Conference Coverage

Hematology-oncology patients who receive treatment in the intensive care unit often develop delirium, and according to new findings, mechanical ventilation, high-dose corticosteroid use, and brain metastases were identified as independent risk factors.

Roughly half of all hematology-oncology patients who were admitted to the ICU experienced delirium, explained lead author Rachel Klosko, PharmD, PGY-2 cardiology pharmacy resident at the Ohio State University, Columbus.

“Delirium was associated with increased mortality, an increase in hospital length of stay, and increased length of stay in the ICU,” she said.

Dr. Klosko presented the study results at the at the Critical Care Congress sponsored by the Society of Critical Care Medicine (SCCM), which was held virtually this year.

Delirium is an acute and fluctuating disturbance of consciousness and cognition and fluctuates in severity. Critically ill patients are subject to numerous risk factors for delirium. “It can occur in independently of any known neurological disorder,” said Dr. Klosko, adding that its occurrence has been associated with poorer outcomes in ICU patients.

In this study, Dr. Klosko and colleagues sought to determine the incidence of delirium in cancer patients who were admitted to the ICU, as well as identify the associated risk factors and recognize potential consequences of the development of delirium in this patient population.

They conducted a single center, retrospective, cohort study that evaluated patients between the ages of 18 and 89 years who were admitted to the hematology-oncology medical or surgical ICU between July 1, 2018, and June 30, 2019.

The study’s primary endpoint was the incidence of delirium within 7 days of ICU admission, defined as two positive Confusion Assessment Method for the ICU (CAM-ICU) assessments within 24 hours. Patients identified with delirium were compared to those without it, for the evaluation of secondary endpoints that included hospital mortality and ICU and hospital length of stay. The researchers also sought to identify independent risk factors for delirium in this population.

A total of 244 patients were included in the final analysis. Of this group, 125 (51.2%) experienced delirium during their stay in the ICU, and 119 (48.8%) did not.

Mortality in the delirium group was significantly higher at 32.8% vs. 15.1% (P = .001). In addition, the delirium group was associated with significantly higher ICU length of stay (6 days vs. 3 days, P < .001) and hospital length of stay (21 days vs. 12 days, P < .001).

“When comparing the baseline characteristics between the two groups, the delirium group had a longer hospital length prior to ICU admission, a higher SOFA score, a higher rate of brain metastases, a higher rate of shock, and higher receipt of high-dose steroids, benzodiazepines, and immunotherapy,” said Dr. Klosko.

After multivariable regression, four variables were included in the final model. Among patients with delirium, the SOFA score increased by 25% (odds ratio[OR] 1.25, P < .001), while the odds of delirium were almost four times higher among those treated with high-dose corticosteroids (OR 3.79, P = .004). Delirium was also eight times higher (OR 8.48, P < .001) among those who received mechanical ventilation and five times higher in (OR 5.38, P = .015) in patients with brain metastases.

Dr. Klosko noted that the main limitations for this study were that it was a single center retrospective analysis, and that patients were reviewed within the first 7 days of ICU admission. “This potentially missed patients who developed delirium outside of this time frame,” she said. In addition, “too few patients received high-dose benzodiazepines,” and “none of the patients received continuous neuromuscular blockade.”

However, in “contrast to these limitations, this is the largest study to date that has analyzed delirium in this population,” Dr. Klosko said.

Commenting on the study, Brenda Pun, DNP, RN, director of data quality at the Vanderbilt Critical Illness, Brain Dysfunction, and Survivorship Center, Nashville, Tenn., pointed out that the goal of this study was to describe delirium in this specific population. “But I will take a step backward and say that they are just confirming that these patients look like other ICU patients in many regards,” she said.

She explained that the sicker patients are, the higher the rates of delirium. “We have implemented strategies to lower these rates, and they have improved,” Dr. Pun said. “Ten years ago, I would say that 80% of patients who were on a ventilator would have delirium but now the rates are around 50% and that’s what we are typically seeing now.”

Dr. Pun emphasized that this study shows that delirium is like the “canary in the coal mine” or a red flag. “It’s a sign that something is wrong and that we need to pay attention, because the patient’s outcome may be worse,” she said. “So this is saying that we need to see if there is something that can be changed or modified to decrease the incidence of delirium—these are important questions.”

There was no outside sponsor. The authors had no disclosures. Dr. Pun has no disclosures.

Hematology-oncology patients who receive treatment in the intensive care unit often develop delirium, and according to new findings, mechanical ventilation, high-dose corticosteroid use, and brain metastases were identified as independent risk factors.

Roughly half of all hematology-oncology patients who were admitted to the ICU experienced delirium, explained lead author Rachel Klosko, PharmD, PGY-2 cardiology pharmacy resident at the Ohio State University, Columbus.

“Delirium was associated with increased mortality, an increase in hospital length of stay, and increased length of stay in the ICU,” she said.

Dr. Klosko presented the study results at the at the Critical Care Congress sponsored by the Society of Critical Care Medicine (SCCM), which was held virtually this year.

Delirium is an acute and fluctuating disturbance of consciousness and cognition and fluctuates in severity. Critically ill patients are subject to numerous risk factors for delirium. “It can occur in independently of any known neurological disorder,” said Dr. Klosko, adding that its occurrence has been associated with poorer outcomes in ICU patients.

In this study, Dr. Klosko and colleagues sought to determine the incidence of delirium in cancer patients who were admitted to the ICU, as well as identify the associated risk factors and recognize potential consequences of the development of delirium in this patient population.

They conducted a single center, retrospective, cohort study that evaluated patients between the ages of 18 and 89 years who were admitted to the hematology-oncology medical or surgical ICU between July 1, 2018, and June 30, 2019.

The study’s primary endpoint was the incidence of delirium within 7 days of ICU admission, defined as two positive Confusion Assessment Method for the ICU (CAM-ICU) assessments within 24 hours. Patients identified with delirium were compared to those without it, for the evaluation of secondary endpoints that included hospital mortality and ICU and hospital length of stay. The researchers also sought to identify independent risk factors for delirium in this population.

A total of 244 patients were included in the final analysis. Of this group, 125 (51.2%) experienced delirium during their stay in the ICU, and 119 (48.8%) did not.

Mortality in the delirium group was significantly higher at 32.8% vs. 15.1% (P = .001). In addition, the delirium group was associated with significantly higher ICU length of stay (6 days vs. 3 days, P < .001) and hospital length of stay (21 days vs. 12 days, P < .001).

“When comparing the baseline characteristics between the two groups, the delirium group had a longer hospital length prior to ICU admission, a higher SOFA score, a higher rate of brain metastases, a higher rate of shock, and higher receipt of high-dose steroids, benzodiazepines, and immunotherapy,” said Dr. Klosko.

After multivariable regression, four variables were included in the final model. Among patients with delirium, the SOFA score increased by 25% (odds ratio[OR] 1.25, P < .001), while the odds of delirium were almost four times higher among those treated with high-dose corticosteroids (OR 3.79, P = .004). Delirium was also eight times higher (OR 8.48, P < .001) among those who received mechanical ventilation and five times higher in (OR 5.38, P = .015) in patients with brain metastases.

Dr. Klosko noted that the main limitations for this study were that it was a single center retrospective analysis, and that patients were reviewed within the first 7 days of ICU admission. “This potentially missed patients who developed delirium outside of this time frame,” she said. In addition, “too few patients received high-dose benzodiazepines,” and “none of the patients received continuous neuromuscular blockade.”

However, in “contrast to these limitations, this is the largest study to date that has analyzed delirium in this population,” Dr. Klosko said.

Commenting on the study, Brenda Pun, DNP, RN, director of data quality at the Vanderbilt Critical Illness, Brain Dysfunction, and Survivorship Center, Nashville, Tenn., pointed out that the goal of this study was to describe delirium in this specific population. “But I will take a step backward and say that they are just confirming that these patients look like other ICU patients in many regards,” she said.

She explained that the sicker patients are, the higher the rates of delirium. “We have implemented strategies to lower these rates, and they have improved,” Dr. Pun said. “Ten years ago, I would say that 80% of patients who were on a ventilator would have delirium but now the rates are around 50% and that’s what we are typically seeing now.”

Dr. Pun emphasized that this study shows that delirium is like the “canary in the coal mine” or a red flag. “It’s a sign that something is wrong and that we need to pay attention, because the patient’s outcome may be worse,” she said. “So this is saying that we need to see if there is something that can be changed or modified to decrease the incidence of delirium—these are important questions.”

There was no outside sponsor. The authors had no disclosures. Dr. Pun has no disclosures.

Hematology-oncology patients who receive treatment in the intensive care unit often develop delirium, and according to new findings, mechanical ventilation, high-dose corticosteroid use, and brain metastases were identified as independent risk factors.

