Conference Coverage

At-home, noninvasive auricular vagus nerve stimulation (aVNS) therapy is well-tolerated and associated with a significant reduction in postpartum depressive and anxiety symptoms, new research suggests.

In a small proof-of-concept pilot study of 25 women with postpartum depression receiving 6 weeks of daily aVNS treatment, results showed that 74% achieved response and 61% achieved remission, as shown in reduced scores on the Hamilton Rating Scale for Depression (HAM-D17).

Although invasive electrical stimulation of the vagus nerve was approved by the U.S. Food and Drug Administration for treatment-resistant depression in 2005, it involves risk for implantation, infection, and significant side effects, coinvestigator Kristina M. Deligiannidis, MD, director, Women’s Behavioral Health, Zucker Hillside Hospital, Northwell Health, Glen Oaks, New York, told this news organization.

Courtesy The Feinstein Institutes

Potential alternative to meds

“Given that aVNS is a non-invasive treatment which can be administered at home, we wanted to test if this approach was safe, feasible, and could reduce depressive symptoms in women with postpartum depression, as many of these women have barriers to accessing current treatments,” Dr. Deligiannidis said.

Auricular VNS uses surface skin electrodes to stimulate nerve endings of a branch of the vagus nerve, located on the surface of the outer ear. Those nerve endings travel to the brain where they have been shown to modulate brain communication in areas important for mood and anxiety regulation, she said.

Dr. Deligiannidis noted that evidence-based treatments for postpartum depression include psychotherapies and antidepressants. However, some women have difficulty accessing weekly psychotherapy, and, when antidepressants are indicated, many are reluctant to take them if they are breastfeeding because of concerns about the medications getting into their breast milk, she said.

Although most antidepressants are safe in lactation, many women postpone antidepressant treatment until they have finished breastfeeding, which can postpone their postpartum depression treatment, Dr. Deligiannidis added.

“At home treatments reduce many barriers women have to current treatments, and this intervention [of aVNS] does not impact breastfeeding, as it is not a medication approach,” she said.

The researchers enrolled 25 women (mean age, 33.7 years) diagnosed with postpartum depression. Ten of the women (40%) were on a stable dose of antidepressant medication.

The participants self-administered 6 weeks of open-label aVNS for 15 minutes daily at home. They were then observed without intervention for an additional 2 weeks. The women also completed medical, psychiatric, and safety interviews throughout the study period.
 

Promising findings

At baseline, the mean HAM-D17 was 18.4 and was similar for those on (17.8) and off (18.9) antidepressants.

By week 6, the mean HAM-D17 total score decreased by 9.7 points overall, compared with baseline score. For participants on antidepressants, the HAM-D17 decreased by 8.7 points; for women off antidepressants, it decreased by 10.3 points.

In addition, 74% of the women achieved a response to the therapy, and 61% achieved remission of their depressive symptoms.

The most common adverse effects were discomfort (n = 5 patients), headache (n = 3), and dizziness (n = 2). All resolved without intervention.

Commenting on the findings, Anita Clayton, MD, professor and chair, department of psychiatry and neurobehavioral sciences, University of Virginia School of Medicine, Charlottesville, said the study was “quite interesting.”

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

At-home, noninvasive auricular vagus nerve stimulation (aVNS) therapy is well-tolerated and associated with a significant reduction in postpartum depressive and anxiety symptoms, new research suggests.

In a small proof-of-concept pilot study of 25 women with postpartum depression receiving 6 weeks of daily aVNS treatment, results showed that 74% achieved response and 61% achieved remission, as shown in reduced scores on the Hamilton Rating Scale for Depression (HAM-D17).

Although invasive electrical stimulation of the vagus nerve was approved by the U.S. Food and Drug Administration for treatment-resistant depression in 2005, it involves risk for implantation, infection, and significant side effects, coinvestigator Kristina M. Deligiannidis, MD, director, Women’s Behavioral Health, Zucker Hillside Hospital, Northwell Health, Glen Oaks, New York, told this news organization.

Courtesy The Feinstein Institutes

Potential alternative to meds

“Given that aVNS is a non-invasive treatment which can be administered at home, we wanted to test if this approach was safe, feasible, and could reduce depressive symptoms in women with postpartum depression, as many of these women have barriers to accessing current treatments,” Dr. Deligiannidis said.

Auricular VNS uses surface skin electrodes to stimulate nerve endings of a branch of the vagus nerve, located on the surface of the outer ear. Those nerve endings travel to the brain where they have been shown to modulate brain communication in areas important for mood and anxiety regulation, she said.

Dr. Deligiannidis noted that evidence-based treatments for postpartum depression include psychotherapies and antidepressants. However, some women have difficulty accessing weekly psychotherapy, and, when antidepressants are indicated, many are reluctant to take them if they are breastfeeding because of concerns about the medications getting into their breast milk, she said.

Although most antidepressants are safe in lactation, many women postpone antidepressant treatment until they have finished breastfeeding, which can postpone their postpartum depression treatment, Dr. Deligiannidis added.

“At home treatments reduce many barriers women have to current treatments, and this intervention [of aVNS] does not impact breastfeeding, as it is not a medication approach,” she said.

The researchers enrolled 25 women (mean age, 33.7 years) diagnosed with postpartum depression. Ten of the women (40%) were on a stable dose of antidepressant medication.

The participants self-administered 6 weeks of open-label aVNS for 15 minutes daily at home. They were then observed without intervention for an additional 2 weeks. The women also completed medical, psychiatric, and safety interviews throughout the study period.
 

Promising findings

At baseline, the mean HAM-D17 was 18.4 and was similar for those on (17.8) and off (18.9) antidepressants.

By week 6, the mean HAM-D17 total score decreased by 9.7 points overall, compared with baseline score. For participants on antidepressants, the HAM-D17 decreased by 8.7 points; for women off antidepressants, it decreased by 10.3 points.

In addition, 74% of the women achieved a response to the therapy, and 61% achieved remission of their depressive symptoms.

The most common adverse effects were discomfort (n = 5 patients), headache (n = 3), and dizziness (n = 2). All resolved without intervention.

Commenting on the findings, Anita Clayton, MD, professor and chair, department of psychiatry and neurobehavioral sciences, University of Virginia School of Medicine, Charlottesville, said the study was “quite interesting.”

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

At-home, noninvasive auricular vagus nerve stimulation (aVNS) therapy is well-tolerated and associated with a significant reduction in postpartum depressive and anxiety symptoms, new research suggests.

In a small proof-of-concept pilot study of 25 women with postpartum depression receiving 6 weeks of daily aVNS treatment, results showed that 74% achieved response and 61% achieved remission, as shown in reduced scores on the Hamilton Rating Scale for Depression (HAM-D17).

Although invasive electrical stimulation of the vagus nerve was approved by the U.S. Food and Drug Administration for treatment-resistant depression in 2005, it involves risk for implantation, infection, and significant side effects, coinvestigator Kristina M. Deligiannidis, MD, director, Women’s Behavioral Health, Zucker Hillside Hospital, Northwell Health, Glen Oaks, New York, told this news organization.

Courtesy The Feinstein Institutes

Potential alternative to meds

“Given that aVNS is a non-invasive treatment which can be administered at home, we wanted to test if this approach was safe, feasible, and could reduce depressive symptoms in women with postpartum depression, as many of these women have barriers to accessing current treatments,” Dr. Deligiannidis said.

Auricular VNS uses surface skin electrodes to stimulate nerve endings of a branch of the vagus nerve, located on the surface of the outer ear. Those nerve endings travel to the brain where they have been shown to modulate brain communication in areas important for mood and anxiety regulation, she said.

Dr. Deligiannidis noted that evidence-based treatments for postpartum depression include psychotherapies and antidepressants. However, some women have difficulty accessing weekly psychotherapy, and, when antidepressants are indicated, many are reluctant to take them if they are breastfeeding because of concerns about the medications getting into their breast milk, she said.

Although most antidepressants are safe in lactation, many women postpone antidepressant treatment until they have finished breastfeeding, which can postpone their postpartum depression treatment, Dr. Deligiannidis added.

“At home treatments reduce many barriers women have to current treatments, and this intervention [of aVNS] does not impact breastfeeding, as it is not a medication approach,” she said.

The researchers enrolled 25 women (mean age, 33.7 years) diagnosed with postpartum depression. Ten of the women (40%) were on a stable dose of antidepressant medication.

The participants self-administered 6 weeks of open-label aVNS for 15 minutes daily at home. They were then observed without intervention for an additional 2 weeks. The women also completed medical, psychiatric, and safety interviews throughout the study period.
 

Promising findings

At baseline, the mean HAM-D17 was 18.4 and was similar for those on (17.8) and off (18.9) antidepressants.

By week 6, the mean HAM-D17 total score decreased by 9.7 points overall, compared with baseline score. For participants on antidepressants, the HAM-D17 decreased by 8.7 points; for women off antidepressants, it decreased by 10.3 points.

In addition, 74% of the women achieved a response to the therapy, and 61% achieved remission of their depressive symptoms.

The most common adverse effects were discomfort (n = 5 patients), headache (n = 3), and dizziness (n = 2). All resolved without intervention.

Commenting on the findings, Anita Clayton, MD, professor and chair, department of psychiatry and neurobehavioral sciences, University of Virginia School of Medicine, Charlottesville, said the study was “quite interesting.”

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

NEW ORLEANS – Adult patients who completed an intensive outpatient program (IOP) for post-traumatic stress disorder were significantly less likely over the following year to require inpatient or emergency psychiatric treatment, according to a new study released at the annual meeting of the American Psychiatric Association.

In an analysis of 256 individuals, over the 12 months before they joined the IOP, 28.7% and 24.8% had inpatient and emergency department encounters, respectively, according to the researchers. Afterward, those numbers fell to 15.9% (P < .01) and 18.2% (P = .04), respectively.

“Engagement in IOP for patients with PTSD may help avoid the need for higher levels of care such as residential or inpatient treatment,” Nathan Lingafelter, MD, a psychiatrist and researcher at Kaiser Permanente in Oakland, Calif., said in an interview.

Dr. Lingafelter described IOP programs as typically “offering patients a combination of individual therapy, group therapy, and medication management all at an increased frequency of about 3 half-days per week. IOPs are thought to be helpful in helping patients with severe symptoms while they are still in the community – i.e., living in their homes, with their families, occasionally still working at reduced time.”

While other studies have examined the effects of IOP, “the existing literature focuses on how IOP reduces symptoms, rather than looking at how IOP involvement might be associated with patients utilizing different acute care resources,” he said. “Prior studies have also been conducted mostly in veteran populations and in populations with less diversity than our population in Oakland.”

For the new study, researchers tracked 256 IOP participants (83% female; mean age = 39; 44% White, 27% Black, 14% Hispanic, and 7% Asian). The wide majority – 85% – had comorbid depressive disorders.

“Patients are assigned a case manager when they enter the program who they can meet with individually, and they spend time attending group therapy sessions. Patients are also able to meet with a psychiatrist to discuss medications,” Dr. Lingafelter said. “A major component in both the group and individual therapy is helping patients identify which kind of interventions work for them and what we can do now that will help. IOP can really help clarify for patients what their trauma responses are and how to start treatments that actually fit their symptoms.”

The subjects had a mean 0.3 psychiatric encounters in the year before joining the program and 0.2 in the year after (P < .01). Their mean emergency department visits related to mental health fell from 0.5 to 0.3 (P = .03).

The study has limitations. Participants took part in IOP therapy from 2017 to 2018, before the pandemic disrupted mental health treatment. It does not examine whether medication use changed after IOP treatment. It is retrospective and doesn’t confirm that IOP had any positive effect.
 

Multiple benefits of IOP

In an interview, Deborah C. Beidel, PhD, director of UCF RESTORES at the University of Central Florida, Orlando, said IOP has several advantages as a treatment for PTSD. Her clinic, which focuses on PTSD treatment for military veterans, has used the approach to treat hundreds of people.

“First, IOPs can address the stigma that surrounds mental health treatment. If you have a physical injury, you take time off from work to go to physical therapy, which is time-limited. If you have a stress injury, why not do the same? Take a few weeks, get it treated, and get back to work,” she said. “The second reason is that the most effective treatment for PTSD is exposure therapy, which is more effective when treatment sessions occur in a daily as opposed to a weekly or monthly time frame. Third, from a cost and feasibility perspective, an intensive program could reduce overall medical costs and get people back to work sooner.”

The new study is “definitely useful” since it examines the impact of IOP over a longer term, Dr. Beidel said. This kind of data “can influence policy, particularly with insurance companies. If we can build the evidence that short, intensive treatment produces better long-term outcomes, insurance companies will be more likely to pay for the IOP.”

The University of Central Florida program is funded by federal research grants and state funding, she said. “When we calculate the cost, it comes to about $10,000 in therapy time plus an average of about $3,000 in travel related costs – transportation, lodging, meals – for those who travel from out of state for our program.”

What’s next? “Further study is needed to characterize whether these findings are applicable to other practice settings, including virtual treatment programs; the long-term durability of these findings; and whether similar patterns of reduced resource use extend to non–mental health–specific care utilization,” said Dr. Lingafelter, the study’s lead author.

No study funding and no author disclosures were reported. Dr. Beidel disclosed IOP-related research support from the U.S. Army Medical Research and Development Command–Military Operational Medicine Research Program.

NEW ORLEANS – Adult patients who completed an intensive outpatient program (IOP) for post-traumatic stress disorder were significantly less likely over the following year to require inpatient or emergency psychiatric treatment, according to a new study released at the annual meeting of the American Psychiatric Association.

In an analysis of 256 individuals, over the 12 months before they joined the IOP, 28.7% and 24.8% had inpatient and emergency department encounters, respectively, according to the researchers. Afterward, those numbers fell to 15.9% (P < .01) and 18.2% (P = .04), respectively.

“Engagement in IOP for patients with PTSD may help avoid the need for higher levels of care such as residential or inpatient treatment,” Nathan Lingafelter, MD, a psychiatrist and researcher at Kaiser Permanente in Oakland, Calif., said in an interview.

Dr. Lingafelter described IOP programs as typically “offering patients a combination of individual therapy, group therapy, and medication management all at an increased frequency of about 3 half-days per week. IOPs are thought to be helpful in helping patients with severe symptoms while they are still in the community – i.e., living in their homes, with their families, occasionally still working at reduced time.”

While other studies have examined the effects of IOP, “the existing literature focuses on how IOP reduces symptoms, rather than looking at how IOP involvement might be associated with patients utilizing different acute care resources,” he said. “Prior studies have also been conducted mostly in veteran populations and in populations with less diversity than our population in Oakland.”

For the new study, researchers tracked 256 IOP participants (83% female; mean age = 39; 44% White, 27% Black, 14% Hispanic, and 7% Asian). The wide majority – 85% – had comorbid depressive disorders.

“Patients are assigned a case manager when they enter the program who they can meet with individually, and they spend time attending group therapy sessions. Patients are also able to meet with a psychiatrist to discuss medications,” Dr. Lingafelter said. “A major component in both the group and individual therapy is helping patients identify which kind of interventions work for them and what we can do now that will help. IOP can really help clarify for patients what their trauma responses are and how to start treatments that actually fit their symptoms.”

The subjects had a mean 0.3 psychiatric encounters in the year before joining the program and 0.2 in the year after (P < .01). Their mean emergency department visits related to mental health fell from 0.5 to 0.3 (P = .03).

The study has limitations. Participants took part in IOP therapy from 2017 to 2018, before the pandemic disrupted mental health treatment. It does not examine whether medication use changed after IOP treatment. It is retrospective and doesn’t confirm that IOP had any positive effect.
 

Multiple benefits of IOP

In an interview, Deborah C. Beidel, PhD, director of UCF RESTORES at the University of Central Florida, Orlando, said IOP has several advantages as a treatment for PTSD. Her clinic, which focuses on PTSD treatment for military veterans, has used the approach to treat hundreds of people.

“First, IOPs can address the stigma that surrounds mental health treatment. If you have a physical injury, you take time off from work to go to physical therapy, which is time-limited. If you have a stress injury, why not do the same? Take a few weeks, get it treated, and get back to work,” she said. “The second reason is that the most effective treatment for PTSD is exposure therapy, which is more effective when treatment sessions occur in a daily as opposed to a weekly or monthly time frame. Third, from a cost and feasibility perspective, an intensive program could reduce overall medical costs and get people back to work sooner.”

The new study is “definitely useful” since it examines the impact of IOP over a longer term, Dr. Beidel said. This kind of data “can influence policy, particularly with insurance companies. If we can build the evidence that short, intensive treatment produces better long-term outcomes, insurance companies will be more likely to pay for the IOP.”

The University of Central Florida program is funded by federal research grants and state funding, she said. “When we calculate the cost, it comes to about $10,000 in therapy time plus an average of about $3,000 in travel related costs – transportation, lodging, meals – for those who travel from out of state for our program.”

What’s next? “Further study is needed to characterize whether these findings are applicable to other practice settings, including virtual treatment programs; the long-term durability of these findings; and whether similar patterns of reduced resource use extend to non–mental health–specific care utilization,” said Dr. Lingafelter, the study’s lead author.

No study funding and no author disclosures were reported. Dr. Beidel disclosed IOP-related research support from the U.S. Army Medical Research and Development Command–Military Operational Medicine Research Program.

NEW ORLEANS – Adult patients who completed an intensive outpatient program (IOP) for post-traumatic stress disorder were significantly less likely over the following year to require inpatient or emergency psychiatric treatment, according to a new study released at the annual meeting of the American Psychiatric Association.

In an analysis of 256 individuals, over the 12 months before they joined the IOP, 28.7% and 24.8% had inpatient and emergency department encounters, respectively, according to the researchers. Afterward, those numbers fell to 15.9% (P < .01) and 18.2% (P = .04), respectively.

“Engagement in IOP for patients with PTSD may help avoid the need for higher levels of care such as residential or inpatient treatment,” Nathan Lingafelter, MD, a psychiatrist and researcher at Kaiser Permanente in Oakland, Calif., said in an interview.

Dr. Lingafelter described IOP programs as typically “offering patients a combination of individual therapy, group therapy, and medication management all at an increased frequency of about 3 half-days per week. IOPs are thought to be helpful in helping patients with severe symptoms while they are still in the community – i.e., living in their homes, with their families, occasionally still working at reduced time.”

