From the earliest days of the COVID-19 pandemic, people of color have been hardest hit by the virus. Now, many doctors and researchers are seeing big disparities come about in who gets care for long COVID.

Long COVID can affect patients from all walks of life. But many of the same issues that have made the virus particularly devastating in communities of color are also shaping who gets diagnosed and treated for long COVID, said Alba Miranda Azola, MD, codirector of the post–acute COVID-19 team at Johns Hopkins University, Baltimore.

Non-White patients are more apt to lack access to primary care, face insurance barriers to see specialists, struggle with time off work or transportation for appointments, and have financial barriers to care as copayments for therapy pile up.

“We are getting a very skewed population of Caucasian wealthy people who are coming to our clinic because they have the ability to access care, they have good insurance, and they are looking on the internet and find us,” Dr. Azola said.

This mix of patients at Dr. Azola’s clinic is out of step with the demographics of Baltimore, where the majority of residents are Black, half of them earn less than $52,000 a year, and one in five live in poverty. And this isn’t unique to Hopkins. Many of the dozens of specialized long COVID clinics that have cropped up around the country are also seeing an unequal share of affluent White patients, experts say.

It’s also a patient mix that very likely doesn’t reflect who is most apt to have long COVID.

During the pandemic, people who identified as Black, Hispanic, American Indian, or Alaska Native were more likely to be diagnosed with COVID than people who identified as White, according to the Centers for Disease Control and Prevention. These people of color were also at least twice as likely to be hospitalized with severe infections, and at least 70% more likely to die.

“Data repeatedly show the disproportionate impact of COVID-19 on racial and ethnic minority populations, as well as other population groups such as people living in rural or frontier areas, people experiencing homelessness, essential and frontline workers, people with disabilities, people with substance use disorders, people who are incarcerated, and non–U.S.-born persons,” John Brooks, MD, chief medical officer for COVID-19 response at the CDC, said during testimony before the U.S. House Energy and Commerce Subcommittee on Health in April 2021.

“While we do not yet have clear data on the impact of post-COVID conditions on racial and ethnic minority populations and other disadvantaged communities, we do believe that they are likely to be disproportionately impacted ... and less likely to be able to access health care services,” Dr. Brooks said at the time.

The picture that’s emerging of long COVID suggests that the condition impacts about one in five adults. It’s more common among Hispanic adults than among people who identify as Black, Asian, or White. It’s also more common among those who identify as other races or multiple races, according survey data collected by the CDC.

It’s hard to say how accurate this snapshot is because researchers need to do a better job of identifying and following people with long COVID, said Monica Verduzco-Gutierrez, MD, chair of rehabilitation medicine and director of the COVID-19 Recovery Clinic at the University of Texas Health Science Center at San Antonio. A major limitation of surveys like the ones done by the CDC to monitor long COVID is that only people who realize they have the condition can get counted.

“Some people from historically marginalized groups may have less health literacy to know about impacts of long COVID,” she said.

Lack of awareness may keep people with persistent symptoms from seeking medical attention, leaving many long COVID cases undiagnosed.

When some patients do seek help, their complaints may not be acknowledged or understood. Often, cultural bias or structural racism can get in the way of diagnosis and treatment, Dr. Azola said.

“I hate to say this, but there is probably bias among providers,” she said. “For example, I am Puerto Rican, and the way we describe symptoms as Latinos may sound exaggerated or may be brushed aside or lost in translation. I think we miss a lot of patients being diagnosed or referred to specialists because the primary care provider they see maybe leans into this cultural bias of thinking this is just a Latino being dramatic.”

There’s some evidence that treatment for long COVID may differ by race even when symptoms are similar. One study of more than 400,000 patients, for example, found no racial differences in the proportion of people who have six common long COVID symptoms: shortness of breath, fatigue, weakness, pain, trouble with thinking skills, and a hard time getting around. Despite this, Black patients were significantly less likely to receive outpatient rehabilitation services to treat these symptoms.

Benjamin Abramoff, MD, who leads the long COVID collaborative for the American Academy of Physical Medicine and Rehabilitation, draws parallels between what happens with long COVID to another common health problem often undertreated among patients of color: pain. With both long COVID and chronic pain, one major barrier to care is “just getting taken seriously by providers,” he said.

“There is significant evidence that racial bias has led to less prescription of pain medications to people of color,” Dr. Abramoff said. “Just as pain can be difficult to get objective measures of, long COVID symptoms can also be difficult to objectively measure and requires trust between the provider and patient.”

Geography can be another barrier to care, said Aaron Friedberg, MD, clinical colead of the post-COVID recovery program at Ohio State University Wexner Medical Center, Columbus. Many communities hardest hit by COVID – particularly in high-poverty urban neighborhoods – have long had limited access to care. The pandemic worsened staffing shortages at many hospitals and clinics in these communities, leaving patients even fewer options close to home.

“I often have patients driving several hours to come to our clinic, and that can create significant challenges both because of the financial burden and time required to coordinate that type of travel, but also because post-COVID symptoms can make it extremely challenging to tolerate that type of travel,” Dr. Friedberg said.

Even though the complete picture of who has long COVID – and who’s getting treated and getting good outcomes – is still emerging, it’s very clear at this point in the pandemic that access isn’t equal among everyone and that many low-income and non-White patients are missing out on needed treatments, Friedberg said.

“One thing that is clear is that there are many people suffering alone from these conditions,” he said.

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

From the earliest days of the COVID-19 pandemic, people of color have been hardest hit by the virus. Now, many doctors and researchers are seeing big disparities come about in who gets care for long COVID.

Long COVID can affect patients from all walks of life. But many of the same issues that have made the virus particularly devastating in communities of color are also shaping who gets diagnosed and treated for long COVID, said Alba Miranda Azola, MD, codirector of the post–acute COVID-19 team at Johns Hopkins University, Baltimore.

Non-White patients are more apt to lack access to primary care, face insurance barriers to see specialists, struggle with time off work or transportation for appointments, and have financial barriers to care as copayments for therapy pile up.

“We are getting a very skewed population of Caucasian wealthy people who are coming to our clinic because they have the ability to access care, they have good insurance, and they are looking on the internet and find us,” Dr. Azola said.

This mix of patients at Dr. Azola’s clinic is out of step with the demographics of Baltimore, where the majority of residents are Black, half of them earn less than $52,000 a year, and one in five live in poverty. And this isn’t unique to Hopkins. Many of the dozens of specialized long COVID clinics that have cropped up around the country are also seeing an unequal share of affluent White patients, experts say.

It’s also a patient mix that very likely doesn’t reflect who is most apt to have long COVID.

During the pandemic, people who identified as Black, Hispanic, American Indian, or Alaska Native were more likely to be diagnosed with COVID than people who identified as White, according to the Centers for Disease Control and Prevention. These people of color were also at least twice as likely to be hospitalized with severe infections, and at least 70% more likely to die.

“Data repeatedly show the disproportionate impact of COVID-19 on racial and ethnic minority populations, as well as other population groups such as people living in rural or frontier areas, people experiencing homelessness, essential and frontline workers, people with disabilities, people with substance use disorders, people who are incarcerated, and non–U.S.-born persons,” John Brooks, MD, chief medical officer for COVID-19 response at the CDC, said during testimony before the U.S. House Energy and Commerce Subcommittee on Health in April 2021.

“While we do not yet have clear data on the impact of post-COVID conditions on racial and ethnic minority populations and other disadvantaged communities, we do believe that they are likely to be disproportionately impacted ... and less likely to be able to access health care services,” Dr. Brooks said at the time.

The picture that’s emerging of long COVID suggests that the condition impacts about one in five adults. It’s more common among Hispanic adults than among people who identify as Black, Asian, or White. It’s also more common among those who identify as other races or multiple races, according survey data collected by the CDC.

It’s hard to say how accurate this snapshot is because researchers need to do a better job of identifying and following people with long COVID, said Monica Verduzco-Gutierrez, MD, chair of rehabilitation medicine and director of the COVID-19 Recovery Clinic at the University of Texas Health Science Center at San Antonio. A major limitation of surveys like the ones done by the CDC to monitor long COVID is that only people who realize they have the condition can get counted.

“Some people from historically marginalized groups may have less health literacy to know about impacts of long COVID,” she said.

Lack of awareness may keep people with persistent symptoms from seeking medical attention, leaving many long COVID cases undiagnosed.

When some patients do seek help, their complaints may not be acknowledged or understood. Often, cultural bias or structural racism can get in the way of diagnosis and treatment, Dr. Azola said.

“I hate to say this, but there is probably bias among providers,” she said. “For example, I am Puerto Rican, and the way we describe symptoms as Latinos may sound exaggerated or may be brushed aside or lost in translation. I think we miss a lot of patients being diagnosed or referred to specialists because the primary care provider they see maybe leans into this cultural bias of thinking this is just a Latino being dramatic.”

There’s some evidence that treatment for long COVID may differ by race even when symptoms are similar. One study of more than 400,000 patients, for example, found no racial differences in the proportion of people who have six common long COVID symptoms: shortness of breath, fatigue, weakness, pain, trouble with thinking skills, and a hard time getting around. Despite this, Black patients were significantly less likely to receive outpatient rehabilitation services to treat these symptoms.

Benjamin Abramoff, MD, who leads the long COVID collaborative for the American Academy of Physical Medicine and Rehabilitation, draws parallels between what happens with long COVID to another common health problem often undertreated among patients of color: pain. With both long COVID and chronic pain, one major barrier to care is “just getting taken seriously by providers,” he said.

“There is significant evidence that racial bias has led to less prescription of pain medications to people of color,” Dr. Abramoff said. “Just as pain can be difficult to get objective measures of, long COVID symptoms can also be difficult to objectively measure and requires trust between the provider and patient.”

Geography can be another barrier to care, said Aaron Friedberg, MD, clinical colead of the post-COVID recovery program at Ohio State University Wexner Medical Center, Columbus. Many communities hardest hit by COVID – particularly in high-poverty urban neighborhoods – have long had limited access to care. The pandemic worsened staffing shortages at many hospitals and clinics in these communities, leaving patients even fewer options close to home.

“I often have patients driving several hours to come to our clinic, and that can create significant challenges both because of the financial burden and time required to coordinate that type of travel, but also because post-COVID symptoms can make it extremely challenging to tolerate that type of travel,” Dr. Friedberg said.

Even though the complete picture of who has long COVID – and who’s getting treated and getting good outcomes – is still emerging, it’s very clear at this point in the pandemic that access isn’t equal among everyone and that many low-income and non-White patients are missing out on needed treatments, Friedberg said.

“One thing that is clear is that there are many people suffering alone from these conditions,” he said.

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

From the earliest days of the COVID-19 pandemic, people of color have been hardest hit by the virus. Now, many doctors and researchers are seeing big disparities come about in who gets care for long COVID.

Long COVID can affect patients from all walks of life. But many of the same issues that have made the virus particularly devastating in communities of color are also shaping who gets diagnosed and treated for long COVID, said Alba Miranda Azola, MD, codirector of the post–acute COVID-19 team at Johns Hopkins University, Baltimore.

Non-White patients are more apt to lack access to primary care, face insurance barriers to see specialists, struggle with time off work or transportation for appointments, and have financial barriers to care as copayments for therapy pile up.

“We are getting a very skewed population of Caucasian wealthy people who are coming to our clinic because they have the ability to access care, they have good insurance, and they are looking on the internet and find us,” Dr. Azola said.

This mix of patients at Dr. Azola’s clinic is out of step with the demographics of Baltimore, where the majority of residents are Black, half of them earn less than $52,000 a year, and one in five live in poverty. And this isn’t unique to Hopkins. Many of the dozens of specialized long COVID clinics that have cropped up around the country are also seeing an unequal share of affluent White patients, experts say.

It’s also a patient mix that very likely doesn’t reflect who is most apt to have long COVID.

During the pandemic, people who identified as Black, Hispanic, American Indian, or Alaska Native were more likely to be diagnosed with COVID than people who identified as White, according to the Centers for Disease Control and Prevention. These people of color were also at least twice as likely to be hospitalized with severe infections, and at least 70% more likely to die.

“Data repeatedly show the disproportionate impact of COVID-19 on racial and ethnic minority populations, as well as other population groups such as people living in rural or frontier areas, people experiencing homelessness, essential and frontline workers, people with disabilities, people with substance use disorders, people who are incarcerated, and non–U.S.-born persons,” John Brooks, MD, chief medical officer for COVID-19 response at the CDC, said during testimony before the U.S. House Energy and Commerce Subcommittee on Health in April 2021.

“While we do not yet have clear data on the impact of post-COVID conditions on racial and ethnic minority populations and other disadvantaged communities, we do believe that they are likely to be disproportionately impacted ... and less likely to be able to access health care services,” Dr. Brooks said at the time.

The picture that’s emerging of long COVID suggests that the condition impacts about one in five adults. It’s more common among Hispanic adults than among people who identify as Black, Asian, or White. It’s also more common among those who identify as other races or multiple races, according survey data collected by the CDC.

It’s hard to say how accurate this snapshot is because researchers need to do a better job of identifying and following people with long COVID, said Monica Verduzco-Gutierrez, MD, chair of rehabilitation medicine and director of the COVID-19 Recovery Clinic at the University of Texas Health Science Center at San Antonio. A major limitation of surveys like the ones done by the CDC to monitor long COVID is that only people who realize they have the condition can get counted.

“Some people from historically marginalized groups may have less health literacy to know about impacts of long COVID,” she said.

Lack of awareness may keep people with persistent symptoms from seeking medical attention, leaving many long COVID cases undiagnosed.

When some patients do seek help, their complaints may not be acknowledged or understood. Often, cultural bias or structural racism can get in the way of diagnosis and treatment, Dr. Azola said.

“I hate to say this, but there is probably bias among providers,” she said. “For example, I am Puerto Rican, and the way we describe symptoms as Latinos may sound exaggerated or may be brushed aside or lost in translation. I think we miss a lot of patients being diagnosed or referred to specialists because the primary care provider they see maybe leans into this cultural bias of thinking this is just a Latino being dramatic.”

There’s some evidence that treatment for long COVID may differ by race even when symptoms are similar. One study of more than 400,000 patients, for example, found no racial differences in the proportion of people who have six common long COVID symptoms: shortness of breath, fatigue, weakness, pain, trouble with thinking skills, and a hard time getting around. Despite this, Black patients were significantly less likely to receive outpatient rehabilitation services to treat these symptoms.

Benjamin Abramoff, MD, who leads the long COVID collaborative for the American Academy of Physical Medicine and Rehabilitation, draws parallels between what happens with long COVID to another common health problem often undertreated among patients of color: pain. With both long COVID and chronic pain, one major barrier to care is “just getting taken seriously by providers,” he said.

“There is significant evidence that racial bias has led to less prescription of pain medications to people of color,” Dr. Abramoff said. “Just as pain can be difficult to get objective measures of, long COVID symptoms can also be difficult to objectively measure and requires trust between the provider and patient.”

Geography can be another barrier to care, said Aaron Friedberg, MD, clinical colead of the post-COVID recovery program at Ohio State University Wexner Medical Center, Columbus. Many communities hardest hit by COVID – particularly in high-poverty urban neighborhoods – have long had limited access to care. The pandemic worsened staffing shortages at many hospitals and clinics in these communities, leaving patients even fewer options close to home.

“I often have patients driving several hours to come to our clinic, and that can create significant challenges both because of the financial burden and time required to coordinate that type of travel, but also because post-COVID symptoms can make it extremely challenging to tolerate that type of travel,” Dr. Friedberg said.

Even though the complete picture of who has long COVID – and who’s getting treated and getting good outcomes – is still emerging, it’s very clear at this point in the pandemic that access isn’t equal among everyone and that many low-income and non-White patients are missing out on needed treatments, Friedberg said.

“One thing that is clear is that there are many people suffering alone from these conditions,” he said.

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

BARCELONA – For patients with emphysema who are suitable candidates for lung volume reduction surgery, there were no differences at 1 year in either lung function, dyspnea, or exercise capacity between patients who were assigned to undergo standard lung volume reduction surgery (LVRS) or bronchoscopic lung volume reduction with endobrachial valves (BLVR-EBV) in a randomized trial.

Among patients with emphysema amenable to surgery, there were similar improvements between the treatment groups at 12-month follow-up as assessed by the iBODE score, a composite disease severity measure incorporating body mass index, airflow obstruction, dyspnea, and exercise capacity (incremental shuttle walk test), reported Sara Buttery, BSc, a research physiotherapist and PhD candidate at the National Heart and Lung Institute at Imperial College London.