Roughly half of all hematology-oncology patients who were admitted to the ICU experienced delirium, explained lead author Rachel Klosko, PharmD, PGY-2 cardiology pharmacy resident at the Ohio State University, Columbus.

“Delirium was associated with increased mortality, an increase in hospital length of stay, and increased length of stay in the ICU,” she said.

Dr. Klosko presented the study results at the at the Critical Care Congress sponsored by the Society of Critical Care Medicine (SCCM), which was held virtually this year.

Delirium is an acute and fluctuating disturbance of consciousness and cognition and fluctuates in severity. Critically ill patients are subject to numerous risk factors for delirium. “It can occur in independently of any known neurological disorder,” said Dr. Klosko, adding that its occurrence has been associated with poorer outcomes in ICU patients.

In this study, Dr. Klosko and colleagues sought to determine the incidence of delirium in cancer patients who were admitted to the ICU, as well as identify the associated risk factors and recognize potential consequences of the development of delirium in this patient population.

They conducted a single center, retrospective, cohort study that evaluated patients between the ages of 18 and 89 years who were admitted to the hematology-oncology medical or surgical ICU between July 1, 2018, and June 30, 2019.

The study’s primary endpoint was the incidence of delirium within 7 days of ICU admission, defined as two positive Confusion Assessment Method for the ICU (CAM-ICU) assessments within 24 hours. Patients identified with delirium were compared to those without it, for the evaluation of secondary endpoints that included hospital mortality and ICU and hospital length of stay. The researchers also sought to identify independent risk factors for delirium in this population.

A total of 244 patients were included in the final analysis. Of this group, 125 (51.2%) experienced delirium during their stay in the ICU, and 119 (48.8%) did not.

Mortality in the delirium group was significantly higher at 32.8% vs. 15.1% (P = .001). In addition, the delirium group was associated with significantly higher ICU length of stay (6 days vs. 3 days, P < .001) and hospital length of stay (21 days vs. 12 days, P < .001).

“When comparing the baseline characteristics between the two groups, the delirium group had a longer hospital length prior to ICU admission, a higher SOFA score, a higher rate of brain metastases, a higher rate of shock, and higher receipt of high-dose steroids, benzodiazepines, and immunotherapy,” said Dr. Klosko.

After multivariable regression, four variables were included in the final model. Among patients with delirium, the SOFA score increased by 25% (odds ratio[OR] 1.25, P < .001), while the odds of delirium were almost four times higher among those treated with high-dose corticosteroids (OR 3.79, P = .004). Delirium was also eight times higher (OR 8.48, P < .001) among those who received mechanical ventilation and five times higher in (OR 5.38, P = .015) in patients with brain metastases.

Dr. Klosko noted that the main limitations for this study were that it was a single center retrospective analysis, and that patients were reviewed within the first 7 days of ICU admission. “This potentially missed patients who developed delirium outside of this time frame,” she said. In addition, “too few patients received high-dose benzodiazepines,” and “none of the patients received continuous neuromuscular blockade.”

However, in “contrast to these limitations, this is the largest study to date that has analyzed delirium in this population,” Dr. Klosko said.

Commenting on the study, Brenda Pun, DNP, RN, director of data quality at the Vanderbilt Critical Illness, Brain Dysfunction, and Survivorship Center, Nashville, Tenn., pointed out that the goal of this study was to describe delirium in this specific population. “But I will take a step backward and say that they are just confirming that these patients look like other ICU patients in many regards,” she said.

She explained that the sicker patients are, the higher the rates of delirium. “We have implemented strategies to lower these rates, and they have improved,” Dr. Pun said. “Ten years ago, I would say that 80% of patients who were on a ventilator would have delirium but now the rates are around 50% and that’s what we are typically seeing now.”

Dr. Pun emphasized that this study shows that delirium is like the “canary in the coal mine” or a red flag. “It’s a sign that something is wrong and that we need to pay attention, because the patient’s outcome may be worse,” she said. “So this is saying that we need to see if there is something that can be changed or modified to decrease the incidence of delirium—these are important questions.”

There was no outside sponsor. The authors had no disclosures. Dr. Pun has no disclosures.

These days deciding when to stop targeted treatment for chronic hepatitis B is a bigger challenge than knowing when to start, Norah A. Terrault, MD, MPH, observed at the Gastroenterology Updates, IBD, Liver Disease Conference.

Tetra Images/Getty Images

That’s because the treatment paradigm is in flux. The strategy is shifting from achieving hepatitis B virus (HBV) DNA suppression through indefinite use of nucleoside analogues to striving for functional cure, which means eliminating hepatitis B surface antigen (HBsAg) and sustained inactive chronic hepatitis B off therapy. It’s a goal that recognizes that, while suppression is worthwhile because it reduces a patient’s risk of hepatocellular carcinoma, HBsAg clearance is better because it’s associated with an even lower risk of the malignancy, explained Dr. Terrault, professor of medicine and chief of gastroenterology and liver diseases at the University of Southern California, Los Angeles.

The current strategy in patients who are hepatitis B e antigen (HBeAg) positive at the outset is to treat with a nucleoside analogue until seroconversion, followed by a further year or more of consolidation therapy then treatment withdrawal. It’s a rational approach whose primary benefit is it allows identification of the roughly 50% of patients who can remain off treatment with inactive chronic hepatitis B. The other 50% – those who experience clinical relapse – will need retreatment.

Factors predictive of increased likelihood of a sustained off-treatment response include age younger than 40 years at the time of seroconversion, more than 1 year of consolidation therapy, and undetectable HBV DNA at cessation of treatment.

“In my own practice now, I actually extend the consolidation period for 2 years before I consider stopping, and I really favor doing a trial of stopping treatment in those who are younger,” Dr. Terrault said.

The biggest change in thinking involves the duration of therapy in patients who are HBeAg negative. The strategy has been to treat indefinitely unless there is a compelling reason to stop, such as toxicity, cost, or patient preference. However, it has now been demonstrated in at least nine published studies that withdrawal of therapy has a favorable immunologic effect in noncirrhotic patients with HBeAg-negative chronic hepatitis B who have been HBV DNA negative on nucleoside analogues for at least 3 years. This trial off therapy can bring major benefits because roughly 50% of patients will have sustained inactive chronic hepatitis B off-treatment and 20% of patients will become HbsAg negative with functional cure at 3-5 years of follow-up.

“This is what’s impressive: that 20% of patients have lost surface antigen, because if you continue HbeAg-negative patients on nucleoside analogue therapy, essentially none of them lose surface antigen. This is an impressive number, and you’re also able to identify about 50% of patients who didn’t need to be on treatment because they now have immune control and can remain inactive carriers off treatment,” the gastroenterologist commented.

Treatment withdrawal in HBeAg-negative patients usually is followed by disease flares 8-12 weeks later because of host immune clearance, and therein lies a problem.

“The challenge with the withdrawal strategy is these flares that appear to be necessary and important, can be good or bad, and we’re really not very good at predicting what the flare is going to look like and how severe it’s going to be,” according to Dr. Terrault, first author of the current American Association for the Study of Liver Diseases guidance on prevention, diagnosis, and treatment of chronic hepatitis B.

The good flares are accompanied by a reductions in HBV DNA and viral proteins, loss of HbsAg, and preserved liver function. The bad flares entail excessive host immune clearance leading to liver dysfunction or failure, with no reduction in viral proteins. The search is on for predictors of response to treatment withdrawal in HbeAg-negative patients. Potential differences in outcomes with the three available nucleoside analogues are being looked at, as are duration of viral suppression on treatment and differences in patient characteristics. A low quantitative HbsAg level at the time of drug withdrawal may also be important as a predictor of a higher likelihood of HBsAg loss over time off treatment.

“The studies that have been done are basically withdrawing everyone and then seeing what happens. I think we want to have a more refined approach,” she said.

This is an unfolding story. The encouraging news is that the drug development pipeline is rich with agents with a variety of mechanisms aimed at achieving HbsAg loss with finite therapy. Some of the studies are now in phase 2 and 3.

“We should be extremely excited,” Dr. Terrault said. “I think in the future we’re very likely to have curative therapies in a much greater proportion of our patients.”
 

When to start nucleoside analogues

Three antiviral oral nucleoside analogues are available as preferred therapies for chronic HBV: entecavir (Baraclude), tenofovir alafenamide (Vemlidy), and tenofovir disoproxil (Viread). All three provide high antiviral efficacy and low risk for resistance. The treatment goal is to prevent disease progression and HBV complications, including hepatocellular carcinoma, in individuals with active chronic hepatitis B.

