skin psoriasis (PsO) before 2 pivotal studies demonstrated efficacy in PsA. TOF or adalimumab (ADA) were compared with placebo in patients who had failed conventional synthetic disease-modifying antirheumatic drugs (DMARD).¹ ACR20 response was superior with TOF 5 mg twice daily (BID) (50%) and 10 mg BID (61%) vs placebo (33%), and it was comparable to ADA (52%), which was used in this study as an active comparator. The overall rate of adverse events was similar with both doses of TOF when compared with ADA; however, patients taking TOF had numerically more cases of cancer, serious infection, and herpes zoster. 

Another study evaluated TOF compared with placebo in patients with PsA who had an inadequate response to tumor necrosis factor inhibitor (TNFi) therapy.² The study showed an ACR20 response of 50% in patients taking TOF 5 mg BID and 47% in patients taking 10 mg BID, compared with 24% in those taking placebo. Patients who received the 10 mg TOF dose continuously had higher rates of adverse events compared to TOF 5 mg, placebo, and patients who crossed over from placebo to TOF at either dose. In the TOF groups, there were cases of serious infection and herpes zoster, as well as 2 patients with major adverse cardiovascular events (MACE). Following review of these data, the FDA approved only the 5 mg BID dose, and later an 11-mg daily extended-release formulation that was pharmacokinetically similar.

The efficacy for UPA in PsA was shown in 2 pivotal phase 3 trials. SELECT-PsA1 compared UPA at 2 doses, 15 mg and 30 mg daily, vs placebo and vs ADA in patients with biologic DMARD (bDMARD)-naïve PsA.³ This trial demonstrated superiority of UPA in the ACR20 response at both doses (71% and 79%, respectively) compared with placebo (36%). The 15-mg dose of UPA was comparable to ADA (65%), while the 30-mg dose achieved superiority compared to ADA. Secondary outcomes including skin activity, patient-reported symptoms, and inhibition of radiographic progression were also superior in UPA compared with placebo and similar or greater with UPA compared with ADA, depending on the specific outcome.⁴ SELECT-PsA2 compared UPA 15 mg, 30 mg, and placebo in patients with prior incomplete response or intolerance to a bDMARD.⁵ At week 12 of the study, patients taking UPA 15 mg and 30 mg had an ACR20 response of 57% and 64%, respectively, compared with placebo (24%). At week 24, minimal disease activity was achieved by 25% of patients taking UPA 15 mg and 29% of patients taking UPA 30 mg, which was superior to placebo (3%). 

Both studies found a significant increase in infections, including serious infections, at the 30-mg UPA dose compared with the placebo and adalimumab groups. Cytopenia and elevated creatine kinase (CK) level also occurred more frequently in the UPA 30-mg group. Rates of cancer were low overall and comparable between the patients treated with UPA and ADA. Given the higher incidence of adverse events with the 30-mg dose and the relatively similar efficacy, the sponsor elected to submit only the lower dose to the FDA for approval.

In the last few years, concerns for safety with JAKi use grew after the publication of data from the ORAL SURVEILLANCE trial, an FDA-mandated, post-approval safety study of TOF in RA. In this trial, patients with active RA over 50 years of age and with at least 1 additional cardiovascular risk factor were randomized to TOF at 1 of 2 doses, 5 mg or 10 mg BID, or a TNFi.⁶ This trial was designed as a noninferiority study, and TOF did not meet the noninferiority threshold compared to TNFi, with hazard ratios of 1.33 and 1.48 for MACE and malignancy, respectively. The results of this trial prompted the FDA to add a black box warning to the label for all JAKi, pointing out the risk of malignancy and MACE, as well as infection, mortality, and thrombosis. 

In the ORAL SURVEILLANCE trial, the increased risk of MACE and malignancy was primarily seen in the study patients with high risk for a cardiovascular event. To address the question of whether a similar risk profile exists when using JAKi to treat PsA, or whether this is a disease-specific process related to RA, a post hoc analysis of 3 PsA trials and 7 PsO trials of patients treated with TOF was conducted.⁷ The analysis found that patients with a history of atherosclerotic cardiovascular disease (ASCVD) or metabolic syndrome, or patients at high risk for ASCVD (score > 20%) had increased incidence rates of MACE compared with those with low risk scores for ASCVD. Interestingly, as in RA, increased incidence rates of malignancy were seen in patients with preexisting or at high risk for ASCVD.