While other studies have examined the effects of IOP, “the existing literature focuses on how IOP reduces symptoms, rather than looking at how IOP involvement might be associated with patients utilizing different acute care resources,” he said. “Prior studies have also been conducted mostly in veteran populations and in populations with less diversity than our population in Oakland.”

For the new study, researchers tracked 256 IOP participants (83% female; mean age = 39; 44% White, 27% Black, 14% Hispanic, and 7% Asian). The wide majority – 85% – had comorbid depressive disorders.

“Patients are assigned a case manager when they enter the program who they can meet with individually, and they spend time attending group therapy sessions. Patients are also able to meet with a psychiatrist to discuss medications,” Dr. Lingafelter said. “A major component in both the group and individual therapy is helping patients identify which kind of interventions work for them and what we can do now that will help. IOP can really help clarify for patients what their trauma responses are and how to start treatments that actually fit their symptoms.”

The subjects had a mean 0.3 psychiatric encounters in the year before joining the program and 0.2 in the year after (P < .01). Their mean emergency department visits related to mental health fell from 0.5 to 0.3 (P = .03).

The study has limitations. Participants took part in IOP therapy from 2017 to 2018, before the pandemic disrupted mental health treatment. It does not examine whether medication use changed after IOP treatment. It is retrospective and doesn’t confirm that IOP had any positive effect.
 

Multiple benefits of IOP

In an interview, Deborah C. Beidel, PhD, director of UCF RESTORES at the University of Central Florida, Orlando, said IOP has several advantages as a treatment for PTSD. Her clinic, which focuses on PTSD treatment for military veterans, has used the approach to treat hundreds of people.

“First, IOPs can address the stigma that surrounds mental health treatment. If you have a physical injury, you take time off from work to go to physical therapy, which is time-limited. If you have a stress injury, why not do the same? Take a few weeks, get it treated, and get back to work,” she said. “The second reason is that the most effective treatment for PTSD is exposure therapy, which is more effective when treatment sessions occur in a daily as opposed to a weekly or monthly time frame. Third, from a cost and feasibility perspective, an intensive program could reduce overall medical costs and get people back to work sooner.”

The new study is “definitely useful” since it examines the impact of IOP over a longer term, Dr. Beidel said. This kind of data “can influence policy, particularly with insurance companies. If we can build the evidence that short, intensive treatment produces better long-term outcomes, insurance companies will be more likely to pay for the IOP.”

The University of Central Florida program is funded by federal research grants and state funding, she said. “When we calculate the cost, it comes to about $10,000 in therapy time plus an average of about $3,000 in travel related costs – transportation, lodging, meals – for those who travel from out of state for our program.”

What’s next? “Further study is needed to characterize whether these findings are applicable to other practice settings, including virtual treatment programs; the long-term durability of these findings; and whether similar patterns of reduced resource use extend to non–mental health–specific care utilization,” said Dr. Lingafelter, the study’s lead author.

No study funding and no author disclosures were reported. Dr. Beidel disclosed IOP-related research support from the U.S. Army Medical Research and Development Command–Military Operational Medicine Research Program.

COPENHAGEN – The Janus kinase (JAK) inhibitor upadacitinib (Rinvoq, AbbVie) was associated with significant improvements in disease activity, pain, function, and quality of life, compared with placebo, in patients with nonradiographic axial spondyloarthritis (nr-axSpA), results of the first efficacy analysis of the phase 3, randomized SELECT-AXIS-2 trial showed.

The trial met its primary endpoint of an improvement of Assessment of SpondyloArthritis International Society 40% (ASAS 40) response criteria in the prespecified efficacy analysis at week 14, reported Filip Van den Bosch, MD, PhD, Ghent (Belgium) University.

In all, 45% of patients randomized to receive upadacitinib achieved an ASAS 40, compared with 23% of those assigned to placebo (P < .001).

“This is the first study showing efficacy and showing that the JAK inhibitor upadacitinib might be a therapeutic option in patients with active, nonradiographic spondyloarthritis,” Van den Bosch said at the annual European Congress of Rheumatology.

Although JAK inhibitors have previously been shown to be efficacious and safe for the treatment of ankylosing spondylitis, the SELECT-AXIS-2 trial is the first to evaluate a JAK inhibitor in nonradiographic axSpA, he added.
 

Study details

Patients 18 years and older with rheumatologist-diagnosed nr-axSpA were eligible for the study if they also met 2009 ASAS classification criteria for axSpA but not the radiologic criterion of modified New York criteria; had objective signs of active inflammation consistent with axSpA on MRI of the sacroiliac joints and/or high-sensitivity C-reactive protein above the upper limit of normal (2.87 mg/L) at screening; and had Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and patient-assessment of total back pain scores of 4 or greater based on a 0-10 numeric rating scale at study entry.

Patients were screened with MRI imaging of the spine and x-rays of the sacroiliac joints and spine, and then randomized to receive either placebo (157 patients) or upadacitinib 15 mg daily (158 patients) for 52 weeks. At the end of 52 weeks, all patients on upadacitinib will continue on the drug at the same dose level, and those assigned to placebo will be switched over to 15 mg upadacitinib daily maintenance.

As well as meeting the primary endpoint at week 14, response rates with the JAK inhibitor were higher at all time points over this initial time period, Dr. Van den Bosch noted.
 

Most targets hit

Of 14 multiplicity-controlled secondary endpoints, 12 were statistically better with upadacitinib, including change from baseline in patient’s assessment of total back pain, Bath Ankylosing Spondylitis Functional Index, Ankylosing Spondylitis Disease Activity Score, Low Disease Activity, Ankylosing Spondylitis Quality of Life, and MRI Spondyloarthritis Research Consortium of Canada score for sacroiliac joints.

Only the BASDAI and Maastricht Ankylosing Spondylitis Enthesitis Score were not significantly better with the JAK inhibitor.

The safety of upadacitinib in this setting was consistent with its known safety profile, Dr. Van den Bosch said.

Approximately half of all patients in each trial arm had an adverse event. Serious adverse events were reported in four patients assigned to upadacitinib versus two on placebo, and serious adverse events requiring drug discontinuation occurred in two and four patients, respectively.
 

‘Important’ data

Fabian Proft, MD, head of the clinical trials unit at Charite University Hospital, Berlin, who was not involved in the study, said in an interview that the findings were not surprising.

“We know the efficacy of upadacitinib already in radiographic axial spondyloarthritis, and from all the other drugs that we also know that are effective in radiographic axial spondyloarthritis that are similarly effective in nonradiographic disease,” he said.

“I think it is really important because it is the first data on JAK inhibition also in non-radiographic axial spondyloarthritis – an important step,” said Dr. Proft, who was comoderator of the oral abstract session where Van den Bosch reported the data.

The trial was supported by AbbVie. Dr. Van den Bosch disclosed speaker and consulting fees from AbbVie and others. Dr. Proft disclosed speaker and consulting fees from AbbVie as well.

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

COPENHAGEN – The Janus kinase (JAK) inhibitor upadacitinib (Rinvoq, AbbVie) was associated with significant improvements in disease activity, pain, function, and quality of life, compared with placebo, in patients with nonradiographic axial spondyloarthritis (nr-axSpA), results of the first efficacy analysis of the phase 3, randomized SELECT-AXIS-2 trial showed.

The trial met its primary endpoint of an improvement of Assessment of SpondyloArthritis International Society 40% (ASAS 40) response criteria in the prespecified efficacy analysis at week 14, reported Filip Van den Bosch, MD, PhD, Ghent (Belgium) University.

In all, 45% of patients randomized to receive upadacitinib achieved an ASAS 40, compared with 23% of those assigned to placebo (P < .001).

“This is the first study showing efficacy and showing that the JAK inhibitor upadacitinib might be a therapeutic option in patients with active, nonradiographic spondyloarthritis,” Van den Bosch said at the annual European Congress of Rheumatology.

Although JAK inhibitors have previously been shown to be efficacious and safe for the treatment of ankylosing spondylitis, the SELECT-AXIS-2 trial is the first to evaluate a JAK inhibitor in nonradiographic axSpA, he added.
 

Study details

Patients 18 years and older with rheumatologist-diagnosed nr-axSpA were eligible for the study if they also met 2009 ASAS classification criteria for axSpA but not the radiologic criterion of modified New York criteria; had objective signs of active inflammation consistent with axSpA on MRI of the sacroiliac joints and/or high-sensitivity C-reactive protein above the upper limit of normal (2.87 mg/L) at screening; and had Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and patient-assessment of total back pain scores of 4 or greater based on a 0-10 numeric rating scale at study entry.

Patients were screened with MRI imaging of the spine and x-rays of the sacroiliac joints and spine, and then randomized to receive either placebo (157 patients) or upadacitinib 15 mg daily (158 patients) for 52 weeks. At the end of 52 weeks, all patients on upadacitinib will continue on the drug at the same dose level, and those assigned to placebo will be switched over to 15 mg upadacitinib daily maintenance.

As well as meeting the primary endpoint at week 14, response rates with the JAK inhibitor were higher at all time points over this initial time period, Dr. Van den Bosch noted.
 

Most targets hit

Of 14 multiplicity-controlled secondary endpoints, 12 were statistically better with upadacitinib, including change from baseline in patient’s assessment of total back pain, Bath Ankylosing Spondylitis Functional Index, Ankylosing Spondylitis Disease Activity Score, Low Disease Activity, Ankylosing Spondylitis Quality of Life, and MRI Spondyloarthritis Research Consortium of Canada score for sacroiliac joints.

Only the BASDAI and Maastricht Ankylosing Spondylitis Enthesitis Score were not significantly better with the JAK inhibitor.

The safety of upadacitinib in this setting was consistent with its known safety profile, Dr. Van den Bosch said.

Approximately half of all patients in each trial arm had an adverse event. Serious adverse events were reported in four patients assigned to upadacitinib versus two on placebo, and serious adverse events requiring drug discontinuation occurred in two and four patients, respectively.
 

‘Important’ data

Fabian Proft, MD, head of the clinical trials unit at Charite University Hospital, Berlin, who was not involved in the study, said in an interview that the findings were not surprising.

“We know the efficacy of upadacitinib already in radiographic axial spondyloarthritis, and from all the other drugs that we also know that are effective in radiographic axial spondyloarthritis that are similarly effective in nonradiographic disease,” he said.

“I think it is really important because it is the first data on JAK inhibition also in non-radiographic axial spondyloarthritis – an important step,” said Dr. Proft, who was comoderator of the oral abstract session where Van den Bosch reported the data.

The trial was supported by AbbVie. Dr. Van den Bosch disclosed speaker and consulting fees from AbbVie and others. Dr. Proft disclosed speaker and consulting fees from AbbVie as well.

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

COPENHAGEN – The Janus kinase (JAK) inhibitor upadacitinib (Rinvoq, AbbVie) was associated with significant improvements in disease activity, pain, function, and quality of life, compared with placebo, in patients with nonradiographic axial spondyloarthritis (nr-axSpA), results of the first efficacy analysis of the phase 3, randomized SELECT-AXIS-2 trial showed.

The trial met its primary endpoint of an improvement of Assessment of SpondyloArthritis International Society 40% (ASAS 40) response criteria in the prespecified efficacy analysis at week 14, reported Filip Van den Bosch, MD, PhD, Ghent (Belgium) University.

In all, 45% of patients randomized to receive upadacitinib achieved an ASAS 40, compared with 23% of those assigned to placebo (P < .001).

“This is the first study showing efficacy and showing that the JAK inhibitor upadacitinib might be a therapeutic option in patients with active, nonradiographic spondyloarthritis,” Van den Bosch said at the annual European Congress of Rheumatology.

Although JAK inhibitors have previously been shown to be efficacious and safe for the treatment of ankylosing spondylitis, the SELECT-AXIS-2 trial is the first to evaluate a JAK inhibitor in nonradiographic axSpA, he added.
 

Study details

Patients 18 years and older with rheumatologist-diagnosed nr-axSpA were eligible for the study if they also met 2009 ASAS classification criteria for axSpA but not the radiologic criterion of modified New York criteria; had objective signs of active inflammation consistent with axSpA on MRI of the sacroiliac joints and/or high-sensitivity C-reactive protein above the upper limit of normal (2.87 mg/L) at screening; and had Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and patient-assessment of total back pain scores of 4 or greater based on a 0-10 numeric rating scale at study entry.

Patients were screened with MRI imaging of the spine and x-rays of the sacroiliac joints and spine, and then randomized to receive either placebo (157 patients) or upadacitinib 15 mg daily (158 patients) for 52 weeks. At the end of 52 weeks, all patients on upadacitinib will continue on the drug at the same dose level, and those assigned to placebo will be switched over to 15 mg upadacitinib daily maintenance.

As well as meeting the primary endpoint at week 14, response rates with the JAK inhibitor were higher at all time points over this initial time period, Dr. Van den Bosch noted.
 

Most targets hit

Of 14 multiplicity-controlled secondary endpoints, 12 were statistically better with upadacitinib, including change from baseline in patient’s assessment of total back pain, Bath Ankylosing Spondylitis Functional Index, Ankylosing Spondylitis Disease Activity Score, Low Disease Activity, Ankylosing Spondylitis Quality of Life, and MRI Spondyloarthritis Research Consortium of Canada score for sacroiliac joints.

Only the BASDAI and Maastricht Ankylosing Spondylitis Enthesitis Score were not significantly better with the JAK inhibitor.

The safety of upadacitinib in this setting was consistent with its known safety profile, Dr. Van den Bosch said.

Approximately half of all patients in each trial arm had an adverse event. Serious adverse events were reported in four patients assigned to upadacitinib versus two on placebo, and serious adverse events requiring drug discontinuation occurred in two and four patients, respectively.
 

‘Important’ data

Fabian Proft, MD, head of the clinical trials unit at Charite University Hospital, Berlin, who was not involved in the study, said in an interview that the findings were not surprising.

“We know the efficacy of upadacitinib already in radiographic axial spondyloarthritis, and from all the other drugs that we also know that are effective in radiographic axial spondyloarthritis that are similarly effective in nonradiographic disease,” he said.

“I think it is really important because it is the first data on JAK inhibition also in non-radiographic axial spondyloarthritis – an important step,” said Dr. Proft, who was comoderator of the oral abstract session where Van den Bosch reported the data.

The trial was supported by AbbVie. Dr. Van den Bosch disclosed speaker and consulting fees from AbbVie and others. Dr. Proft disclosed speaker and consulting fees from AbbVie as well.

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

MAR DEL PLATA, ARGENTINA – Psychiatrists should prescribe metformin early to patients who experience rapid weight gain after they begin taking antipsychotic drugs, according to a new evidence-based Irish guideline for the management of this common complication in adults with psychoses who are taking medications.

The document was discussed during one of the sessions of the XXXV Argentine Congress of Psychiatry of the Association of Argentine Psychiatrists. The document also was presented by one of its authors at the European Congress on Obesity 2022.

The guideline encourages psychiatrists not to underestimate the adverse metabolic effects of their treatments and encourages them to contemplate and carry out this prevention and management strategy, commented María Delia Michat, PhD, professor of clinical psychiatry and psychopharmacology at the APSA Postgraduate Training Institute, Buenos Aires.

“Although it is always good to work as a team, it is usually we psychiatrists who coordinate the pharmacological treatment of our patients, and we have to know how to manage drugs that can prevent cardiovascular disease,” Dr. Michat said in an interview.

“The new guideline is helpful because it protocolizes the use of metformin, which is the cheapest drug and has the most evidence for antipsychotic-induced weight gain,” she added.
 

Avoiding metabolic syndrome

In patients with schizophrenia, obesity rates are 40% higher than in the general population, and 80% of patients develop weight gain after their first treatment, noted Dr. Michat. “Right away, weight gain is seen in the first month. And it is a serious problem, because patients with schizophrenia, major depression, or bipolar disorder already have an increased risk of premature mortality, especially from cardiovascular diseases, and they have an increased risk of metabolic syndrome. And we sometimes give drugs that further increase that risk,” she said.

Being overweight is a major criterion for defining metabolic syndrome. Dr. Michat noted that, among the antipsychotic drugs that increase weight the most are clozapine, olanzapine, chlorpromazine, quetiapine, and risperidone, in addition to other psychoactive drugs, such as valproic acid, lithium, mirtazapine, and tricyclic antidepressants.

Several clinical trials, such as a pioneering Chinese study from 2008, have shown the potential of metformin to mitigate the weight gain induced by this type of drug.

However, Dr. Michat noted that so far the major guidelines (for example, the Canadian Network for Mood and Anxiety Treatments [CANMAT]/International Society for Bipolar Disorders [ISBD] for bipolar disorder and the American Psychiatric Association [APA] for schizophrenia) “say very little” on how to address this complication. They propose what she defined as a “problematic” order of action in which the initial emphasis is on promoting lifestyle changes, which are difficult for these patients to carry out, as well as general proposals for changing medication (which is not simple to implement when the patient’s condition is stabilized) and eventual consultation with a clinician to start therapy with metformin or other drugs, such as liraglutide, semaglutide, and topiramate.

The new clinical practice guideline, which was published in Evidence-Based Mental Health (of the BMJ journal group), was written by a multidisciplinary team of pharmacists, psychiatrists, and mental health nurses from Ireland. It aims to fill that gap. The investigators reviewed 1,270 scientific articles and analyzed 26 of them in depth, including seven randomized clinical trials and a 2016 systematic review and meta-analysis. The authors made a “strong” recommendation, for which there was moderate-quality evidence, that for patients for whom a lifestyle intervention is unacceptable or inappropriate the use of metformin is an “alternative first-line intervention” for antipsychotic drug–induced weight gain.

Likewise, as a strong recommendation with moderate-quality evidence, the guidance encourages the use of metformin when nonpharmacologic intervention does not seem to be effective.

The guideline also says it is preferable to start metformin early for patients who gain more than 7% of their baseline weight within the first month of antipsychotic treatment. It also endorses metformin when weight gain is established.

Other recommendations include evaluating baseline kidney function before starting metformin treatment and suggest a dose adjustment when the estimated glomerular filtration rate (eGFR) is < 60 mL/min/1.73 m². The guidance says the use of metformin is contraindicated for patients in whom eGFR is <30 mL/min per 1.73 m². The proposed starting dosage is 500 mg twice per day with meals, with increments of 500 mg every 1-2 weeks until reaching a target dose of 2,000 mg/day. The guidance recommends that consideration always be given to individual tolerability and efficacy.