“Until now there had been no direct comparison of the two to inform decision-making when a person seems to be suitable for either. Bronchoscopic lung volume reduction is a less invasive option and is thought to be ‘less risky’ but, until now, there has not been substantial research to support this,” she said at the annual congress of the European Respiratory Society.

Ms. Buttery and colleagues conducted a randomized, controlled, single-blinded superiority trial to see whether LVRS could be superior to BLVR with valves. They enrolled 88 patients (52% male) with a mean age of 64, and randomly assigned them to receive either LVRS (41 patients) or the less-invasive BLVR (47 patients).

As noted before, there were no significant differences in outcomes at 1 year, with similar degrees of improvement between the surgical techniques for both the composite iBODE score (–1.10 for LVRS vs. –0.82 for BLVR, nonsignificant), and for the individual components of the score.

In addition, the treatments were associated with similar reductions in gas trapping, with residual volume percentage predicted –36.1 with LVRS versus –30.5 with BLVR (nonsignificant).

One patient in each group died during the 12 months of follow-up. The death of the patient in the BLVR group was deemed to be treatment related; the death of the patient in the LVRS group was related to a noninfective exacerbation of chronic obstructive pulmonary disease.

Invited discussant Isabelle Opitz, MD, from University Hospital Zürich told Ms. Buttery: “I have to congratulate you for this very first randomized controlled trial comparing both procedures in a superiority design.”

She pointed out, however, that the number of patients lost to follow-up and crossover of some patients randomized to bronchoscopy raised questions about the powering of the study.

“We did a sensitivity analysis to have a look to see if there was any difference between the patients who did return and the ones who didn’t, and there was no difference at baseline between those patients.” Ms. Buttery said.

She noted that follow-up visits were hampered by the COVID-19 pandemic and the inability of many patients to come into the clinic.

Dr. Opitz also asked about COPD Assessment Test (CAT) scores that were included in the trial design but not reported in the presentation. Ms. Buttery said that the CAT results favored the LVRS group, and that the results would be included in a future economic analysis.

“The results from this first randomized controlled trial suggest that BLVR may be a good therapeutic option for those patients for whom either procedure is suitable,” said Alexander Mathioudakis, MD, PhD, from the University of Manchester (England), who was not involved with this study but commented on it in a press statement. “Lung volume reduction surgery is an invasive operation as it requires a small incision to be made in the chest, which is stitched up after the procedure. As such, it has risks associated with surgery and it takes longer to recover from than bronchoscopic lung volume reduction. On the other hand, endobronchial valves placement is also associated with side effects, such as pneumonia, or valve displacement. Therefore, both the safety and effectiveness of the two procedures need to be investigated further, in larger groups of patients, but the results from this trial are very encouraging.”

The study is supported by the U.K. National Institute of Health Research. Ms. Buttery, Dr. Opitz, and Dr. Mathioudakis reported no relevant financial relationships.

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

BARCELONA – For patients with emphysema who are suitable candidates for lung volume reduction surgery, there were no differences at 1 year in either lung function, dyspnea, or exercise capacity between patients who were assigned to undergo standard lung volume reduction surgery (LVRS) or bronchoscopic lung volume reduction with endobrachial valves (BLVR-EBV) in a randomized trial.

Among patients with emphysema amenable to surgery, there were similar improvements between the treatment groups at 12-month follow-up as assessed by the iBODE score, a composite disease severity measure incorporating body mass index, airflow obstruction, dyspnea, and exercise capacity (incremental shuttle walk test), reported Sara Buttery, BSc, a research physiotherapist and PhD candidate at the National Heart and Lung Institute at Imperial College London.

“Until now there had been no direct comparison of the two to inform decision-making when a person seems to be suitable for either. Bronchoscopic lung volume reduction is a less invasive option and is thought to be ‘less risky’ but, until now, there has not been substantial research to support this,” she said at the annual congress of the European Respiratory Society.

Ms. Buttery and colleagues conducted a randomized, controlled, single-blinded superiority trial to see whether LVRS could be superior to BLVR with valves. They enrolled 88 patients (52% male) with a mean age of 64, and randomly assigned them to receive either LVRS (41 patients) or the less-invasive BLVR (47 patients).

As noted before, there were no significant differences in outcomes at 1 year, with similar degrees of improvement between the surgical techniques for both the composite iBODE score (–1.10 for LVRS vs. –0.82 for BLVR, nonsignificant), and for the individual components of the score.

In addition, the treatments were associated with similar reductions in gas trapping, with residual volume percentage predicted –36.1 with LVRS versus –30.5 with BLVR (nonsignificant).

One patient in each group died during the 12 months of follow-up. The death of the patient in the BLVR group was deemed to be treatment related; the death of the patient in the LVRS group was related to a noninfective exacerbation of chronic obstructive pulmonary disease.

Invited discussant Isabelle Opitz, MD, from University Hospital Zürich told Ms. Buttery: “I have to congratulate you for this very first randomized controlled trial comparing both procedures in a superiority design.”

She pointed out, however, that the number of patients lost to follow-up and crossover of some patients randomized to bronchoscopy raised questions about the powering of the study.

“We did a sensitivity analysis to have a look to see if there was any difference between the patients who did return and the ones who didn’t, and there was no difference at baseline between those patients.” Ms. Buttery said.

She noted that follow-up visits were hampered by the COVID-19 pandemic and the inability of many patients to come into the clinic.

Dr. Opitz also asked about COPD Assessment Test (CAT) scores that were included in the trial design but not reported in the presentation. Ms. Buttery said that the CAT results favored the LVRS group, and that the results would be included in a future economic analysis.

“The results from this first randomized controlled trial suggest that BLVR may be a good therapeutic option for those patients for whom either procedure is suitable,” said Alexander Mathioudakis, MD, PhD, from the University of Manchester (England), who was not involved with this study but commented on it in a press statement. “Lung volume reduction surgery is an invasive operation as it requires a small incision to be made in the chest, which is stitched up after the procedure. As such, it has risks associated with surgery and it takes longer to recover from than bronchoscopic lung volume reduction. On the other hand, endobronchial valves placement is also associated with side effects, such as pneumonia, or valve displacement. Therefore, both the safety and effectiveness of the two procedures need to be investigated further, in larger groups of patients, but the results from this trial are very encouraging.”

The study is supported by the U.K. National Institute of Health Research. Ms. Buttery, Dr. Opitz, and Dr. Mathioudakis reported no relevant financial relationships.

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

BARCELONA – For patients with emphysema who are suitable candidates for lung volume reduction surgery, there were no differences at 1 year in either lung function, dyspnea, or exercise capacity between patients who were assigned to undergo standard lung volume reduction surgery (LVRS) or bronchoscopic lung volume reduction with endobrachial valves (BLVR-EBV) in a randomized trial.

Among patients with emphysema amenable to surgery, there were similar improvements between the treatment groups at 12-month follow-up as assessed by the iBODE score, a composite disease severity measure incorporating body mass index, airflow obstruction, dyspnea, and exercise capacity (incremental shuttle walk test), reported Sara Buttery, BSc, a research physiotherapist and PhD candidate at the National Heart and Lung Institute at Imperial College London.

“Until now there had been no direct comparison of the two to inform decision-making when a person seems to be suitable for either. Bronchoscopic lung volume reduction is a less invasive option and is thought to be ‘less risky’ but, until now, there has not been substantial research to support this,” she said at the annual congress of the European Respiratory Society.

Ms. Buttery and colleagues conducted a randomized, controlled, single-blinded superiority trial to see whether LVRS could be superior to BLVR with valves. They enrolled 88 patients (52% male) with a mean age of 64, and randomly assigned them to receive either LVRS (41 patients) or the less-invasive BLVR (47 patients).

As noted before, there were no significant differences in outcomes at 1 year, with similar degrees of improvement between the surgical techniques for both the composite iBODE score (–1.10 for LVRS vs. –0.82 for BLVR, nonsignificant), and for the individual components of the score.

In addition, the treatments were associated with similar reductions in gas trapping, with residual volume percentage predicted –36.1 with LVRS versus –30.5 with BLVR (nonsignificant).

One patient in each group died during the 12 months of follow-up. The death of the patient in the BLVR group was deemed to be treatment related; the death of the patient in the LVRS group was related to a noninfective exacerbation of chronic obstructive pulmonary disease.

Invited discussant Isabelle Opitz, MD, from University Hospital Zürich told Ms. Buttery: “I have to congratulate you for this very first randomized controlled trial comparing both procedures in a superiority design.”

She pointed out, however, that the number of patients lost to follow-up and crossover of some patients randomized to bronchoscopy raised questions about the powering of the study.

“We did a sensitivity analysis to have a look to see if there was any difference between the patients who did return and the ones who didn’t, and there was no difference at baseline between those patients.” Ms. Buttery said.

She noted that follow-up visits were hampered by the COVID-19 pandemic and the inability of many patients to come into the clinic.

Dr. Opitz also asked about COPD Assessment Test (CAT) scores that were included in the trial design but not reported in the presentation. Ms. Buttery said that the CAT results favored the LVRS group, and that the results would be included in a future economic analysis.

“The results from this first randomized controlled trial suggest that BLVR may be a good therapeutic option for those patients for whom either procedure is suitable,” said Alexander Mathioudakis, MD, PhD, from the University of Manchester (England), who was not involved with this study but commented on it in a press statement. “Lung volume reduction surgery is an invasive operation as it requires a small incision to be made in the chest, which is stitched up after the procedure. As such, it has risks associated with surgery and it takes longer to recover from than bronchoscopic lung volume reduction. On the other hand, endobronchial valves placement is also associated with side effects, such as pneumonia, or valve displacement. Therefore, both the safety and effectiveness of the two procedures need to be investigated further, in larger groups of patients, but the results from this trial are very encouraging.”

The study is supported by the U.K. National Institute of Health Research. Ms. Buttery, Dr. Opitz, and Dr. Mathioudakis reported no relevant financial relationships.

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

Monkey see, monkey do (advanced medical procedures)

We don’t tend to think too kindly of our prehistoric ancestors. We throw around the word “caveman” – hardly a term of endearment – and depictions of Paleolithic humans rarely flatter their subjects. In many ways, though, our conceptions are correct. Humans of the Stone Age lived short, often brutish lives, but civilization had to start somewhere, and our prehistoric ancestors were often far more capable than we give them credit for.

Tim Maloney/Nature

Case in point is a recent discovery from an archaeological dig in Borneo: A young adult who lived 31,000 years ago was discovered with the lower third of their left leg amputated. Save the clever retort about the person’s untimely death, because this individual did not die from the surgery. The amputation occurred when the individual was a child and the subject lived for several years after the operation.

Amputation is usually unnecessary given our current level of medical technology, but it’s actually quite an advanced procedure, and this example predates the previous first case of amputation by nearly 25,000 years. Not only did the surgeon need to cut at an appropriate place, they needed to understand blood loss, the risk of infection, and the need to preserve skin in order to seal the wound back up. That’s quite a lot for our Paleolithic doctor to know, and it’s even more impressive considering the, shall we say, limited tools they would have had available to perform the operation.

Rocks. They cut off the leg with a rock. And it worked.

This discovery also gives insight into the amputee’s society. Someone knew that amputation was the right move for this person, indicating that it had been done before. In addition, the individual would not have been able to spring back into action hunting mammoths right away, they would require care for the rest of their lives. And clearly the community provided, given the individual’s continued life post operation and their burial in a place of honor.

If only the American health care system was capable of such feats of compassion, but that would require the majority of politicians to be as clever as cavemen. We’re not hopeful on those odds.
 

The first step is admitting you have a crying baby. The second step is … a step

Knock, knock.

Who’s there?

Crying baby.

Crying baby who?

Current Biology/Ohmura et al.

Crying baby who … umm … doesn’t have a punchline. Let’s try this again.

A priest, a rabbi, and a crying baby walk into a bar and … nope, that’s not going to work.

Why did the crying baby cross the road? Ugh, never mind.

Clearly, crying babies are no laughing matter. What crying babies need is science. And the latest innovation – it’s fresh from a study conducted at the RIKEN Center for Brain Science in Saitama, Japan – in the science of crying babies is … walking. Researchers observed 21 unhappy infants and compared their responses to four strategies: being held by their walking mothers, held by their sitting mothers, lying in a motionless crib, or lying in a rocking cot.

The best strategy is for the mother – the experiment only involved mothers, but the results should apply to any caregiver – to pick up the crying baby, walk around for 5 minutes, sit for another 5-8 minutes, and then put the infant back to bed, the researchers said in a written statement.

The walking strategy, however, isn’t perfect. “Walking for 5 minutes promoted sleep, but only for crying infants. Surprisingly, this effect was absent when babies were already calm beforehand,” lead author Kumi O. Kuroda, MD, PhD, explained in a separate statement from the center.

It also doesn’t work on adults. We could not get a crying LOTME writer to fall asleep no matter how long his mother carried him around the office.
 

New way to detect Parkinson’s has already passed the sniff test

We humans aren’t generally known for our superpowers, but a woman from Scotland may just be the Smelling Superhero. Not only was she able to literally smell Parkinson’s disease (PD) on her husband 12 years before his diagnosis; she is also the reason that scientists have found a new way to test for PD.

© Siri Stafford/Thinkstock

Joy Milne, a retired nurse, told the BBC that her husband “had this musty rather unpleasant smell especially round his shoulders and the back of his neck and his skin had definitely changed.” She put two and two together after he had been diagnosed with PD and she came in contact with others with the same scent at a support group.

Researchers at the University of Manchester, working with Ms. Milne, have now created a skin test that uses mass spectroscopy to analyze a sample of the patient’s sebum in just 3 minutes and is 95% accurate. They tested 79 people with Parkinson’s and 71 without using this method and found “specific compounds unique to PD sebum samples when compared to healthy controls. Furthermore, we have identified two classes of lipids, namely, triacylglycerides and diglycerides, as components of human sebum that are significantly differentially expressed in PD,” they said in JACS Au.

This test could be available to general physicians within 2 years, which would provide new opportunities to the people who are waiting in line for neurologic consults. Ms. Milne’s husband passed away in 2015, but her courageous help and amazing nasal abilities may help millions down the line.
 

The power of flirting

It’s a common office stereotype: Women flirt with the boss to get ahead in the workplace, while men in power sexually harass women in subordinate positions. Nobody ever suspects the guys in the cubicles. A recent study takes a different look and paints a different picture.

Mart Production/Pexels

The investigators conducted multiple online and lab experiments in how social sexual identity drives behavior in a workplace setting in relation to job placement. They found that it was most often men in lower-power positions who are insecure about their roles who initiate social sexual behavior, even though they know it’s offensive. Why? Power.

They randomly paired over 200 undergraduate students in a male/female fashion, placed them in subordinate and boss-like roles, and asked them to choose from a series of social sexual questions they wanted to ask their teammate. Male participants who were placed in subordinate positions to a female boss chose social sexual questions more often than did male bosses, female subordinates, and female bosses.

So what does this say about the threat of workplace harassment? The researchers found that men and women differ in their strategy for flirtation. For men, it’s a way to gain more power. But problems arise when they rationalize their behavior with a character trait like being a “big flirt.”

“When we take on that identity, it leads to certain behavioral patterns that reinforce the identity. And then, people use that identity as an excuse,” lead author Laura Kray of the University of California, Berkeley, said in a statement from the school.

The researchers make a point to note that the study isn’t about whether flirting is good or bad, nor are they suggesting that people in powerful positions don’t sexually harass underlings. It’s meant to provide insight to improve corporate sexual harassment training. A comment or conversation held in jest could potentially be a warning sign for future behavior.

Monkey see, monkey do (advanced medical procedures)

We don’t tend to think too kindly of our prehistoric ancestors. We throw around the word “caveman” – hardly a term of endearment – and depictions of Paleolithic humans rarely flatter their subjects. In many ways, though, our conceptions are correct. Humans of the Stone Age lived short, often brutish lives, but civilization had to start somewhere, and our prehistoric ancestors were often far more capable than we give them credit for.

Tim Maloney/Nature

Case in point is a recent discovery from an archaeological dig in Borneo: A young adult who lived 31,000 years ago was discovered with the lower third of their left leg amputated. Save the clever retort about the person’s untimely death, because this individual did not die from the surgery. The amputation occurred when the individual was a child and the subject lived for several years after the operation.