While the FDA recommends JAKi use in patients who have failed or are inappropriate for treatment with a TNFi, we would consider the use of JAKi for first-line therapy in PsA on an individual basis. One advantage of JAKi is their efficacy across multiple PsA domains, including peripheral arthritis, axial disease, enthesitis, dactylitis, and skin disease (although the approved dose of TOF was not statistically effective for PsO in the pivotal trials). Based on this efficacy, we believe that patients with overlapping, multifaceted disease may benefit the most from these medications. Patient risk factors and comorbidities are a prominent consideration in our use of JAKi to ensure safety, as the risk for MACE and malignancy is informed partly by baseline cardiovascular status. In younger patients without cardiovascular risk factors, JAKi may be a strong candidate for first-line therapy, particularly in patients averse to subcutaneous or intravenous therapy. We do counsel all patients on the increased risk of infection, and we do recommend inactivated herpes zoster vaccination in previously unvaccinated patients planning to start JAKi therapy. 

On the horizon are the development of novel, oral agents targeting tyrosine kinase 2 (TYK2), which is a member of the JAK family of signaling proteins. In fact, the TYK2 inhibitor deucravacitinib was approved by the FDA in 2022 for the treatment of PsO. TYK2 inhibitors appear to have the advantage of a more selective mechanism of action, with fewer off-target effects. There were fewer adverse events in the deucravacitinib trials, which led to its prompt PsO authorization, and the FDA approval for the drug did not include the same black box warning that appears in the label for other JAKi.⁸ A phase 2 study showed early promise for the efficacy and safety of deucravacitinib in PsA.⁹ Further investigation will be needed to better understand the role of deucravacitinib and other TYK2 inhibitors being developed for the treatment of PsA. In the meantime, JAKi continue to be a prominent consideration for first-line PsA therapy in a carefully selected patient population. 

Janus kinase inhibitors (JAKi) are a novel class of oral, targeted small-molecule inhibitors that are increasingly used to treat several different autoimmune conditions. In terms of rheumatologic indications, the FDA first approved tofacitinib (TOF) for use in moderate to severe rheumatoid arthritis (RA) unresponsive to methotrexate therapy. Eleven years later, the indications for JAKi use have expanded to include ulcerative colitis, ankylosing spondylitis, and psoriatic arthritis (PsA), among other diseases. As with any new therapeutic mechanism, there are questions as to how JAKi should be incorporated into the treatment paradigm of PsA. In this article, we briefly review the efficacy and safety data of these agents and discuss our approach to their use in PsA.

Two JAKi are currently FDA approved for the treatment of PsA: tofacitinib (TOF) and upadacitinib (UPA). Other JAKi, such as filgotinib and peficitinib, are only approved outside the United States and will not be discussed here. 

TOF was originally studied in skin psoriasis (PsO) before 2 pivotal studies demonstrated efficacy in PsA. TOF or adalimumab (ADA) were compared with placebo in patients who had failed conventional synthetic disease-modifying antirheumatic drugs (DMARD).¹ ACR20 response was superior with TOF 5 mg twice daily (BID) (50%) and 10 mg BID (61%) vs placebo (33%), and it was comparable to ADA (52%), which was used in this study as an active comparator. The overall rate of adverse events was similar with both doses of TOF when compared with ADA; however, patients taking TOF had numerically more cases of cancer, serious infection, and herpes zoster. 

Another study evaluated TOF compared with placebo in patients with PsA who had an inadequate response to tumor necrosis factor inhibitor (TNFi) therapy.² The study showed an ACR20 response of 50% in patients taking TOF 5 mg BID and 47% in patients taking 10 mg BID, compared with 24% in those taking placebo. Patients who received the 10 mg TOF dose continuously had higher rates of adverse events compared to TOF 5 mg, placebo, and patients who crossed over from placebo to TOF at either dose. In the TOF groups, there were cases of serious infection and herpes zoster, as well as 2 patients with major adverse cardiovascular events (MACE). Following review of these data, the FDA approved only the 5 mg BID dose, and later an 11-mg daily extended-release formulation that was pharmacokinetically similar.