Treatment goals should be personalized and agreed upon with patients. In the case of early intervention, the guideline proposes initially stabilizing the weight gained or, if possible, reverse excess weight. When weight gain is established, the goal would be to lose at least 5% of the weight within the next 6 months.

The authors also recommend monitoring kidney function annually, as well as vitamin B₁₂ levels and individual tolerability and compliance. Gastrointestinal adverse effects can be managed by dose reduction or slower dose titration. The risk of lactic acidosis, which affects 4.3 per 100,000 person-years among those taking metformin, can be attenuated by adjusting the dose according to kidney function or avoiding prescribing it to patients who have a history of alcohol abuse or who are receiving treatment that may interact with the drug.
 

Validating pharmacologic management

The lead author of the new guideline, Ita Fitzgerald, a teacher in clinical pharmacy and senior pharmacist at St. Patrick’s Mental Health Services in Dublin, pointed out that there is a bias toward not using drugs for weight management and shifting the responsibility onto the patients themselves, something that is very often out of their control.

“The purpose of the guideline was to decide on a range of criteria to maximize the use of metformin, to recognize that for many people, pharmacological management is a valid and important option that could and should be more widely used and to provide precise and practical guidance to physicians to facilitate a more widespread use,” Ms. Fitzgerald said in an interview.

According to Fitzgerald, who is pursuing her doctorate at University College Cork (Ireland), one of the most outstanding results of the work is that it highlights that the main benefit of metformin is to flatten rather than reverse antipsychotic-induced weight gain and that indicating it late can nullify that effect.

“In all the recommendations, we try very hard to shift the focus from metformin’s role as a weight reversal agent to one as a weight management agent that should be used early in treatment, which is when most weight gain occurs. If metformin succeeds in flattening that increase, that’s a huge potential benefit for an inexpensive and easily accessible drug. When people have already established weight gain, metformin may not be enough and alternative treatments should be used,” she said.

In addition to its effects on weight, metformin has many other potential health benefits. Of particular importance is that it reduces hyperphagia-mediated antipsychotic-induced weight gain, Ms. Fitzgerald pointed out.

“This is subjectively very important for patients and provides a more positive experience when taking antipsychotics. Antipsychotic-induced weight gain is one of the main reasons for premature discontinuation or incomplete adherence to these drugs and therefore needs to be addressed proactively,” she concluded.

Ms. Fitzgerald and Dr. Michat have disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com. This article was translated from the Medscape Spanish edition.

MAR DEL PLATA, ARGENTINA – Psychiatrists should prescribe metformin early to patients who experience rapid weight gain after they begin taking antipsychotic drugs, according to a new evidence-based Irish guideline for the management of this common complication in adults with psychoses who are taking medications.

The document was discussed during one of the sessions of the XXXV Argentine Congress of Psychiatry of the Association of Argentine Psychiatrists. The document also was presented by one of its authors at the European Congress on Obesity 2022.

The guideline encourages psychiatrists not to underestimate the adverse metabolic effects of their treatments and encourages them to contemplate and carry out this prevention and management strategy, commented María Delia Michat, PhD, professor of clinical psychiatry and psychopharmacology at the APSA Postgraduate Training Institute, Buenos Aires.

“Although it is always good to work as a team, it is usually we psychiatrists who coordinate the pharmacological treatment of our patients, and we have to know how to manage drugs that can prevent cardiovascular disease,” Dr. Michat said in an interview.

“The new guideline is helpful because it protocolizes the use of metformin, which is the cheapest drug and has the most evidence for antipsychotic-induced weight gain,” she added.
 

Avoiding metabolic syndrome

In patients with schizophrenia, obesity rates are 40% higher than in the general population, and 80% of patients develop weight gain after their first treatment, noted Dr. Michat. “Right away, weight gain is seen in the first month. And it is a serious problem, because patients with schizophrenia, major depression, or bipolar disorder already have an increased risk of premature mortality, especially from cardiovascular diseases, and they have an increased risk of metabolic syndrome. And we sometimes give drugs that further increase that risk,” she said.

Being overweight is a major criterion for defining metabolic syndrome. Dr. Michat noted that, among the antipsychotic drugs that increase weight the most are clozapine, olanzapine, chlorpromazine, quetiapine, and risperidone, in addition to other psychoactive drugs, such as valproic acid, lithium, mirtazapine, and tricyclic antidepressants.

Several clinical trials, such as a pioneering Chinese study from 2008, have shown the potential of metformin to mitigate the weight gain induced by this type of drug.

However, Dr. Michat noted that so far the major guidelines (for example, the Canadian Network for Mood and Anxiety Treatments [CANMAT]/International Society for Bipolar Disorders [ISBD] for bipolar disorder and the American Psychiatric Association [APA] for schizophrenia) “say very little” on how to address this complication. They propose what she defined as a “problematic” order of action in which the initial emphasis is on promoting lifestyle changes, which are difficult for these patients to carry out, as well as general proposals for changing medication (which is not simple to implement when the patient’s condition is stabilized) and eventual consultation with a clinician to start therapy with metformin or other drugs, such as liraglutide, semaglutide, and topiramate.

The new clinical practice guideline, which was published in Evidence-Based Mental Health (of the BMJ journal group), was written by a multidisciplinary team of pharmacists, psychiatrists, and mental health nurses from Ireland. It aims to fill that gap. The investigators reviewed 1,270 scientific articles and analyzed 26 of them in depth, including seven randomized clinical trials and a 2016 systematic review and meta-analysis. The authors made a “strong” recommendation, for which there was moderate-quality evidence, that for patients for whom a lifestyle intervention is unacceptable or inappropriate the use of metformin is an “alternative first-line intervention” for antipsychotic drug–induced weight gain.

Likewise, as a strong recommendation with moderate-quality evidence, the guidance encourages the use of metformin when nonpharmacologic intervention does not seem to be effective.

The guideline also says it is preferable to start metformin early for patients who gain more than 7% of their baseline weight within the first month of antipsychotic treatment. It also endorses metformin when weight gain is established.

Other recommendations include evaluating baseline kidney function before starting metformin treatment and suggest a dose adjustment when the estimated glomerular filtration rate (eGFR) is < 60 mL/min/1.73 m². The guidance says the use of metformin is contraindicated for patients in whom eGFR is <30 mL/min per 1.73 m². The proposed starting dosage is 500 mg twice per day with meals, with increments of 500 mg every 1-2 weeks until reaching a target dose of 2,000 mg/day. The guidance recommends that consideration always be given to individual tolerability and efficacy.

Treatment goals should be personalized and agreed upon with patients. In the case of early intervention, the guideline proposes initially stabilizing the weight gained or, if possible, reverse excess weight. When weight gain is established, the goal would be to lose at least 5% of the weight within the next 6 months.

The authors also recommend monitoring kidney function annually, as well as vitamin B₁₂ levels and individual tolerability and compliance. Gastrointestinal adverse effects can be managed by dose reduction or slower dose titration. The risk of lactic acidosis, which affects 4.3 per 100,000 person-years among those taking metformin, can be attenuated by adjusting the dose according to kidney function or avoiding prescribing it to patients who have a history of alcohol abuse or who are receiving treatment that may interact with the drug.
 

Validating pharmacologic management

The lead author of the new guideline, Ita Fitzgerald, a teacher in clinical pharmacy and senior pharmacist at St. Patrick’s Mental Health Services in Dublin, pointed out that there is a bias toward not using drugs for weight management and shifting the responsibility onto the patients themselves, something that is very often out of their control.

“The purpose of the guideline was to decide on a range of criteria to maximize the use of metformin, to recognize that for many people, pharmacological management is a valid and important option that could and should be more widely used and to provide precise and practical guidance to physicians to facilitate a more widespread use,” Ms. Fitzgerald said in an interview.

According to Fitzgerald, who is pursuing her doctorate at University College Cork (Ireland), one of the most outstanding results of the work is that it highlights that the main benefit of metformin is to flatten rather than reverse antipsychotic-induced weight gain and that indicating it late can nullify that effect.

“In all the recommendations, we try very hard to shift the focus from metformin’s role as a weight reversal agent to one as a weight management agent that should be used early in treatment, which is when most weight gain occurs. If metformin succeeds in flattening that increase, that’s a huge potential benefit for an inexpensive and easily accessible drug. When people have already established weight gain, metformin may not be enough and alternative treatments should be used,” she said.

In addition to its effects on weight, metformin has many other potential health benefits. Of particular importance is that it reduces hyperphagia-mediated antipsychotic-induced weight gain, Ms. Fitzgerald pointed out.

“This is subjectively very important for patients and provides a more positive experience when taking antipsychotics. Antipsychotic-induced weight gain is one of the main reasons for premature discontinuation or incomplete adherence to these drugs and therefore needs to be addressed proactively,” she concluded.

Ms. Fitzgerald and Dr. Michat have disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com. This article was translated from the Medscape Spanish edition.

MAR DEL PLATA, ARGENTINA – Psychiatrists should prescribe metformin early to patients who experience rapid weight gain after they begin taking antipsychotic drugs, according to a new evidence-based Irish guideline for the management of this common complication in adults with psychoses who are taking medications.

The document was discussed during one of the sessions of the XXXV Argentine Congress of Psychiatry of the Association of Argentine Psychiatrists. The document also was presented by one of its authors at the European Congress on Obesity 2022.

The guideline encourages psychiatrists not to underestimate the adverse metabolic effects of their treatments and encourages them to contemplate and carry out this prevention and management strategy, commented María Delia Michat, PhD, professor of clinical psychiatry and psychopharmacology at the APSA Postgraduate Training Institute, Buenos Aires.

“Although it is always good to work as a team, it is usually we psychiatrists who coordinate the pharmacological treatment of our patients, and we have to know how to manage drugs that can prevent cardiovascular disease,” Dr. Michat said in an interview.

“The new guideline is helpful because it protocolizes the use of metformin, which is the cheapest drug and has the most evidence for antipsychotic-induced weight gain,” she added.
 

Avoiding metabolic syndrome

In patients with schizophrenia, obesity rates are 40% higher than in the general population, and 80% of patients develop weight gain after their first treatment, noted Dr. Michat. “Right away, weight gain is seen in the first month. And it is a serious problem, because patients with schizophrenia, major depression, or bipolar disorder already have an increased risk of premature mortality, especially from cardiovascular diseases, and they have an increased risk of metabolic syndrome. And we sometimes give drugs that further increase that risk,” she said.

Being overweight is a major criterion for defining metabolic syndrome. Dr. Michat noted that, among the antipsychotic drugs that increase weight the most are clozapine, olanzapine, chlorpromazine, quetiapine, and risperidone, in addition to other psychoactive drugs, such as valproic acid, lithium, mirtazapine, and tricyclic antidepressants.

Several clinical trials, such as a pioneering Chinese study from 2008, have shown the potential of metformin to mitigate the weight gain induced by this type of drug.

However, Dr. Michat noted that so far the major guidelines (for example, the Canadian Network for Mood and Anxiety Treatments [CANMAT]/International Society for Bipolar Disorders [ISBD] for bipolar disorder and the American Psychiatric Association [APA] for schizophrenia) “say very little” on how to address this complication. They propose what she defined as a “problematic” order of action in which the initial emphasis is on promoting lifestyle changes, which are difficult for these patients to carry out, as well as general proposals for changing medication (which is not simple to implement when the patient’s condition is stabilized) and eventual consultation with a clinician to start therapy with metformin or other drugs, such as liraglutide, semaglutide, and topiramate.

The new clinical practice guideline, which was published in Evidence-Based Mental Health (of the BMJ journal group), was written by a multidisciplinary team of pharmacists, psychiatrists, and mental health nurses from Ireland. It aims to fill that gap. The investigators reviewed 1,270 scientific articles and analyzed 26 of them in depth, including seven randomized clinical trials and a 2016 systematic review and meta-analysis. The authors made a “strong” recommendation, for which there was moderate-quality evidence, that for patients for whom a lifestyle intervention is unacceptable or inappropriate the use of metformin is an “alternative first-line intervention” for antipsychotic drug–induced weight gain.

Likewise, as a strong recommendation with moderate-quality evidence, the guidance encourages the use of metformin when nonpharmacologic intervention does not seem to be effective.

The guideline also says it is preferable to start metformin early for patients who gain more than 7% of their baseline weight within the first month of antipsychotic treatment. It also endorses metformin when weight gain is established.

Other recommendations include evaluating baseline kidney function before starting metformin treatment and suggest a dose adjustment when the estimated glomerular filtration rate (eGFR) is < 60 mL/min/1.73 m². The guidance says the use of metformin is contraindicated for patients in whom eGFR is <30 mL/min per 1.73 m². The proposed starting dosage is 500 mg twice per day with meals, with increments of 500 mg every 1-2 weeks until reaching a target dose of 2,000 mg/day. The guidance recommends that consideration always be given to individual tolerability and efficacy.

Treatment goals should be personalized and agreed upon with patients. In the case of early intervention, the guideline proposes initially stabilizing the weight gained or, if possible, reverse excess weight. When weight gain is established, the goal would be to lose at least 5% of the weight within the next 6 months.

The authors also recommend monitoring kidney function annually, as well as vitamin B₁₂ levels and individual tolerability and compliance. Gastrointestinal adverse effects can be managed by dose reduction or slower dose titration. The risk of lactic acidosis, which affects 4.3 per 100,000 person-years among those taking metformin, can be attenuated by adjusting the dose according to kidney function or avoiding prescribing it to patients who have a history of alcohol abuse or who are receiving treatment that may interact with the drug.
 

Validating pharmacologic management

The lead author of the new guideline, Ita Fitzgerald, a teacher in clinical pharmacy and senior pharmacist at St. Patrick’s Mental Health Services in Dublin, pointed out that there is a bias toward not using drugs for weight management and shifting the responsibility onto the patients themselves, something that is very often out of their control.

“The purpose of the guideline was to decide on a range of criteria to maximize the use of metformin, to recognize that for many people, pharmacological management is a valid and important option that could and should be more widely used and to provide precise and practical guidance to physicians to facilitate a more widespread use,” Ms. Fitzgerald said in an interview.

According to Fitzgerald, who is pursuing her doctorate at University College Cork (Ireland), one of the most outstanding results of the work is that it highlights that the main benefit of metformin is to flatten rather than reverse antipsychotic-induced weight gain and that indicating it late can nullify that effect.

“In all the recommendations, we try very hard to shift the focus from metformin’s role as a weight reversal agent to one as a weight management agent that should be used early in treatment, which is when most weight gain occurs. If metformin succeeds in flattening that increase, that’s a huge potential benefit for an inexpensive and easily accessible drug. When people have already established weight gain, metformin may not be enough and alternative treatments should be used,” she said.

In addition to its effects on weight, metformin has many other potential health benefits. Of particular importance is that it reduces hyperphagia-mediated antipsychotic-induced weight gain, Ms. Fitzgerald pointed out.

“This is subjectively very important for patients and provides a more positive experience when taking antipsychotics. Antipsychotic-induced weight gain is one of the main reasons for premature discontinuation or incomplete adherence to these drugs and therefore needs to be addressed proactively,” she concluded.

Ms. Fitzgerald and Dr. Michat have disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com. This article was translated from the Medscape Spanish edition.

The 2022 Pediatric Academic Societies meeting included an excellent session on the acute and delayed effects of COVID-19 on children’s hearts. Data on the risk for cardiac injury during acute COVID-19, return-to-play guidelines after COVID-19–related heart injury, and post–vaccine-associated myocarditis were reviewed.

COVID-induced cardiac injury

The risk for COVID-induced cardiac injury is directly associated with age. Recent Centers for Disease Control and Prevention data revealed a “myocarditis or pericarditis” rate in the range of 12-17 cases per 100,000 SARS-CoV-2 infections among male children aged 5-11 years (lower rates for females); the rate jumps to 50-65 cases per 100,000 infections among male children aged 12-17 years. So cardiac injury caused by acute COVID-19 appears rare, but the risk is clearly associated with male sex and adolescent age.

Return to play after COVID-19

Clinicians may be pressed by patients and parents for advice on return to play after illness with COVID-19. In July 2020, the American College of Cardiology published an algorithm that has been adjusted over time, most recently in 2022 by the American Academy of Pediatrics. These algorithms stratify recommendations by degree of illness. One rule of thumb: Patients with severe COVID-19 (ICU care or multisystem inflammatory syndrome in children [MIS-C]) have only one box on the algorithm, and that is to rest for 3-6 months and only return to usual activity after cardiac clearance. Moderate disease (defined as ≥ 4 days of fever > 100.4 °F; ≥ 1 week of myalgia, chills, lethargy, or any non-ICU hospital stay; and no evidence of MIS-C) require undergoing an ECG to look for cardiac dysfunction, followed by at least 10 days of rest if the ECG is negative or referral for cardiac evaluation if either ECG or exam by a pediatric cardiologist is abnormal.

Clinicians can perhaps be more permissible with patients who are younger or who have had less severe disease. For example, if a patient aged younger than 12 years is asymptomatic with routine activity at the time of evaluation, an ECG is not indicated. For patients aged 12-15 years who are asymptomatic at the time of evaluation but participate in a high-intensity sport, clinicians might consider obtaining an ECG. As few as 3 days of rest might be enough for select patients who are asymptomatic at presentation. For other patients, clinicians should work with parents to introduce activity gradually and make it clear to parents that any activity intolerance requires quick reevaluation. On existing athlete registries, no deaths that are attributable to post–COVID-19 cardiac effects have been confirmed in children; however, all data presented during the session were from prior to the Omicron variant surge in early 2022, so more information may be forthcoming.
 

Considerations for MIS-C

Among children experiencing MIS-C, 35% had ECG changes, 40% exhibited left ventricular systolic or diastolic dysfunction, and 30% had mitral regurgitation, meaning that a large percentage of patients with MIS-C show some degree of cardiac dysfunction. Unfortunately, we are still in the data-gathering phase for long-term outcomes. Functional parameters tend to improve within a week, and most patients will return to normal cardiac function by 3-4 months.

Return to play after MIS-C is quite different from that for acute COVID-19. Patients with MIS-C should be treated much like other patients with myocarditis with an expected return to play in 3-6 months and only after cardiac follow-up. Another good-to-remember recommendation is to delay COVID-19 vaccination for at least 90 days after an episode of MIS-C.
 