The major liver disease medical societies differ only slightly on the criteria for starting treatment. Broadly, they recommend starting therapy in all patients with cirrhosis, as well as in patients without cirrhosis who have both a serum ALT level more than twice the upper limit of normal and elevated HBV DNA levels. The treatment threshold for HBV DNA levels is higher in patients who are HBeAg positive than it is for patients who are HBeAg negative; for example, the American Association for the Study of Liver Diseases recommends that an HbeAg-positive patient should have a HBV DNA titer greater than 20,000 IU/mL, which is a level 10 times higher than the group’s treatment threshold in HBeAg-negative patients. However, these thresholds are intended as guidance, not absolute rules, Dr. Terrault emphasized. Nearly 40% of patients don’t meet the dual ALT and HBV DNA thresholds, and serial monitoring of such patients for 6-12 months is recommended because they may be in transition.

The choice of nucleoside analogue is largely based on comorbidities. Any of the three preferred antivirals can be used when there are none. Tenofovir disoproxil is preferred in pregnancy because of its safety profile in that setting. In patients who are aged over 60 years or have bone disease or renal impairment, tenofovir alafenamide and entecavir are preferred. Entecavir should be avoided in favor of either form of tenofovir in patients who are HIV positive or have prior exposure to lamivudine.

Regarding treatment with these drugs, the recommendations target those whose liver disease is being driven by active HBV rather than fatty liver disease or some other cause. That’s the reason for the reserving treatment for patients with both high HBV DNA and high serum ALT.

“There’s definitely a camp that feels these are safe drugs, easy to use, and we should treat more people. I have to say I’m not hanging out in that camp. I still feel we should do targeted treatment, especially since there are many new drugs coming where we’re going to be able to offer cure to more people. So I feel like putting everybody on suppressive therapy isn’t the answer,” she said.

Dr. Terrault receives research grants from and/or serves as a consultant to numerous pharmaceutical companies.

bjancin@mdedge.com

These days deciding when to stop targeted treatment for chronic hepatitis B is a bigger challenge than knowing when to start, Norah A. Terrault, MD, MPH, observed at the Gastroenterology Updates, IBD, Liver Disease Conference.

Tetra Images/Getty Images

That’s because the treatment paradigm is in flux. The strategy is shifting from achieving hepatitis B virus (HBV) DNA suppression through indefinite use of nucleoside analogues to striving for functional cure, which means eliminating hepatitis B surface antigen (HBsAg) and sustained inactive chronic hepatitis B off therapy. It’s a goal that recognizes that, while suppression is worthwhile because it reduces a patient’s risk of hepatocellular carcinoma, HBsAg clearance is better because it’s associated with an even lower risk of the malignancy, explained Dr. Terrault, professor of medicine and chief of gastroenterology and liver diseases at the University of Southern California, Los Angeles.

The current strategy in patients who are hepatitis B e antigen (HBeAg) positive at the outset is to treat with a nucleoside analogue until seroconversion, followed by a further year or more of consolidation therapy then treatment withdrawal. It’s a rational approach whose primary benefit is it allows identification of the roughly 50% of patients who can remain off treatment with inactive chronic hepatitis B. The other 50% – those who experience clinical relapse – will need retreatment.

Factors predictive of increased likelihood of a sustained off-treatment response include age younger than 40 years at the time of seroconversion, more than 1 year of consolidation therapy, and undetectable HBV DNA at cessation of treatment.

“In my own practice now, I actually extend the consolidation period for 2 years before I consider stopping, and I really favor doing a trial of stopping treatment in those who are younger,” Dr. Terrault said.

The biggest change in thinking involves the duration of therapy in patients who are HBeAg negative. The strategy has been to treat indefinitely unless there is a compelling reason to stop, such as toxicity, cost, or patient preference. However, it has now been demonstrated in at least nine published studies that withdrawal of therapy has a favorable immunologic effect in noncirrhotic patients with HBeAg-negative chronic hepatitis B who have been HBV DNA negative on nucleoside analogues for at least 3 years. This trial off therapy can bring major benefits because roughly 50% of patients will have sustained inactive chronic hepatitis B off-treatment and 20% of patients will become HbsAg negative with functional cure at 3-5 years of follow-up.

“This is what’s impressive: that 20% of patients have lost surface antigen, because if you continue HbeAg-negative patients on nucleoside analogue therapy, essentially none of them lose surface antigen. This is an impressive number, and you’re also able to identify about 50% of patients who didn’t need to be on treatment because they now have immune control and can remain inactive carriers off treatment,” the gastroenterologist commented.

Treatment withdrawal in HBeAg-negative patients usually is followed by disease flares 8-12 weeks later because of host immune clearance, and therein lies a problem.

“The challenge with the withdrawal strategy is these flares that appear to be necessary and important, can be good or bad, and we’re really not very good at predicting what the flare is going to look like and how severe it’s going to be,” according to Dr. Terrault, first author of the current American Association for the Study of Liver Diseases guidance on prevention, diagnosis, and treatment of chronic hepatitis B.

The good flares are accompanied by a reductions in HBV DNA and viral proteins, loss of HbsAg, and preserved liver function. The bad flares entail excessive host immune clearance leading to liver dysfunction or failure, with no reduction in viral proteins. The search is on for predictors of response to treatment withdrawal in HbeAg-negative patients. Potential differences in outcomes with the three available nucleoside analogues are being looked at, as are duration of viral suppression on treatment and differences in patient characteristics. A low quantitative HbsAg level at the time of drug withdrawal may also be important as a predictor of a higher likelihood of HBsAg loss over time off treatment.

“The studies that have been done are basically withdrawing everyone and then seeing what happens. I think we want to have a more refined approach,” she said.

This is an unfolding story. The encouraging news is that the drug development pipeline is rich with agents with a variety of mechanisms aimed at achieving HbsAg loss with finite therapy. Some of the studies are now in phase 2 and 3.

“We should be extremely excited,” Dr. Terrault said. “I think in the future we’re very likely to have curative therapies in a much greater proportion of our patients.”
 

When to start nucleoside analogues

Three antiviral oral nucleoside analogues are available as preferred therapies for chronic HBV: entecavir (Baraclude), tenofovir alafenamide (Vemlidy), and tenofovir disoproxil (Viread). All three provide high antiviral efficacy and low risk for resistance. The treatment goal is to prevent disease progression and HBV complications, including hepatocellular carcinoma, in individuals with active chronic hepatitis B.

The major liver disease medical societies differ only slightly on the criteria for starting treatment. Broadly, they recommend starting therapy in all patients with cirrhosis, as well as in patients without cirrhosis who have both a serum ALT level more than twice the upper limit of normal and elevated HBV DNA levels. The treatment threshold for HBV DNA levels is higher in patients who are HBeAg positive than it is for patients who are HBeAg negative; for example, the American Association for the Study of Liver Diseases recommends that an HbeAg-positive patient should have a HBV DNA titer greater than 20,000 IU/mL, which is a level 10 times higher than the group’s treatment threshold in HBeAg-negative patients. However, these thresholds are intended as guidance, not absolute rules, Dr. Terrault emphasized. Nearly 40% of patients don’t meet the dual ALT and HBV DNA thresholds, and serial monitoring of such patients for 6-12 months is recommended because they may be in transition.

The choice of nucleoside analogue is largely based on comorbidities. Any of the three preferred antivirals can be used when there are none. Tenofovir disoproxil is preferred in pregnancy because of its safety profile in that setting. In patients who are aged over 60 years or have bone disease or renal impairment, tenofovir alafenamide and entecavir are preferred. Entecavir should be avoided in favor of either form of tenofovir in patients who are HIV positive or have prior exposure to lamivudine.

Regarding treatment with these drugs, the recommendations target those whose liver disease is being driven by active HBV rather than fatty liver disease or some other cause. That’s the reason for the reserving treatment for patients with both high HBV DNA and high serum ALT.

“There’s definitely a camp that feels these are safe drugs, easy to use, and we should treat more people. I have to say I’m not hanging out in that camp. I still feel we should do targeted treatment, especially since there are many new drugs coming where we’re going to be able to offer cure to more people. So I feel like putting everybody on suppressive therapy isn’t the answer,” she said.

Dr. Terrault receives research grants from and/or serves as a consultant to numerous pharmaceutical companies.

bjancin@mdedge.com

These days deciding when to stop targeted treatment for chronic hepatitis B is a bigger challenge than knowing when to start, Norah A. Terrault, MD, MPH, observed at the Gastroenterology Updates, IBD, Liver Disease Conference.

Tetra Images/Getty Images

That’s because the treatment paradigm is in flux. The strategy is shifting from achieving hepatitis B virus (HBV) DNA suppression through indefinite use of nucleoside analogues to striving for functional cure, which means eliminating hepatitis B surface antigen (HBsAg) and sustained inactive chronic hepatitis B off therapy. It’s a goal that recognizes that, while suppression is worthwhile because it reduces a patient’s risk of hepatocellular carcinoma, HBsAg clearance is better because it’s associated with an even lower risk of the malignancy, explained Dr. Terrault, professor of medicine and chief of gastroenterology and liver diseases at the University of Southern California, Los Angeles.