The efficacy for UPA in PsA was shown in 2 pivotal phase 3 trials. SELECT-PsA1 compared UPA at 2 doses, 15 mg and 30 mg daily, vs placebo and vs ADA in patients with biologic DMARD (bDMARD)-naïve PsA.³ This trial demonstrated superiority of UPA in the ACR20 response at both doses (71% and 79%, respectively) compared with placebo (36%). The 15-mg dose of UPA was comparable to ADA (65%), while the 30-mg dose achieved superiority compared to ADA. Secondary outcomes including skin activity, patient-reported symptoms, and inhibition of radiographic progression were also superior in UPA compared with placebo and similar or greater with UPA compared with ADA, depending on the specific outcome.⁴ SELECT-PsA2 compared UPA 15 mg, 30 mg, and placebo in patients with prior incomplete response or intolerance to a bDMARD.⁵ At week 12 of the study, patients taking UPA 15 mg and 30 mg had an ACR20 response of 57% and 64%, respectively, compared with placebo (24%). At week 24, minimal disease activity was achieved by 25% of patients taking UPA 15 mg and 29% of patients taking UPA 30 mg, which was superior to placebo (3%). 

Both studies found a significant increase in infections, including serious infections, at the 30-mg UPA dose compared with the placebo and adalimumab groups. Cytopenia and elevated creatine kinase (CK) level also occurred more frequently in the UPA 30-mg group. Rates of cancer were low overall and comparable between the patients treated with UPA and ADA. Given the higher incidence of adverse events with the 30-mg dose and the relatively similar efficacy, the sponsor elected to submit only the lower dose to the FDA for approval.

In the last few years, concerns for safety with JAKi use grew after the publication of data from the ORAL SURVEILLANCE trial, an FDA-mandated, post-approval safety study of TOF in RA. In this trial, patients with active RA over 50 years of age and with at least 1 additional cardiovascular risk factor were randomized to TOF at 1 of 2 doses, 5 mg or 10 mg BID, or a TNFi.⁶ This trial was designed as a noninferiority study, and TOF did not meet the noninferiority threshold compared to TNFi, with hazard ratios of 1.33 and 1.48 for MACE and malignancy, respectively. The results of this trial prompted the FDA to add a black box warning to the label for all JAKi, pointing out the risk of malignancy and MACE, as well as infection, mortality, and thrombosis. 

In the ORAL SURVEILLANCE trial, the increased risk of MACE and malignancy was primarily seen in the study patients with high risk for a cardiovascular event. To address the question of whether a similar risk profile exists when using JAKi to treat PsA, or whether this is a disease-specific process related to RA, a post hoc analysis of 3 PsA trials and 7 PsO trials of patients treated with TOF was conducted.⁷ The analysis found that patients with a history of atherosclerotic cardiovascular disease (ASCVD) or metabolic syndrome, or patients at high risk for ASCVD (score > 20%) had increased incidence rates of MACE compared with those with low risk scores for ASCVD. Interestingly, as in RA, increased incidence rates of malignancy were seen in patients with preexisting or at high risk for ASCVD.

While the FDA recommends JAKi use in patients who have failed or are inappropriate for treatment with a TNFi, we would consider the use of JAKi for first-line therapy in PsA on an individual basis. One advantage of JAKi is their efficacy across multiple PsA domains, including peripheral arthritis, axial disease, enthesitis, dactylitis, and skin disease (although the approved dose of TOF was not statistically effective for PsO in the pivotal trials). Based on this efficacy, we believe that patients with overlapping, multifaceted disease may benefit the most from these medications. Patient risk factors and comorbidities are a prominent consideration in our use of JAKi to ensure safety, as the risk for MACE and malignancy is informed partly by baseline cardiovascular status. In younger patients without cardiovascular risk factors, JAKi may be a strong candidate for first-line therapy, particularly in patients averse to subcutaneous or intravenous therapy. We do counsel all patients on the increased risk of infection, and we do recommend inactivated herpes zoster vaccination in previously unvaccinated patients planning to start JAKi therapy. 