Vaccine-related myocarditis

Once again, older age appears to be a risk factor because most patients with postvaccine myocarditis have been in their mid-teens to early 20s, with events more likely after the second vaccine dose and also more likely in male children (4:1 ratio to female children). No deaths have occurred from postvaccination myocarditis in patients younger than 30 years. Still, many individuals have exhibited residual MRI enhancement in the cardiac tissue for some time after experiencing postvaccination myocarditis; it’s currently unclear whether that has clinical implications. By comparison, CDC data demonstrates convincingly that the risk for cardiac effects is much greater after acute COVID-19 than after COVID-19 vaccination, with risk ratios often higher than 20, depending on age and condition (for example, myocarditis vs. pericarditis). Data are still insufficient to determine whether clinicians should recommend or avoid COVID-19 vaccination in children with congenital heart disease.

In summary, administering COVID-19 vaccines requires a great deal of shared decision-making with parents, and the clinician’s role is to educate parents about all potential risks related to both the vaccine and COVID-19 illness. Research has consistently shown that acute COVID-19 myocarditis and myocarditis associated with MIS-C are much more likely to occur in unvaccinated youth and more likely than postvaccination myocarditis, regardless of age.

William T. Basco, Jr., MD, MS, is a professor of pediatrics at the Medical University of South Carolina, Charleston, and director of the division of general pediatrics. He is an active health services researcher and has published more than 60 manuscripts in the peer-reviewed literature.

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

The 2022 Pediatric Academic Societies meeting included an excellent session on the acute and delayed effects of COVID-19 on children’s hearts. Data on the risk for cardiac injury during acute COVID-19, return-to-play guidelines after COVID-19–related heart injury, and post–vaccine-associated myocarditis were reviewed.

COVID-induced cardiac injury

The risk for COVID-induced cardiac injury is directly associated with age. Recent Centers for Disease Control and Prevention data revealed a “myocarditis or pericarditis” rate in the range of 12-17 cases per 100,000 SARS-CoV-2 infections among male children aged 5-11 years (lower rates for females); the rate jumps to 50-65 cases per 100,000 infections among male children aged 12-17 years. So cardiac injury caused by acute COVID-19 appears rare, but the risk is clearly associated with male sex and adolescent age.

Return to play after COVID-19

Clinicians may be pressed by patients and parents for advice on return to play after illness with COVID-19. In July 2020, the American College of Cardiology published an algorithm that has been adjusted over time, most recently in 2022 by the American Academy of Pediatrics. These algorithms stratify recommendations by degree of illness. One rule of thumb: Patients with severe COVID-19 (ICU care or multisystem inflammatory syndrome in children [MIS-C]) have only one box on the algorithm, and that is to rest for 3-6 months and only return to usual activity after cardiac clearance. Moderate disease (defined as ≥ 4 days of fever > 100.4 °F; ≥ 1 week of myalgia, chills, lethargy, or any non-ICU hospital stay; and no evidence of MIS-C) require undergoing an ECG to look for cardiac dysfunction, followed by at least 10 days of rest if the ECG is negative or referral for cardiac evaluation if either ECG or exam by a pediatric cardiologist is abnormal.

Clinicians can perhaps be more permissible with patients who are younger or who have had less severe disease. For example, if a patient aged younger than 12 years is asymptomatic with routine activity at the time of evaluation, an ECG is not indicated. For patients aged 12-15 years who are asymptomatic at the time of evaluation but participate in a high-intensity sport, clinicians might consider obtaining an ECG. As few as 3 days of rest might be enough for select patients who are asymptomatic at presentation. For other patients, clinicians should work with parents to introduce activity gradually and make it clear to parents that any activity intolerance requires quick reevaluation. On existing athlete registries, no deaths that are attributable to post–COVID-19 cardiac effects have been confirmed in children; however, all data presented during the session were from prior to the Omicron variant surge in early 2022, so more information may be forthcoming.
 

Considerations for MIS-C

Among children experiencing MIS-C, 35% had ECG changes, 40% exhibited left ventricular systolic or diastolic dysfunction, and 30% had mitral regurgitation, meaning that a large percentage of patients with MIS-C show some degree of cardiac dysfunction. Unfortunately, we are still in the data-gathering phase for long-term outcomes. Functional parameters tend to improve within a week, and most patients will return to normal cardiac function by 3-4 months.

Return to play after MIS-C is quite different from that for acute COVID-19. Patients with MIS-C should be treated much like other patients with myocarditis with an expected return to play in 3-6 months and only after cardiac follow-up. Another good-to-remember recommendation is to delay COVID-19 vaccination for at least 90 days after an episode of MIS-C.
 

Vaccine-related myocarditis

Once again, older age appears to be a risk factor because most patients with postvaccine myocarditis have been in their mid-teens to early 20s, with events more likely after the second vaccine dose and also more likely in male children (4:1 ratio to female children). No deaths have occurred from postvaccination myocarditis in patients younger than 30 years. Still, many individuals have exhibited residual MRI enhancement in the cardiac tissue for some time after experiencing postvaccination myocarditis; it’s currently unclear whether that has clinical implications. By comparison, CDC data demonstrates convincingly that the risk for cardiac effects is much greater after acute COVID-19 than after COVID-19 vaccination, with risk ratios often higher than 20, depending on age and condition (for example, myocarditis vs. pericarditis). Data are still insufficient to determine whether clinicians should recommend or avoid COVID-19 vaccination in children with congenital heart disease.

In summary, administering COVID-19 vaccines requires a great deal of shared decision-making with parents, and the clinician’s role is to educate parents about all potential risks related to both the vaccine and COVID-19 illness. Research has consistently shown that acute COVID-19 myocarditis and myocarditis associated with MIS-C are much more likely to occur in unvaccinated youth and more likely than postvaccination myocarditis, regardless of age.

William T. Basco, Jr., MD, MS, is a professor of pediatrics at the Medical University of South Carolina, Charleston, and director of the division of general pediatrics. He is an active health services researcher and has published more than 60 manuscripts in the peer-reviewed literature.

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

The 2022 Pediatric Academic Societies meeting included an excellent session on the acute and delayed effects of COVID-19 on children’s hearts. Data on the risk for cardiac injury during acute COVID-19, return-to-play guidelines after COVID-19–related heart injury, and post–vaccine-associated myocarditis were reviewed.

COVID-induced cardiac injury

The risk for COVID-induced cardiac injury is directly associated with age. Recent Centers for Disease Control and Prevention data revealed a “myocarditis or pericarditis” rate in the range of 12-17 cases per 100,000 SARS-CoV-2 infections among male children aged 5-11 years (lower rates for females); the rate jumps to 50-65 cases per 100,000 infections among male children aged 12-17 years. So cardiac injury caused by acute COVID-19 appears rare, but the risk is clearly associated with male sex and adolescent age.

Return to play after COVID-19

Clinicians may be pressed by patients and parents for advice on return to play after illness with COVID-19. In July 2020, the American College of Cardiology published an algorithm that has been adjusted over time, most recently in 2022 by the American Academy of Pediatrics. These algorithms stratify recommendations by degree of illness. One rule of thumb: Patients with severe COVID-19 (ICU care or multisystem inflammatory syndrome in children [MIS-C]) have only one box on the algorithm, and that is to rest for 3-6 months and only return to usual activity after cardiac clearance. Moderate disease (defined as ≥ 4 days of fever > 100.4 °F; ≥ 1 week of myalgia, chills, lethargy, or any non-ICU hospital stay; and no evidence of MIS-C) require undergoing an ECG to look for cardiac dysfunction, followed by at least 10 days of rest if the ECG is negative or referral for cardiac evaluation if either ECG or exam by a pediatric cardiologist is abnormal.

Clinicians can perhaps be more permissible with patients who are younger or who have had less severe disease. For example, if a patient aged younger than 12 years is asymptomatic with routine activity at the time of evaluation, an ECG is not indicated. For patients aged 12-15 years who are asymptomatic at the time of evaluation but participate in a high-intensity sport, clinicians might consider obtaining an ECG. As few as 3 days of rest might be enough for select patients who are asymptomatic at presentation. For other patients, clinicians should work with parents to introduce activity gradually and make it clear to parents that any activity intolerance requires quick reevaluation. On existing athlete registries, no deaths that are attributable to post–COVID-19 cardiac effects have been confirmed in children; however, all data presented during the session were from prior to the Omicron variant surge in early 2022, so more information may be forthcoming.
 

Considerations for MIS-C

Among children experiencing MIS-C, 35% had ECG changes, 40% exhibited left ventricular systolic or diastolic dysfunction, and 30% had mitral regurgitation, meaning that a large percentage of patients with MIS-C show some degree of cardiac dysfunction. Unfortunately, we are still in the data-gathering phase for long-term outcomes. Functional parameters tend to improve within a week, and most patients will return to normal cardiac function by 3-4 months.

Return to play after MIS-C is quite different from that for acute COVID-19. Patients with MIS-C should be treated much like other patients with myocarditis with an expected return to play in 3-6 months and only after cardiac follow-up. Another good-to-remember recommendation is to delay COVID-19 vaccination for at least 90 days after an episode of MIS-C.
 

Vaccine-related myocarditis

Once again, older age appears to be a risk factor because most patients with postvaccine myocarditis have been in their mid-teens to early 20s, with events more likely after the second vaccine dose and also more likely in male children (4:1 ratio to female children). No deaths have occurred from postvaccination myocarditis in patients younger than 30 years. Still, many individuals have exhibited residual MRI enhancement in the cardiac tissue for some time after experiencing postvaccination myocarditis; it’s currently unclear whether that has clinical implications. By comparison, CDC data demonstrates convincingly that the risk for cardiac effects is much greater after acute COVID-19 than after COVID-19 vaccination, with risk ratios often higher than 20, depending on age and condition (for example, myocarditis vs. pericarditis). Data are still insufficient to determine whether clinicians should recommend or avoid COVID-19 vaccination in children with congenital heart disease.

In summary, administering COVID-19 vaccines requires a great deal of shared decision-making with parents, and the clinician’s role is to educate parents about all potential risks related to both the vaccine and COVID-19 illness. Research has consistently shown that acute COVID-19 myocarditis and myocarditis associated with MIS-C are much more likely to occur in unvaccinated youth and more likely than postvaccination myocarditis, regardless of age.

William T. Basco, Jr., MD, MS, is a professor of pediatrics at the Medical University of South Carolina, Charleston, and director of the division of general pediatrics. He is an active health services researcher and has published more than 60 manuscripts in the peer-reviewed literature.

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

MILAN – The increased risk for atherosclerotic cardiovascular disease events caused by elevated lipoprotein(a) levels can potentially be precisely offset by lowering LDL cholesterol to specific levels, suggests a novel study that underscores the importance or early intervention.

The results, derived from an analysis of data on Lp(a) and LDL cholesterol levels and associated genetic risk scores in almost 500,000 individuals from the United Kingdom, have been used to develop a series of age-related targets for lowering LDL cholesterol levels to counter the risk associated with lifetime Lp(a) exposure.

Measuring Lp(a) levels can “substantially refine individual estimates of absolute risk of atherosclerotic cardiovascular disease,” said study presenter Brian A. Ference, MD, Centre for Naturally Randomized Trials, University of Cambridge (England).

This can “directly inform treatment decisions about the intensity of LDL lowering or other risk-factor modification needed to overcome the increased risk caused by Lp(a).”

Dr. Ference said this will allow clinicians to personalize the prevention of atherosclerotic cardiovascular disease and identify people “who may benefit from potent Lp(a)-lowering therapies when they become available.”

The research was presented at the European Atherosclerosis Society (EAS) 2022 congress on May 24.

In addition to producing a tabular version of the intensification of LDL-cholesterol reduction needed to overcome the increased cardiovascular risk at different levels of Lp(a), stratified by age, Dr. Ference is working with the EAS to develop an app to further deliver on that personalized prevention.

It will display an individual’s lifetime risk for myocardial infarction or stroke, with and without the inclusion of Lp(a) levels, and determine not only the percentage of increased risk caused by Lp(a), but also the amount by which LDL cholesterol needs to be lowered to overcome that risk.

“The whole rationale for this study was to say, how can we give practical advice on how to use Lp(a) to inform clinical decisions about how to individualize personal risk reduction,” Dr. Ference told this news organization.

“What the app will do is make it very easy for clinicians to, first, understand how much Lp(a) increases risk, but specifically how they can use that information to directly inform their treatment decisions.”

In addition, Dr. Ference said that it will “show patients why it’s important for them” to intensify LDL lowering to overcome their particular level of Lp(a).

Other key takeaways from the results is the importance of intervention as early as possible to minimize the impact of lifetime exposure to increased Lp(a), and that the reduction in LDL cholesterol required to achieve that remains relatively modest.

For Dr. Ference, this means ideally beginning comprehensive health checks at 30 years of age and starting lipid-lowering interventions immediately for those at risk.

“The good thing about LDL and other causes of atherosclerotic cardiovascular disease is it doesn’t really matter how you lower it,” he said, noting that it could be with diet, lifestyle interventions, or medication.
 

Handy tool

The new app could be a “handy tool to counsel patients,” Florian Kronenberg, MD, Institute of Genetic Epidemiology, Medical University of Innsbruck, Austria, told this news organization.

“We can say, look, you have high Lp(a),” he said. “This is coming from nature, from your genetics, but here we have a point where we can act on your high risk by lowering LDL further. This is important to explain to the patient,” said Dr. Kronenberg, who was not involved in the study.

He emphasized that it is crucial to get across the idea of an individual’s global risk, with not just Lp(a) or cholesterol levels influencing their likelihood of cardiovascular events, but also their age, blood pressure, smoking status, and underlying genetic risk.

Dr. Kronenberg said the current data will be helpful in explaining to clinicians why they should lower LDL-cholesterol levels when a patients had high Lp(a), again centered on the idea of lowering their global risk.

During his presentation, Dr. Ference noted that an increase in Lp(a) levels is associated with a log-linear increase in atherosclerotic cardiovascular disease that is proportional to the absolute, rather than relative, magnitude of Lp(a) increase.

“Unfortunately, unlike other proteins,” he continued, diet and exercise do not affect levels, and there are currently no effective therapies to lower the risks associated with increased Lp(a) concentrations.

“For that reason,” he said, the 2019 ESC/EAS guidelines for the management of dyslipidemias, on which Dr. Ference was a coauthor, “recommend that we intensify life risk-factor modification in persons with elevated risks.”

However, he added, “this guidance is not specific enough to be useful, and that has created a great deal of inertia among clinicians,” with some concluding that they don’t need to measure Lp(a) “because there’s nothing they can do for it.”

Until the development of novel therapies that directly target Lp(a), the authors sought to quantify the amount of LDL lowering needed to “overcome the increased risk caused by Lp(a),” he said.

They studied data on 455,765 individuals from the UK Biobank who did not have a history of cardiovascular events, diabetes, or any cancer before the age of 30. They also had LDL cholesterol levels below 5 mmol/L at the time of enrollment to exclude people with presumed familial hypercholesterolemia.

The researchers used an Lp(a) genetic risk score based on the variants rs10455872 and rs3798220 and an LDL instrumental variable genetic score comprised of 100 variants to randomly categorize individuals with average Lp(a) levels, higher Lp(a) levels, or higher Lp(a) and lower LDL-cholesterol levels.

The data showed that, with elevated absolute levels of measured Lp(a) and with elevated genetic risk scores, there was a progressive increase in the lifetime risk for major coronary events.

When looking at the combination of both increased Lp(a) levels and lower LDL-cholesterol levels, they found that the increase in risk for major coronary events at Lp(a) of 123 nmol/L could be offset by a reduction in LDL-cholesterol levels of 19.5 mg/dL.

For people with an Lp(a) level of 251 nmol/L, the increase in risk for major coronary events was offset by a reduction in LDL-cholesterol levels of 36.1 mg/dL.

Furthermore, the researchers found that the magnitude of intensification of LDL-cholesterol lowering needed to overcome the risk caused by elevated Lp(a) levels varied by age.

For example, in individuals with an Lp(a) level of 220 nmol/L, the reduction in LDL-cholesterol levels needed to offset the risk for major coronary events was calculated to be 0.8 mmol/L if lipid-lowering was started at 30 years of age, rising to 0.9 mmol/L if started at 40 years, 1.2 mmol/L if started at 50 years, and 1.5 mmol/L if started at 60 years.

This, Dr. Ference said, suggests that “diet and lifestyle modification is unlikely to be an effective strategy if started later.”

No funding was declared. Dr. Ference declared relationships with Amgen, Novartis, Merck, Esperion Therapeutics, Pfizer, Regeneron, Sanofi, AstraZeneca, Eli Lilly, Novo Nordisk, The Medicines Company, Mylan, Daiichi Sankyo, Viatris, Ionis Pharmaceuticals, dalCOR, CiVi Pharma, and KrKa Pharmaceuticals. Dr. Kronenberg declared relationships with Amgen, Novartis, and Kaneka.

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

MILAN – The increased risk for atherosclerotic cardiovascular disease events caused by elevated lipoprotein(a) levels can potentially be precisely offset by lowering LDL cholesterol to specific levels, suggests a novel study that underscores the importance or early intervention.

The results, derived from an analysis of data on Lp(a) and LDL cholesterol levels and associated genetic risk scores in almost 500,000 individuals from the United Kingdom, have been used to develop a series of age-related targets for lowering LDL cholesterol levels to counter the risk associated with lifetime Lp(a) exposure.

Measuring Lp(a) levels can “substantially refine individual estimates of absolute risk of atherosclerotic cardiovascular disease,” said study presenter Brian A. Ference, MD, Centre for Naturally Randomized Trials, University of Cambridge (England).

This can “directly inform treatment decisions about the intensity of LDL lowering or other risk-factor modification needed to overcome the increased risk caused by Lp(a).”

Dr. Ference said this will allow clinicians to personalize the prevention of atherosclerotic cardiovascular disease and identify people “who may benefit from potent Lp(a)-lowering therapies when they become available.”

The research was presented at the European Atherosclerosis Society (EAS) 2022 congress on May 24.

In addition to producing a tabular version of the intensification of LDL-cholesterol reduction needed to overcome the increased cardiovascular risk at different levels of Lp(a), stratified by age, Dr. Ference is working with the EAS to develop an app to further deliver on that personalized prevention.

It will display an individual’s lifetime risk for myocardial infarction or stroke, with and without the inclusion of Lp(a) levels, and determine not only the percentage of increased risk caused by Lp(a), but also the amount by which LDL cholesterol needs to be lowered to overcome that risk.

“The whole rationale for this study was to say, how can we give practical advice on how to use Lp(a) to inform clinical decisions about how to individualize personal risk reduction,” Dr. Ference told this news organization.