Amputation is usually unnecessary given our current level of medical technology, but it’s actually quite an advanced procedure, and this example predates the previous first case of amputation by nearly 25,000 years. Not only did the surgeon need to cut at an appropriate place, they needed to understand blood loss, the risk of infection, and the need to preserve skin in order to seal the wound back up. That’s quite a lot for our Paleolithic doctor to know, and it’s even more impressive considering the, shall we say, limited tools they would have had available to perform the operation.

Rocks. They cut off the leg with a rock. And it worked.

This discovery also gives insight into the amputee’s society. Someone knew that amputation was the right move for this person, indicating that it had been done before. In addition, the individual would not have been able to spring back into action hunting mammoths right away, they would require care for the rest of their lives. And clearly the community provided, given the individual’s continued life post operation and their burial in a place of honor.

If only the American health care system was capable of such feats of compassion, but that would require the majority of politicians to be as clever as cavemen. We’re not hopeful on those odds.
 

The first step is admitting you have a crying baby. The second step is … a step

Knock, knock.

Who’s there?

Crying baby.

Crying baby who?

Current Biology/Ohmura et al.

Crying baby who … umm … doesn’t have a punchline. Let’s try this again.

A priest, a rabbi, and a crying baby walk into a bar and … nope, that’s not going to work.

Why did the crying baby cross the road? Ugh, never mind.

Clearly, crying babies are no laughing matter. What crying babies need is science. And the latest innovation – it’s fresh from a study conducted at the RIKEN Center for Brain Science in Saitama, Japan – in the science of crying babies is … walking. Researchers observed 21 unhappy infants and compared their responses to four strategies: being held by their walking mothers, held by their sitting mothers, lying in a motionless crib, or lying in a rocking cot.

The best strategy is for the mother – the experiment only involved mothers, but the results should apply to any caregiver – to pick up the crying baby, walk around for 5 minutes, sit for another 5-8 minutes, and then put the infant back to bed, the researchers said in a written statement.

The walking strategy, however, isn’t perfect. “Walking for 5 minutes promoted sleep, but only for crying infants. Surprisingly, this effect was absent when babies were already calm beforehand,” lead author Kumi O. Kuroda, MD, PhD, explained in a separate statement from the center.

It also doesn’t work on adults. We could not get a crying LOTME writer to fall asleep no matter how long his mother carried him around the office.
 

New way to detect Parkinson’s has already passed the sniff test

We humans aren’t generally known for our superpowers, but a woman from Scotland may just be the Smelling Superhero. Not only was she able to literally smell Parkinson’s disease (PD) on her husband 12 years before his diagnosis; she is also the reason that scientists have found a new way to test for PD.

© Siri Stafford/Thinkstock

Joy Milne, a retired nurse, told the BBC that her husband “had this musty rather unpleasant smell especially round his shoulders and the back of his neck and his skin had definitely changed.” She put two and two together after he had been diagnosed with PD and she came in contact with others with the same scent at a support group.

Researchers at the University of Manchester, working with Ms. Milne, have now created a skin test that uses mass spectroscopy to analyze a sample of the patient’s sebum in just 3 minutes and is 95% accurate. They tested 79 people with Parkinson’s and 71 without using this method and found “specific compounds unique to PD sebum samples when compared to healthy controls. Furthermore, we have identified two classes of lipids, namely, triacylglycerides and diglycerides, as components of human sebum that are significantly differentially expressed in PD,” they said in JACS Au.

This test could be available to general physicians within 2 years, which would provide new opportunities to the people who are waiting in line for neurologic consults. Ms. Milne’s husband passed away in 2015, but her courageous help and amazing nasal abilities may help millions down the line.
 

The power of flirting

It’s a common office stereotype: Women flirt with the boss to get ahead in the workplace, while men in power sexually harass women in subordinate positions. Nobody ever suspects the guys in the cubicles. A recent study takes a different look and paints a different picture.

Mart Production/Pexels

The investigators conducted multiple online and lab experiments in how social sexual identity drives behavior in a workplace setting in relation to job placement. They found that it was most often men in lower-power positions who are insecure about their roles who initiate social sexual behavior, even though they know it’s offensive. Why? Power.

They randomly paired over 200 undergraduate students in a male/female fashion, placed them in subordinate and boss-like roles, and asked them to choose from a series of social sexual questions they wanted to ask their teammate. Male participants who were placed in subordinate positions to a female boss chose social sexual questions more often than did male bosses, female subordinates, and female bosses.

So what does this say about the threat of workplace harassment? The researchers found that men and women differ in their strategy for flirtation. For men, it’s a way to gain more power. But problems arise when they rationalize their behavior with a character trait like being a “big flirt.”

“When we take on that identity, it leads to certain behavioral patterns that reinforce the identity. And then, people use that identity as an excuse,” lead author Laura Kray of the University of California, Berkeley, said in a statement from the school.

The researchers make a point to note that the study isn’t about whether flirting is good or bad, nor are they suggesting that people in powerful positions don’t sexually harass underlings. It’s meant to provide insight to improve corporate sexual harassment training. A comment or conversation held in jest could potentially be a warning sign for future behavior.

Monkey see, monkey do (advanced medical procedures)

We don’t tend to think too kindly of our prehistoric ancestors. We throw around the word “caveman” – hardly a term of endearment – and depictions of Paleolithic humans rarely flatter their subjects. In many ways, though, our conceptions are correct. Humans of the Stone Age lived short, often brutish lives, but civilization had to start somewhere, and our prehistoric ancestors were often far more capable than we give them credit for.

Tim Maloney/Nature

Case in point is a recent discovery from an archaeological dig in Borneo: A young adult who lived 31,000 years ago was discovered with the lower third of their left leg amputated. Save the clever retort about the person’s untimely death, because this individual did not die from the surgery. The amputation occurred when the individual was a child and the subject lived for several years after the operation.

Amputation is usually unnecessary given our current level of medical technology, but it’s actually quite an advanced procedure, and this example predates the previous first case of amputation by nearly 25,000 years. Not only did the surgeon need to cut at an appropriate place, they needed to understand blood loss, the risk of infection, and the need to preserve skin in order to seal the wound back up. That’s quite a lot for our Paleolithic doctor to know, and it’s even more impressive considering the, shall we say, limited tools they would have had available to perform the operation.

Rocks. They cut off the leg with a rock. And it worked.

This discovery also gives insight into the amputee’s society. Someone knew that amputation was the right move for this person, indicating that it had been done before. In addition, the individual would not have been able to spring back into action hunting mammoths right away, they would require care for the rest of their lives. And clearly the community provided, given the individual’s continued life post operation and their burial in a place of honor.

If only the American health care system was capable of such feats of compassion, but that would require the majority of politicians to be as clever as cavemen. We’re not hopeful on those odds.
 

The first step is admitting you have a crying baby. The second step is … a step

Knock, knock.

Who’s there?

Crying baby.

Crying baby who?

Current Biology/Ohmura et al.

Crying baby who … umm … doesn’t have a punchline. Let’s try this again.

A priest, a rabbi, and a crying baby walk into a bar and … nope, that’s not going to work.

Why did the crying baby cross the road? Ugh, never mind.

Clearly, crying babies are no laughing matter. What crying babies need is science. And the latest innovation – it’s fresh from a study conducted at the RIKEN Center for Brain Science in Saitama, Japan – in the science of crying babies is … walking. Researchers observed 21 unhappy infants and compared their responses to four strategies: being held by their walking mothers, held by their sitting mothers, lying in a motionless crib, or lying in a rocking cot.

The best strategy is for the mother – the experiment only involved mothers, but the results should apply to any caregiver – to pick up the crying baby, walk around for 5 minutes, sit for another 5-8 minutes, and then put the infant back to bed, the researchers said in a written statement.

The walking strategy, however, isn’t perfect. “Walking for 5 minutes promoted sleep, but only for crying infants. Surprisingly, this effect was absent when babies were already calm beforehand,” lead author Kumi O. Kuroda, MD, PhD, explained in a separate statement from the center.

It also doesn’t work on adults. We could not get a crying LOTME writer to fall asleep no matter how long his mother carried him around the office.
 

New way to detect Parkinson’s has already passed the sniff test

We humans aren’t generally known for our superpowers, but a woman from Scotland may just be the Smelling Superhero. Not only was she able to literally smell Parkinson’s disease (PD) on her husband 12 years before his diagnosis; she is also the reason that scientists have found a new way to test for PD.

© Siri Stafford/Thinkstock

Joy Milne, a retired nurse, told the BBC that her husband “had this musty rather unpleasant smell especially round his shoulders and the back of his neck and his skin had definitely changed.” She put two and two together after he had been diagnosed with PD and she came in contact with others with the same scent at a support group.

Researchers at the University of Manchester, working with Ms. Milne, have now created a skin test that uses mass spectroscopy to analyze a sample of the patient’s sebum in just 3 minutes and is 95% accurate. They tested 79 people with Parkinson’s and 71 without using this method and found “specific compounds unique to PD sebum samples when compared to healthy controls. Furthermore, we have identified two classes of lipids, namely, triacylglycerides and diglycerides, as components of human sebum that are significantly differentially expressed in PD,” they said in JACS Au.

This test could be available to general physicians within 2 years, which would provide new opportunities to the people who are waiting in line for neurologic consults. Ms. Milne’s husband passed away in 2015, but her courageous help and amazing nasal abilities may help millions down the line.
 

The power of flirting

It’s a common office stereotype: Women flirt with the boss to get ahead in the workplace, while men in power sexually harass women in subordinate positions. Nobody ever suspects the guys in the cubicles. A recent study takes a different look and paints a different picture.

Mart Production/Pexels

The investigators conducted multiple online and lab experiments in how social sexual identity drives behavior in a workplace setting in relation to job placement. They found that it was most often men in lower-power positions who are insecure about their roles who initiate social sexual behavior, even though they know it’s offensive. Why? Power.

They randomly paired over 200 undergraduate students in a male/female fashion, placed them in subordinate and boss-like roles, and asked them to choose from a series of social sexual questions they wanted to ask their teammate. Male participants who were placed in subordinate positions to a female boss chose social sexual questions more often than did male bosses, female subordinates, and female bosses.

So what does this say about the threat of workplace harassment? The researchers found that men and women differ in their strategy for flirtation. For men, it’s a way to gain more power. But problems arise when they rationalize their behavior with a character trait like being a “big flirt.”

“When we take on that identity, it leads to certain behavioral patterns that reinforce the identity. And then, people use that identity as an excuse,” lead author Laura Kray of the University of California, Berkeley, said in a statement from the school.

The researchers make a point to note that the study isn’t about whether flirting is good or bad, nor are they suggesting that people in powerful positions don’t sexually harass underlings. It’s meant to provide insight to improve corporate sexual harassment training. A comment or conversation held in jest could potentially be a warning sign for future behavior.

Introduction

Hematologists and oncologists (HO) face mortality daily. “Death Cafe” (DC) is a safe space set aside for open dialogue about death and dying. Despite origins outside the healthcare setting, DC has been used as a framework to help health care students and workers process death and dying. We aim to assess if DC sessions are perceived to have value by HO trainees and faculty.

Methods

HO fellows from Baylor College of Medicine (BCM) and HO Faculty from BCM, mostly those at the Houston Michael E. DeBakey Veterans Affairs Hospital (VA), were offered the opportunity to participate in the DC sessions. Our VA Cancer Center Chaplain was present for all sessions and helped facilitate the conversation. HO fellows who were invited to a DC and attended were emailed a survey questionnaire after the activity via survey monkey. The sessions and the surveys were not compulsory. Their participation in the session and completion of surveys implied informed consent. After IRB approval, we reviewed responses for the study groups. Sessions were held in person pre-pandemic in 2019 and virtually during the COVID-19 pandemic in 2022.

Results

Five fellows responded to our survey in 2019 and 7 in 2022 for a total of 12 respondents. 100% of respondents had been emotionally affected by a patient’s death. 82% had been emotionally affected by a patient’s death during the preceding 3 months. 90% had previously discussed their emotions relating to patient death with others. 83% would participate in DC again and 92% would recommend DC to a colleague. One 2019 participant commented that they thought attendings needed the session more than fellows, 2 2022 participants commented that they believe the meeting would be better in person. One 2022 participant commented they thought DC “is a good platform to vent emotions, identify self-destructive thoughts and better coping mechanisms.”

Conclusions 

DC provides a framework for HC to share personal and professional experience with mortality from a human perspective and support each other. This approach may be useful for HO departments or fellowships to offer as an opportunity to process end-of-life matters experienced as providers and finite humans.

Introduction

Hematologists and oncologists (HO) face mortality daily. “Death Cafe” (DC) is a safe space set aside for open dialogue about death and dying. Despite origins outside the healthcare setting, DC has been used as a framework to help health care students and workers process death and dying. We aim to assess if DC sessions are perceived to have value by HO trainees and faculty.

Methods

HO fellows from Baylor College of Medicine (BCM) and HO Faculty from BCM, mostly those at the Houston Michael E. DeBakey Veterans Affairs Hospital (VA), were offered the opportunity to participate in the DC sessions. Our VA Cancer Center Chaplain was present for all sessions and helped facilitate the conversation. HO fellows who were invited to a DC and attended were emailed a survey questionnaire after the activity via survey monkey. The sessions and the surveys were not compulsory. Their participation in the session and completion of surveys implied informed consent. After IRB approval, we reviewed responses for the study groups. Sessions were held in person pre-pandemic in 2019 and virtually during the COVID-19 pandemic in 2022.

Results

Five fellows responded to our survey in 2019 and 7 in 2022 for a total of 12 respondents. 100% of respondents had been emotionally affected by a patient’s death. 82% had been emotionally affected by a patient’s death during the preceding 3 months. 90% had previously discussed their emotions relating to patient death with others. 83% would participate in DC again and 92% would recommend DC to a colleague. One 2019 participant commented that they thought attendings needed the session more than fellows, 2 2022 participants commented that they believe the meeting would be better in person. One 2022 participant commented they thought DC “is a good platform to vent emotions, identify self-destructive thoughts and better coping mechanisms.”

Conclusions 

DC provides a framework for HC to share personal and professional experience with mortality from a human perspective and support each other. This approach may be useful for HO departments or fellowships to offer as an opportunity to process end-of-life matters experienced as providers and finite humans.

Introduction

Hematologists and oncologists (HO) face mortality daily. “Death Cafe” (DC) is a safe space set aside for open dialogue about death and dying. Despite origins outside the healthcare setting, DC has been used as a framework to help health care students and workers process death and dying. We aim to assess if DC sessions are perceived to have value by HO trainees and faculty.

Methods

HO fellows from Baylor College of Medicine (BCM) and HO Faculty from BCM, mostly those at the Houston Michael E. DeBakey Veterans Affairs Hospital (VA), were offered the opportunity to participate in the DC sessions. Our VA Cancer Center Chaplain was present for all sessions and helped facilitate the conversation. HO fellows who were invited to a DC and attended were emailed a survey questionnaire after the activity via survey monkey. The sessions and the surveys were not compulsory. Their participation in the session and completion of surveys implied informed consent. After IRB approval, we reviewed responses for the study groups. Sessions were held in person pre-pandemic in 2019 and virtually during the COVID-19 pandemic in 2022.

Results

Five fellows responded to our survey in 2019 and 7 in 2022 for a total of 12 respondents. 100% of respondents had been emotionally affected by a patient’s death. 82% had been emotionally affected by a patient’s death during the preceding 3 months. 90% had previously discussed their emotions relating to patient death with others. 83% would participate in DC again and 92% would recommend DC to a colleague. One 2019 participant commented that they thought attendings needed the session more than fellows, 2 2022 participants commented that they believe the meeting would be better in person. One 2022 participant commented they thought DC “is a good platform to vent emotions, identify self-destructive thoughts and better coping mechanisms.”

Conclusions 

DC provides a framework for HC to share personal and professional experience with mortality from a human perspective and support each other. This approach may be useful for HO departments or fellowships to offer as an opportunity to process end-of-life matters experienced as providers and finite humans.

MILAN – The therapeutic value of inhibiting the activity of IgE in patients with chronic spontaneous urticaria (CSU) was reinforced by two large phase 3 trials with ligelizumab, a drug characterized as a new generation anti-IgE monoclonal antibody.

Both doses of ligelizumab evaluated met the primary endpoint of superiority to placebo for a complete response at 16 weeks of therapy, reported Marcus Maurer, MD, director of the Urticaria Center for Reference and Excellence at the Charité Hospital, Berlin.