On the horizon are the development of novel, oral agents targeting tyrosine kinase 2 (TYK2), which is a member of the JAK family of signaling proteins. In fact, the TYK2 inhibitor deucravacitinib was approved by the FDA in 2022 for the treatment of PsO. TYK2 inhibitors appear to have the advantage of a more selective mechanism of action, with fewer off-target effects. There were fewer adverse events in the deucravacitinib trials, which led to its prompt PsO authorization, and the FDA approval for the drug did not include the same black box warning that appears in the label for other JAKi.⁸ A phase 2 study showed early promise for the efficacy and safety of deucravacitinib in PsA.⁹ Further investigation will be needed to better understand the role of deucravacitinib and other TYK2 inhibitors being developed for the treatment of PsA. In the meantime, JAKi continue to be a prominent consideration for first-line PsA therapy in a carefully selected patient population. 

Janus kinase inhibitors (JAKi) are a novel class of oral, targeted small-molecule inhibitors that are increasingly used to treat several different autoimmune conditions. In terms of rheumatologic indications, the FDA first approved tofacitinib (TOF) for use in moderate to severe rheumatoid arthritis (RA) unresponsive to methotrexate therapy. Eleven years later, the indications for JAKi use have expanded to include ulcerative colitis, ankylosing spondylitis, and psoriatic arthritis (PsA), among other diseases. As with any new therapeutic mechanism, there are questions as to how JAKi should be incorporated into the treatment paradigm of PsA. In this article, we briefly review the efficacy and safety data of these agents and discuss our approach to their use in PsA.

Two JAKi are currently FDA approved for the treatment of PsA: tofacitinib (TOF) and upadacitinib (UPA). Other JAKi, such as filgotinib and peficitinib, are only approved outside the United States and will not be discussed here. 

TOF was originally studied in skin psoriasis (PsO) before 2 pivotal studies demonstrated efficacy in PsA. TOF or adalimumab (ADA) were compared with placebo in patients who had failed conventional synthetic disease-modifying antirheumatic drugs (DMARD).¹ ACR20 response was superior with TOF 5 mg twice daily (BID) (50%) and 10 mg BID (61%) vs placebo (33%), and it was comparable to ADA (52%), which was used in this study as an active comparator. The overall rate of adverse events was similar with both doses of TOF when compared with ADA; however, patients taking TOF had numerically more cases of cancer, serious infection, and herpes zoster. 

Another study evaluated TOF compared with placebo in patients with PsA who had an inadequate response to tumor necrosis factor inhibitor (TNFi) therapy.² The study showed an ACR20 response of 50% in patients taking TOF 5 mg BID and 47% in patients taking 10 mg BID, compared with 24% in those taking placebo. Patients who received the 10 mg TOF dose continuously had higher rates of adverse events compared to TOF 5 mg, placebo, and patients who crossed over from placebo to TOF at either dose. In the TOF groups, there were cases of serious infection and herpes zoster, as well as 2 patients with major adverse cardiovascular events (MACE). Following review of these data, the FDA approved only the 5 mg BID dose, and later an 11-mg daily extended-release formulation that was pharmacokinetically similar.

The efficacy for UPA in PsA was shown in 2 pivotal phase 3 trials. SELECT-PsA1 compared UPA at 2 doses, 15 mg and 30 mg daily, vs placebo and vs ADA in patients with biologic DMARD (bDMARD)-naïve PsA.³ This trial demonstrated superiority of UPA in the ACR20 response at both doses (71% and 79%, respectively) compared with placebo (36%). The 15-mg dose of UPA was comparable to ADA (65%), while the 30-mg dose achieved superiority compared to ADA. Secondary outcomes including skin activity, patient-reported symptoms, and inhibition of radiographic progression were also superior in UPA compared with placebo and similar or greater with UPA compared with ADA, depending on the specific outcome.⁴ SELECT-PsA2 compared UPA 15 mg, 30 mg, and placebo in patients with prior incomplete response or intolerance to a bDMARD.⁵ At week 12 of the study, patients taking UPA 15 mg and 30 mg had an ACR20 response of 57% and 64%, respectively, compared with placebo (24%). At week 24, minimal disease activity was achieved by 25% of patients taking UPA 15 mg and 29% of patients taking UPA 30 mg, which was superior to placebo (3%). 