“What the app will do is make it very easy for clinicians to, first, understand how much Lp(a) increases risk, but specifically how they can use that information to directly inform their treatment decisions.”

In addition, Dr. Ference said that it will “show patients why it’s important for them” to intensify LDL lowering to overcome their particular level of Lp(a).

Other key takeaways from the results is the importance of intervention as early as possible to minimize the impact of lifetime exposure to increased Lp(a), and that the reduction in LDL cholesterol required to achieve that remains relatively modest.

For Dr. Ference, this means ideally beginning comprehensive health checks at 30 years of age and starting lipid-lowering interventions immediately for those at risk.

“The good thing about LDL and other causes of atherosclerotic cardiovascular disease is it doesn’t really matter how you lower it,” he said, noting that it could be with diet, lifestyle interventions, or medication.
 

Handy tool

The new app could be a “handy tool to counsel patients,” Florian Kronenberg, MD, Institute of Genetic Epidemiology, Medical University of Innsbruck, Austria, told this news organization.

“We can say, look, you have high Lp(a),” he said. “This is coming from nature, from your genetics, but here we have a point where we can act on your high risk by lowering LDL further. This is important to explain to the patient,” said Dr. Kronenberg, who was not involved in the study.

He emphasized that it is crucial to get across the idea of an individual’s global risk, with not just Lp(a) or cholesterol levels influencing their likelihood of cardiovascular events, but also their age, blood pressure, smoking status, and underlying genetic risk.

Dr. Kronenberg said the current data will be helpful in explaining to clinicians why they should lower LDL-cholesterol levels when a patients had high Lp(a), again centered on the idea of lowering their global risk.

During his presentation, Dr. Ference noted that an increase in Lp(a) levels is associated with a log-linear increase in atherosclerotic cardiovascular disease that is proportional to the absolute, rather than relative, magnitude of Lp(a) increase.

“Unfortunately, unlike other proteins,” he continued, diet and exercise do not affect levels, and there are currently no effective therapies to lower the risks associated with increased Lp(a) concentrations.

“For that reason,” he said, the 2019 ESC/EAS guidelines for the management of dyslipidemias, on which Dr. Ference was a coauthor, “recommend that we intensify life risk-factor modification in persons with elevated risks.”

However, he added, “this guidance is not specific enough to be useful, and that has created a great deal of inertia among clinicians,” with some concluding that they don’t need to measure Lp(a) “because there’s nothing they can do for it.”

Until the development of novel therapies that directly target Lp(a), the authors sought to quantify the amount of LDL lowering needed to “overcome the increased risk caused by Lp(a),” he said.

They studied data on 455,765 individuals from the UK Biobank who did not have a history of cardiovascular events, diabetes, or any cancer before the age of 30. They also had LDL cholesterol levels below 5 mmol/L at the time of enrollment to exclude people with presumed familial hypercholesterolemia.

The researchers used an Lp(a) genetic risk score based on the variants rs10455872 and rs3798220 and an LDL instrumental variable genetic score comprised of 100 variants to randomly categorize individuals with average Lp(a) levels, higher Lp(a) levels, or higher Lp(a) and lower LDL-cholesterol levels.

The data showed that, with elevated absolute levels of measured Lp(a) and with elevated genetic risk scores, there was a progressive increase in the lifetime risk for major coronary events.

When looking at the combination of both increased Lp(a) levels and lower LDL-cholesterol levels, they found that the increase in risk for major coronary events at Lp(a) of 123 nmol/L could be offset by a reduction in LDL-cholesterol levels of 19.5 mg/dL.

For people with an Lp(a) level of 251 nmol/L, the increase in risk for major coronary events was offset by a reduction in LDL-cholesterol levels of 36.1 mg/dL.

Furthermore, the researchers found that the magnitude of intensification of LDL-cholesterol lowering needed to overcome the risk caused by elevated Lp(a) levels varied by age.

For example, in individuals with an Lp(a) level of 220 nmol/L, the reduction in LDL-cholesterol levels needed to offset the risk for major coronary events was calculated to be 0.8 mmol/L if lipid-lowering was started at 30 years of age, rising to 0.9 mmol/L if started at 40 years, 1.2 mmol/L if started at 50 years, and 1.5 mmol/L if started at 60 years.

This, Dr. Ference said, suggests that “diet and lifestyle modification is unlikely to be an effective strategy if started later.”

No funding was declared. Dr. Ference declared relationships with Amgen, Novartis, Merck, Esperion Therapeutics, Pfizer, Regeneron, Sanofi, AstraZeneca, Eli Lilly, Novo Nordisk, The Medicines Company, Mylan, Daiichi Sankyo, Viatris, Ionis Pharmaceuticals, dalCOR, CiVi Pharma, and KrKa Pharmaceuticals. Dr. Kronenberg declared relationships with Amgen, Novartis, and Kaneka.

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

MILAN – The increased risk for atherosclerotic cardiovascular disease events caused by elevated lipoprotein(a) levels can potentially be precisely offset by lowering LDL cholesterol to specific levels, suggests a novel study that underscores the importance or early intervention.

The results, derived from an analysis of data on Lp(a) and LDL cholesterol levels and associated genetic risk scores in almost 500,000 individuals from the United Kingdom, have been used to develop a series of age-related targets for lowering LDL cholesterol levels to counter the risk associated with lifetime Lp(a) exposure.

Measuring Lp(a) levels can “substantially refine individual estimates of absolute risk of atherosclerotic cardiovascular disease,” said study presenter Brian A. Ference, MD, Centre for Naturally Randomized Trials, University of Cambridge (England).

This can “directly inform treatment decisions about the intensity of LDL lowering or other risk-factor modification needed to overcome the increased risk caused by Lp(a).”

Dr. Ference said this will allow clinicians to personalize the prevention of atherosclerotic cardiovascular disease and identify people “who may benefit from potent Lp(a)-lowering therapies when they become available.”

The research was presented at the European Atherosclerosis Society (EAS) 2022 congress on May 24.

In addition to producing a tabular version of the intensification of LDL-cholesterol reduction needed to overcome the increased cardiovascular risk at different levels of Lp(a), stratified by age, Dr. Ference is working with the EAS to develop an app to further deliver on that personalized prevention.

It will display an individual’s lifetime risk for myocardial infarction or stroke, with and without the inclusion of Lp(a) levels, and determine not only the percentage of increased risk caused by Lp(a), but also the amount by which LDL cholesterol needs to be lowered to overcome that risk.

“The whole rationale for this study was to say, how can we give practical advice on how to use Lp(a) to inform clinical decisions about how to individualize personal risk reduction,” Dr. Ference told this news organization.

“What the app will do is make it very easy for clinicians to, first, understand how much Lp(a) increases risk, but specifically how they can use that information to directly inform their treatment decisions.”

In addition, Dr. Ference said that it will “show patients why it’s important for them” to intensify LDL lowering to overcome their particular level of Lp(a).

Other key takeaways from the results is the importance of intervention as early as possible to minimize the impact of lifetime exposure to increased Lp(a), and that the reduction in LDL cholesterol required to achieve that remains relatively modest.

For Dr. Ference, this means ideally beginning comprehensive health checks at 30 years of age and starting lipid-lowering interventions immediately for those at risk.

“The good thing about LDL and other causes of atherosclerotic cardiovascular disease is it doesn’t really matter how you lower it,” he said, noting that it could be with diet, lifestyle interventions, or medication.
 

Handy tool

The new app could be a “handy tool to counsel patients,” Florian Kronenberg, MD, Institute of Genetic Epidemiology, Medical University of Innsbruck, Austria, told this news organization.

“We can say, look, you have high Lp(a),” he said. “This is coming from nature, from your genetics, but here we have a point where we can act on your high risk by lowering LDL further. This is important to explain to the patient,” said Dr. Kronenberg, who was not involved in the study.

He emphasized that it is crucial to get across the idea of an individual’s global risk, with not just Lp(a) or cholesterol levels influencing their likelihood of cardiovascular events, but also their age, blood pressure, smoking status, and underlying genetic risk.

Dr. Kronenberg said the current data will be helpful in explaining to clinicians why they should lower LDL-cholesterol levels when a patients had high Lp(a), again centered on the idea of lowering their global risk.

During his presentation, Dr. Ference noted that an increase in Lp(a) levels is associated with a log-linear increase in atherosclerotic cardiovascular disease that is proportional to the absolute, rather than relative, magnitude of Lp(a) increase.

“Unfortunately, unlike other proteins,” he continued, diet and exercise do not affect levels, and there are currently no effective therapies to lower the risks associated with increased Lp(a) concentrations.

“For that reason,” he said, the 2019 ESC/EAS guidelines for the management of dyslipidemias, on which Dr. Ference was a coauthor, “recommend that we intensify life risk-factor modification in persons with elevated risks.”

However, he added, “this guidance is not specific enough to be useful, and that has created a great deal of inertia among clinicians,” with some concluding that they don’t need to measure Lp(a) “because there’s nothing they can do for it.”

Until the development of novel therapies that directly target Lp(a), the authors sought to quantify the amount of LDL lowering needed to “overcome the increased risk caused by Lp(a),” he said.

They studied data on 455,765 individuals from the UK Biobank who did not have a history of cardiovascular events, diabetes, or any cancer before the age of 30. They also had LDL cholesterol levels below 5 mmol/L at the time of enrollment to exclude people with presumed familial hypercholesterolemia.

The researchers used an Lp(a) genetic risk score based on the variants rs10455872 and rs3798220 and an LDL instrumental variable genetic score comprised of 100 variants to randomly categorize individuals with average Lp(a) levels, higher Lp(a) levels, or higher Lp(a) and lower LDL-cholesterol levels.

The data showed that, with elevated absolute levels of measured Lp(a) and with elevated genetic risk scores, there was a progressive increase in the lifetime risk for major coronary events.

When looking at the combination of both increased Lp(a) levels and lower LDL-cholesterol levels, they found that the increase in risk for major coronary events at Lp(a) of 123 nmol/L could be offset by a reduction in LDL-cholesterol levels of 19.5 mg/dL.

For people with an Lp(a) level of 251 nmol/L, the increase in risk for major coronary events was offset by a reduction in LDL-cholesterol levels of 36.1 mg/dL.

Furthermore, the researchers found that the magnitude of intensification of LDL-cholesterol lowering needed to overcome the risk caused by elevated Lp(a) levels varied by age.

For example, in individuals with an Lp(a) level of 220 nmol/L, the reduction in LDL-cholesterol levels needed to offset the risk for major coronary events was calculated to be 0.8 mmol/L if lipid-lowering was started at 30 years of age, rising to 0.9 mmol/L if started at 40 years, 1.2 mmol/L if started at 50 years, and 1.5 mmol/L if started at 60 years.

This, Dr. Ference said, suggests that “diet and lifestyle modification is unlikely to be an effective strategy if started later.”

No funding was declared. Dr. Ference declared relationships with Amgen, Novartis, Merck, Esperion Therapeutics, Pfizer, Regeneron, Sanofi, AstraZeneca, Eli Lilly, Novo Nordisk, The Medicines Company, Mylan, Daiichi Sankyo, Viatris, Ionis Pharmaceuticals, dalCOR, CiVi Pharma, and KrKa Pharmaceuticals. Dr. Kronenberg declared relationships with Amgen, Novartis, and Kaneka.

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

The first randomized controlled study comparing the use of the emerging distal radial artery access to the traditional proximal access for cardiac catheterization has found no significant differences in postprocedure hand function and other secondary outcomes a month afterward, along with similar rates of bleeding and gaining successful RA access at the time of the procedure.

Karim Al-Azizi, MD, reported results of the single-center, Distal vs. Proximal Radial Artery (DIPRA) study at the Society for Cardiovascular Angiography and Interventions annual scientific sessions. DIPRA randomized 300 patients on a 1:1 basis to cardiac catheterization via either the distal or proximal RAs (dRA or pRA). The trial was conducted at the Baylor Scott & White Health The Heart Hospital–Plano in Richardson, Texas, where Dr. Al-Azizi is an interventional cardiologist and structural heart disease specialist.

“Distal radial artery access is a safe strategy for access for cardiovascular patients with a low complication rate,” Dr. Al-Azizi said. “Similarly, the success with distal vs. radial artery access was noted in the study: No significant bleeding or hematomas were noted in the dRA cohort.”

In an interview, Dr. Al-Azizi added, “Our study is the first of its kind and the first to evaluate the true hand function post distal/radial.”

He explained the rationale for the study. “One of the biggest criticisms that came up a few years ago when distal access was being developed and started gaining some momentum is the fact that it is yet unknown what would be the effect on hand function given the proximity to the fingers, proximity to the nerve, and despite that RA occlusion rates were lower.”

The final DIPRA analysis included 254 patients who completed their 30-day follow-up, 128 of whom were randomized to dRA access, 126 to pRA access. Demographics and procedural characteristics were balanced between both arms. The latter included similarities in sheath size used (6-French in 99.3% of both arms) and type of procedure (35.9% in the dRA and 32.9% in pRA arms had percutaneous coronary angioplasty).

To evaluate the primary outcome of hand function in the catheterization hand, the study used a composite of the Quick Disabilities of Arm, Shoulder, and Hand (DASH) questionnaire, hand-grip test, and thumb/forefinger pinch test. The composite score changed ­–.4 and .1 in the dRA and pRA arms, respectively (P = .07), which didn’t reach statistical significance, Dr. Al-Azizi said.

Outcomes at the time of intervention were similar. Successful RA access failed in six dRA patients, who were converted to pRA, and in two pRA patients. Overall rates for successful RA access were 96.7% in the distal arm and 98% in the proximal arm (P = .72). Bleeding rates were 0% and 1.4% in the respective arms (P = .25).

Dr. Al-Azizi said that he and his coinvestigators are collecting 1-year outcomes data that they will present next year.

The DIPRA findings “provide reassurance that hand function is not compromised regardless of access site,” Sunil V. Rao, MD, moderator of the session where Dr. Al-Azizi reported the results, said in an interview.

“Prior studies indicated no difference in hand function between radial and femoral access, and now these data indicate no difference between distal radial and proximal radial access.” Dr. Rao, the incoming SCAI president, is a professor at Duke University Medical Center in Durham, N.C., and cardiology section chief at Durham Veterans Affairs Medical Center.

“We do need more patient-reported outcomes in percutaneous coronary intervention studies. The DIPRA study is a great example of this,” Dr. Rao added. “The DIPRA study adds to the body of literature indicating that access site choice is an important aspect of the PCI procedure. With meticulous procedural technique, patients can have an excellent outcome from PCI procedures.”

Dr. Al-Azizi disclosed consulting for Edwards Lifesciences and Phillips. Dr. Rao has no disclosures.

The first randomized controlled study comparing the use of the emerging distal radial artery access to the traditional proximal access for cardiac catheterization has found no significant differences in postprocedure hand function and other secondary outcomes a month afterward, along with similar rates of bleeding and gaining successful RA access at the time of the procedure.

Karim Al-Azizi, MD, reported results of the single-center, Distal vs. Proximal Radial Artery (DIPRA) study at the Society for Cardiovascular Angiography and Interventions annual scientific sessions. DIPRA randomized 300 patients on a 1:1 basis to cardiac catheterization via either the distal or proximal RAs (dRA or pRA). The trial was conducted at the Baylor Scott & White Health The Heart Hospital–Plano in Richardson, Texas, where Dr. Al-Azizi is an interventional cardiologist and structural heart disease specialist.

“Distal radial artery access is a safe strategy for access for cardiovascular patients with a low complication rate,” Dr. Al-Azizi said. “Similarly, the success with distal vs. radial artery access was noted in the study: No significant bleeding or hematomas were noted in the dRA cohort.”

In an interview, Dr. Al-Azizi added, “Our study is the first of its kind and the first to evaluate the true hand function post distal/radial.”

He explained the rationale for the study. “One of the biggest criticisms that came up a few years ago when distal access was being developed and started gaining some momentum is the fact that it is yet unknown what would be the effect on hand function given the proximity to the fingers, proximity to the nerve, and despite that RA occlusion rates were lower.”

The final DIPRA analysis included 254 patients who completed their 30-day follow-up, 128 of whom were randomized to dRA access, 126 to pRA access. Demographics and procedural characteristics were balanced between both arms. The latter included similarities in sheath size used (6-French in 99.3% of both arms) and type of procedure (35.9% in the dRA and 32.9% in pRA arms had percutaneous coronary angioplasty).

To evaluate the primary outcome of hand function in the catheterization hand, the study used a composite of the Quick Disabilities of Arm, Shoulder, and Hand (DASH) questionnaire, hand-grip test, and thumb/forefinger pinch test. The composite score changed ­–.4 and .1 in the dRA and pRA arms, respectively (P = .07), which didn’t reach statistical significance, Dr. Al-Azizi said.

Outcomes at the time of intervention were similar. Successful RA access failed in six dRA patients, who were converted to pRA, and in two pRA patients. Overall rates for successful RA access were 96.7% in the distal arm and 98% in the proximal arm (P = .72). Bleeding rates were 0% and 1.4% in the respective arms (P = .25).

Dr. Al-Azizi said that he and his coinvestigators are collecting 1-year outcomes data that they will present next year.

The DIPRA findings “provide reassurance that hand function is not compromised regardless of access site,” Sunil V. Rao, MD, moderator of the session where Dr. Al-Azizi reported the results, said in an interview.

“Prior studies indicated no difference in hand function between radial and femoral access, and now these data indicate no difference between distal radial and proximal radial access.” Dr. Rao, the incoming SCAI president, is a professor at Duke University Medical Center in Durham, N.C., and cardiology section chief at Durham Veterans Affairs Medical Center.

“We do need more patient-reported outcomes in percutaneous coronary intervention studies. The DIPRA study is a great example of this,” Dr. Rao added. “The DIPRA study adds to the body of literature indicating that access site choice is an important aspect of the PCI procedure. With meticulous procedural technique, patients can have an excellent outcome from PCI procedures.”

Dr. Al-Azizi disclosed consulting for Edwards Lifesciences and Phillips. Dr. Rao has no disclosures.

The first randomized controlled study comparing the use of the emerging distal radial artery access to the traditional proximal access for cardiac catheterization has found no significant differences in postprocedure hand function and other secondary outcomes a month afterward, along with similar rates of bleeding and gaining successful RA access at the time of the procedure.