The data from the two identically designed trials, PEARL 1 and PEARL 2, were presented at the annual congress of the European Academy of Dermatology and Venereology. The two ligelizumab experimental arms (72 mg or 120 mg administered subcutaneously every 4 weeks) and the active comparative arm of omalizumab (300 mg administered subcutaneously every 4 weeks) demonstrated similar efficacy, all three of which were highly superior to placebo.

The data show that “another anti-IgE therapy – ligelizumab – is effective in CSU,” Dr. Maurer said.

“While the benefit was not different from omalizumab, ligelizumab showed remarkable results in disease activity and by demonstrating just how many patients achieved what we want them to achieve, which is to have no more signs and symptoms,” he added.
 

Majority of participants with severe urticaria

All of the patients entered into the two trials had severe (about 65%) or moderate (about 35%) symptoms at baseline. The results of the two trials were almost identical. In the randomization arms, a weekly Urticaria Activity Score (UAS7) of 0, which was the primary endpoint, was achieved at week 16 by 31.0% of those receiving 72-mg ligelizumab, 38.3% of those receiving 120-mg ligelizumab, and 34.1% of those receiving omalizumab (Xolair). The placebo response was 5.7%.

The UAS7 score is drawn from two components, wheals and itch. The range is 0 (no symptoms) to 42 (most severe). At baseline, the average patients’ scores were about 30, which correlates with a substantial symptom burden, according to Dr. Maurer.

The mean reduction in the UAS7 score in PEARL 2, which differed from PEARL 1 by no more than 0.4 points for any treatment group, was 19.2 points in the 72-mg ligelizumab group, 19.3 points in the 120-mg ligelizumab group, 19.6 points in the omalizumab group, and 9.2 points in the placebo group. There were no significant differences between any active treatment arm.

Complete symptom relief, meaning a UAS7 score of 0, was selected as the primary endpoint, because Dr. Maurer said that this is the goal of treatment. Although he admitted that a UAS7 score of 0 is analogous to a PASI score in psoriasis of 100 (complete clearing), he said, “Chronic urticaria is a debilitating disease, and we want to eliminate the symptoms. Gone is gone.”

Combined, the two phase 3 trials represent “the biggest chronic urticaria program ever,” according to Dr. Maurer. The 1,034 patients enrolled in PEARL 1 and the 1,023 enrolled in PEARL 2 were randomized in a 3:3:3:1 ratio with placebo representing the smaller group.

The planned follow-up is 52 weeks, but the placebo group will be switched to 120 mg ligelizumab every 4 weeks at the end of 24 weeks. The switch is required because “you cannot maintain patients with this disease on placebo over a long period,” Dr. Maurer said.
 

Ligelizumab associated with low discontinuation rate

Adverse events overall and stratified by severity have been similar across treatment arms, including placebo. The possible exception was a lower rate of moderate events (16.5%) in the placebo arm relative to the 72-mg ligelizumab arm (19.8%), the 120-mg ligelizumab arm (21.6%), and the omalizumab arm (22.3%). Discontinuations because of an adverse event were under 4% in every treatment arm.

Although Dr. Maurer did not present outcomes at 52 weeks, he did note that “only 15% of those who enrolled in these trials have discontinued treatment.” He considered this remarkable in that the study was conducted in the midst of the COVID-19 pandemic, and it appears that at least some of those left the trial did so because of concern for clinic visits.

Despite the similar benefit provided by ligelizumab and omalizumab, Dr. Maurer said that subgroup analyses will be coming. The possibility that some patients benefit more from one than the another cannot yet be ruled out. There are also, as of yet, no data to determine whether at least some patients respond to one after an inadequate response to the other.

Still, given the efficacy and the safety of ligelizumab, Dr. Maurer indicated that the drug is likely to find a role in routine management of CSU if approved.

“We only have two options for chronic spontaneous urticaria. There are antihistamines, which do not usually work, and omalizumab,” he said. “It is very important we develop more treatment options.”

Adam Friedman, MD, professor and chair of dermatology, George Washington University, Washington, agreed.

“More therapeutic options, especially for disease states that have a small armament – even if equivalent in efficacy to established therapies – is always a win for patients as it almost always increases access to treatment,” Dr. Friedman said in an interview.

“Furthermore, the heterogeneous nature of inflammatory skin diseases is often not captured in even phase 3 studies. Therefore, having additional options could offer relief where previous therapies have failed,” he added.

Dr. Maurer reports financial relationships with more than 10 pharmaceutical companies, including Novartis, which is developing ligelizumab. Dr. Friedman has a financial relationship with more than 20 pharmaceutical companies but has no current financial association with Novartis and was not involved in the PEARL 1 and 2 trials.

MILAN – The therapeutic value of inhibiting the activity of IgE in patients with chronic spontaneous urticaria (CSU) was reinforced by two large phase 3 trials with ligelizumab, a drug characterized as a new generation anti-IgE monoclonal antibody.

Both doses of ligelizumab evaluated met the primary endpoint of superiority to placebo for a complete response at 16 weeks of therapy, reported Marcus Maurer, MD, director of the Urticaria Center for Reference and Excellence at the Charité Hospital, Berlin.

The data from the two identically designed trials, PEARL 1 and PEARL 2, were presented at the annual congress of the European Academy of Dermatology and Venereology. The two ligelizumab experimental arms (72 mg or 120 mg administered subcutaneously every 4 weeks) and the active comparative arm of omalizumab (300 mg administered subcutaneously every 4 weeks) demonstrated similar efficacy, all three of which were highly superior to placebo.

The data show that “another anti-IgE therapy – ligelizumab – is effective in CSU,” Dr. Maurer said.

“While the benefit was not different from omalizumab, ligelizumab showed remarkable results in disease activity and by demonstrating just how many patients achieved what we want them to achieve, which is to have no more signs and symptoms,” he added.
 

Majority of participants with severe urticaria

All of the patients entered into the two trials had severe (about 65%) or moderate (about 35%) symptoms at baseline. The results of the two trials were almost identical. In the randomization arms, a weekly Urticaria Activity Score (UAS7) of 0, which was the primary endpoint, was achieved at week 16 by 31.0% of those receiving 72-mg ligelizumab, 38.3% of those receiving 120-mg ligelizumab, and 34.1% of those receiving omalizumab (Xolair). The placebo response was 5.7%.

The UAS7 score is drawn from two components, wheals and itch. The range is 0 (no symptoms) to 42 (most severe). At baseline, the average patients’ scores were about 30, which correlates with a substantial symptom burden, according to Dr. Maurer.

The mean reduction in the UAS7 score in PEARL 2, which differed from PEARL 1 by no more than 0.4 points for any treatment group, was 19.2 points in the 72-mg ligelizumab group, 19.3 points in the 120-mg ligelizumab group, 19.6 points in the omalizumab group, and 9.2 points in the placebo group. There were no significant differences between any active treatment arm.

Complete symptom relief, meaning a UAS7 score of 0, was selected as the primary endpoint, because Dr. Maurer said that this is the goal of treatment. Although he admitted that a UAS7 score of 0 is analogous to a PASI score in psoriasis of 100 (complete clearing), he said, “Chronic urticaria is a debilitating disease, and we want to eliminate the symptoms. Gone is gone.”

Combined, the two phase 3 trials represent “the biggest chronic urticaria program ever,” according to Dr. Maurer. The 1,034 patients enrolled in PEARL 1 and the 1,023 enrolled in PEARL 2 were randomized in a 3:3:3:1 ratio with placebo representing the smaller group.

The planned follow-up is 52 weeks, but the placebo group will be switched to 120 mg ligelizumab every 4 weeks at the end of 24 weeks. The switch is required because “you cannot maintain patients with this disease on placebo over a long period,” Dr. Maurer said.
 

Ligelizumab associated with low discontinuation rate

Adverse events overall and stratified by severity have been similar across treatment arms, including placebo. The possible exception was a lower rate of moderate events (16.5%) in the placebo arm relative to the 72-mg ligelizumab arm (19.8%), the 120-mg ligelizumab arm (21.6%), and the omalizumab arm (22.3%). Discontinuations because of an adverse event were under 4% in every treatment arm.

Although Dr. Maurer did not present outcomes at 52 weeks, he did note that “only 15% of those who enrolled in these trials have discontinued treatment.” He considered this remarkable in that the study was conducted in the midst of the COVID-19 pandemic, and it appears that at least some of those left the trial did so because of concern for clinic visits.

Despite the similar benefit provided by ligelizumab and omalizumab, Dr. Maurer said that subgroup analyses will be coming. The possibility that some patients benefit more from one than the another cannot yet be ruled out. There are also, as of yet, no data to determine whether at least some patients respond to one after an inadequate response to the other.

Still, given the efficacy and the safety of ligelizumab, Dr. Maurer indicated that the drug is likely to find a role in routine management of CSU if approved.

“We only have two options for chronic spontaneous urticaria. There are antihistamines, which do not usually work, and omalizumab,” he said. “It is very important we develop more treatment options.”

Adam Friedman, MD, professor and chair of dermatology, George Washington University, Washington, agreed.

“More therapeutic options, especially for disease states that have a small armament – even if equivalent in efficacy to established therapies – is always a win for patients as it almost always increases access to treatment,” Dr. Friedman said in an interview.

“Furthermore, the heterogeneous nature of inflammatory skin diseases is often not captured in even phase 3 studies. Therefore, having additional options could offer relief where previous therapies have failed,” he added.

Dr. Maurer reports financial relationships with more than 10 pharmaceutical companies, including Novartis, which is developing ligelizumab. Dr. Friedman has a financial relationship with more than 20 pharmaceutical companies but has no current financial association with Novartis and was not involved in the PEARL 1 and 2 trials.

MILAN – The therapeutic value of inhibiting the activity of IgE in patients with chronic spontaneous urticaria (CSU) was reinforced by two large phase 3 trials with ligelizumab, a drug characterized as a new generation anti-IgE monoclonal antibody.

Both doses of ligelizumab evaluated met the primary endpoint of superiority to placebo for a complete response at 16 weeks of therapy, reported Marcus Maurer, MD, director of the Urticaria Center for Reference and Excellence at the Charité Hospital, Berlin.

The data from the two identically designed trials, PEARL 1 and PEARL 2, were presented at the annual congress of the European Academy of Dermatology and Venereology. The two ligelizumab experimental arms (72 mg or 120 mg administered subcutaneously every 4 weeks) and the active comparative arm of omalizumab (300 mg administered subcutaneously every 4 weeks) demonstrated similar efficacy, all three of which were highly superior to placebo.

The data show that “another anti-IgE therapy – ligelizumab – is effective in CSU,” Dr. Maurer said.

“While the benefit was not different from omalizumab, ligelizumab showed remarkable results in disease activity and by demonstrating just how many patients achieved what we want them to achieve, which is to have no more signs and symptoms,” he added.
 

Majority of participants with severe urticaria

All of the patients entered into the two trials had severe (about 65%) or moderate (about 35%) symptoms at baseline. The results of the two trials were almost identical. In the randomization arms, a weekly Urticaria Activity Score (UAS7) of 0, which was the primary endpoint, was achieved at week 16 by 31.0% of those receiving 72-mg ligelizumab, 38.3% of those receiving 120-mg ligelizumab, and 34.1% of those receiving omalizumab (Xolair). The placebo response was 5.7%.

The UAS7 score is drawn from two components, wheals and itch. The range is 0 (no symptoms) to 42 (most severe). At baseline, the average patients’ scores were about 30, which correlates with a substantial symptom burden, according to Dr. Maurer.

The mean reduction in the UAS7 score in PEARL 2, which differed from PEARL 1 by no more than 0.4 points for any treatment group, was 19.2 points in the 72-mg ligelizumab group, 19.3 points in the 120-mg ligelizumab group, 19.6 points in the omalizumab group, and 9.2 points in the placebo group. There were no significant differences between any active treatment arm.

Complete symptom relief, meaning a UAS7 score of 0, was selected as the primary endpoint, because Dr. Maurer said that this is the goal of treatment. Although he admitted that a UAS7 score of 0 is analogous to a PASI score in psoriasis of 100 (complete clearing), he said, “Chronic urticaria is a debilitating disease, and we want to eliminate the symptoms. Gone is gone.”

Combined, the two phase 3 trials represent “the biggest chronic urticaria program ever,” according to Dr. Maurer. The 1,034 patients enrolled in PEARL 1 and the 1,023 enrolled in PEARL 2 were randomized in a 3:3:3:1 ratio with placebo representing the smaller group.

The planned follow-up is 52 weeks, but the placebo group will be switched to 120 mg ligelizumab every 4 weeks at the end of 24 weeks. The switch is required because “you cannot maintain patients with this disease on placebo over a long period,” Dr. Maurer said.
 

Ligelizumab associated with low discontinuation rate

Adverse events overall and stratified by severity have been similar across treatment arms, including placebo. The possible exception was a lower rate of moderate events (16.5%) in the placebo arm relative to the 72-mg ligelizumab arm (19.8%), the 120-mg ligelizumab arm (21.6%), and the omalizumab arm (22.3%). Discontinuations because of an adverse event were under 4% in every treatment arm.

Although Dr. Maurer did not present outcomes at 52 weeks, he did note that “only 15% of those who enrolled in these trials have discontinued treatment.” He considered this remarkable in that the study was conducted in the midst of the COVID-19 pandemic, and it appears that at least some of those left the trial did so because of concern for clinic visits.

Despite the similar benefit provided by ligelizumab and omalizumab, Dr. Maurer said that subgroup analyses will be coming. The possibility that some patients benefit more from one than the another cannot yet be ruled out. There are also, as of yet, no data to determine whether at least some patients respond to one after an inadequate response to the other.

Still, given the efficacy and the safety of ligelizumab, Dr. Maurer indicated that the drug is likely to find a role in routine management of CSU if approved.

“We only have two options for chronic spontaneous urticaria. There are antihistamines, which do not usually work, and omalizumab,” he said. “It is very important we develop more treatment options.”

Adam Friedman, MD, professor and chair of dermatology, George Washington University, Washington, agreed.

“More therapeutic options, especially for disease states that have a small armament – even if equivalent in efficacy to established therapies – is always a win for patients as it almost always increases access to treatment,” Dr. Friedman said in an interview.

“Furthermore, the heterogeneous nature of inflammatory skin diseases is often not captured in even phase 3 studies. Therefore, having additional options could offer relief where previous therapies have failed,” he added.

Dr. Maurer reports financial relationships with more than 10 pharmaceutical companies, including Novartis, which is developing ligelizumab. Dr. Friedman has a financial relationship with more than 20 pharmaceutical companies but has no current financial association with Novartis and was not involved in the PEARL 1 and 2 trials.

Two prospective studies that followed individuals with genetic or familiar risk for pancreatic cancer found that patients whose cancer was found through screening had better overall survival than those diagnosed symptomatically, suggesting that surveillance in this population may improve outcomes.

Opponents of screening for pancreatic cancer in this population suggested that screening may identify cancers at an earlier stage but doesn’t necessarily improve outcomes – an effect referred to as lead-time bias. “The data from these studies strongly refute this, now showing substantially better outcomes for those with screen-detected pancreatic cancer. In other words, these data now strongly suggest that, for some cases, earlier detection truly leads to superior outcomes, including what appears to be substantially higher likelihood of long-term cure,” said Matthew B. Yurgelun, MD, who wrote an accompanying editorial that was published in the Journal of Clinical Oncology, in response to two studies published in June in the journal.

“Individuals with genetic or familial risk of pancreatic cancer who develop screen-detected pancreatic cancer, as opposed to pancreatic cancer detected due to symptoms and in the absence of screening, appear to have significantly better outcomes compared to historical pancreatic cancer outcomes data,” said Dr. Yurgelun, who is an assistant professor of medicine at Harvard Medical School and director of the Dana-Farber Cancer Institute Lynch Syndrome Center, Boston.

In one report, researchers reported outcomes from 1,461 genetic high-risk participants in Cancer of Pancreas Screening-5 (CAPS5). 48.5% had a pathogenic version of a PDAC-susceptibility gene. 10 individuals were diagnosed with PDAC, 9 during surveillance, and 1 after having dropped out of the surveillance program for 4 years. 7 of the 9 surveillance cancers were stage 1, 1 was stage 2, and 1 was stage 3. 8 of 9 were resectable. The cancer found outside of surveillance was metastatic. In the overall cohort of 1,731 individuals, there were 19 PDACs detected during surveillance and 7 diagnosed outside of surveillance. 57.9% of surveillance-discovered were stage 1 and 5.2% were stage 4. On the other hand, 6 of the 7 tumors found outside of surveillance were stage 4. Median survival was 9.8 years in the screen-detected group versus 1.5 years outside surveillance (hazard ratio, 0.13; P = .003).