The current strategy in patients who are hepatitis B e antigen (HBeAg) positive at the outset is to treat with a nucleoside analogue until seroconversion, followed by a further year or more of consolidation therapy then treatment withdrawal. It’s a rational approach whose primary benefit is it allows identification of the roughly 50% of patients who can remain off treatment with inactive chronic hepatitis B. The other 50% – those who experience clinical relapse – will need retreatment.

Factors predictive of increased likelihood of a sustained off-treatment response include age younger than 40 years at the time of seroconversion, more than 1 year of consolidation therapy, and undetectable HBV DNA at cessation of treatment.

“In my own practice now, I actually extend the consolidation period for 2 years before I consider stopping, and I really favor doing a trial of stopping treatment in those who are younger,” Dr. Terrault said.

The biggest change in thinking involves the duration of therapy in patients who are HBeAg negative. The strategy has been to treat indefinitely unless there is a compelling reason to stop, such as toxicity, cost, or patient preference. However, it has now been demonstrated in at least nine published studies that withdrawal of therapy has a favorable immunologic effect in noncirrhotic patients with HBeAg-negative chronic hepatitis B who have been HBV DNA negative on nucleoside analogues for at least 3 years. This trial off therapy can bring major benefits because roughly 50% of patients will have sustained inactive chronic hepatitis B off-treatment and 20% of patients will become HbsAg negative with functional cure at 3-5 years of follow-up.

“This is what’s impressive: that 20% of patients have lost surface antigen, because if you continue HbeAg-negative patients on nucleoside analogue therapy, essentially none of them lose surface antigen. This is an impressive number, and you’re also able to identify about 50% of patients who didn’t need to be on treatment because they now have immune control and can remain inactive carriers off treatment,” the gastroenterologist commented.

Treatment withdrawal in HBeAg-negative patients usually is followed by disease flares 8-12 weeks later because of host immune clearance, and therein lies a problem.

“The challenge with the withdrawal strategy is these flares that appear to be necessary and important, can be good or bad, and we’re really not very good at predicting what the flare is going to look like and how severe it’s going to be,” according to Dr. Terrault, first author of the current American Association for the Study of Liver Diseases guidance on prevention, diagnosis, and treatment of chronic hepatitis B.

The good flares are accompanied by a reductions in HBV DNA and viral proteins, loss of HbsAg, and preserved liver function. The bad flares entail excessive host immune clearance leading to liver dysfunction or failure, with no reduction in viral proteins. The search is on for predictors of response to treatment withdrawal in HbeAg-negative patients. Potential differences in outcomes with the three available nucleoside analogues are being looked at, as are duration of viral suppression on treatment and differences in patient characteristics. A low quantitative HbsAg level at the time of drug withdrawal may also be important as a predictor of a higher likelihood of HBsAg loss over time off treatment.

“The studies that have been done are basically withdrawing everyone and then seeing what happens. I think we want to have a more refined approach,” she said.

This is an unfolding story. The encouraging news is that the drug development pipeline is rich with agents with a variety of mechanisms aimed at achieving HbsAg loss with finite therapy. Some of the studies are now in phase 2 and 3.

“We should be extremely excited,” Dr. Terrault said. “I think in the future we’re very likely to have curative therapies in a much greater proportion of our patients.”
 

When to start nucleoside analogues

Three antiviral oral nucleoside analogues are available as preferred therapies for chronic HBV: entecavir (Baraclude), tenofovir alafenamide (Vemlidy), and tenofovir disoproxil (Viread). All three provide high antiviral efficacy and low risk for resistance. The treatment goal is to prevent disease progression and HBV complications, including hepatocellular carcinoma, in individuals with active chronic hepatitis B.

The major liver disease medical societies differ only slightly on the criteria for starting treatment. Broadly, they recommend starting therapy in all patients with cirrhosis, as well as in patients without cirrhosis who have both a serum ALT level more than twice the upper limit of normal and elevated HBV DNA levels. The treatment threshold for HBV DNA levels is higher in patients who are HBeAg positive than it is for patients who are HBeAg negative; for example, the American Association for the Study of Liver Diseases recommends that an HbeAg-positive patient should have a HBV DNA titer greater than 20,000 IU/mL, which is a level 10 times higher than the group’s treatment threshold in HBeAg-negative patients. However, these thresholds are intended as guidance, not absolute rules, Dr. Terrault emphasized. Nearly 40% of patients don’t meet the dual ALT and HBV DNA thresholds, and serial monitoring of such patients for 6-12 months is recommended because they may be in transition.

The choice of nucleoside analogue is largely based on comorbidities. Any of the three preferred antivirals can be used when there are none. Tenofovir disoproxil is preferred in pregnancy because of its safety profile in that setting. In patients who are aged over 60 years or have bone disease or renal impairment, tenofovir alafenamide and entecavir are preferred. Entecavir should be avoided in favor of either form of tenofovir in patients who are HIV positive or have prior exposure to lamivudine.

Regarding treatment with these drugs, the recommendations target those whose liver disease is being driven by active HBV rather than fatty liver disease or some other cause. That’s the reason for the reserving treatment for patients with both high HBV DNA and high serum ALT.

“There’s definitely a camp that feels these are safe drugs, easy to use, and we should treat more people. I have to say I’m not hanging out in that camp. I still feel we should do targeted treatment, especially since there are many new drugs coming where we’re going to be able to offer cure to more people. So I feel like putting everybody on suppressive therapy isn’t the answer,” she said.

Dr. Terrault receives research grants from and/or serves as a consultant to numerous pharmaceutical companies.

bjancin@mdedge.com

Lowering the starting dose of lenvatinib for recurrent, advanced endometrial cancer reduces adverse events without compromising efficacy, according to a retrospective study.

The study included 70 patients who received lenvatinib in combination with pembrolizumab. Patients who were started on 14 mg of lenvatinib per day had fewer dose reductions and a longer time to the first dose reduction, compared with patients who were started on the recommended 20-mg dose. There were no significant differences in response, progression-free survival, or overall survival between the two dose groups.

“Published studies and these results may support using lenvatinib at a starting dose of 14 mg daily in clinical practice,” said Jeffrey How, MD, a gynecologic oncology fellow at MD Anderson Cancer Center in Houston.

Dr. How presented the results at the Society of Gynecologic Oncology’s Virtual Annual Meeting on Women’s Cancer (Abstract 10775).

This is not the first time a recommended starting dose has been deemed too high to use in practice, according to Carol Aghajanian, MD, chief of gynecologic medical oncology at Memorial Sloan Kettering Cancer Center in New York and a panelist for the session where Dr. How presented his research.

Dr. Aghajanian noted that pegylated liposomal doxorubicin and topotecan are “rarely, if ever” started at the labeling doses for recurrent ovarian cancer. Those doses proved to be too high for general practice and “not tolerable with multicycle treatment,” she said.

“We may again be experiencing the effect of single-cycle, dose-limiting toxicity information not guiding us well in how to treat patients over time,” she added.
 

Study rationale

Based on a 38% overall response rate in the phase 2 KEYNOTE-146 trial, lenvatinib plus pembrolizumab was approved in September 2019 to treat patients with advanced endometrial carcinoma that is not microsatellite instability–high or mismatch repair deficient who have progressed on systemic therapy and are not candidates for curative surgery or radiation.

However, the rate of grade 3/4 adverse events with the combination was 66.9% in the trial, leading to dose interruptions or reductions and a discontinuation rate of 17.7%.

MD Anderson oncologists noticed similar toxicity rates at the approved lenvatinib dose of 20 mg per day when they started using the combination in October 2019. It raised a question about the feasibility of implementing the regimen in general practice as well as concerns about compliance, Dr. How said.

“As a consequence, our team started patients on a reduced dose of lenvatinib to improve safety and tolerability,” he added.

The mean dose intensity in the phase 2 trial was 14.4 mg/day, so the team began to start patients on 14 mg daily.
 

Results and implications

Of the 70 patients studied, 16 were started at 20 mg, and 54 were started at 14 mg. There were no significant differences between the two groups at baseline.

In the entire cohort, the median age was 65.5 years, and patients had received a median of two prior lines of therapy (range, one to nine). Most patients (90%) had a performance status of 0 or 1, 92.9% had microsatellite stable tumors, and 27.1% each had endometrioid or serous histology.

There was no significant difference between the dose groups with regard to any hospitalization (P = .46), hospitalization due to treatment-related adverse events (P = .55), dose interruption (P = .18), or treatment discontinuation due to treatment-related adverse events (P = .54).