Karim Al-Azizi, MD, reported results of the single-center, Distal vs. Proximal Radial Artery (DIPRA) study at the Society for Cardiovascular Angiography and Interventions annual scientific sessions. DIPRA randomized 300 patients on a 1:1 basis to cardiac catheterization via either the distal or proximal RAs (dRA or pRA). The trial was conducted at the Baylor Scott & White Health The Heart Hospital–Plano in Richardson, Texas, where Dr. Al-Azizi is an interventional cardiologist and structural heart disease specialist.

“Distal radial artery access is a safe strategy for access for cardiovascular patients with a low complication rate,” Dr. Al-Azizi said. “Similarly, the success with distal vs. radial artery access was noted in the study: No significant bleeding or hematomas were noted in the dRA cohort.”

In an interview, Dr. Al-Azizi added, “Our study is the first of its kind and the first to evaluate the true hand function post distal/radial.”

He explained the rationale for the study. “One of the biggest criticisms that came up a few years ago when distal access was being developed and started gaining some momentum is the fact that it is yet unknown what would be the effect on hand function given the proximity to the fingers, proximity to the nerve, and despite that RA occlusion rates were lower.”

The final DIPRA analysis included 254 patients who completed their 30-day follow-up, 128 of whom were randomized to dRA access, 126 to pRA access. Demographics and procedural characteristics were balanced between both arms. The latter included similarities in sheath size used (6-French in 99.3% of both arms) and type of procedure (35.9% in the dRA and 32.9% in pRA arms had percutaneous coronary angioplasty).

To evaluate the primary outcome of hand function in the catheterization hand, the study used a composite of the Quick Disabilities of Arm, Shoulder, and Hand (DASH) questionnaire, hand-grip test, and thumb/forefinger pinch test. The composite score changed ­–.4 and .1 in the dRA and pRA arms, respectively (P = .07), which didn’t reach statistical significance, Dr. Al-Azizi said.

Outcomes at the time of intervention were similar. Successful RA access failed in six dRA patients, who were converted to pRA, and in two pRA patients. Overall rates for successful RA access were 96.7% in the distal arm and 98% in the proximal arm (P = .72). Bleeding rates were 0% and 1.4% in the respective arms (P = .25).

Dr. Al-Azizi said that he and his coinvestigators are collecting 1-year outcomes data that they will present next year.

The DIPRA findings “provide reassurance that hand function is not compromised regardless of access site,” Sunil V. Rao, MD, moderator of the session where Dr. Al-Azizi reported the results, said in an interview.

“Prior studies indicated no difference in hand function between radial and femoral access, and now these data indicate no difference between distal radial and proximal radial access.” Dr. Rao, the incoming SCAI president, is a professor at Duke University Medical Center in Durham, N.C., and cardiology section chief at Durham Veterans Affairs Medical Center.

“We do need more patient-reported outcomes in percutaneous coronary intervention studies. The DIPRA study is a great example of this,” Dr. Rao added. “The DIPRA study adds to the body of literature indicating that access site choice is an important aspect of the PCI procedure. With meticulous procedural technique, patients can have an excellent outcome from PCI procedures.”

Dr. Al-Azizi disclosed consulting for Edwards Lifesciences and Phillips. Dr. Rao has no disclosures.

A new study suggests that, at least for certain male patients, the answer to infertility might lie with epigenetics.

According to the study, a commercially available test of epigenetic anomalies – factors that affect how genes express themselves – can grade the likelihood that sperm are viable for conception.

“The uniqueness of epigenetics is that some of the abnormalities detected have the potential to be modified with lifestyle,” said Larry I. Lipshultz, MD, head of the Division of Male Reproductive Medicine and Surgery at Baylor College of Medicine, Houston, who presented the new findings at the 2022 annual meeting of the American Urological Association.

For decades, semen analysis has been based on motility, morphology, and concentration. But these measures, while useful, are limited. Semen can still have low capacity for producing a pregnancy even when all three parameters are normal, Dr. Lipshultz told this news organization.

The test, called Path SpermQT (Inherent Biosciences) detects unstable gene promotors, which are the epigenetic markers for gene expression. In previous work with more than 1,300 gene samples, expression of the specific genes regulated by these promoters were linked to a wide variety of functions relevant to fertilization, such as spermatogenesis.

The test does not attempt to look for expression of specific unstable promoters but rather quantifies them to characterize sperm quality as excellent (≤ 10 unstable promoters), average (11-42), or poor (≥ 43).

In the studies that led to development of the SpermQT test, the number of unstable promoters correlated with pregnancy success. Pregnancy was achieved even among those in the group with poor sperm quality – but at very low rates.

Of the 172 semen samples collected so far in the ongoing analysis, sperm quality was characterized as excellent in 31%, average in 59%, and poor in 10%.

The stratifications for sperm quality were not significantly correlated with common measures of sperm viability, such as concentration, Dr. Lipshultz reported.

Certain patient characteristics were associated with greater sperm quality. These included use of antioxidant supplementation and low estrogen levels, as seen in men who had taken aromatase inhibitors.

So far, only one natural conception has occurred in the group with poor sperm versus eight in those with average or excellent quality.

The prognostic role of the test is only part of the picture.

“The exciting thing about this area of research is that epigenetics can be changed,” Dr. Lipshultz said in an interview. Based on the data so far, he said he is already starting to consider antioxidant supplementation and hormone modifications when sperm quality is poor.

The value of the Path SpermQT test for identifying treatment targets might eventually revolutionize the management of male infertility, Dr. Lipshultz said, but it has more immediate potential in helping couples decide whether to proceed with in vitro fertilization (IVF).

“We often see patients at an impasse when they are trying to decide to move to IVF,” he said. “A test like this could provide some direction. If sperm quality is good, the advice might be to keep trying. If poor, then a couple might want to move to IVF more quickly.”

A test of sperm quality on the basis of epigenetics “could change how we look at couples attempting to conceive,” agreed Peter N. Schlegel, MD, professor of urology and reproductive medicine, Weill Cornell Medicine, New York.

Dr. Schlegel praised several characteristics of the epigenetics test, including that 70%-80% of men with poor quality with SpermQT have normal results on standard assessments of semen. This finding suggests the tool is providing unique information about patients. He also noted that the studies so far indicate that sperm of poor quality for natural conception is still viable for IVF fertilization – which could be useful for couples weighing their options.

However, while the test is already available, Dr. Schlegel cautioned that much of the promise has yet to be documented.

“The results to date, despite being statistically significant, have only been gleaned from a small group of patients,” he said. “Much larger studies are needed before a change in practice is warranted.”

The value of SpermQT for identifying modifiable risks might be even further away.

“It is well recognized that environmental and lifestyle changes can affect methylation, but it is not known if the abnormalities seen so far could be influenced by lifestyle changes,” Dr. Schlegel said. Among the numerous steps needed to answer this question, he suggested that it might first be important “to evaluate why such changes in methylation occur.”

Dr. Lipshultz has financial relationships with several pharmaceutical companies, including Inherent Biosciences, which is marketing the SpermQT test. Dr. Schlegel has financial relationships with Theralogix, Posterity Health, and Roman Health.

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

A new study suggests that, at least for certain male patients, the answer to infertility might lie with epigenetics.

According to the study, a commercially available test of epigenetic anomalies – factors that affect how genes express themselves – can grade the likelihood that sperm are viable for conception.

“The uniqueness of epigenetics is that some of the abnormalities detected have the potential to be modified with lifestyle,” said Larry I. Lipshultz, MD, head of the Division of Male Reproductive Medicine and Surgery at Baylor College of Medicine, Houston, who presented the new findings at the 2022 annual meeting of the American Urological Association.

For decades, semen analysis has been based on motility, morphology, and concentration. But these measures, while useful, are limited. Semen can still have low capacity for producing a pregnancy even when all three parameters are normal, Dr. Lipshultz told this news organization.

The test, called Path SpermQT (Inherent Biosciences) detects unstable gene promotors, which are the epigenetic markers for gene expression. In previous work with more than 1,300 gene samples, expression of the specific genes regulated by these promoters were linked to a wide variety of functions relevant to fertilization, such as spermatogenesis.

The test does not attempt to look for expression of specific unstable promoters but rather quantifies them to characterize sperm quality as excellent (≤ 10 unstable promoters), average (11-42), or poor (≥ 43).

In the studies that led to development of the SpermQT test, the number of unstable promoters correlated with pregnancy success. Pregnancy was achieved even among those in the group with poor sperm quality – but at very low rates.

Of the 172 semen samples collected so far in the ongoing analysis, sperm quality was characterized as excellent in 31%, average in 59%, and poor in 10%.

The stratifications for sperm quality were not significantly correlated with common measures of sperm viability, such as concentration, Dr. Lipshultz reported.

Certain patient characteristics were associated with greater sperm quality. These included use of antioxidant supplementation and low estrogen levels, as seen in men who had taken aromatase inhibitors.

So far, only one natural conception has occurred in the group with poor sperm versus eight in those with average or excellent quality.

The prognostic role of the test is only part of the picture.

“The exciting thing about this area of research is that epigenetics can be changed,” Dr. Lipshultz said in an interview. Based on the data so far, he said he is already starting to consider antioxidant supplementation and hormone modifications when sperm quality is poor.

The value of the Path SpermQT test for identifying treatment targets might eventually revolutionize the management of male infertility, Dr. Lipshultz said, but it has more immediate potential in helping couples decide whether to proceed with in vitro fertilization (IVF).

“We often see patients at an impasse when they are trying to decide to move to IVF,” he said. “A test like this could provide some direction. If sperm quality is good, the advice might be to keep trying. If poor, then a couple might want to move to IVF more quickly.”

A test of sperm quality on the basis of epigenetics “could change how we look at couples attempting to conceive,” agreed Peter N. Schlegel, MD, professor of urology and reproductive medicine, Weill Cornell Medicine, New York.

Dr. Schlegel praised several characteristics of the epigenetics test, including that 70%-80% of men with poor quality with SpermQT have normal results on standard assessments of semen. This finding suggests the tool is providing unique information about patients. He also noted that the studies so far indicate that sperm of poor quality for natural conception is still viable for IVF fertilization – which could be useful for couples weighing their options.

However, while the test is already available, Dr. Schlegel cautioned that much of the promise has yet to be documented.

“The results to date, despite being statistically significant, have only been gleaned from a small group of patients,” he said. “Much larger studies are needed before a change in practice is warranted.”

The value of SpermQT for identifying modifiable risks might be even further away.

“It is well recognized that environmental and lifestyle changes can affect methylation, but it is not known if the abnormalities seen so far could be influenced by lifestyle changes,” Dr. Schlegel said. Among the numerous steps needed to answer this question, he suggested that it might first be important “to evaluate why such changes in methylation occur.”

Dr. Lipshultz has financial relationships with several pharmaceutical companies, including Inherent Biosciences, which is marketing the SpermQT test. Dr. Schlegel has financial relationships with Theralogix, Posterity Health, and Roman Health.

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

A new study suggests that, at least for certain male patients, the answer to infertility might lie with epigenetics.

According to the study, a commercially available test of epigenetic anomalies – factors that affect how genes express themselves – can grade the likelihood that sperm are viable for conception.

“The uniqueness of epigenetics is that some of the abnormalities detected have the potential to be modified with lifestyle,” said Larry I. Lipshultz, MD, head of the Division of Male Reproductive Medicine and Surgery at Baylor College of Medicine, Houston, who presented the new findings at the 2022 annual meeting of the American Urological Association.

For decades, semen analysis has been based on motility, morphology, and concentration. But these measures, while useful, are limited. Semen can still have low capacity for producing a pregnancy even when all three parameters are normal, Dr. Lipshultz told this news organization.

The test, called Path SpermQT (Inherent Biosciences) detects unstable gene promotors, which are the epigenetic markers for gene expression. In previous work with more than 1,300 gene samples, expression of the specific genes regulated by these promoters were linked to a wide variety of functions relevant to fertilization, such as spermatogenesis.

The test does not attempt to look for expression of specific unstable promoters but rather quantifies them to characterize sperm quality as excellent (≤ 10 unstable promoters), average (11-42), or poor (≥ 43).

In the studies that led to development of the SpermQT test, the number of unstable promoters correlated with pregnancy success. Pregnancy was achieved even among those in the group with poor sperm quality – but at very low rates.

Of the 172 semen samples collected so far in the ongoing analysis, sperm quality was characterized as excellent in 31%, average in 59%, and poor in 10%.

The stratifications for sperm quality were not significantly correlated with common measures of sperm viability, such as concentration, Dr. Lipshultz reported.

Certain patient characteristics were associated with greater sperm quality. These included use of antioxidant supplementation and low estrogen levels, as seen in men who had taken aromatase inhibitors.

So far, only one natural conception has occurred in the group with poor sperm versus eight in those with average or excellent quality.

The prognostic role of the test is only part of the picture.

“The exciting thing about this area of research is that epigenetics can be changed,” Dr. Lipshultz said in an interview. Based on the data so far, he said he is already starting to consider antioxidant supplementation and hormone modifications when sperm quality is poor.

The value of the Path SpermQT test for identifying treatment targets might eventually revolutionize the management of male infertility, Dr. Lipshultz said, but it has more immediate potential in helping couples decide whether to proceed with in vitro fertilization (IVF).

“We often see patients at an impasse when they are trying to decide to move to IVF,” he said. “A test like this could provide some direction. If sperm quality is good, the advice might be to keep trying. If poor, then a couple might want to move to IVF more quickly.”

A test of sperm quality on the basis of epigenetics “could change how we look at couples attempting to conceive,” agreed Peter N. Schlegel, MD, professor of urology and reproductive medicine, Weill Cornell Medicine, New York.

Dr. Schlegel praised several characteristics of the epigenetics test, including that 70%-80% of men with poor quality with SpermQT have normal results on standard assessments of semen. This finding suggests the tool is providing unique information about patients. He also noted that the studies so far indicate that sperm of poor quality for natural conception is still viable for IVF fertilization – which could be useful for couples weighing their options.

However, while the test is already available, Dr. Schlegel cautioned that much of the promise has yet to be documented.

“The results to date, despite being statistically significant, have only been gleaned from a small group of patients,” he said. “Much larger studies are needed before a change in practice is warranted.”

The value of SpermQT for identifying modifiable risks might be even further away.

“It is well recognized that environmental and lifestyle changes can affect methylation, but it is not known if the abnormalities seen so far could be influenced by lifestyle changes,” Dr. Schlegel said. Among the numerous steps needed to answer this question, he suggested that it might first be important “to evaluate why such changes in methylation occur.”

Dr. Lipshultz has financial relationships with several pharmaceutical companies, including Inherent Biosciences, which is marketing the SpermQT test. Dr. Schlegel has financial relationships with Theralogix, Posterity Health, and Roman Health.

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

Patients receiving treatment with ibrutinib for chronic lymphocytic leukemia (CLL) show significant increases in the risk for bleeding when undergoing Mohs micrographic surgery for skin cancer, indicating the need for temporary treatment interruptions, new research shows.

“Our cohort of CLL patients on ibrutinib had a two-times greater risk of bleeding complications relative to those on anticoagulants and a nearly 40-times greater risk of bleeding complications relative to those patients on no anticoagulants or CLL therapy,” Kelsey E. Hirotsu, MD, first author of one of two studies on the issue presented at the American College of Mohs Surgery annual meeting, told this news organization.

“It was definitely surprising to see this doubled risk with ibrutinib relative to anticoagulants, and certainly highlights the clinically relevant increased bleeding risk in patients on ibrutinib,” said Dr. Hirotsu, a Mohs micrographic surgery fellow in the department of dermatology, University of California, San Diego (UCSD).

With CLL associated with an increased risk for aggressive skin cancers, particularly squamous cell carcinoma, Mohs surgeons may commonly find themselves treating patients with these unique considerations. Surgical treatment of those cancers can be complicated not only because of potential underlying thrombocytopenia, which occurs in about 5% of untreated CLL patients, but also because of the increased risk for bleeding that is associated with the use of the Bruton tyrosine kinase inhibitor ibrutinib, commonly used for CLL.

While the nature of the increased bleeding-related complications among patients with CLL undergoing Mohs surgery has been documented in some case reports, evidence from larger studies has been lacking.

In one of the studies presented at the ACMS meeting, Dr. Hirotsu and her colleagues evaluated data on patients with CLL who underwent at least one Mohs surgery procedure at UCSD Dermatologic Surgery over 10 years. Of the 362 Mohs cases among 98 patients with CLL, 32 cases had at least one complication. Patients on anticoagulants, including antiplatelet agents, Coumadin, and direct oral anticoagulants (DOACs), not surprisingly, had higher rates of complications, particularly bleeding.

However, those treated with ibrutinib had the highest rates of complications among all of the patients (40.6%), with all of their complications involving bleeding-related events. In comparison, the complication rates, for instance, of patients treated with antiplatelets were 21.9%; Coumadin, 6.2%; and DOACs, 15.6%.

The incidence of bleeding-related complications among the cases in the ibrutinib-treated patients was 30.2% compared with 13.2% among those on blood thinners and no CLL therapy (relative risk [RR], 2.08; 95% confidence interval [CI], 0.85-5.11; P = .11). “Although not statistically significant, these results could trend toward significance with larger sample sizes,” Dr. Hirotsu said.

The risk for bleeding among patients on ibrutinib compared with patients on no medications, however, was significant, with a relative risk of 39.0 (95% CI, 2.35-646; P = .011).

Of note, among 12 patients on ibrutinib who experienced bleeding complications, 7 had previously undergone Mohs surgeries when they were not taking ibrutinib and no bleeding complications had occurred in those procedures. “This may further implicate ibrutinib as a cause of the bleeding-related complications,” Dr. Hirotsu said.

In investigating the role of thrombocytopenia at the time of Mohs surgery, the authors found that, among ibrutinib-treated patients who had no complications, 30% had thrombocytopenia, compared with 70% of those who did have bleeding while on ibrutinib at the time of surgery.

“It was interesting that thrombocytopenia is more common in ibrutinib patients with bleeding-related complications, but further research needs to be done to determine the clinical relevance and possible management implications,” Dr. Hirotsu said.

In a separate study presented at the meeting, 37 patients treated with ibrutinib for CLL while undergoing cutaneous surgery that included Mohs surgery and excisions had a significantly increased bleeding complication rate compared with a control group of 64 age- and sex-matched patients with CLL undergoing cutaneous surgery: 6 of 75 procedures (8%) versus 1 of 115 procedures (0.9%; P = .02).