In a second study, researchers followed 47 individuals with inherited pathogenic variants for a median of 56 years. 8.9% were diagnosed with PDAC over a median follow-up of 5.6 years. By age 70, 20.7% had been diagnosed with PDAC. 83.3% of cases were identified as resectable at imaging, and 71.0% underwent resection. 33.3% of cases were stage I. Following primary PDAC diagnosis, the median survival was 26.8 months. 5-year survival was 32.4% (95% confidence interval; 19.1-54.8%). Among those who underwent rsection, the 5-year survival was 44.1% (95% CI, 27.2-71.3%). 2.6% of the population underwent surgery to remove a suspected malignant lesion which turned out not to be PDAC. 5 had low-grade dysplasia.

The results reinforce existing clinical practice guidelines that suggest MRI or endoscopic ultrasound screening for individuals with both a family and genetic risk of PDAC and could inform deliberations about extending such screening to all patients with inherited risk factors, according to Dr. Yurgelun.

Screening does not come without drawbacks. Research has demonstrated that about 40% of individuals who present for high-risk screening have pancreatic abnormalities, typically cystic lesions. These are also common in the general population. Very few such lesions require intervention, but they should be monitored, according to Dr. Yurgelun. Biopsies can be tricky, and removal requires major abdominal surgery, and magnetic resonance imaging or endoscopic ultrasonic can be nuanced, “which highlights the importance of this screening being performed and interpreted by health care providers experienced in high-risk surveillance,” Dr. Yurgelun said.

Dr. Yurgelun has no relevant financial disclosures.

Two prospective studies that followed individuals with genetic or familiar risk for pancreatic cancer found that patients whose cancer was found through screening had better overall survival than those diagnosed symptomatically, suggesting that surveillance in this population may improve outcomes.

Opponents of screening for pancreatic cancer in this population suggested that screening may identify cancers at an earlier stage but doesn’t necessarily improve outcomes – an effect referred to as lead-time bias. “The data from these studies strongly refute this, now showing substantially better outcomes for those with screen-detected pancreatic cancer. In other words, these data now strongly suggest that, for some cases, earlier detection truly leads to superior outcomes, including what appears to be substantially higher likelihood of long-term cure,” said Matthew B. Yurgelun, MD, who wrote an accompanying editorial that was published in the Journal of Clinical Oncology, in response to two studies published in June in the journal.

“Individuals with genetic or familial risk of pancreatic cancer who develop screen-detected pancreatic cancer, as opposed to pancreatic cancer detected due to symptoms and in the absence of screening, appear to have significantly better outcomes compared to historical pancreatic cancer outcomes data,” said Dr. Yurgelun, who is an assistant professor of medicine at Harvard Medical School and director of the Dana-Farber Cancer Institute Lynch Syndrome Center, Boston.

In one report, researchers reported outcomes from 1,461 genetic high-risk participants in Cancer of Pancreas Screening-5 (CAPS5). 48.5% had a pathogenic version of a PDAC-susceptibility gene. 10 individuals were diagnosed with PDAC, 9 during surveillance, and 1 after having dropped out of the surveillance program for 4 years. 7 of the 9 surveillance cancers were stage 1, 1 was stage 2, and 1 was stage 3. 8 of 9 were resectable. The cancer found outside of surveillance was metastatic. In the overall cohort of 1,731 individuals, there were 19 PDACs detected during surveillance and 7 diagnosed outside of surveillance. 57.9% of surveillance-discovered were stage 1 and 5.2% were stage 4. On the other hand, 6 of the 7 tumors found outside of surveillance were stage 4. Median survival was 9.8 years in the screen-detected group versus 1.5 years outside surveillance (hazard ratio, 0.13; P = .003).

In a second study, researchers followed 47 individuals with inherited pathogenic variants for a median of 56 years. 8.9% were diagnosed with PDAC over a median follow-up of 5.6 years. By age 70, 20.7% had been diagnosed with PDAC. 83.3% of cases were identified as resectable at imaging, and 71.0% underwent resection. 33.3% of cases were stage I. Following primary PDAC diagnosis, the median survival was 26.8 months. 5-year survival was 32.4% (95% confidence interval; 19.1-54.8%). Among those who underwent rsection, the 5-year survival was 44.1% (95% CI, 27.2-71.3%). 2.6% of the population underwent surgery to remove a suspected malignant lesion which turned out not to be PDAC. 5 had low-grade dysplasia.

The results reinforce existing clinical practice guidelines that suggest MRI or endoscopic ultrasound screening for individuals with both a family and genetic risk of PDAC and could inform deliberations about extending such screening to all patients with inherited risk factors, according to Dr. Yurgelun.

Screening does not come without drawbacks. Research has demonstrated that about 40% of individuals who present for high-risk screening have pancreatic abnormalities, typically cystic lesions. These are also common in the general population. Very few such lesions require intervention, but they should be monitored, according to Dr. Yurgelun. Biopsies can be tricky, and removal requires major abdominal surgery, and magnetic resonance imaging or endoscopic ultrasonic can be nuanced, “which highlights the importance of this screening being performed and interpreted by health care providers experienced in high-risk surveillance,” Dr. Yurgelun said.

Dr. Yurgelun has no relevant financial disclosures.

Two prospective studies that followed individuals with genetic or familiar risk for pancreatic cancer found that patients whose cancer was found through screening had better overall survival than those diagnosed symptomatically, suggesting that surveillance in this population may improve outcomes.

Opponents of screening for pancreatic cancer in this population suggested that screening may identify cancers at an earlier stage but doesn’t necessarily improve outcomes – an effect referred to as lead-time bias. “The data from these studies strongly refute this, now showing substantially better outcomes for those with screen-detected pancreatic cancer. In other words, these data now strongly suggest that, for some cases, earlier detection truly leads to superior outcomes, including what appears to be substantially higher likelihood of long-term cure,” said Matthew B. Yurgelun, MD, who wrote an accompanying editorial that was published in the Journal of Clinical Oncology, in response to two studies published in June in the journal.

“Individuals with genetic or familial risk of pancreatic cancer who develop screen-detected pancreatic cancer, as opposed to pancreatic cancer detected due to symptoms and in the absence of screening, appear to have significantly better outcomes compared to historical pancreatic cancer outcomes data,” said Dr. Yurgelun, who is an assistant professor of medicine at Harvard Medical School and director of the Dana-Farber Cancer Institute Lynch Syndrome Center, Boston.

In one report, researchers reported outcomes from 1,461 genetic high-risk participants in Cancer of Pancreas Screening-5 (CAPS5). 48.5% had a pathogenic version of a PDAC-susceptibility gene. 10 individuals were diagnosed with PDAC, 9 during surveillance, and 1 after having dropped out of the surveillance program for 4 years. 7 of the 9 surveillance cancers were stage 1, 1 was stage 2, and 1 was stage 3. 8 of 9 were resectable. The cancer found outside of surveillance was metastatic. In the overall cohort of 1,731 individuals, there were 19 PDACs detected during surveillance and 7 diagnosed outside of surveillance. 57.9% of surveillance-discovered were stage 1 and 5.2% were stage 4. On the other hand, 6 of the 7 tumors found outside of surveillance were stage 4. Median survival was 9.8 years in the screen-detected group versus 1.5 years outside surveillance (hazard ratio, 0.13; P = .003).

In a second study, researchers followed 47 individuals with inherited pathogenic variants for a median of 56 years. 8.9% were diagnosed with PDAC over a median follow-up of 5.6 years. By age 70, 20.7% had been diagnosed with PDAC. 83.3% of cases were identified as resectable at imaging, and 71.0% underwent resection. 33.3% of cases were stage I. Following primary PDAC diagnosis, the median survival was 26.8 months. 5-year survival was 32.4% (95% confidence interval; 19.1-54.8%). Among those who underwent rsection, the 5-year survival was 44.1% (95% CI, 27.2-71.3%). 2.6% of the population underwent surgery to remove a suspected malignant lesion which turned out not to be PDAC. 5 had low-grade dysplasia.

The results reinforce existing clinical practice guidelines that suggest MRI or endoscopic ultrasound screening for individuals with both a family and genetic risk of PDAC and could inform deliberations about extending such screening to all patients with inherited risk factors, according to Dr. Yurgelun.

Screening does not come without drawbacks. Research has demonstrated that about 40% of individuals who present for high-risk screening have pancreatic abnormalities, typically cystic lesions. These are also common in the general population. Very few such lesions require intervention, but they should be monitored, according to Dr. Yurgelun. Biopsies can be tricky, and removal requires major abdominal surgery, and magnetic resonance imaging or endoscopic ultrasonic can be nuanced, “which highlights the importance of this screening being performed and interpreted by health care providers experienced in high-risk surveillance,” Dr. Yurgelun said.

Dr. Yurgelun has no relevant financial disclosures.

Managing psychiatric illnesses is rapidly becoming routine practice for primary care pediatricians, whether screening for symptoms of anxiety and depression, starting medication, or providing psychoeducation to youth and parents. Pediatricians can provide strategies to address the impairments of sleep, energy, motivation and appetite that can accompany these illnesses. Psychotherapy, a relationship based on understanding and providing support, should be a core element of treatment for emotional disorders, but there is a great deal of uncertainty around what therapies are supported by evidence. This month, we offer a primer on the evidence-based psychotherapies for youth and we also recognize that research defining the effectiveness of psychotherapy is limited and complex.

Cognitive-behavioral psychotherapy (CBT)

Mention psychotherapy and most people think of a patient reclining on a couch free-associating about their childhood while a therapist sits behind them taking notes. This potent image stems from psychoanalytic psychotherapy, developed in the 19th century by Sigmund Freud, and was based on his theory that unconscious conflicts drove most of the puzzling behaviors and emotional distress associated with “neurosis.” Psychoanalysis became popular in 20th century America, even for use with children. Evidence is hard to develop since psychoanalytic therapy often lasts years, there are a limited number of patients, and the method is hard to standardize.

A focus on how to shape behaviors directly also emerged in the early 20th century (in the work of John Watson and Ivan Pavlov). Aaron Beck, MD, the father of CBT, observed in his psychoanalytic treatments that many patients appeared to be experiencing emotional distress around thoughts that were not unconscious. Instead, his patients were experiencing “automatic thoughts,” or rapid, often-distorted thoughts that have the force of truth in the thinker. These thoughts create emotional distress and behaviors that may reinforce the thoughts and emotional distress. For example, a depressed patient who is uncomfortable in social situations may think “nobody ever likes me.” This may cause them to appear uncomfortable or unfriendly in a new social situation and prevent them from making connections, perpetuating a cycle of isolation, insecurity, and loneliness. Identifying these automatic thoughts, and their connection to painful feelings and perpetuating behaviors is at the core of CBT.

In CBT the therapist is much more active than in psychoanalysis. They engage patients in identifying thought distortions together, challenging them on the truth of these thoughts and recognizing the connection to emotional distress. They also identify maladaptive behaviors and focus on strategies to build new more effective behavioral responses to thoughts, feelings, and situations. This is often done with gradual “exposures” to new behaviors, which are naturally reinforced by better outcomes or lowered distress. When performed with high fidelity, CBT is a very structured treatment that is closer to an emotionally supportive form of coaching and skill building. CBT is at the core of most evidence-based psychotherapies that have emerged in the past 60 years.

CBT is the first-line treatment for anxiety disorders in children, adolescents, and adults. A variant called “exposure and response prevention” is the first-line treatment for obsessive-compulsive disorder, and is predominantly behavioral. It is focused on preventing patients with anxiety disorders from engaging in the maladaptive behaviors that lower their anxiety in the short term but cause worsened anxiety and impairment over time (such as avoiding social situations when they are worried that others won’t like them).

CBT is also a first-line treatment for major depressive episodes in teenagers and adults, although those for whom the symptoms are severe often need medication to be able to fully participate in therapy. There are variants of CBT that have demonstrated efficacy in the treatment of posttraumatic stress disorder, bulimia, and even psychosis. It makes developmental sense that therapies with a problem-focused coaching approach might be more effective in children and adolescents than open-ended exploratory psychotherapies.

Traditional CBT was not very effective for patients with a variant of depression that is marked by stormy relationships, irritability, chronic suicidality, and impulsive attempts to regulate discomfort (including bingeing, purging, sexual acting-out, drug use, and self-injury or cutting), a symptom pattern called “borderline personality disorder.” These patients often ended up on multiple medications with only modest improvements in their function and well-being.

But in the 1990s, a research psychologist named Marsha Linnehan developed a modified version of CBT to use with these patients called dialectical-behavioral therapy (DBT). The “dialectic” emphasizes the role of two things being true at once, in this case the need for acceptance and change. DBT helps patients develop distress tolerance and emotional regulation skills alongside adaptive social and communication skills. DBT has demonstrated efficacy in the treatment of these patients as well as in the treatment of other disorders marked by poor distress tolerance and self-regulation (such as substance use disorders, binge-eating disorder, and PTSD).

DBT was adapted for use in adolescents given the prevalence of these problems in this age group, and it is the first-line treatment for adolescents with these specific mood and behavioral symptoms. High-fidelity DBT has an individual, group, and family component that are all essential for the treatment to be effective.

Instruction about the principles of CBT and DBT is a part of graduate school in psychology, but not every postgraduate training program includes thorough training in their practice. Completion of this specialized training leads to certification. It is very important that families understand that anyone may call themselves a psychotherapist. Those therapists who have master’s degrees (MSW, MFT, PCC, and others) may not have had exposure to these evidence-based treatments in their shorter graduate programs. Even doctoral-level training programs often do not include complete training in the high-fidelity delivery of these therapies.

It is critical that you help families be educated consumers and ask therapists if they have training and certification in the recommended therapy. The Psychology Today website has a therapist referral resource that includes this information. Training programs can provide access to therapists who are learning these therapies; with skilled supervision, they can provide excellent treatment.

We should note that there are several other evidence-based therapies, including family-based treatment for anorexia nervosa, motivational interviewing for substance use disorders, and interpersonal psychotherapy for depression associated with high family conflict in adolescents.

There is good evidence that the quality of the alliance between therapist and patient is a critical predictor of whether a therapy will be effective. It is appropriate for your patient to look for a therapist that they can trust and talk to and that their therapist be trained in the recommended psychotherapy. Otherwise, your patient is spending valuable time and money on an enterprise that may not be effective. This can leave them and their parents feeling discouraged or even hopeless about the prospects for recovery and promote an overreliance on medications. In addition to providing your patients with effective screening, initiating medication treatment, and psychoeducation, you can enhance their ability to find an optimal therapist to relieve their suffering.

Dr. Swick is physician in chief at Ohana, Center for Child and Adolescent Behavioral Health, Community Hospital of the Monterey (Calif.) Peninsula. Dr. Jellinek is professor emeritus of psychiatry and pediatrics, Harvard Medical School, Boston. Email them at [email protected].

Managing psychiatric illnesses is rapidly becoming routine practice for primary care pediatricians, whether screening for symptoms of anxiety and depression, starting medication, or providing psychoeducation to youth and parents. Pediatricians can provide strategies to address the impairments of sleep, energy, motivation and appetite that can accompany these illnesses. Psychotherapy, a relationship based on understanding and providing support, should be a core element of treatment for emotional disorders, but there is a great deal of uncertainty around what therapies are supported by evidence. This month, we offer a primer on the evidence-based psychotherapies for youth and we also recognize that research defining the effectiveness of psychotherapy is limited and complex.

Cognitive-behavioral psychotherapy (CBT)

Mention psychotherapy and most people think of a patient reclining on a couch free-associating about their childhood while a therapist sits behind them taking notes. This potent image stems from psychoanalytic psychotherapy, developed in the 19th century by Sigmund Freud, and was based on his theory that unconscious conflicts drove most of the puzzling behaviors and emotional distress associated with “neurosis.” Psychoanalysis became popular in 20th century America, even for use with children. Evidence is hard to develop since psychoanalytic therapy often lasts years, there are a limited number of patients, and the method is hard to standardize.