However, the average number of dose reductions per patient was higher in the 20-mg group than in the 14-mg group – 1.1 and 0.4, respectively (P = .003).

The increased dose reductions with the higher starting dose were due mostly to gastrointestinal and hematologic adverse events as well as fatigue and anorexia, all of which were far more common in patients started at 20 mg.

Patients in the 14-mg group had a longer time to the first dose reduction or discontinuation due to toxicity – 107 days vs. 42 days in the 20-mg group (P = .001).

There was no significant difference in response rates between the 14-mg and 20-mg groups – 38.2% and 28.6%, respectively (P = .51) – and no significant difference in clinical benefit rates – 72.3% and 57.1%, respectively.

The median progression-free survival was 3.2 months in the 20-mg group and 5.5 months in the 14-mg group (P = .25). The median overall survival was 8.6 months and 10.3 months, respectively (P = .95).

Dr. How noted that this study was limited by its retrospective nature, and the small number of women started at 20 mg may have limited the ability to detect differences with a lower starting dose. Still, these results seem to support a starting dose of 14 mg, he concluded.

In a discussion after Dr. How’s presentation, panelist Judith Smith, PharmD, of UT Health in Houston, noted that her practice is starting women on lenvatinib at 12 mg per day.

“You can use the 14-mg convenience pack, but, from a cost perspective ... we have to be cognizant of the financial toxicity,” she said. “[Combining the] 10-mg and 4-mg tablets is going to be more expensive, so we’ve been using the 4-mg tablets [three per day] and starting at 12 mg.”

This study was funded by MD Anderson and the National Institutes of Health. Dr. How reported having no conflicts of interest. Dr. Aghajanian and Dr. Smith did not provide disclosures.

aotto@mdedge.com

Lowering the starting dose of lenvatinib for recurrent, advanced endometrial cancer reduces adverse events without compromising efficacy, according to a retrospective study.

The study included 70 patients who received lenvatinib in combination with pembrolizumab. Patients who were started on 14 mg of lenvatinib per day had fewer dose reductions and a longer time to the first dose reduction, compared with patients who were started on the recommended 20-mg dose. There were no significant differences in response, progression-free survival, or overall survival between the two dose groups.

“Published studies and these results may support using lenvatinib at a starting dose of 14 mg daily in clinical practice,” said Jeffrey How, MD, a gynecologic oncology fellow at MD Anderson Cancer Center in Houston.

Dr. How presented the results at the Society of Gynecologic Oncology’s Virtual Annual Meeting on Women’s Cancer (Abstract 10775).

This is not the first time a recommended starting dose has been deemed too high to use in practice, according to Carol Aghajanian, MD, chief of gynecologic medical oncology at Memorial Sloan Kettering Cancer Center in New York and a panelist for the session where Dr. How presented his research.

Dr. Aghajanian noted that pegylated liposomal doxorubicin and topotecan are “rarely, if ever” started at the labeling doses for recurrent ovarian cancer. Those doses proved to be too high for general practice and “not tolerable with multicycle treatment,” she said.

“We may again be experiencing the effect of single-cycle, dose-limiting toxicity information not guiding us well in how to treat patients over time,” she added.
 

Study rationale

Based on a 38% overall response rate in the phase 2 KEYNOTE-146 trial, lenvatinib plus pembrolizumab was approved in September 2019 to treat patients with advanced endometrial carcinoma that is not microsatellite instability–high or mismatch repair deficient who have progressed on systemic therapy and are not candidates for curative surgery or radiation.

However, the rate of grade 3/4 adverse events with the combination was 66.9% in the trial, leading to dose interruptions or reductions and a discontinuation rate of 17.7%.

MD Anderson oncologists noticed similar toxicity rates at the approved lenvatinib dose of 20 mg per day when they started using the combination in October 2019. It raised a question about the feasibility of implementing the regimen in general practice as well as concerns about compliance, Dr. How said.

“As a consequence, our team started patients on a reduced dose of lenvatinib to improve safety and tolerability,” he added.

The mean dose intensity in the phase 2 trial was 14.4 mg/day, so the team began to start patients on 14 mg daily.
 

Results and implications

Of the 70 patients studied, 16 were started at 20 mg, and 54 were started at 14 mg. There were no significant differences between the two groups at baseline.

In the entire cohort, the median age was 65.5 years, and patients had received a median of two prior lines of therapy (range, one to nine). Most patients (90%) had a performance status of 0 or 1, 92.9% had microsatellite stable tumors, and 27.1% each had endometrioid or serous histology.

There was no significant difference between the dose groups with regard to any hospitalization (P = .46), hospitalization due to treatment-related adverse events (P = .55), dose interruption (P = .18), or treatment discontinuation due to treatment-related adverse events (P = .54).

However, the average number of dose reductions per patient was higher in the 20-mg group than in the 14-mg group – 1.1 and 0.4, respectively (P = .003).

The increased dose reductions with the higher starting dose were due mostly to gastrointestinal and hematologic adverse events as well as fatigue and anorexia, all of which were far more common in patients started at 20 mg.

Patients in the 14-mg group had a longer time to the first dose reduction or discontinuation due to toxicity – 107 days vs. 42 days in the 20-mg group (P = .001).

There was no significant difference in response rates between the 14-mg and 20-mg groups – 38.2% and 28.6%, respectively (P = .51) – and no significant difference in clinical benefit rates – 72.3% and 57.1%, respectively.

The median progression-free survival was 3.2 months in the 20-mg group and 5.5 months in the 14-mg group (P = .25). The median overall survival was 8.6 months and 10.3 months, respectively (P = .95).

Dr. How noted that this study was limited by its retrospective nature, and the small number of women started at 20 mg may have limited the ability to detect differences with a lower starting dose. Still, these results seem to support a starting dose of 14 mg, he concluded.

In a discussion after Dr. How’s presentation, panelist Judith Smith, PharmD, of UT Health in Houston, noted that her practice is starting women on lenvatinib at 12 mg per day.

“You can use the 14-mg convenience pack, but, from a cost perspective ... we have to be cognizant of the financial toxicity,” she said. “[Combining the] 10-mg and 4-mg tablets is going to be more expensive, so we’ve been using the 4-mg tablets [three per day] and starting at 12 mg.”

This study was funded by MD Anderson and the National Institutes of Health. Dr. How reported having no conflicts of interest. Dr. Aghajanian and Dr. Smith did not provide disclosures.

aotto@mdedge.com

Lowering the starting dose of lenvatinib for recurrent, advanced endometrial cancer reduces adverse events without compromising efficacy, according to a retrospective study.

The study included 70 patients who received lenvatinib in combination with pembrolizumab. Patients who were started on 14 mg of lenvatinib per day had fewer dose reductions and a longer time to the first dose reduction, compared with patients who were started on the recommended 20-mg dose. There were no significant differences in response, progression-free survival, or overall survival between the two dose groups.

“Published studies and these results may support using lenvatinib at a starting dose of 14 mg daily in clinical practice,” said Jeffrey How, MD, a gynecologic oncology fellow at MD Anderson Cancer Center in Houston.

Dr. How presented the results at the Society of Gynecologic Oncology’s Virtual Annual Meeting on Women’s Cancer (Abstract 10775).

This is not the first time a recommended starting dose has been deemed too high to use in practice, according to Carol Aghajanian, MD, chief of gynecologic medical oncology at Memorial Sloan Kettering Cancer Center in New York and a panelist for the session where Dr. How presented his research.

Dr. Aghajanian noted that pegylated liposomal doxorubicin and topotecan are “rarely, if ever” started at the labeling doses for recurrent ovarian cancer. Those doses proved to be too high for general practice and “not tolerable with multicycle treatment,” she said.

“We may again be experiencing the effect of single-cycle, dose-limiting toxicity information not guiding us well in how to treat patients over time,” she added.
 

Study rationale

Based on a 38% overall response rate in the phase 2 KEYNOTE-146 trial, lenvatinib plus pembrolizumab was approved in September 2019 to treat patients with advanced endometrial carcinoma that is not microsatellite instability–high or mismatch repair deficient who have progressed on systemic therapy and are not candidates for curative surgery or radiation.

However, the rate of grade 3/4 adverse events with the combination was 66.9% in the trial, leading to dose interruptions or reductions and a discontinuation rate of 17.7%.

MD Anderson oncologists noticed similar toxicity rates at the approved lenvatinib dose of 20 mg per day when they started using the combination in October 2019. It raised a question about the feasibility of implementing the regimen in general practice as well as concerns about compliance, Dr. How said.

“As a consequence, our team started patients on a reduced dose of lenvatinib to improve safety and tolerability,” he added.

The mean dose intensity in the phase 2 trial was 14.4 mg/day, so the team began to start patients on 14 mg daily.
 