Those with bleeding complications while on ibrutinib were all male, older (mean age, 82.7 vs. 73.0; P = .01), and had lower mean platelet counts (104 K/mcL vs. 150.5 K/mcL; P = .03).

There were no significant differences between the case and control groups in terms of anatomic site, type of procedure (Mohs versus excision), tumor diagnosis, lesion size, or type of reconstruction, while the control group was more likely to be on aspirin or other anticoagulants (P < .0001).

In an interview, senior author Nahid Y. Vidal, MD, a Mohs surgeon and dermatologic oncologist at the Mayo Clinic, Rochester, Minn., said that “the take-home message is that patients on ibrutinib should be considered higher risk for bleeding events, regardless of whether they are having a simpler surgery [excision] or more involved skin surgery procedure [Mohs with flap].”

Holding treatment

To offset the bleeding risk, Dr. Vidal notes that holding the treatment is considered safe and that the manufacturer recommends holding ibrutinib for at least 3-7 days pre- and post surgery, “depending on type of surgery and risk of bleeding.”

“In our institution, with the hematologist/oncologist’s input, we hold ibrutinib for 5 days preop and 3 days post op, and have not had bleed complications in these patients,” she said, noting that there were no bleeding events in the patients in the study when ibrutinib was held.

Likewise, Dr. Hirotsu noted that at her center at UCSD, patients on ibrutinib are asked during the preop call to hold treatment for 3 days before and after Mohs surgery – but are advised to discuss the decision with their hematologist/oncologist for approval.

The measure isn’t always successful in preventing bleeding, however, as seen in a case study describing two patients who experienced bleeding complications following Mohs surgery despite being taken off ibrutinib 3 days prior to the procedure.

The senior author of that study, Kira Minkis, MD, PhD, department of dermatology, Weill Cornell/New York Presbyterian, New York, told this news organization that her team concluded that in those cases ibrutinib perhaps should have been held longer than 3 days.

“In some cases, especially if the Mohs surgery is a large procedure with a more advanced reconstruction, such as a large flap, it might be more prudent to continue it longer than 3 days,” Dr. Minkis said. She noted that the high bleeding risk observed in the studies at ACMS was notable – but not unexpected.

“I’m not that surprised because if you look at the hematologic literature, the risk is indeed pretty significant, so it makes sense that it would also occur with Mohs surgeries,” she said.

She underscored that a 3-day hold of ibrutinib should be considered the minimum, “and in some cases, it should be held up to 7 days prior to surgery, depending on the specific surgery,” with the important caveat of consulting with the patient’s hematology team.

“Multidisciplinary decision-making is necessary for these cases, and the interruption of therapy should always be discussed with their hematology team,” she added. That said, Dr. Minkis noted that “I’ve never had a hematologist who had any concerns for withholding ibrutinib even for a week around the time of a surgery.”

Dr. Hirotsu, Dr. Vidal, and Dr. Minkis reported no relevant financial relationships.

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

Patients receiving treatment with ibrutinib for chronic lymphocytic leukemia (CLL) show significant increases in the risk for bleeding when undergoing Mohs micrographic surgery for skin cancer, indicating the need for temporary treatment interruptions, new research shows.

“Our cohort of CLL patients on ibrutinib had a two-times greater risk of bleeding complications relative to those on anticoagulants and a nearly 40-times greater risk of bleeding complications relative to those patients on no anticoagulants or CLL therapy,” Kelsey E. Hirotsu, MD, first author of one of two studies on the issue presented at the American College of Mohs Surgery annual meeting, told this news organization.

“It was definitely surprising to see this doubled risk with ibrutinib relative to anticoagulants, and certainly highlights the clinically relevant increased bleeding risk in patients on ibrutinib,” said Dr. Hirotsu, a Mohs micrographic surgery fellow in the department of dermatology, University of California, San Diego (UCSD).

With CLL associated with an increased risk for aggressive skin cancers, particularly squamous cell carcinoma, Mohs surgeons may commonly find themselves treating patients with these unique considerations. Surgical treatment of those cancers can be complicated not only because of potential underlying thrombocytopenia, which occurs in about 5% of untreated CLL patients, but also because of the increased risk for bleeding that is associated with the use of the Bruton tyrosine kinase inhibitor ibrutinib, commonly used for CLL.

While the nature of the increased bleeding-related complications among patients with CLL undergoing Mohs surgery has been documented in some case reports, evidence from larger studies has been lacking.

In one of the studies presented at the ACMS meeting, Dr. Hirotsu and her colleagues evaluated data on patients with CLL who underwent at least one Mohs surgery procedure at UCSD Dermatologic Surgery over 10 years. Of the 362 Mohs cases among 98 patients with CLL, 32 cases had at least one complication. Patients on anticoagulants, including antiplatelet agents, Coumadin, and direct oral anticoagulants (DOACs), not surprisingly, had higher rates of complications, particularly bleeding.

However, those treated with ibrutinib had the highest rates of complications among all of the patients (40.6%), with all of their complications involving bleeding-related events. In comparison, the complication rates, for instance, of patients treated with antiplatelets were 21.9%; Coumadin, 6.2%; and DOACs, 15.6%.

The incidence of bleeding-related complications among the cases in the ibrutinib-treated patients was 30.2% compared with 13.2% among those on blood thinners and no CLL therapy (relative risk [RR], 2.08; 95% confidence interval [CI], 0.85-5.11; P = .11). “Although not statistically significant, these results could trend toward significance with larger sample sizes,” Dr. Hirotsu said.

The risk for bleeding among patients on ibrutinib compared with patients on no medications, however, was significant, with a relative risk of 39.0 (95% CI, 2.35-646; P = .011).

Of note, among 12 patients on ibrutinib who experienced bleeding complications, 7 had previously undergone Mohs surgeries when they were not taking ibrutinib and no bleeding complications had occurred in those procedures. “This may further implicate ibrutinib as a cause of the bleeding-related complications,” Dr. Hirotsu said.

In investigating the role of thrombocytopenia at the time of Mohs surgery, the authors found that, among ibrutinib-treated patients who had no complications, 30% had thrombocytopenia, compared with 70% of those who did have bleeding while on ibrutinib at the time of surgery.

“It was interesting that thrombocytopenia is more common in ibrutinib patients with bleeding-related complications, but further research needs to be done to determine the clinical relevance and possible management implications,” Dr. Hirotsu said.

In a separate study presented at the meeting, 37 patients treated with ibrutinib for CLL while undergoing cutaneous surgery that included Mohs surgery and excisions had a significantly increased bleeding complication rate compared with a control group of 64 age- and sex-matched patients with CLL undergoing cutaneous surgery: 6 of 75 procedures (8%) versus 1 of 115 procedures (0.9%; P = .02).

Those with bleeding complications while on ibrutinib were all male, older (mean age, 82.7 vs. 73.0; P = .01), and had lower mean platelet counts (104 K/mcL vs. 150.5 K/mcL; P = .03).

There were no significant differences between the case and control groups in terms of anatomic site, type of procedure (Mohs versus excision), tumor diagnosis, lesion size, or type of reconstruction, while the control group was more likely to be on aspirin or other anticoagulants (P < .0001).

In an interview, senior author Nahid Y. Vidal, MD, a Mohs surgeon and dermatologic oncologist at the Mayo Clinic, Rochester, Minn., said that “the take-home message is that patients on ibrutinib should be considered higher risk for bleeding events, regardless of whether they are having a simpler surgery [excision] or more involved skin surgery procedure [Mohs with flap].”

Holding treatment

To offset the bleeding risk, Dr. Vidal notes that holding the treatment is considered safe and that the manufacturer recommends holding ibrutinib for at least 3-7 days pre- and post surgery, “depending on type of surgery and risk of bleeding.”

“In our institution, with the hematologist/oncologist’s input, we hold ibrutinib for 5 days preop and 3 days post op, and have not had bleed complications in these patients,” she said, noting that there were no bleeding events in the patients in the study when ibrutinib was held.

Likewise, Dr. Hirotsu noted that at her center at UCSD, patients on ibrutinib are asked during the preop call to hold treatment for 3 days before and after Mohs surgery – but are advised to discuss the decision with their hematologist/oncologist for approval.

The measure isn’t always successful in preventing bleeding, however, as seen in a case study describing two patients who experienced bleeding complications following Mohs surgery despite being taken off ibrutinib 3 days prior to the procedure.

The senior author of that study, Kira Minkis, MD, PhD, department of dermatology, Weill Cornell/New York Presbyterian, New York, told this news organization that her team concluded that in those cases ibrutinib perhaps should have been held longer than 3 days.

“In some cases, especially if the Mohs surgery is a large procedure with a more advanced reconstruction, such as a large flap, it might be more prudent to continue it longer than 3 days,” Dr. Minkis said. She noted that the high bleeding risk observed in the studies at ACMS was notable – but not unexpected.

“I’m not that surprised because if you look at the hematologic literature, the risk is indeed pretty significant, so it makes sense that it would also occur with Mohs surgeries,” she said.

She underscored that a 3-day hold of ibrutinib should be considered the minimum, “and in some cases, it should be held up to 7 days prior to surgery, depending on the specific surgery,” with the important caveat of consulting with the patient’s hematology team.

“Multidisciplinary decision-making is necessary for these cases, and the interruption of therapy should always be discussed with their hematology team,” she added. That said, Dr. Minkis noted that “I’ve never had a hematologist who had any concerns for withholding ibrutinib even for a week around the time of a surgery.”

Dr. Hirotsu, Dr. Vidal, and Dr. Minkis reported no relevant financial relationships.

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

Patients receiving treatment with ibrutinib for chronic lymphocytic leukemia (CLL) show significant increases in the risk for bleeding when undergoing Mohs micrographic surgery for skin cancer, indicating the need for temporary treatment interruptions, new research shows.

“Our cohort of CLL patients on ibrutinib had a two-times greater risk of bleeding complications relative to those on anticoagulants and a nearly 40-times greater risk of bleeding complications relative to those patients on no anticoagulants or CLL therapy,” Kelsey E. Hirotsu, MD, first author of one of two studies on the issue presented at the American College of Mohs Surgery annual meeting, told this news organization.

“It was definitely surprising to see this doubled risk with ibrutinib relative to anticoagulants, and certainly highlights the clinically relevant increased bleeding risk in patients on ibrutinib,” said Dr. Hirotsu, a Mohs micrographic surgery fellow in the department of dermatology, University of California, San Diego (UCSD).

With CLL associated with an increased risk for aggressive skin cancers, particularly squamous cell carcinoma, Mohs surgeons may commonly find themselves treating patients with these unique considerations. Surgical treatment of those cancers can be complicated not only because of potential underlying thrombocytopenia, which occurs in about 5% of untreated CLL patients, but also because of the increased risk for bleeding that is associated with the use of the Bruton tyrosine kinase inhibitor ibrutinib, commonly used for CLL.

While the nature of the increased bleeding-related complications among patients with CLL undergoing Mohs surgery has been documented in some case reports, evidence from larger studies has been lacking.

In one of the studies presented at the ACMS meeting, Dr. Hirotsu and her colleagues evaluated data on patients with CLL who underwent at least one Mohs surgery procedure at UCSD Dermatologic Surgery over 10 years. Of the 362 Mohs cases among 98 patients with CLL, 32 cases had at least one complication. Patients on anticoagulants, including antiplatelet agents, Coumadin, and direct oral anticoagulants (DOACs), not surprisingly, had higher rates of complications, particularly bleeding.

However, those treated with ibrutinib had the highest rates of complications among all of the patients (40.6%), with all of their complications involving bleeding-related events. In comparison, the complication rates, for instance, of patients treated with antiplatelets were 21.9%; Coumadin, 6.2%; and DOACs, 15.6%.

The incidence of bleeding-related complications among the cases in the ibrutinib-treated patients was 30.2% compared with 13.2% among those on blood thinners and no CLL therapy (relative risk [RR], 2.08; 95% confidence interval [CI], 0.85-5.11; P = .11). “Although not statistically significant, these results could trend toward significance with larger sample sizes,” Dr. Hirotsu said.

The risk for bleeding among patients on ibrutinib compared with patients on no medications, however, was significant, with a relative risk of 39.0 (95% CI, 2.35-646; P = .011).

Of note, among 12 patients on ibrutinib who experienced bleeding complications, 7 had previously undergone Mohs surgeries when they were not taking ibrutinib and no bleeding complications had occurred in those procedures. “This may further implicate ibrutinib as a cause of the bleeding-related complications,” Dr. Hirotsu said.

In investigating the role of thrombocytopenia at the time of Mohs surgery, the authors found that, among ibrutinib-treated patients who had no complications, 30% had thrombocytopenia, compared with 70% of those who did have bleeding while on ibrutinib at the time of surgery.

“It was interesting that thrombocytopenia is more common in ibrutinib patients with bleeding-related complications, but further research needs to be done to determine the clinical relevance and possible management implications,” Dr. Hirotsu said.

In a separate study presented at the meeting, 37 patients treated with ibrutinib for CLL while undergoing cutaneous surgery that included Mohs surgery and excisions had a significantly increased bleeding complication rate compared with a control group of 64 age- and sex-matched patients with CLL undergoing cutaneous surgery: 6 of 75 procedures (8%) versus 1 of 115 procedures (0.9%; P = .02).

Those with bleeding complications while on ibrutinib were all male, older (mean age, 82.7 vs. 73.0; P = .01), and had lower mean platelet counts (104 K/mcL vs. 150.5 K/mcL; P = .03).

There were no significant differences between the case and control groups in terms of anatomic site, type of procedure (Mohs versus excision), tumor diagnosis, lesion size, or type of reconstruction, while the control group was more likely to be on aspirin or other anticoagulants (P < .0001).

In an interview, senior author Nahid Y. Vidal, MD, a Mohs surgeon and dermatologic oncologist at the Mayo Clinic, Rochester, Minn., said that “the take-home message is that patients on ibrutinib should be considered higher risk for bleeding events, regardless of whether they are having a simpler surgery [excision] or more involved skin surgery procedure [Mohs with flap].”

Holding treatment

To offset the bleeding risk, Dr. Vidal notes that holding the treatment is considered safe and that the manufacturer recommends holding ibrutinib for at least 3-7 days pre- and post surgery, “depending on type of surgery and risk of bleeding.”

“In our institution, with the hematologist/oncologist’s input, we hold ibrutinib for 5 days preop and 3 days post op, and have not had bleed complications in these patients,” she said, noting that there were no bleeding events in the patients in the study when ibrutinib was held.

Likewise, Dr. Hirotsu noted that at her center at UCSD, patients on ibrutinib are asked during the preop call to hold treatment for 3 days before and after Mohs surgery – but are advised to discuss the decision with their hematologist/oncologist for approval.

The measure isn’t always successful in preventing bleeding, however, as seen in a case study describing two patients who experienced bleeding complications following Mohs surgery despite being taken off ibrutinib 3 days prior to the procedure.

The senior author of that study, Kira Minkis, MD, PhD, department of dermatology, Weill Cornell/New York Presbyterian, New York, told this news organization that her team concluded that in those cases ibrutinib perhaps should have been held longer than 3 days.

“In some cases, especially if the Mohs surgery is a large procedure with a more advanced reconstruction, such as a large flap, it might be more prudent to continue it longer than 3 days,” Dr. Minkis said. She noted that the high bleeding risk observed in the studies at ACMS was notable – but not unexpected.

“I’m not that surprised because if you look at the hematologic literature, the risk is indeed pretty significant, so it makes sense that it would also occur with Mohs surgeries,” she said.

She underscored that a 3-day hold of ibrutinib should be considered the minimum, “and in some cases, it should be held up to 7 days prior to surgery, depending on the specific surgery,” with the important caveat of consulting with the patient’s hematology team.

“Multidisciplinary decision-making is necessary for these cases, and the interruption of therapy should always be discussed with their hematology team,” she added. That said, Dr. Minkis noted that “I’ve never had a hematologist who had any concerns for withholding ibrutinib even for a week around the time of a surgery.”

Dr. Hirotsu, Dr. Vidal, and Dr. Minkis reported no relevant financial relationships.

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

NEW ORLEANS – Patients experiencing brain fog and other persistent symptoms of long COVID show significant deficits on neuropsychiatric testing that correspond with prior acute COVID-19 infection, adding to mounting evidence of the significant toll the chronic condition can have on mental health.

“Many clinicians have observed the symptoms we describe in this study, however this report is among the first which identify the specific deficits using neuropsychological testing to better characterize the syndrome,” Sean T. Lynch, MD, first author of a study on the issue presented at the annual meeting of the American Psychiatric Association, said in an interview.

Dr. Lynch, of the department of psychiatry, Westchester Medical Center Health System, Valhalla, N.Y., and his colleagues enrolled 60 participants who had experienced acute COVID-19 disease 6-8 months earlier and had undergone neuropsychological, psychiatric, medical, functional, and quality-of-life assessments. Results from the study were published online in the Journal of the Academy of Consultation–Liaison Psychiatry (2022 Jan 25. doi: 10.1016/j.jaclp.2022.01.003).

Among the study participants, 32 were seeking treatment for brain fog in a clinical program for survivors of COVID-19, while the remaining 28 were part of an ongoing longitudinal investigation of neuropsychological, medical, and psychiatric sequelae of COVID-19, but were not seeking care for the persistent symptoms.

Assessments for neurocognitive impairment included a battery of tests used in infectious and other diseases, including the Test of Premorbid Function, the Patient Assessment of Own Function, the Trail Making Test parts A and B, the Stroop Color and Word Test, and others.

Overall, the battery of assessments showed that 37 (62%) of participants had neuropsychological test impairment, with results below the 16th percentile in two tests, while 16 (27%) showed scores indicative of severe impairment (below the second percentile in at least one test and below the 16th percentile in one test).

Those reporting brain fog had scores that were even lower than expected on tests of attention, processing speed, memory, and executive function. And among those reporting brain fog, significantly more had scores reflecting severe impairment compared with the controls (38% vs. 14%; P < .04).

“Based on what we’ve observed in our patients and what others have previously reported, we did expect to find some impairment in this study sample,” Dr. Lynch noted.

“However, we were surprised to find that 27% of the study sample had extremely low neuropsychological test scores, meaning that they scored at least two standard deviations below the expected score on at least one neuropsychological test based on their age and level of education.”

The brain fog group also reported significantly higher levels of depression, fatigue, PTSD, and functional difficulties, and lower quality of life.

Severe impairment on the neuropsychological tests correlated with the extent of acute COVID-19 symptoms, as well as depression scores, number of medical comorbidities, and subjective cognitive complaints.