A focus on how to shape behaviors directly also emerged in the early 20th century (in the work of John Watson and Ivan Pavlov). Aaron Beck, MD, the father of CBT, observed in his psychoanalytic treatments that many patients appeared to be experiencing emotional distress around thoughts that were not unconscious. Instead, his patients were experiencing “automatic thoughts,” or rapid, often-distorted thoughts that have the force of truth in the thinker. These thoughts create emotional distress and behaviors that may reinforce the thoughts and emotional distress. For example, a depressed patient who is uncomfortable in social situations may think “nobody ever likes me.” This may cause them to appear uncomfortable or unfriendly in a new social situation and prevent them from making connections, perpetuating a cycle of isolation, insecurity, and loneliness. Identifying these automatic thoughts, and their connection to painful feelings and perpetuating behaviors is at the core of CBT.

In CBT the therapist is much more active than in psychoanalysis. They engage patients in identifying thought distortions together, challenging them on the truth of these thoughts and recognizing the connection to emotional distress. They also identify maladaptive behaviors and focus on strategies to build new more effective behavioral responses to thoughts, feelings, and situations. This is often done with gradual “exposures” to new behaviors, which are naturally reinforced by better outcomes or lowered distress. When performed with high fidelity, CBT is a very structured treatment that is closer to an emotionally supportive form of coaching and skill building. CBT is at the core of most evidence-based psychotherapies that have emerged in the past 60 years.

CBT is the first-line treatment for anxiety disorders in children, adolescents, and adults. A variant called “exposure and response prevention” is the first-line treatment for obsessive-compulsive disorder, and is predominantly behavioral. It is focused on preventing patients with anxiety disorders from engaging in the maladaptive behaviors that lower their anxiety in the short term but cause worsened anxiety and impairment over time (such as avoiding social situations when they are worried that others won’t like them).

CBT is also a first-line treatment for major depressive episodes in teenagers and adults, although those for whom the symptoms are severe often need medication to be able to fully participate in therapy. There are variants of CBT that have demonstrated efficacy in the treatment of posttraumatic stress disorder, bulimia, and even psychosis. It makes developmental sense that therapies with a problem-focused coaching approach might be more effective in children and adolescents than open-ended exploratory psychotherapies.

Traditional CBT was not very effective for patients with a variant of depression that is marked by stormy relationships, irritability, chronic suicidality, and impulsive attempts to regulate discomfort (including bingeing, purging, sexual acting-out, drug use, and self-injury or cutting), a symptom pattern called “borderline personality disorder.” These patients often ended up on multiple medications with only modest improvements in their function and well-being.

But in the 1990s, a research psychologist named Marsha Linnehan developed a modified version of CBT to use with these patients called dialectical-behavioral therapy (DBT). The “dialectic” emphasizes the role of two things being true at once, in this case the need for acceptance and change. DBT helps patients develop distress tolerance and emotional regulation skills alongside adaptive social and communication skills. DBT has demonstrated efficacy in the treatment of these patients as well as in the treatment of other disorders marked by poor distress tolerance and self-regulation (such as substance use disorders, binge-eating disorder, and PTSD).

DBT was adapted for use in adolescents given the prevalence of these problems in this age group, and it is the first-line treatment for adolescents with these specific mood and behavioral symptoms. High-fidelity DBT has an individual, group, and family component that are all essential for the treatment to be effective.

Instruction about the principles of CBT and DBT is a part of graduate school in psychology, but not every postgraduate training program includes thorough training in their practice. Completion of this specialized training leads to certification. It is very important that families understand that anyone may call themselves a psychotherapist. Those therapists who have master’s degrees (MSW, MFT, PCC, and others) may not have had exposure to these evidence-based treatments in their shorter graduate programs. Even doctoral-level training programs often do not include complete training in the high-fidelity delivery of these therapies.

It is critical that you help families be educated consumers and ask therapists if they have training and certification in the recommended therapy. The Psychology Today website has a therapist referral resource that includes this information. Training programs can provide access to therapists who are learning these therapies; with skilled supervision, they can provide excellent treatment.

We should note that there are several other evidence-based therapies, including family-based treatment for anorexia nervosa, motivational interviewing for substance use disorders, and interpersonal psychotherapy for depression associated with high family conflict in adolescents.

There is good evidence that the quality of the alliance between therapist and patient is a critical predictor of whether a therapy will be effective. It is appropriate for your patient to look for a therapist that they can trust and talk to and that their therapist be trained in the recommended psychotherapy. Otherwise, your patient is spending valuable time and money on an enterprise that may not be effective. This can leave them and their parents feeling discouraged or even hopeless about the prospects for recovery and promote an overreliance on medications. In addition to providing your patients with effective screening, initiating medication treatment, and psychoeducation, you can enhance their ability to find an optimal therapist to relieve their suffering.

Dr. Swick is physician in chief at Ohana, Center for Child and Adolescent Behavioral Health, Community Hospital of the Monterey (Calif.) Peninsula. Dr. Jellinek is professor emeritus of psychiatry and pediatrics, Harvard Medical School, Boston. Email them at [email protected].

Managing psychiatric illnesses is rapidly becoming routine practice for primary care pediatricians, whether screening for symptoms of anxiety and depression, starting medication, or providing psychoeducation to youth and parents. Pediatricians can provide strategies to address the impairments of sleep, energy, motivation and appetite that can accompany these illnesses. Psychotherapy, a relationship based on understanding and providing support, should be a core element of treatment for emotional disorders, but there is a great deal of uncertainty around what therapies are supported by evidence. This month, we offer a primer on the evidence-based psychotherapies for youth and we also recognize that research defining the effectiveness of psychotherapy is limited and complex.

Cognitive-behavioral psychotherapy (CBT)

Mention psychotherapy and most people think of a patient reclining on a couch free-associating about their childhood while a therapist sits behind them taking notes. This potent image stems from psychoanalytic psychotherapy, developed in the 19th century by Sigmund Freud, and was based on his theory that unconscious conflicts drove most of the puzzling behaviors and emotional distress associated with “neurosis.” Psychoanalysis became popular in 20th century America, even for use with children. Evidence is hard to develop since psychoanalytic therapy often lasts years, there are a limited number of patients, and the method is hard to standardize.

A focus on how to shape behaviors directly also emerged in the early 20th century (in the work of John Watson and Ivan Pavlov). Aaron Beck, MD, the father of CBT, observed in his psychoanalytic treatments that many patients appeared to be experiencing emotional distress around thoughts that were not unconscious. Instead, his patients were experiencing “automatic thoughts,” or rapid, often-distorted thoughts that have the force of truth in the thinker. These thoughts create emotional distress and behaviors that may reinforce the thoughts and emotional distress. For example, a depressed patient who is uncomfortable in social situations may think “nobody ever likes me.” This may cause them to appear uncomfortable or unfriendly in a new social situation and prevent them from making connections, perpetuating a cycle of isolation, insecurity, and loneliness. Identifying these automatic thoughts, and their connection to painful feelings and perpetuating behaviors is at the core of CBT.

In CBT the therapist is much more active than in psychoanalysis. They engage patients in identifying thought distortions together, challenging them on the truth of these thoughts and recognizing the connection to emotional distress. They also identify maladaptive behaviors and focus on strategies to build new more effective behavioral responses to thoughts, feelings, and situations. This is often done with gradual “exposures” to new behaviors, which are naturally reinforced by better outcomes or lowered distress. When performed with high fidelity, CBT is a very structured treatment that is closer to an emotionally supportive form of coaching and skill building. CBT is at the core of most evidence-based psychotherapies that have emerged in the past 60 years.

CBT is the first-line treatment for anxiety disorders in children, adolescents, and adults. A variant called “exposure and response prevention” is the first-line treatment for obsessive-compulsive disorder, and is predominantly behavioral. It is focused on preventing patients with anxiety disorders from engaging in the maladaptive behaviors that lower their anxiety in the short term but cause worsened anxiety and impairment over time (such as avoiding social situations when they are worried that others won’t like them).

CBT is also a first-line treatment for major depressive episodes in teenagers and adults, although those for whom the symptoms are severe often need medication to be able to fully participate in therapy. There are variants of CBT that have demonstrated efficacy in the treatment of posttraumatic stress disorder, bulimia, and even psychosis. It makes developmental sense that therapies with a problem-focused coaching approach might be more effective in children and adolescents than open-ended exploratory psychotherapies.

Traditional CBT was not very effective for patients with a variant of depression that is marked by stormy relationships, irritability, chronic suicidality, and impulsive attempts to regulate discomfort (including bingeing, purging, sexual acting-out, drug use, and self-injury or cutting), a symptom pattern called “borderline personality disorder.” These patients often ended up on multiple medications with only modest improvements in their function and well-being.

But in the 1990s, a research psychologist named Marsha Linnehan developed a modified version of CBT to use with these patients called dialectical-behavioral therapy (DBT). The “dialectic” emphasizes the role of two things being true at once, in this case the need for acceptance and change. DBT helps patients develop distress tolerance and emotional regulation skills alongside adaptive social and communication skills. DBT has demonstrated efficacy in the treatment of these patients as well as in the treatment of other disorders marked by poor distress tolerance and self-regulation (such as substance use disorders, binge-eating disorder, and PTSD).

DBT was adapted for use in adolescents given the prevalence of these problems in this age group, and it is the first-line treatment for adolescents with these specific mood and behavioral symptoms. High-fidelity DBT has an individual, group, and family component that are all essential for the treatment to be effective.

Instruction about the principles of CBT and DBT is a part of graduate school in psychology, but not every postgraduate training program includes thorough training in their practice. Completion of this specialized training leads to certification. It is very important that families understand that anyone may call themselves a psychotherapist. Those therapists who have master’s degrees (MSW, MFT, PCC, and others) may not have had exposure to these evidence-based treatments in their shorter graduate programs. Even doctoral-level training programs often do not include complete training in the high-fidelity delivery of these therapies.

It is critical that you help families be educated consumers and ask therapists if they have training and certification in the recommended therapy. The Psychology Today website has a therapist referral resource that includes this information. Training programs can provide access to therapists who are learning these therapies; with skilled supervision, they can provide excellent treatment.

We should note that there are several other evidence-based therapies, including family-based treatment for anorexia nervosa, motivational interviewing for substance use disorders, and interpersonal psychotherapy for depression associated with high family conflict in adolescents.

There is good evidence that the quality of the alliance between therapist and patient is a critical predictor of whether a therapy will be effective. It is appropriate for your patient to look for a therapist that they can trust and talk to and that their therapist be trained in the recommended psychotherapy. Otherwise, your patient is spending valuable time and money on an enterprise that may not be effective. This can leave them and their parents feeling discouraged or even hopeless about the prospects for recovery and promote an overreliance on medications. In addition to providing your patients with effective screening, initiating medication treatment, and psychoeducation, you can enhance their ability to find an optimal therapist to relieve their suffering.

Dr. Swick is physician in chief at Ohana, Center for Child and Adolescent Behavioral Health, Community Hospital of the Monterey (Calif.) Peninsula. Dr. Jellinek is professor emeritus of psychiatry and pediatrics, Harvard Medical School, Boston. Email them at [email protected].

Chronic pruritus occurs in 1 out of 3 patients with multiple sclerosis (MS) and may be associated with more advanced disease, according to investigators.

Itch is historically underrecognized as a symptom of MS, but physicians should know that it is common and may negatively impact quality of life, reported lead author Giuseppe Ingrasci, MD, a dermatology research fellow at the University of Miami, Miller School of Medicine, and colleagues.

A common problem that may indicate more severe disease

At the Multiple Sclerosis Center of Excellence in Miami, 27 out of 79 outpatients with MS (35%) reported pruritus, with an average severity of 5.42 out of 10. Among those with itch, the extremities were affected in about half of the patients, while the face, scalp, and trunk were affected in about one-third of the patients. Many described paroxysmal itch that was aggravated by heat, and about half experienced itch on a weekly basis.

Further investigation showed that itch was associated with more severe MS. Compared with patients not experiencing itch, those with itch were significantly more likely to report fatigue (77% vs. 44%), anxiety or depression (48% vs. 16%), and cognitive impairment (62% vs. 26%).

MRI findings backed up these clinical results. Compared with patients not experiencing itch, patients with itch had significantly more T2 hyperintensities in the posterior cervical cord (74.1% vs. 46.0%) and anterior pons/ventromedial medulla (62% vs. 26%). These hyperintensities in the medulla were also associated with an 11-fold increased rate of itch on the face or scalp (odds ratio, 11.3; 95% confidence interval, 1.6-78.6, P = 0.025).

“Health care providers should be aware of episodes of localized, neuropathic itch in MS patients, as they appear to be more prevalent than previously thought and may impair these patients’ quality of life,” the investigators concluded.
 

Challenges with symptom characterization, management

“This is an important study for both patients and clinicians,” said Justin Abbatemarco, MD, of Cleveland Clinic’s Mellen Center for Multiple Sclerosis, in a written comment. “As the authors mention, many of our patients experience transient symptoms, including many different types of sensory disturbance (that is, pins & needles, burning, electrical shocks, and itching). These symptoms can be really distressing for patients and their caregivers.”

While Dr. Abbatemarco has encountered severe itching in “several patients” with MS, he maintained that it is “relatively uncommon” and noted that MS symptomatology is an inherently cloudy subject.

Cool the itch?

Noting how heat appears to aggravate itch in patients with MS, Dr. Yosipovitch suggested that one of those unique – and simple – treatment approaches may be cooling itchy areas. Alternatively, clinicians may consider oral agents, like gabapentin to dampen neural transmission, or compounded formulations applied to the skin to reduce neural sensitivity, such as topical ketamine. Finally, Dr. Yosipovitch speculated that newer antibody agents for MS could potentially reduce itch.

All these treatment suggestions are purely hypothetical, he said, and require further investigation before they can be recommended with confidence.

The investigators disclosed relationships with Galderma, Pfizer, Novartis, and others. Dr. Abbatemarco disclosed no conflicts of interest.

Correction, 9/19/22: An earlier version of this article misidentified the photo of Dr. Justin Abbatemarco.

Chronic pruritus occurs in 1 out of 3 patients with multiple sclerosis (MS) and may be associated with more advanced disease, according to investigators.

Itch is historically underrecognized as a symptom of MS, but physicians should know that it is common and may negatively impact quality of life, reported lead author Giuseppe Ingrasci, MD, a dermatology research fellow at the University of Miami, Miller School of Medicine, and colleagues.

A common problem that may indicate more severe disease

At the Multiple Sclerosis Center of Excellence in Miami, 27 out of 79 outpatients with MS (35%) reported pruritus, with an average severity of 5.42 out of 10. Among those with itch, the extremities were affected in about half of the patients, while the face, scalp, and trunk were affected in about one-third of the patients. Many described paroxysmal itch that was aggravated by heat, and about half experienced itch on a weekly basis.

Further investigation showed that itch was associated with more severe MS. Compared with patients not experiencing itch, those with itch were significantly more likely to report fatigue (77% vs. 44%), anxiety or depression (48% vs. 16%), and cognitive impairment (62% vs. 26%).

MRI findings backed up these clinical results. Compared with patients not experiencing itch, patients with itch had significantly more T2 hyperintensities in the posterior cervical cord (74.1% vs. 46.0%) and anterior pons/ventromedial medulla (62% vs. 26%). These hyperintensities in the medulla were also associated with an 11-fold increased rate of itch on the face or scalp (odds ratio, 11.3; 95% confidence interval, 1.6-78.6, P = 0.025).

“Health care providers should be aware of episodes of localized, neuropathic itch in MS patients, as they appear to be more prevalent than previously thought and may impair these patients’ quality of life,” the investigators concluded.
 

Challenges with symptom characterization, management

“This is an important study for both patients and clinicians,” said Justin Abbatemarco, MD, of Cleveland Clinic’s Mellen Center for Multiple Sclerosis, in a written comment. “As the authors mention, many of our patients experience transient symptoms, including many different types of sensory disturbance (that is, pins & needles, burning, electrical shocks, and itching). These symptoms can be really distressing for patients and their caregivers.”

While Dr. Abbatemarco has encountered severe itching in “several patients” with MS, he maintained that it is “relatively uncommon” and noted that MS symptomatology is an inherently cloudy subject.

Cool the itch?