Results and implications

Of the 70 patients studied, 16 were started at 20 mg, and 54 were started at 14 mg. There were no significant differences between the two groups at baseline.

In the entire cohort, the median age was 65.5 years, and patients had received a median of two prior lines of therapy (range, one to nine). Most patients (90%) had a performance status of 0 or 1, 92.9% had microsatellite stable tumors, and 27.1% each had endometrioid or serous histology.

There was no significant difference between the dose groups with regard to any hospitalization (P = .46), hospitalization due to treatment-related adverse events (P = .55), dose interruption (P = .18), or treatment discontinuation due to treatment-related adverse events (P = .54).

However, the average number of dose reductions per patient was higher in the 20-mg group than in the 14-mg group – 1.1 and 0.4, respectively (P = .003).

The increased dose reductions with the higher starting dose were due mostly to gastrointestinal and hematologic adverse events as well as fatigue and anorexia, all of which were far more common in patients started at 20 mg.

Patients in the 14-mg group had a longer time to the first dose reduction or discontinuation due to toxicity – 107 days vs. 42 days in the 20-mg group (P = .001).

There was no significant difference in response rates between the 14-mg and 20-mg groups – 38.2% and 28.6%, respectively (P = .51) – and no significant difference in clinical benefit rates – 72.3% and 57.1%, respectively.

The median progression-free survival was 3.2 months in the 20-mg group and 5.5 months in the 14-mg group (P = .25). The median overall survival was 8.6 months and 10.3 months, respectively (P = .95).

Dr. How noted that this study was limited by its retrospective nature, and the small number of women started at 20 mg may have limited the ability to detect differences with a lower starting dose. Still, these results seem to support a starting dose of 14 mg, he concluded.

In a discussion after Dr. How’s presentation, panelist Judith Smith, PharmD, of UT Health in Houston, noted that her practice is starting women on lenvatinib at 12 mg per day.

“You can use the 14-mg convenience pack, but, from a cost perspective ... we have to be cognizant of the financial toxicity,” she said. “[Combining the] 10-mg and 4-mg tablets is going to be more expensive, so we’ve been using the 4-mg tablets [three per day] and starting at 12 mg.”

This study was funded by MD Anderson and the National Institutes of Health. Dr. How reported having no conflicts of interest. Dr. Aghajanian and Dr. Smith did not provide disclosures.

aotto@mdedge.com

Oral sarecycline proved rapidly effective for the treatment of moderate to severe papulopustular rosacea in a proof-of-concept pilot study, Linda Stein Gold, MD, said at Innovations in Dermatology: Virtual Spring Conference 2021.

Patrick McNamara Photography

The oral broad-spectrum second-generation tetracyclines doxycycline and minocycline have long been considered first-line therapy for papulopustular rosacea that isn’t cleared using topical agents. But the widespread use of these oral tetracyclines has encouraged the development of antimicrobial resistance. In contrast, sarecycline (Seysara) is a third-generation, narrow-spectrum tetracycline designed to minimize antibiotic resistance. The Food and Drug Administration approved the drug for treatment of moderate to severe acne vulgaris in 2018.

At the meeting, Dr. Stein Gold, director of dermatology clinical research at the Henry Ford Health System in Detroit, highlighted a recent pilot study of oral sarecycline for papulopustular rosacea carried out by James Q. Del Rosso, DO, of Las Vegas and coinvestigators. Although she wasn’t involved in the study, she is a veteran clinical trialist with vast experience leading studies of new therapies for rosacea, acne, and other major dermatologic disorders.

The 12-week, prospective, investigator-blinded study included 97 adults with moderate to severe papulopustular rosacea; 72 were randomized to weight-based dosing of once-daily sarecycline, while the 25 controls took a daily oral vitamin.

One coprimary endpoint was achievement of an Investigator Global Assessment score of 0 or 1, meaning clear or almost clear skin, at week 12. The rates were 75% in the sarecycline group and 16% in controls. The other coprimary endpoint was the percent reduction from baseline to week 12 in inflammatory lesion count. Here again, there was a statistically significant difference in favor of the third-generation tetracycline derivative, which achieved an 80% reduction, compared with 50% in the control group.

Of note, the difference was already significant at the first evaluation at week 4, with a 58% reduction in inflammatory lesions in the sarecycline group versus 31% decrease in controls, Dr. Stein Gold observed at the conference, sponsored by MedscapeLIVE! and the producers of the Hawaii Dermatology Seminar and Caribbean Dermatology Symposium.

Also at week 12, 96% of patients on sarecycline reported having no or only trace symptoms of facial burning, 63% had no or only trace facial erythema, and 94% had no or trace facial itch, compared with 76%, 12%, and 76% of controls, respectively. The sarecycline group was also significantly more likely to report no or trace skin dryness and oiliness.

The side-effect profile was favorable and the same as encountered with the use of sarecycline for acne: no major photosensitivity issues, no serious adverse events, and only 2 of the original 75 patients in the active-treatment arm discontinued sarecycline for treatment-emergent headache or gastroenteritis considered “probably” related to the study drug. The investigators deemed further studies of sarecycline for rosacea to be warranted as a potential expanded indication.

Aiming for clear skin rather than ‘almost clear’

Dr. Stein Gold shared her mantra for rosacea therapy: “Always aim for clear skin.”

She cited a study led by Guy Webster, MD, professor of dermatology, Thomas Jefferson University, Philadelphia, in which he and his coinvestigators looked at the durability of treatment response in a pooled analysis of 1,366 rosacea patients in four clinical trials. If patients improved to “almost clear” after treatment, their median time to relapse was 3 months; if they reached “clear,” it was more than 8 months. Also, more clear patients rated their outcomes as excellent and reported that their skin disease no longer had any effect on their quality of life.

“That’s more than a 5-month difference,” Dr. Stein Gold noted. “It shows the importance of really striving to get that skin completely clear.”

The sarecycline study was funded by Almirall, which markets the antibiotic. Dr. Stein Gold, who has no financial relationship with Almirall, has received research funding from and/or served as a consultant to roughly a dozen other pharmaceutical companies. MedscapeLIVE! and this news organization are owned by the same parent company.
 

bjancin@mdedge.com

Oral sarecycline proved rapidly effective for the treatment of moderate to severe papulopustular rosacea in a proof-of-concept pilot study, Linda Stein Gold, MD, said at Innovations in Dermatology: Virtual Spring Conference 2021.

Patrick McNamara Photography

The oral broad-spectrum second-generation tetracyclines doxycycline and minocycline have long been considered first-line therapy for papulopustular rosacea that isn’t cleared using topical agents. But the widespread use of these oral tetracyclines has encouraged the development of antimicrobial resistance. In contrast, sarecycline (Seysara) is a third-generation, narrow-spectrum tetracycline designed to minimize antibiotic resistance. The Food and Drug Administration approved the drug for treatment of moderate to severe acne vulgaris in 2018.

At the meeting, Dr. Stein Gold, director of dermatology clinical research at the Henry Ford Health System in Detroit, highlighted a recent pilot study of oral sarecycline for papulopustular rosacea carried out by James Q. Del Rosso, DO, of Las Vegas and coinvestigators. Although she wasn’t involved in the study, she is a veteran clinical trialist with vast experience leading studies of new therapies for rosacea, acne, and other major dermatologic disorders.

The 12-week, prospective, investigator-blinded study included 97 adults with moderate to severe papulopustular rosacea; 72 were randomized to weight-based dosing of once-daily sarecycline, while the 25 controls took a daily oral vitamin.

One coprimary endpoint was achievement of an Investigator Global Assessment score of 0 or 1, meaning clear or almost clear skin, at week 12. The rates were 75% in the sarecycline group and 16% in controls. The other coprimary endpoint was the percent reduction from baseline to week 12 in inflammatory lesion count. Here again, there was a statistically significant difference in favor of the third-generation tetracycline derivative, which achieved an 80% reduction, compared with 50% in the control group.

Of note, the difference was already significant at the first evaluation at week 4, with a 58% reduction in inflammatory lesions in the sarecycline group versus 31% decrease in controls, Dr. Stein Gold observed at the conference, sponsored by MedscapeLIVE! and the producers of the Hawaii Dermatology Seminar and Caribbean Dermatology Symposium.

Also at week 12, 96% of patients on sarecycline reported having no or only trace symptoms of facial burning, 63% had no or only trace facial erythema, and 94% had no or trace facial itch, compared with 76%, 12%, and 76% of controls, respectively. The sarecycline group was also significantly more likely to report no or trace skin dryness and oiliness.

The side-effect profile was favorable and the same as encountered with the use of sarecycline for acne: no major photosensitivity issues, no serious adverse events, and only 2 of the original 75 patients in the active-treatment arm discontinued sarecycline for treatment-emergent headache or gastroenteritis considered “probably” related to the study drug. The investigators deemed further studies of sarecycline for rosacea to be warranted as a potential expanded indication.