Both studies found a significant increase in infections, including serious infections, at the 30-mg UPA dose compared with the placebo and adalimumab groups. Cytopenia and elevated creatine kinase (CK) level also occurred more frequently in the UPA 30-mg group. Rates of cancer were low overall and comparable between the patients treated with UPA and ADA. Given the higher incidence of adverse events with the 30-mg dose and the relatively similar efficacy, the sponsor elected to submit only the lower dose to the FDA for approval.

In the last few years, concerns for safety with JAKi use grew after the publication of data from the ORAL SURVEILLANCE trial, an FDA-mandated, post-approval safety study of TOF in RA. In this trial, patients with active RA over 50 years of age and with at least 1 additional cardiovascular risk factor were randomized to TOF at 1 of 2 doses, 5 mg or 10 mg BID, or a TNFi.⁶ This trial was designed as a noninferiority study, and TOF did not meet the noninferiority threshold compared to TNFi, with hazard ratios of 1.33 and 1.48 for MACE and malignancy, respectively. The results of this trial prompted the FDA to add a black box warning to the label for all JAKi, pointing out the risk of malignancy and MACE, as well as infection, mortality, and thrombosis. 

In the ORAL SURVEILLANCE trial, the increased risk of MACE and malignancy was primarily seen in the study patients with high risk for a cardiovascular event. To address the question of whether a similar risk profile exists when using JAKi to treat PsA, or whether this is a disease-specific process related to RA, a post hoc analysis of 3 PsA trials and 7 PsO trials of patients treated with TOF was conducted.⁷ The analysis found that patients with a history of atherosclerotic cardiovascular disease (ASCVD) or metabolic syndrome, or patients at high risk for ASCVD (score > 20%) had increased incidence rates of MACE compared with those with low risk scores for ASCVD. Interestingly, as in RA, increased incidence rates of malignancy were seen in patients with preexisting or at high risk for ASCVD.

While the FDA recommends JAKi use in patients who have failed or are inappropriate for treatment with a TNFi, we would consider the use of JAKi for first-line therapy in PsA on an individual basis. One advantage of JAKi is their efficacy across multiple PsA domains, including peripheral arthritis, axial disease, enthesitis, dactylitis, and skin disease (although the approved dose of TOF was not statistically effective for PsO in the pivotal trials). Based on this efficacy, we believe that patients with overlapping, multifaceted disease may benefit the most from these medications. Patient risk factors and comorbidities are a prominent consideration in our use of JAKi to ensure safety, as the risk for MACE and malignancy is informed partly by baseline cardiovascular status. In younger patients without cardiovascular risk factors, JAKi may be a strong candidate for first-line therapy, particularly in patients averse to subcutaneous or intravenous therapy. We do counsel all patients on the increased risk of infection, and we do recommend inactivated herpes zoster vaccination in previously unvaccinated patients planning to start JAKi therapy. 

On the horizon are the development of novel, oral agents targeting tyrosine kinase 2 (TYK2), which is a member of the JAK family of signaling proteins. In fact, the TYK2 inhibitor deucravacitinib was approved by the FDA in 2022 for the treatment of PsO. TYK2 inhibitors appear to have the advantage of a more selective mechanism of action, with fewer off-target effects. There were fewer adverse events in the deucravacitinib trials, which led to its prompt PsO authorization, and the FDA approval for the drug did not include the same black box warning that appears in the label for other JAKi.⁸ A phase 2 study showed early promise for the efficacy and safety of deucravacitinib in PsA.⁹ Further investigation will be needed to better understand the role of deucravacitinib and other TYK2 inhibitors being developed for the treatment of PsA. In the meantime, JAKi continue to be a prominent consideration for first-line PsA therapy in a carefully selected patient population.