Noting how heat appears to aggravate itch in patients with MS, Dr. Yosipovitch suggested that one of those unique – and simple – treatment approaches may be cooling itchy areas. Alternatively, clinicians may consider oral agents, like gabapentin to dampen neural transmission, or compounded formulations applied to the skin to reduce neural sensitivity, such as topical ketamine. Finally, Dr. Yosipovitch speculated that newer antibody agents for MS could potentially reduce itch.

All these treatment suggestions are purely hypothetical, he said, and require further investigation before they can be recommended with confidence.

The investigators disclosed relationships with Galderma, Pfizer, Novartis, and others. Dr. Abbatemarco disclosed no conflicts of interest.

Correction, 9/19/22: An earlier version of this article misidentified the photo of Dr. Justin Abbatemarco.

Chronic pruritus occurs in 1 out of 3 patients with multiple sclerosis (MS) and may be associated with more advanced disease, according to investigators.

Itch is historically underrecognized as a symptom of MS, but physicians should know that it is common and may negatively impact quality of life, reported lead author Giuseppe Ingrasci, MD, a dermatology research fellow at the University of Miami, Miller School of Medicine, and colleagues.

A common problem that may indicate more severe disease

At the Multiple Sclerosis Center of Excellence in Miami, 27 out of 79 outpatients with MS (35%) reported pruritus, with an average severity of 5.42 out of 10. Among those with itch, the extremities were affected in about half of the patients, while the face, scalp, and trunk were affected in about one-third of the patients. Many described paroxysmal itch that was aggravated by heat, and about half experienced itch on a weekly basis.

Further investigation showed that itch was associated with more severe MS. Compared with patients not experiencing itch, those with itch were significantly more likely to report fatigue (77% vs. 44%), anxiety or depression (48% vs. 16%), and cognitive impairment (62% vs. 26%).

MRI findings backed up these clinical results. Compared with patients not experiencing itch, patients with itch had significantly more T2 hyperintensities in the posterior cervical cord (74.1% vs. 46.0%) and anterior pons/ventromedial medulla (62% vs. 26%). These hyperintensities in the medulla were also associated with an 11-fold increased rate of itch on the face or scalp (odds ratio, 11.3; 95% confidence interval, 1.6-78.6, P = 0.025).

“Health care providers should be aware of episodes of localized, neuropathic itch in MS patients, as they appear to be more prevalent than previously thought and may impair these patients’ quality of life,” the investigators concluded.
 

Challenges with symptom characterization, management

“This is an important study for both patients and clinicians,” said Justin Abbatemarco, MD, of Cleveland Clinic’s Mellen Center for Multiple Sclerosis, in a written comment. “As the authors mention, many of our patients experience transient symptoms, including many different types of sensory disturbance (that is, pins & needles, burning, electrical shocks, and itching). These symptoms can be really distressing for patients and their caregivers.”

While Dr. Abbatemarco has encountered severe itching in “several patients” with MS, he maintained that it is “relatively uncommon” and noted that MS symptomatology is an inherently cloudy subject.

Cool the itch?

Noting how heat appears to aggravate itch in patients with MS, Dr. Yosipovitch suggested that one of those unique – and simple – treatment approaches may be cooling itchy areas. Alternatively, clinicians may consider oral agents, like gabapentin to dampen neural transmission, or compounded formulations applied to the skin to reduce neural sensitivity, such as topical ketamine. Finally, Dr. Yosipovitch speculated that newer antibody agents for MS could potentially reduce itch.

All these treatment suggestions are purely hypothetical, he said, and require further investigation before they can be recommended with confidence.

The investigators disclosed relationships with Galderma, Pfizer, Novartis, and others. Dr. Abbatemarco disclosed no conflicts of interest.

Correction, 9/19/22: An earlier version of this article misidentified the photo of Dr. Justin Abbatemarco.

PARIS – “It’s not just what you give, it’s when you give it,” said the investigator reporting “that the same treatment for resectable melanoma given in a different sequence can generate lower rates of melanoma recurrence.”

Sapna Patel, MD, associate professor of melanoma medical oncology at The University of Texas MD Anderson Cancer Center, Houston, reported the results from the SWOG S1801 trial, which showed that patients with high-risk melanoma who received pembrolizumab both before and after surgery had significantly longer event-free survival than patients who received pembrolizumab after surgery only.

At a median follow-up of almost 15 months, there was a 42% lower rate of recurrence or death.

“Compared to the same treatment given entirely in the adjuvant setting, neoadjuvant pembrolizumab followed by adjuvant pembrolizumab improves event-free survival in resectable melanoma,” Dr. Patel commented.

She suggested that the explanation for the findings was that “inhibiting the PD-1/PD-L1 immune checkpoints before surgery gives an antitumor response at local and distant sites, and this occurs before resection of the tumor bed. This approach tends to leave behind a larger number of anti-tumor T cells ... [and] these T cells can be activated and circulated systematically to recognize and attack micro-metastatic melanoma tumors.”

The findings were presented during a presidential symposium at the European Society for Medical Oncology (ESMO) Congress 2022, Paris.

“This trial provides us with more evidence of when one strategy may be preferred over the other,” commented Maya Dimitrova, MD, medical oncologist at NYU Langone Perlmutter Cancer Center. She was not involved with the trial.

“Neoadjuvant immunotherapy has elicited impressive complete pathologic responses, which thus far have proven to be associated with a durable response. Neoadjuvant therapy may help identify patients who will respond well to checkpoint inhibitors and allow for de-escalation of therapy,” she told this news organization when approached for comment.

“As with all neoadjuvant therapy, we don’t want the treatment to compromise the outcomes of surgery when the intent is curative, and we once again have evidence that this is not the case when it comes to immune therapy,” she said. However, she added that “we will need further survival data to really change the standard of practice in high-risk melanoma and demonstrate whether there is a superior sequence of therapy and surgery.”

 

Details of the new results

The S1801 clinical trial enrolled 345 participants with stage IIIB through stage IV melanoma considered resectable. The cohort was randomized to receive either upfront surgery followed by 18 doses of pembrolizumab 200 mg every 3 weeks for a total of 18 doses or neoadjuvant therapy with pembrolizumab 200 mg (3 doses) followed by 15 doses of adjuvant pembrolizumab.

The primary endpoint was event-free survival (EFS), defined as the time from randomization to the occurrence of one of the following: disease progression or toxicity that resulted in not receiving surgery, failure to begin adjuvant therapy within 84 days of surgery, melanoma recurrence after surgery, or death from any cause.

At a median follow-up of 14.7 months, EFS was significantly higher for patients in the neoadjuvant group, compared with those receiving adjuvant therapy only (HR, 0.58; one-sided log-rank P = .004). A total of 36 participants died in the neoadjuvant and adjuvant groups (14 and 22 patients, extrapolating to a hazard ratio of 0.63; one-sided P = .091).

“With a limited number of events, overall survival is not statistically different at this time,” Dr. Patel said. “Landmark 2-year survival was 72% in the neoadjuvant arm and 49% in the adjuvant arm.”

The authors note that the benefit of neoadjuvant therapy remained consistent across a range of factors, including patient age, sex, performance status, stage of disease, ulceration, and BRAF status. The same proportion of patients in both groups received adjuvant pembrolizumab following surgery.

Rates of adverse events were similar in both groups, and neoadjuvant pembrolizumab did not result in an increase in adverse events related to surgery. In the neoadjuvant group, 28 patients (21%) with submitted pathology reports were noted to have had a complete pathologic response (0% viable tumor) on local review.
 

Questions remain

Invited discussant James Larkin, PhD, FRCP, FMedSci, a clinical researcher at The Royal Marsden Hospital, London, noted that the study had “striking results” and was a landmark trial with a simple but powerful design.

However, he pointed to some questions which need to be addressed in the future. “One important question is what is the optimal duration of neoadjuvant treatment, and can we individualize it?”

Another question is just how much postoperative treatment is really needed and whether pathology help determine that. “Can surgery be safely avoided altogether?” he asked. “Another issue is the need for anti-CTL4 therapy – which patients might benefit from anti-CTL4, in addition to anti-PD-1?”

“And by extension, this paradigm provides a great platform for testing new agents, including combinations in cases where PD-1 is not sufficient to achieve a sufficient response,” said Dr. Larkin. “In the future, trials addressing these questions hand us a major opportunity to individualize and rationally de-escalate treatment.”

Also weighing in on the study, another expert pointed out that neoadjuvant therapy in this setting is already being considered as an option. “The use of immunotherapy before surgery has been reported in some trials such as the OPACIN-neo and PRADO trials,” said Anthony J. Olszanski, RPh, MD, Vice Chair of Research at the Fox Chase Cancer Center, Philadelphia. “Results have been quite exciting and have led the NCCN to list this as a potential option for some patients in the current melanoma guidelines.”

S1801 is funded by the NIH/NCI and in part by MSD through a Cooperative Research and Development Agreement with the NCI. Pembrolizumab (KEYTRUDA) is Merck’s anti-PD-1 therapy. Dr. Patel has declared multiple relationships with industry as noted in the abstract; several co-authors have also made disclosures. Dr. Olszanski has reported participating in advisory boards for BMS, Merck, and InstilBio and running trials for them.

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

PARIS – “It’s not just what you give, it’s when you give it,” said the investigator reporting “that the same treatment for resectable melanoma given in a different sequence can generate lower rates of melanoma recurrence.”

Sapna Patel, MD, associate professor of melanoma medical oncology at The University of Texas MD Anderson Cancer Center, Houston, reported the results from the SWOG S1801 trial, which showed that patients with high-risk melanoma who received pembrolizumab both before and after surgery had significantly longer event-free survival than patients who received pembrolizumab after surgery only.

At a median follow-up of almost 15 months, there was a 42% lower rate of recurrence or death.

“Compared to the same treatment given entirely in the adjuvant setting, neoadjuvant pembrolizumab followed by adjuvant pembrolizumab improves event-free survival in resectable melanoma,” Dr. Patel commented.

She suggested that the explanation for the findings was that “inhibiting the PD-1/PD-L1 immune checkpoints before surgery gives an antitumor response at local and distant sites, and this occurs before resection of the tumor bed. This approach tends to leave behind a larger number of anti-tumor T cells ... [and] these T cells can be activated and circulated systematically to recognize and attack micro-metastatic melanoma tumors.”

The findings were presented during a presidential symposium at the European Society for Medical Oncology (ESMO) Congress 2022, Paris.

“This trial provides us with more evidence of when one strategy may be preferred over the other,” commented Maya Dimitrova, MD, medical oncologist at NYU Langone Perlmutter Cancer Center. She was not involved with the trial.

“Neoadjuvant immunotherapy has elicited impressive complete pathologic responses, which thus far have proven to be associated with a durable response. Neoadjuvant therapy may help identify patients who will respond well to checkpoint inhibitors and allow for de-escalation of therapy,” she told this news organization when approached for comment.

“As with all neoadjuvant therapy, we don’t want the treatment to compromise the outcomes of surgery when the intent is curative, and we once again have evidence that this is not the case when it comes to immune therapy,” she said. However, she added that “we will need further survival data to really change the standard of practice in high-risk melanoma and demonstrate whether there is a superior sequence of therapy and surgery.”

 

Details of the new results

The S1801 clinical trial enrolled 345 participants with stage IIIB through stage IV melanoma considered resectable. The cohort was randomized to receive either upfront surgery followed by 18 doses of pembrolizumab 200 mg every 3 weeks for a total of 18 doses or neoadjuvant therapy with pembrolizumab 200 mg (3 doses) followed by 15 doses of adjuvant pembrolizumab.

The primary endpoint was event-free survival (EFS), defined as the time from randomization to the occurrence of one of the following: disease progression or toxicity that resulted in not receiving surgery, failure to begin adjuvant therapy within 84 days of surgery, melanoma recurrence after surgery, or death from any cause.

At a median follow-up of 14.7 months, EFS was significantly higher for patients in the neoadjuvant group, compared with those receiving adjuvant therapy only (HR, 0.58; one-sided log-rank P = .004). A total of 36 participants died in the neoadjuvant and adjuvant groups (14 and 22 patients, extrapolating to a hazard ratio of 0.63; one-sided P = .091).

“With a limited number of events, overall survival is not statistically different at this time,” Dr. Patel said. “Landmark 2-year survival was 72% in the neoadjuvant arm and 49% in the adjuvant arm.”

The authors note that the benefit of neoadjuvant therapy remained consistent across a range of factors, including patient age, sex, performance status, stage of disease, ulceration, and BRAF status. The same proportion of patients in both groups received adjuvant pembrolizumab following surgery.

Rates of adverse events were similar in both groups, and neoadjuvant pembrolizumab did not result in an increase in adverse events related to surgery. In the neoadjuvant group, 28 patients (21%) with submitted pathology reports were noted to have had a complete pathologic response (0% viable tumor) on local review.
 

Questions remain

Invited discussant James Larkin, PhD, FRCP, FMedSci, a clinical researcher at The Royal Marsden Hospital, London, noted that the study had “striking results” and was a landmark trial with a simple but powerful design.

However, he pointed to some questions which need to be addressed in the future. “One important question is what is the optimal duration of neoadjuvant treatment, and can we individualize it?”

Another question is just how much postoperative treatment is really needed and whether pathology help determine that. “Can surgery be safely avoided altogether?” he asked. “Another issue is the need for anti-CTL4 therapy – which patients might benefit from anti-CTL4, in addition to anti-PD-1?”

“And by extension, this paradigm provides a great platform for testing new agents, including combinations in cases where PD-1 is not sufficient to achieve a sufficient response,” said Dr. Larkin. “In the future, trials addressing these questions hand us a major opportunity to individualize and rationally de-escalate treatment.”

Also weighing in on the study, another expert pointed out that neoadjuvant therapy in this setting is already being considered as an option. “The use of immunotherapy before surgery has been reported in some trials such as the OPACIN-neo and PRADO trials,” said Anthony J. Olszanski, RPh, MD, Vice Chair of Research at the Fox Chase Cancer Center, Philadelphia. “Results have been quite exciting and have led the NCCN to list this as a potential option for some patients in the current melanoma guidelines.”

S1801 is funded by the NIH/NCI and in part by MSD through a Cooperative Research and Development Agreement with the NCI. Pembrolizumab (KEYTRUDA) is Merck’s anti-PD-1 therapy. Dr. Patel has declared multiple relationships with industry as noted in the abstract; several co-authors have also made disclosures. Dr. Olszanski has reported participating in advisory boards for BMS, Merck, and InstilBio and running trials for them.

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

PARIS – “It’s not just what you give, it’s when you give it,” said the investigator reporting “that the same treatment for resectable melanoma given in a different sequence can generate lower rates of melanoma recurrence.”

Sapna Patel, MD, associate professor of melanoma medical oncology at The University of Texas MD Anderson Cancer Center, Houston, reported the results from the SWOG S1801 trial, which showed that patients with high-risk melanoma who received pembrolizumab both before and after surgery had significantly longer event-free survival than patients who received pembrolizumab after surgery only.

At a median follow-up of almost 15 months, there was a 42% lower rate of recurrence or death.

“Compared to the same treatment given entirely in the adjuvant setting, neoadjuvant pembrolizumab followed by adjuvant pembrolizumab improves event-free survival in resectable melanoma,” Dr. Patel commented.

She suggested that the explanation for the findings was that “inhibiting the PD-1/PD-L1 immune checkpoints before surgery gives an antitumor response at local and distant sites, and this occurs before resection of the tumor bed. This approach tends to leave behind a larger number of anti-tumor T cells ... [and] these T cells can be activated and circulated systematically to recognize and attack micro-metastatic melanoma tumors.”

The findings were presented during a presidential symposium at the European Society for Medical Oncology (ESMO) Congress 2022, Paris.

“This trial provides us with more evidence of when one strategy may be preferred over the other,” commented Maya Dimitrova, MD, medical oncologist at NYU Langone Perlmutter Cancer Center. She was not involved with the trial.

“Neoadjuvant immunotherapy has elicited impressive complete pathologic responses, which thus far have proven to be associated with a durable response. Neoadjuvant therapy may help identify patients who will respond well to checkpoint inhibitors and allow for de-escalation of therapy,” she told this news organization when approached for comment.

“As with all neoadjuvant therapy, we don’t want the treatment to compromise the outcomes of surgery when the intent is curative, and we once again have evidence that this is not the case when it comes to immune therapy,” she said. However, she added that “we will need further survival data to really change the standard of practice in high-risk melanoma and demonstrate whether there is a superior sequence of therapy and surgery.”