Aiming for clear skin rather than ‘almost clear’

Dr. Stein Gold shared her mantra for rosacea therapy: “Always aim for clear skin.”

She cited a study led by Guy Webster, MD, professor of dermatology, Thomas Jefferson University, Philadelphia, in which he and his coinvestigators looked at the durability of treatment response in a pooled analysis of 1,366 rosacea patients in four clinical trials. If patients improved to “almost clear” after treatment, their median time to relapse was 3 months; if they reached “clear,” it was more than 8 months. Also, more clear patients rated their outcomes as excellent and reported that their skin disease no longer had any effect on their quality of life.

“That’s more than a 5-month difference,” Dr. Stein Gold noted. “It shows the importance of really striving to get that skin completely clear.”

The sarecycline study was funded by Almirall, which markets the antibiotic. Dr. Stein Gold, who has no financial relationship with Almirall, has received research funding from and/or served as a consultant to roughly a dozen other pharmaceutical companies. MedscapeLIVE! and this news organization are owned by the same parent company.
 

bjancin@mdedge.com

Oral sarecycline proved rapidly effective for the treatment of moderate to severe papulopustular rosacea in a proof-of-concept pilot study, Linda Stein Gold, MD, said at Innovations in Dermatology: Virtual Spring Conference 2021.

Patrick McNamara Photography

The oral broad-spectrum second-generation tetracyclines doxycycline and minocycline have long been considered first-line therapy for papulopustular rosacea that isn’t cleared using topical agents. But the widespread use of these oral tetracyclines has encouraged the development of antimicrobial resistance. In contrast, sarecycline (Seysara) is a third-generation, narrow-spectrum tetracycline designed to minimize antibiotic resistance. The Food and Drug Administration approved the drug for treatment of moderate to severe acne vulgaris in 2018.

At the meeting, Dr. Stein Gold, director of dermatology clinical research at the Henry Ford Health System in Detroit, highlighted a recent pilot study of oral sarecycline for papulopustular rosacea carried out by James Q. Del Rosso, DO, of Las Vegas and coinvestigators. Although she wasn’t involved in the study, she is a veteran clinical trialist with vast experience leading studies of new therapies for rosacea, acne, and other major dermatologic disorders.

The 12-week, prospective, investigator-blinded study included 97 adults with moderate to severe papulopustular rosacea; 72 were randomized to weight-based dosing of once-daily sarecycline, while the 25 controls took a daily oral vitamin.

One coprimary endpoint was achievement of an Investigator Global Assessment score of 0 or 1, meaning clear or almost clear skin, at week 12. The rates were 75% in the sarecycline group and 16% in controls. The other coprimary endpoint was the percent reduction from baseline to week 12 in inflammatory lesion count. Here again, there was a statistically significant difference in favor of the third-generation tetracycline derivative, which achieved an 80% reduction, compared with 50% in the control group.

Of note, the difference was already significant at the first evaluation at week 4, with a 58% reduction in inflammatory lesions in the sarecycline group versus 31% decrease in controls, Dr. Stein Gold observed at the conference, sponsored by MedscapeLIVE! and the producers of the Hawaii Dermatology Seminar and Caribbean Dermatology Symposium.

Also at week 12, 96% of patients on sarecycline reported having no or only trace symptoms of facial burning, 63% had no or only trace facial erythema, and 94% had no or trace facial itch, compared with 76%, 12%, and 76% of controls, respectively. The sarecycline group was also significantly more likely to report no or trace skin dryness and oiliness.

The side-effect profile was favorable and the same as encountered with the use of sarecycline for acne: no major photosensitivity issues, no serious adverse events, and only 2 of the original 75 patients in the active-treatment arm discontinued sarecycline for treatment-emergent headache or gastroenteritis considered “probably” related to the study drug. The investigators deemed further studies of sarecycline for rosacea to be warranted as a potential expanded indication.

Aiming for clear skin rather than ‘almost clear’

Dr. Stein Gold shared her mantra for rosacea therapy: “Always aim for clear skin.”

She cited a study led by Guy Webster, MD, professor of dermatology, Thomas Jefferson University, Philadelphia, in which he and his coinvestigators looked at the durability of treatment response in a pooled analysis of 1,366 rosacea patients in four clinical trials. If patients improved to “almost clear” after treatment, their median time to relapse was 3 months; if they reached “clear,” it was more than 8 months. Also, more clear patients rated their outcomes as excellent and reported that their skin disease no longer had any effect on their quality of life.

“That’s more than a 5-month difference,” Dr. Stein Gold noted. “It shows the importance of really striving to get that skin completely clear.”

The sarecycline study was funded by Almirall, which markets the antibiotic. Dr. Stein Gold, who has no financial relationship with Almirall, has received research funding from and/or served as a consultant to roughly a dozen other pharmaceutical companies. MedscapeLIVE! and this news organization are owned by the same parent company.
 

bjancin@mdedge.com

The National Psoriasis Foundation COVID-19 Task Force now recommends that certain patients on methotrexate consider stopping the drug for 2 weeks after receiving the Johnson & Johnson COVID-19 vaccine, Joel M. Gelfand, MD, said at Innovations in Dermatology: Virtual Spring Conference 2021.

Courtesy Dr. Joel M. Gelfand

The new guidance states: “Patients 60 or older who have at least one comorbidity associated with an increased risk for poor COVID-19 outcomes, and who are taking methotrexate with well-controlled psoriatic disease, may, in consultation with their prescriber, consider holding it for 2 weeks after receiving the Ad26.COV2.S [Johnson & Johnson] vaccine in order to potentially improve vaccine response.”

The key word here is “potentially.” There is no hard evidence that a 2-week hold on methotrexate after receiving the killed adenovirus vaccine will actually provide a clinically meaningful benefit. But it’s a hypothetical possibility. The rationale stems from a small randomized trial conducted in South Korea several years ago in which patients with rheumatoid arthritis were assigned to hold or continue their methotrexate for the first 2 weeks after receiving an inactivated-virus influenza vaccine. The antibody response to the vaccine was better in those who temporarily halted their methotrexate, explained Dr. Gelfand, cochair of the NPF COVID-19 Task Force and professor of dermatology and of epidemiology at the University of Pennsylvania, Philadelphia.

“If you have a patient on methotrexate who’s 60 or older and whose psoriasis is completely controlled and quiescent and the patient is concerned about how well the vaccine is going to work, this is a reasonable thing to consider in someone who’s at higher risk for poor outcomes if they get infected,” he said.

If the informed patient wants to continue on methotrexate without interruption, that’s fine, too, in light of the lack of compelling evidence on this issue, the dermatologist added at the conference, sponsored by MedscapeLIVE! and the producers of the Hawaii Dermatology Seminar and Caribbean Dermatology Symposium.

The NPF task force does not extend the recommendation to consider holding methotrexate in recipients of the mRNA-based Moderna and Pfizer vaccines because of their very different mechanisms of action. Nor is it recommended to hold biologic agents after receiving any of the available COVID-19 vaccines. Studies have shown no altered immunologic response to influenza or pneumococcal vaccines in patients who continued on tumor necrosis factor inhibitors or interleukin-17 inhibitors. The interleukin-23 inhibitors haven’t been studied in this regard.

The task force recommends that most psoriasis patients should continue on treatment throughout the pandemic, and newly diagnosed patients should commence appropriate therapy as if there was no pandemic.

“We’ve learned that many patients who stopped their treatment for psoriatic disease early in the pandemic came to regret that decision because their psoriasis flared and got worse and required reinstitution of therapy,” Dr. Gelfand said. “The current data is largely reassuring that if there is an effect of our therapies on the risk of COVID, it must be rather small and therefore unlikely to be clinically meaningful for our patients.”

Dr. Gelfand reported serving as a consultant to and recipient of institutional research grants from Pfizer and numerous other pharmaceutical companies.

MedscapeLIVE and this news organization are owned by the same parent company.

bjancin@mdedge.com

The National Psoriasis Foundation COVID-19 Task Force now recommends that certain patients on methotrexate consider stopping the drug for 2 weeks after receiving the Johnson & Johnson COVID-19 vaccine, Joel M. Gelfand, MD, said at Innovations in Dermatology: Virtual Spring Conference 2021.

Courtesy Dr. Joel M. Gelfand

The new guidance states: “Patients 60 or older who have at least one comorbidity associated with an increased risk for poor COVID-19 outcomes, and who are taking methotrexate with well-controlled psoriatic disease, may, in consultation with their prescriber, consider holding it for 2 weeks after receiving the Ad26.COV2.S [Johnson & Johnson] vaccine in order to potentially improve vaccine response.”