An analysis of serum levels of the inflammatory markers among 50 of the 60 participants showed that 45% of the patients had an elevated IL-6, 20% had elevated TNF-alpha, and 41% had elevated CRP, compared with reference ranges.

IL-6 levels were found to correlate with acute COVID-19 symptoms, the number of medical comorbidities, fatigue, and measures of executive function, while C-reactive protein (CRP) correlated with current COVID-19 symptoms and depression scores.

In terms of clinical factors that might predict low neuropsychological test scores, Dr. Lynch noted that the “markers that we found to be significant included severity of acute COVID-19 illness, current post-COVID-19 symptoms, measures of depression and anxiety, level of fatigue, and number of medical comorbidities.”

Dr. Lynch noted that the ongoing study will include up to 18-month follow-ups that are currently underway. “The [follow-ups] will examine if symptoms improve over time and evaluate if any intervention that took place was successful,” he said.


 

Survey supports findings

The detrimental effects of mental health symptoms in long COVID were further supported in another study at the APA meeting, an online survey of 787 survivors of acute COVID-19.

In the community survey, presented by Michael Van Ameringen, MD, a professor in the department of psychiatry and behavioral neurosciences at McMaster University, in Hamilton, Ont., all respondents (100%) reported having persistent symptoms of the virus, and as many as 68% indicated that they had not returned to normal functioning, despite only 15% of the respondents having been hospitalized with COVID-19.

A large proportion showed significant depression, anxiety, and posttraumatic stress disorder (PTSD), and the most commonly reported persistent symptoms were fatigue in 75.9% of respondents, brain fog in 67.9%, concentration difficulties in 61.1%, and weakness in 51.2%.

As many as 88.2% of patients said they experienced persistent neurocognitive symptoms, with poor memory and concentration; 56% reported problems with word finding; and 54.1% had slowed thinking.

The respondents showed high rates of anxiety (41.7%) as well as depression (61.4%) as determined by scores above 9 on the Generalized Anxiety Disorder–7 (GAD-7) and Patient Health Questionnaires (PHQ-9).

As many as 40.5% of respondents showed probable PTSD, with scores above 30 on the PTSD checklist (PCL-5). Their mean resilience score on the Brief Resilient Coping Scale was 13.5, suggesting low resilience.

Among the respondents, 43.3% said they had received past treatment for mental health, while 33.5% were currently receiving mental health treatment.

Dr. Van Ameringen noted the important limitation of the study being an online survey with no control group, but said the responses nevertheless raise the question of the role of prior psychiatric disorders in long COVID.

“In our sample, 40% of respondents had a past psychiatric history, so you wonder if that also makes you vulnerable to long COVID,” he said in an interview.

“About a third were getting psychiatric help, but I think the more impaired you are, the more likely you are to seek help.”

Those who were hospitalized with COVID-19 were at a higher risk of PTSD compared with those not hospitalized (P < .001), as were those under the age of 30 (P < .05) or between 31 and 50 vs. over 50 (P < .01).

Dr. Van Ameringen noted that the survey’s high rate of subjects who had not returned to normal functioning was especially striking.

“This is not a minor issue – these are people who are no longer functioning in society,” he said.
 

In pandemics, the brain tends to be ‘overlooked’

Further addressing the neurological effects of COVID-19 at the APA meeting, Avindra Nath, MD, clinical director of the National Institutes of Neurologic Disorders and Stroke in Bethesda, Md., noted that the persisting cognitive and psychiatric symptoms after illness, such as brain fog and depression and anxiety, are not necessarily unique to COVID-19.

“We have seen this before,” he said. “There have been at least seven or eight human coronaviruses, and the interesting thing is each one affects the brain and causes neurological complications.”

The effects are classified differently and have slightly different receptors, “but the consequences are the same.”

Of note, however, research published in The Lancet Psychiatry (2021 May. doi: 10.1016/S2215-0366[21]00084-5) revealed that symptoms such as dementia, mood, and anxiety are significantly higher after COVID-19 compared with other respiratory infections, with the differences increasing at 180 days since the index event.

Dr. Nath noted that, over the decades, he has observed that in pandemics “the brain tends to get overlooked.” He explained that “what can be most important in the end is what happened in the brain, because those are the things that really cause the long-term consequences.”

“These patients are depressed; they have dementia, they have brain fog, and even now that we recognize these issues, we haven’t done a very good job of studying them,” he said. “There’s so much we still don’t know, and a lot of patients are left with these symptoms and nowhere to go.”

Dr. Lynch, Dr. Van Ameringen, and Dr. Nath had no disclosures to report.

NEW ORLEANS – Patients experiencing brain fog and other persistent symptoms of long COVID show significant deficits on neuropsychiatric testing that correspond with prior acute COVID-19 infection, adding to mounting evidence of the significant toll the chronic condition can have on mental health.

“Many clinicians have observed the symptoms we describe in this study, however this report is among the first which identify the specific deficits using neuropsychological testing to better characterize the syndrome,” Sean T. Lynch, MD, first author of a study on the issue presented at the annual meeting of the American Psychiatric Association, said in an interview.

Dr. Lynch, of the department of psychiatry, Westchester Medical Center Health System, Valhalla, N.Y., and his colleagues enrolled 60 participants who had experienced acute COVID-19 disease 6-8 months earlier and had undergone neuropsychological, psychiatric, medical, functional, and quality-of-life assessments. Results from the study were published online in the Journal of the Academy of Consultation–Liaison Psychiatry (2022 Jan 25. doi: 10.1016/j.jaclp.2022.01.003).

Among the study participants, 32 were seeking treatment for brain fog in a clinical program for survivors of COVID-19, while the remaining 28 were part of an ongoing longitudinal investigation of neuropsychological, medical, and psychiatric sequelae of COVID-19, but were not seeking care for the persistent symptoms.

Assessments for neurocognitive impairment included a battery of tests used in infectious and other diseases, including the Test of Premorbid Function, the Patient Assessment of Own Function, the Trail Making Test parts A and B, the Stroop Color and Word Test, and others.

Overall, the battery of assessments showed that 37 (62%) of participants had neuropsychological test impairment, with results below the 16th percentile in two tests, while 16 (27%) showed scores indicative of severe impairment (below the second percentile in at least one test and below the 16th percentile in one test).

Those reporting brain fog had scores that were even lower than expected on tests of attention, processing speed, memory, and executive function. And among those reporting brain fog, significantly more had scores reflecting severe impairment compared with the controls (38% vs. 14%; P < .04).

“Based on what we’ve observed in our patients and what others have previously reported, we did expect to find some impairment in this study sample,” Dr. Lynch noted.

“However, we were surprised to find that 27% of the study sample had extremely low neuropsychological test scores, meaning that they scored at least two standard deviations below the expected score on at least one neuropsychological test based on their age and level of education.”

The brain fog group also reported significantly higher levels of depression, fatigue, PTSD, and functional difficulties, and lower quality of life.

Severe impairment on the neuropsychological tests correlated with the extent of acute COVID-19 symptoms, as well as depression scores, number of medical comorbidities, and subjective cognitive complaints.

An analysis of serum levels of the inflammatory markers among 50 of the 60 participants showed that 45% of the patients had an elevated IL-6, 20% had elevated TNF-alpha, and 41% had elevated CRP, compared with reference ranges.

IL-6 levels were found to correlate with acute COVID-19 symptoms, the number of medical comorbidities, fatigue, and measures of executive function, while C-reactive protein (CRP) correlated with current COVID-19 symptoms and depression scores.

In terms of clinical factors that might predict low neuropsychological test scores, Dr. Lynch noted that the “markers that we found to be significant included severity of acute COVID-19 illness, current post-COVID-19 symptoms, measures of depression and anxiety, level of fatigue, and number of medical comorbidities.”

Dr. Lynch noted that the ongoing study will include up to 18-month follow-ups that are currently underway. “The [follow-ups] will examine if symptoms improve over time and evaluate if any intervention that took place was successful,” he said.


 

Survey supports findings

The detrimental effects of mental health symptoms in long COVID were further supported in another study at the APA meeting, an online survey of 787 survivors of acute COVID-19.

In the community survey, presented by Michael Van Ameringen, MD, a professor in the department of psychiatry and behavioral neurosciences at McMaster University, in Hamilton, Ont., all respondents (100%) reported having persistent symptoms of the virus, and as many as 68% indicated that they had not returned to normal functioning, despite only 15% of the respondents having been hospitalized with COVID-19.

A large proportion showed significant depression, anxiety, and posttraumatic stress disorder (PTSD), and the most commonly reported persistent symptoms were fatigue in 75.9% of respondents, brain fog in 67.9%, concentration difficulties in 61.1%, and weakness in 51.2%.

As many as 88.2% of patients said they experienced persistent neurocognitive symptoms, with poor memory and concentration; 56% reported problems with word finding; and 54.1% had slowed thinking.

The respondents showed high rates of anxiety (41.7%) as well as depression (61.4%) as determined by scores above 9 on the Generalized Anxiety Disorder–7 (GAD-7) and Patient Health Questionnaires (PHQ-9).

As many as 40.5% of respondents showed probable PTSD, with scores above 30 on the PTSD checklist (PCL-5). Their mean resilience score on the Brief Resilient Coping Scale was 13.5, suggesting low resilience.

Among the respondents, 43.3% said they had received past treatment for mental health, while 33.5% were currently receiving mental health treatment.

Dr. Van Ameringen noted the important limitation of the study being an online survey with no control group, but said the responses nevertheless raise the question of the role of prior psychiatric disorders in long COVID.

“In our sample, 40% of respondents had a past psychiatric history, so you wonder if that also makes you vulnerable to long COVID,” he said in an interview.

“About a third were getting psychiatric help, but I think the more impaired you are, the more likely you are to seek help.”

Those who were hospitalized with COVID-19 were at a higher risk of PTSD compared with those not hospitalized (P < .001), as were those under the age of 30 (P < .05) or between 31 and 50 vs. over 50 (P < .01).

Dr. Van Ameringen noted that the survey’s high rate of subjects who had not returned to normal functioning was especially striking.

“This is not a minor issue – these are people who are no longer functioning in society,” he said.
 

In pandemics, the brain tends to be ‘overlooked’

Further addressing the neurological effects of COVID-19 at the APA meeting, Avindra Nath, MD, clinical director of the National Institutes of Neurologic Disorders and Stroke in Bethesda, Md., noted that the persisting cognitive and psychiatric symptoms after illness, such as brain fog and depression and anxiety, are not necessarily unique to COVID-19.

“We have seen this before,” he said. “There have been at least seven or eight human coronaviruses, and the interesting thing is each one affects the brain and causes neurological complications.”

The effects are classified differently and have slightly different receptors, “but the consequences are the same.”

Of note, however, research published in The Lancet Psychiatry (2021 May. doi: 10.1016/S2215-0366[21]00084-5) revealed that symptoms such as dementia, mood, and anxiety are significantly higher after COVID-19 compared with other respiratory infections, with the differences increasing at 180 days since the index event.

Dr. Nath noted that, over the decades, he has observed that in pandemics “the brain tends to get overlooked.” He explained that “what can be most important in the end is what happened in the brain, because those are the things that really cause the long-term consequences.”

“These patients are depressed; they have dementia, they have brain fog, and even now that we recognize these issues, we haven’t done a very good job of studying them,” he said. “There’s so much we still don’t know, and a lot of patients are left with these symptoms and nowhere to go.”

Dr. Lynch, Dr. Van Ameringen, and Dr. Nath had no disclosures to report.

NEW ORLEANS – Patients experiencing brain fog and other persistent symptoms of long COVID show significant deficits on neuropsychiatric testing that correspond with prior acute COVID-19 infection, adding to mounting evidence of the significant toll the chronic condition can have on mental health.

“Many clinicians have observed the symptoms we describe in this study, however this report is among the first which identify the specific deficits using neuropsychological testing to better characterize the syndrome,” Sean T. Lynch, MD, first author of a study on the issue presented at the annual meeting of the American Psychiatric Association, said in an interview.

Dr. Lynch, of the department of psychiatry, Westchester Medical Center Health System, Valhalla, N.Y., and his colleagues enrolled 60 participants who had experienced acute COVID-19 disease 6-8 months earlier and had undergone neuropsychological, psychiatric, medical, functional, and quality-of-life assessments. Results from the study were published online in the Journal of the Academy of Consultation–Liaison Psychiatry (2022 Jan 25. doi: 10.1016/j.jaclp.2022.01.003).

Among the study participants, 32 were seeking treatment for brain fog in a clinical program for survivors of COVID-19, while the remaining 28 were part of an ongoing longitudinal investigation of neuropsychological, medical, and psychiatric sequelae of COVID-19, but were not seeking care for the persistent symptoms.

Assessments for neurocognitive impairment included a battery of tests used in infectious and other diseases, including the Test of Premorbid Function, the Patient Assessment of Own Function, the Trail Making Test parts A and B, the Stroop Color and Word Test, and others.

Overall, the battery of assessments showed that 37 (62%) of participants had neuropsychological test impairment, with results below the 16th percentile in two tests, while 16 (27%) showed scores indicative of severe impairment (below the second percentile in at least one test and below the 16th percentile in one test).

Those reporting brain fog had scores that were even lower than expected on tests of attention, processing speed, memory, and executive function. And among those reporting brain fog, significantly more had scores reflecting severe impairment compared with the controls (38% vs. 14%; P < .04).

“Based on what we’ve observed in our patients and what others have previously reported, we did expect to find some impairment in this study sample,” Dr. Lynch noted.

“However, we were surprised to find that 27% of the study sample had extremely low neuropsychological test scores, meaning that they scored at least two standard deviations below the expected score on at least one neuropsychological test based on their age and level of education.”

The brain fog group also reported significantly higher levels of depression, fatigue, PTSD, and functional difficulties, and lower quality of life.

Severe impairment on the neuropsychological tests correlated with the extent of acute COVID-19 symptoms, as well as depression scores, number of medical comorbidities, and subjective cognitive complaints.

An analysis of serum levels of the inflammatory markers among 50 of the 60 participants showed that 45% of the patients had an elevated IL-6, 20% had elevated TNF-alpha, and 41% had elevated CRP, compared with reference ranges.

IL-6 levels were found to correlate with acute COVID-19 symptoms, the number of medical comorbidities, fatigue, and measures of executive function, while C-reactive protein (CRP) correlated with current COVID-19 symptoms and depression scores.

In terms of clinical factors that might predict low neuropsychological test scores, Dr. Lynch noted that the “markers that we found to be significant included severity of acute COVID-19 illness, current post-COVID-19 symptoms, measures of depression and anxiety, level of fatigue, and number of medical comorbidities.”

Dr. Lynch noted that the ongoing study will include up to 18-month follow-ups that are currently underway. “The [follow-ups] will examine if symptoms improve over time and evaluate if any intervention that took place was successful,” he said.


 

Survey supports findings

The detrimental effects of mental health symptoms in long COVID were further supported in another study at the APA meeting, an online survey of 787 survivors of acute COVID-19.

In the community survey, presented by Michael Van Ameringen, MD, a professor in the department of psychiatry and behavioral neurosciences at McMaster University, in Hamilton, Ont., all respondents (100%) reported having persistent symptoms of the virus, and as many as 68% indicated that they had not returned to normal functioning, despite only 15% of the respondents having been hospitalized with COVID-19.

A large proportion showed significant depression, anxiety, and posttraumatic stress disorder (PTSD), and the most commonly reported persistent symptoms were fatigue in 75.9% of respondents, brain fog in 67.9%, concentration difficulties in 61.1%, and weakness in 51.2%.

As many as 88.2% of patients said they experienced persistent neurocognitive symptoms, with poor memory and concentration; 56% reported problems with word finding; and 54.1% had slowed thinking.

The respondents showed high rates of anxiety (41.7%) as well as depression (61.4%) as determined by scores above 9 on the Generalized Anxiety Disorder–7 (GAD-7) and Patient Health Questionnaires (PHQ-9).

As many as 40.5% of respondents showed probable PTSD, with scores above 30 on the PTSD checklist (PCL-5). Their mean resilience score on the Brief Resilient Coping Scale was 13.5, suggesting low resilience.

Among the respondents, 43.3% said they had received past treatment for mental health, while 33.5% were currently receiving mental health treatment.

Dr. Van Ameringen noted the important limitation of the study being an online survey with no control group, but said the responses nevertheless raise the question of the role of prior psychiatric disorders in long COVID.

“In our sample, 40% of respondents had a past psychiatric history, so you wonder if that also makes you vulnerable to long COVID,” he said in an interview.

“About a third were getting psychiatric help, but I think the more impaired you are, the more likely you are to seek help.”

Those who were hospitalized with COVID-19 were at a higher risk of PTSD compared with those not hospitalized (P < .001), as were those under the age of 30 (P < .05) or between 31 and 50 vs. over 50 (P < .01).

Dr. Van Ameringen noted that the survey’s high rate of subjects who had not returned to normal functioning was especially striking.

“This is not a minor issue – these are people who are no longer functioning in society,” he said.
 

In pandemics, the brain tends to be ‘overlooked’

Further addressing the neurological effects of COVID-19 at the APA meeting, Avindra Nath, MD, clinical director of the National Institutes of Neurologic Disorders and Stroke in Bethesda, Md., noted that the persisting cognitive and psychiatric symptoms after illness, such as brain fog and depression and anxiety, are not necessarily unique to COVID-19.

“We have seen this before,” he said. “There have been at least seven or eight human coronaviruses, and the interesting thing is each one affects the brain and causes neurological complications.”

The effects are classified differently and have slightly different receptors, “but the consequences are the same.”

Of note, however, research published in The Lancet Psychiatry (2021 May. doi: 10.1016/S2215-0366[21]00084-5) revealed that symptoms such as dementia, mood, and anxiety are significantly higher after COVID-19 compared with other respiratory infections, with the differences increasing at 180 days since the index event.

Dr. Nath noted that, over the decades, he has observed that in pandemics “the brain tends to get overlooked.” He explained that “what can be most important in the end is what happened in the brain, because those are the things that really cause the long-term consequences.”

“These patients are depressed; they have dementia, they have brain fog, and even now that we recognize these issues, we haven’t done a very good job of studying them,” he said. “There’s so much we still don’t know, and a lot of patients are left with these symptoms and nowhere to go.”

Dr. Lynch, Dr. Van Ameringen, and Dr. Nath had no disclosures to report.