 

Details of the new results

The S1801 clinical trial enrolled 345 participants with stage IIIB through stage IV melanoma considered resectable. The cohort was randomized to receive either upfront surgery followed by 18 doses of pembrolizumab 200 mg every 3 weeks for a total of 18 doses or neoadjuvant therapy with pembrolizumab 200 mg (3 doses) followed by 15 doses of adjuvant pembrolizumab.

The primary endpoint was event-free survival (EFS), defined as the time from randomization to the occurrence of one of the following: disease progression or toxicity that resulted in not receiving surgery, failure to begin adjuvant therapy within 84 days of surgery, melanoma recurrence after surgery, or death from any cause.

At a median follow-up of 14.7 months, EFS was significantly higher for patients in the neoadjuvant group, compared with those receiving adjuvant therapy only (HR, 0.58; one-sided log-rank P = .004). A total of 36 participants died in the neoadjuvant and adjuvant groups (14 and 22 patients, extrapolating to a hazard ratio of 0.63; one-sided P = .091).

“With a limited number of events, overall survival is not statistically different at this time,” Dr. Patel said. “Landmark 2-year survival was 72% in the neoadjuvant arm and 49% in the adjuvant arm.”

The authors note that the benefit of neoadjuvant therapy remained consistent across a range of factors, including patient age, sex, performance status, stage of disease, ulceration, and BRAF status. The same proportion of patients in both groups received adjuvant pembrolizumab following surgery.

Rates of adverse events were similar in both groups, and neoadjuvant pembrolizumab did not result in an increase in adverse events related to surgery. In the neoadjuvant group, 28 patients (21%) with submitted pathology reports were noted to have had a complete pathologic response (0% viable tumor) on local review.
 

Questions remain

Invited discussant James Larkin, PhD, FRCP, FMedSci, a clinical researcher at The Royal Marsden Hospital, London, noted that the study had “striking results” and was a landmark trial with a simple but powerful design.

However, he pointed to some questions which need to be addressed in the future. “One important question is what is the optimal duration of neoadjuvant treatment, and can we individualize it?”

Another question is just how much postoperative treatment is really needed and whether pathology help determine that. “Can surgery be safely avoided altogether?” he asked. “Another issue is the need for anti-CTL4 therapy – which patients might benefit from anti-CTL4, in addition to anti-PD-1?”

“And by extension, this paradigm provides a great platform for testing new agents, including combinations in cases where PD-1 is not sufficient to achieve a sufficient response,” said Dr. Larkin. “In the future, trials addressing these questions hand us a major opportunity to individualize and rationally de-escalate treatment.”

Also weighing in on the study, another expert pointed out that neoadjuvant therapy in this setting is already being considered as an option. “The use of immunotherapy before surgery has been reported in some trials such as the OPACIN-neo and PRADO trials,” said Anthony J. Olszanski, RPh, MD, Vice Chair of Research at the Fox Chase Cancer Center, Philadelphia. “Results have been quite exciting and have led the NCCN to list this as a potential option for some patients in the current melanoma guidelines.”

S1801 is funded by the NIH/NCI and in part by MSD through a Cooperative Research and Development Agreement with the NCI. Pembrolizumab (KEYTRUDA) is Merck’s anti-PD-1 therapy. Dr. Patel has declared multiple relationships with industry as noted in the abstract; several co-authors have also made disclosures. Dr. Olszanski has reported participating in advisory boards for BMS, Merck, and InstilBio and running trials for them.

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

The immune checkpoint inhibitor nivolumab (Opdivo) appears to prevent the transformation of oral proliferative leukoplakia (PL), a high-risk precancerous disease, into oral cancer, suggest the results from a phase 2 study.

“We think that immunotherapy as a preventative strategy, either as first-line or even secondary prevention, should be further explored,” said lead researcher Glenn J. Hanna, MD, director, Center for Salivary and Rare Head and Neck Cancers, Dana-Farber Cancer Institute, Boston.

The research was presented at the European Society for Medical Oncology Annual Congress in Paris.

Oral leukoplakia refers to a white plaque of “questionable cancer risk” that affects about  4% of the global population, Dr. Hanna explained. However, about 5% of leukoplakia cases develop into oral proliferative leukoplakia, an aggressive form of the disease characterized by multifocal lesions. It has a high risk of transformation to oral squamous cell carcinoma (OSCC), at approaching 10% per year, and the 5-year cancer-free survival rate is estimated to be 47%.

While there are no effective therapies to prevent progression to oral cancer, the condition does have a “rich immune microenvironment,” potentially making it amenable to programmed death (PD)-1 blockade, Dr. Hanna said.

His team conducted a single-arm, phase 2 trial involving 33 patients with proliferative leukoplakia with greater than or equal to 2 multifocal lesions, or contiguous lesions of greater than or equal to 3 cm, or a single lesion greater than or equal to 4 cm with any degree of epithelial dysplasia. The median age was 63.2 years, and 55% were women. Just over half (52%) were never smokers.

The main disease subsite was the oral tongue in 39% of participants, followed by the buccal gingiva in 30%, and 24% of patients had a prior diagnosis of OSCC.

Following a pretreatment biopsy at one to three sites, the patients received four doses of nivolumab every 28 days, followed by rebiopsy. At each visit, the patients had intraoral photographs taken of the lesions and measurements taken.

The median time from study registration to the first dose of nivolumab was 9 days. The majority (88%) of patients completed all four doses of nivolumab.

The median time from the first dose of nivolumab to the posttreatment biopsy was 115 days and ranged from 29 to 171 days.

The overall response rate, defined as a greater than or equal to 40% decrease in a composite score combining the size and degree of dysplasia between the pre- and posttreatment assessments, was observed in 36.4% of patients.

After a median follow-up of 14.7 months, the median cancer-free survival was not reached, with cancer events recorded in 21.2% of patients. The median time from the last dose of nivolumab to the first OSCC event was 3.7 months.

Cancer-free survival at 1 year was calculated to be 77.7%, which was unchanged at 2 years. At the final follow-up, all patients were still alive.

Additional analysis of the biopsies revealed that the lesions had programmed death ligand 1 (PD-L1) combined positive scores that ranged from 0 to 80, with 66.7% of patients having a score of greater than or equal to 1. A cutoff score of greater than or equal to 20 did not reveal any significant differences in cancer-free survival rates.

Turning to safety, Dr. Hanna said that nivolumab was associated with “acceptable toxicity” in this “non-cancer population,” with 21.2% of patients experiencing a grade 3-4 adverse event.

The most common adverse events of any grade were fatigue (55%), diarrhea (27%), elevated alanine transaminase levels (18%), elevated aspartate transaminase levels (18%), and other skin disorders (18%).

With a relatively low rate of adverse events and a “clinical benefit” in up to a third of patients, Dr. Hanna said that this was the “first study to our knowledge to demonstrate the potential efficacy of anti–PD-L1 blockade among patients with a high-risk oral precancerous disease.”

Discussing this study at the meeting, Amanda Psyrri, MD, PhD, professor of medical oncology, Attikon University Hospital, Athens, who was not involved in the research, said these data were “very interesting,” but she expressed some reservations over the way the study was conducted.

She said that the composite score to measure response rates was “defined arbitrarily,” its prognostic value “has not been demonstrated,” and also pointed out that mixed responses by lesions within the same patient led to changes in scores.

In addition, the time interval between the end of treatment and lesion rebiopsy was “highly variable,” and the follow-up period was short.

Consequently, Dr. Psyrri believes the importance of the findings is “unclear,” especially as several patients who responded to nivolumab went on to develop cancer anyway, a finding that needs further investigation.

The study was funded by Bristol Myers Squibb.

Dr. Hanna declared relationships with BMS, Bicara, Exicure, Gateway for Cancer Research, GSK, Kite, NantKwest, Regeneron, Sanofi Genzyme, Maverick, and Merck.

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

The immune checkpoint inhibitor nivolumab (Opdivo) appears to prevent the transformation of oral proliferative leukoplakia (PL), a high-risk precancerous disease, into oral cancer, suggest the results from a phase 2 study.

“We think that immunotherapy as a preventative strategy, either as first-line or even secondary prevention, should be further explored,” said lead researcher Glenn J. Hanna, MD, director, Center for Salivary and Rare Head and Neck Cancers, Dana-Farber Cancer Institute, Boston.

The research was presented at the European Society for Medical Oncology Annual Congress in Paris.

Oral leukoplakia refers to a white plaque of “questionable cancer risk” that affects about  4% of the global population, Dr. Hanna explained. However, about 5% of leukoplakia cases develop into oral proliferative leukoplakia, an aggressive form of the disease characterized by multifocal lesions. It has a high risk of transformation to oral squamous cell carcinoma (OSCC), at approaching 10% per year, and the 5-year cancer-free survival rate is estimated to be 47%.

While there are no effective therapies to prevent progression to oral cancer, the condition does have a “rich immune microenvironment,” potentially making it amenable to programmed death (PD)-1 blockade, Dr. Hanna said.

His team conducted a single-arm, phase 2 trial involving 33 patients with proliferative leukoplakia with greater than or equal to 2 multifocal lesions, or contiguous lesions of greater than or equal to 3 cm, or a single lesion greater than or equal to 4 cm with any degree of epithelial dysplasia. The median age was 63.2 years, and 55% were women. Just over half (52%) were never smokers.

The main disease subsite was the oral tongue in 39% of participants, followed by the buccal gingiva in 30%, and 24% of patients had a prior diagnosis of OSCC.

Following a pretreatment biopsy at one to three sites, the patients received four doses of nivolumab every 28 days, followed by rebiopsy. At each visit, the patients had intraoral photographs taken of the lesions and measurements taken.

The median time from study registration to the first dose of nivolumab was 9 days. The majority (88%) of patients completed all four doses of nivolumab.

The median time from the first dose of nivolumab to the posttreatment biopsy was 115 days and ranged from 29 to 171 days.

The overall response rate, defined as a greater than or equal to 40% decrease in a composite score combining the size and degree of dysplasia between the pre- and posttreatment assessments, was observed in 36.4% of patients.

After a median follow-up of 14.7 months, the median cancer-free survival was not reached, with cancer events recorded in 21.2% of patients. The median time from the last dose of nivolumab to the first OSCC event was 3.7 months.

Cancer-free survival at 1 year was calculated to be 77.7%, which was unchanged at 2 years. At the final follow-up, all patients were still alive.

Additional analysis of the biopsies revealed that the lesions had programmed death ligand 1 (PD-L1) combined positive scores that ranged from 0 to 80, with 66.7% of patients having a score of greater than or equal to 1. A cutoff score of greater than or equal to 20 did not reveal any significant differences in cancer-free survival rates.

Turning to safety, Dr. Hanna said that nivolumab was associated with “acceptable toxicity” in this “non-cancer population,” with 21.2% of patients experiencing a grade 3-4 adverse event.

The most common adverse events of any grade were fatigue (55%), diarrhea (27%), elevated alanine transaminase levels (18%), elevated aspartate transaminase levels (18%), and other skin disorders (18%).

With a relatively low rate of adverse events and a “clinical benefit” in up to a third of patients, Dr. Hanna said that this was the “first study to our knowledge to demonstrate the potential efficacy of anti–PD-L1 blockade among patients with a high-risk oral precancerous disease.”

Discussing this study at the meeting, Amanda Psyrri, MD, PhD, professor of medical oncology, Attikon University Hospital, Athens, who was not involved in the research, said these data were “very interesting,” but she expressed some reservations over the way the study was conducted.

She said that the composite score to measure response rates was “defined arbitrarily,” its prognostic value “has not been demonstrated,” and also pointed out that mixed responses by lesions within the same patient led to changes in scores.

In addition, the time interval between the end of treatment and lesion rebiopsy was “highly variable,” and the follow-up period was short.

Consequently, Dr. Psyrri believes the importance of the findings is “unclear,” especially as several patients who responded to nivolumab went on to develop cancer anyway, a finding that needs further investigation.

The study was funded by Bristol Myers Squibb.

Dr. Hanna declared relationships with BMS, Bicara, Exicure, Gateway for Cancer Research, GSK, Kite, NantKwest, Regeneron, Sanofi Genzyme, Maverick, and Merck.

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

The immune checkpoint inhibitor nivolumab (Opdivo) appears to prevent the transformation of oral proliferative leukoplakia (PL), a high-risk precancerous disease, into oral cancer, suggest the results from a phase 2 study.

“We think that immunotherapy as a preventative strategy, either as first-line or even secondary prevention, should be further explored,” said lead researcher Glenn J. Hanna, MD, director, Center for Salivary and Rare Head and Neck Cancers, Dana-Farber Cancer Institute, Boston.

The research was presented at the European Society for Medical Oncology Annual Congress in Paris.

Oral leukoplakia refers to a white plaque of “questionable cancer risk” that affects about  4% of the global population, Dr. Hanna explained. However, about 5% of leukoplakia cases develop into oral proliferative leukoplakia, an aggressive form of the disease characterized by multifocal lesions. It has a high risk of transformation to oral squamous cell carcinoma (OSCC), at approaching 10% per year, and the 5-year cancer-free survival rate is estimated to be 47%.

While there are no effective therapies to prevent progression to oral cancer, the condition does have a “rich immune microenvironment,” potentially making it amenable to programmed death (PD)-1 blockade, Dr. Hanna said.

His team conducted a single-arm, phase 2 trial involving 33 patients with proliferative leukoplakia with greater than or equal to 2 multifocal lesions, or contiguous lesions of greater than or equal to 3 cm, or a single lesion greater than or equal to 4 cm with any degree of epithelial dysplasia. The median age was 63.2 years, and 55% were women. Just over half (52%) were never smokers.

The main disease subsite was the oral tongue in 39% of participants, followed by the buccal gingiva in 30%, and 24% of patients had a prior diagnosis of OSCC.

Following a pretreatment biopsy at one to three sites, the patients received four doses of nivolumab every 28 days, followed by rebiopsy. At each visit, the patients had intraoral photographs taken of the lesions and measurements taken.

The median time from study registration to the first dose of nivolumab was 9 days. The majority (88%) of patients completed all four doses of nivolumab.

The median time from the first dose of nivolumab to the posttreatment biopsy was 115 days and ranged from 29 to 171 days.

The overall response rate, defined as a greater than or equal to 40% decrease in a composite score combining the size and degree of dysplasia between the pre- and posttreatment assessments, was observed in 36.4% of patients.

After a median follow-up of 14.7 months, the median cancer-free survival was not reached, with cancer events recorded in 21.2% of patients. The median time from the last dose of nivolumab to the first OSCC event was 3.7 months.

Cancer-free survival at 1 year was calculated to be 77.7%, which was unchanged at 2 years. At the final follow-up, all patients were still alive.

Additional analysis of the biopsies revealed that the lesions had programmed death ligand 1 (PD-L1) combined positive scores that ranged from 0 to 80, with 66.7% of patients having a score of greater than or equal to 1. A cutoff score of greater than or equal to 20 did not reveal any significant differences in cancer-free survival rates.

Turning to safety, Dr. Hanna said that nivolumab was associated with “acceptable toxicity” in this “non-cancer population,” with 21.2% of patients experiencing a grade 3-4 adverse event.

The most common adverse events of any grade were fatigue (55%), diarrhea (27%), elevated alanine transaminase levels (18%), elevated aspartate transaminase levels (18%), and other skin disorders (18%).

With a relatively low rate of adverse events and a “clinical benefit” in up to a third of patients, Dr. Hanna said that this was the “first study to our knowledge to demonstrate the potential efficacy of anti–PD-L1 blockade among patients with a high-risk oral precancerous disease.”

Discussing this study at the meeting, Amanda Psyrri, MD, PhD, professor of medical oncology, Attikon University Hospital, Athens, who was not involved in the research, said these data were “very interesting,” but she expressed some reservations over the way the study was conducted.

She said that the composite score to measure response rates was “defined arbitrarily,” its prognostic value “has not been demonstrated,” and also pointed out that mixed responses by lesions within the same patient led to changes in scores.

In addition, the time interval between the end of treatment and lesion rebiopsy was “highly variable,” and the follow-up period was short.

Consequently, Dr. Psyrri believes the importance of the findings is “unclear,” especially as several patients who responded to nivolumab went on to develop cancer anyway, a finding that needs further investigation.

The study was funded by Bristol Myers Squibb.

Dr. Hanna declared relationships with BMS, Bicara, Exicure, Gateway for Cancer Research, GSK, Kite, NantKwest, Regeneron, Sanofi Genzyme, Maverick, and Merck.

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