The key word here is “potentially.” There is no hard evidence that a 2-week hold on methotrexate after receiving the killed adenovirus vaccine will actually provide a clinically meaningful benefit. But it’s a hypothetical possibility. The rationale stems from a small randomized trial conducted in South Korea several years ago in which patients with rheumatoid arthritis were assigned to hold or continue their methotrexate for the first 2 weeks after receiving an inactivated-virus influenza vaccine. The antibody response to the vaccine was better in those who temporarily halted their methotrexate, explained Dr. Gelfand, cochair of the NPF COVID-19 Task Force and professor of dermatology and of epidemiology at the University of Pennsylvania, Philadelphia.

“If you have a patient on methotrexate who’s 60 or older and whose psoriasis is completely controlled and quiescent and the patient is concerned about how well the vaccine is going to work, this is a reasonable thing to consider in someone who’s at higher risk for poor outcomes if they get infected,” he said.

If the informed patient wants to continue on methotrexate without interruption, that’s fine, too, in light of the lack of compelling evidence on this issue, the dermatologist added at the conference, sponsored by MedscapeLIVE! and the producers of the Hawaii Dermatology Seminar and Caribbean Dermatology Symposium.

The NPF task force does not extend the recommendation to consider holding methotrexate in recipients of the mRNA-based Moderna and Pfizer vaccines because of their very different mechanisms of action. Nor is it recommended to hold biologic agents after receiving any of the available COVID-19 vaccines. Studies have shown no altered immunologic response to influenza or pneumococcal vaccines in patients who continued on tumor necrosis factor inhibitors or interleukin-17 inhibitors. The interleukin-23 inhibitors haven’t been studied in this regard.

The task force recommends that most psoriasis patients should continue on treatment throughout the pandemic, and newly diagnosed patients should commence appropriate therapy as if there was no pandemic.

“We’ve learned that many patients who stopped their treatment for psoriatic disease early in the pandemic came to regret that decision because their psoriasis flared and got worse and required reinstitution of therapy,” Dr. Gelfand said. “The current data is largely reassuring that if there is an effect of our therapies on the risk of COVID, it must be rather small and therefore unlikely to be clinically meaningful for our patients.”

Dr. Gelfand reported serving as a consultant to and recipient of institutional research grants from Pfizer and numerous other pharmaceutical companies.

MedscapeLIVE and this news organization are owned by the same parent company.

bjancin@mdedge.com

The National Psoriasis Foundation COVID-19 Task Force now recommends that certain patients on methotrexate consider stopping the drug for 2 weeks after receiving the Johnson & Johnson COVID-19 vaccine, Joel M. Gelfand, MD, said at Innovations in Dermatology: Virtual Spring Conference 2021.

Courtesy Dr. Joel M. Gelfand

The new guidance states: “Patients 60 or older who have at least one comorbidity associated with an increased risk for poor COVID-19 outcomes, and who are taking methotrexate with well-controlled psoriatic disease, may, in consultation with their prescriber, consider holding it for 2 weeks after receiving the Ad26.COV2.S [Johnson & Johnson] vaccine in order to potentially improve vaccine response.”

The key word here is “potentially.” There is no hard evidence that a 2-week hold on methotrexate after receiving the killed adenovirus vaccine will actually provide a clinically meaningful benefit. But it’s a hypothetical possibility. The rationale stems from a small randomized trial conducted in South Korea several years ago in which patients with rheumatoid arthritis were assigned to hold or continue their methotrexate for the first 2 weeks after receiving an inactivated-virus influenza vaccine. The antibody response to the vaccine was better in those who temporarily halted their methotrexate, explained Dr. Gelfand, cochair of the NPF COVID-19 Task Force and professor of dermatology and of epidemiology at the University of Pennsylvania, Philadelphia.

“If you have a patient on methotrexate who’s 60 or older and whose psoriasis is completely controlled and quiescent and the patient is concerned about how well the vaccine is going to work, this is a reasonable thing to consider in someone who’s at higher risk for poor outcomes if they get infected,” he said.

If the informed patient wants to continue on methotrexate without interruption, that’s fine, too, in light of the lack of compelling evidence on this issue, the dermatologist added at the conference, sponsored by MedscapeLIVE! and the producers of the Hawaii Dermatology Seminar and Caribbean Dermatology Symposium.

The NPF task force does not extend the recommendation to consider holding methotrexate in recipients of the mRNA-based Moderna and Pfizer vaccines because of their very different mechanisms of action. Nor is it recommended to hold biologic agents after receiving any of the available COVID-19 vaccines. Studies have shown no altered immunologic response to influenza or pneumococcal vaccines in patients who continued on tumor necrosis factor inhibitors or interleukin-17 inhibitors. The interleukin-23 inhibitors haven’t been studied in this regard.

The task force recommends that most psoriasis patients should continue on treatment throughout the pandemic, and newly diagnosed patients should commence appropriate therapy as if there was no pandemic.

“We’ve learned that many patients who stopped their treatment for psoriatic disease early in the pandemic came to regret that decision because their psoriasis flared and got worse and required reinstitution of therapy,” Dr. Gelfand said. “The current data is largely reassuring that if there is an effect of our therapies on the risk of COVID, it must be rather small and therefore unlikely to be clinically meaningful for our patients.”

Dr. Gelfand reported serving as a consultant to and recipient of institutional research grants from Pfizer and numerous other pharmaceutical companies.

MedscapeLIVE and this news organization are owned by the same parent company.

bjancin@mdedge.com

One of the top publications in gastroenterology in 2020 was a Dutch study demonstrating that a computer-aided system suitable for real-time use in clinical practice detected early neoplasia in patients with Barrett’s esophagus with impressively greater accuracy than did a group of general endoscopists, according to Douglas A. Corley, MD, PhD.

It’s not just his personal opinion that this was one of the major studies of the past year, either. Analytic tools showed the Dutch report was one of the most frequently downloaded studies in 2020 by both clinical gastroenterologists and researchers, said Dr. Corley, director of delivery science and applied research at Kaiser Permanente of Northern California, Oakland, and a faculty gastroenterologist at the University of California, San Francisco.

The deep-learning system developed, evaluated, and externally validated by the Dutch investigators is designed to reduce the rate of failed detection of high-grade dysplasia and early adenocarcinoma in patients undergoing surveillance by general practice gastrointestinal endoscopists. The false-negative rate in looking for the sometimes subtle mucosal surface abnormalities indicative of early neoplasia is known to be higher among these general endoscopists than that among expert endoscopists, and yet it’s the general endoscopists who perform the majority of cancer surveillance in patients with Barrett’s esophagus.

The Dutch group developed the computer-aided detection system by applying artificial intelligence methods to analyze nearly one half-million endoscopic images of confirmed early neoplasia. Once the system was ready to go, they compared its diagnostic accuracy in 80 patients to that of 53 general, nonexpert endoscopists. The deep-learning system had 93% sensitivity and 83% specificity for identification of early neoplasia, significantly better than the 72% sensitivity and 74% specificity for the general endoscopists. The overall accuracy of the computer-assisted detection system was 88%, compared to 73% for the general endoscopists. Moreover, the deep-learning system achieved greater accuracy than did any single one of the endoscopists.

“I think this will be a really helpful addition, the equivalent of a second endoscopist raising a yellow flag to take a closer look at a particular area. It’ll be complementary,” Dr. Corley said at the Gastroenterology Updates, IBD, Liver Disease Conference.

An audience member said he’s aware that other computer-assisted detection systems have also shown outstanding performance for the detection of early neoplasia in Barrett’s esophagus. He asked, why aren’t these being deployed yet in routine clinical practice?

Two reasons, Dr. Corley replied. One is that some of those systems aren’t capable of working during real-time endoscopy. Also, industry seems to be taking a wait-and-see approach. The field of applied artificial intelligence is moving incredibly rapidly, and none of the endoscopic equipment manufacturers wants to incorporate a computer-assisted detection system into their gear when rumor has it that an even better system is going to be announced 6 months later. The manufacturers want to make sure they’re operationalizing the right one.

He suspects the major players in the endoscopic imaging industry are waiting to find a computer-assisted detection system that’s been published and widely accepted as clearly a winner. Then they’ll introduce it into their equipment.

“I do think we’re probably going to be seeing these increasingly. Some computer-assisted detection systems for colon cancer are starting to be put into equipment,” he observed.

Dr. Corley reported having no financial conflicts regarding his presentation.

bjancin@mdedge.com

This article was updated March 31, 2021.

One of the top publications in gastroenterology in 2020 was a Dutch study demonstrating that a computer-aided system suitable for real-time use in clinical practice detected early neoplasia in patients with Barrett’s esophagus with impressively greater accuracy than did a group of general endoscopists, according to Douglas A. Corley, MD, PhD.

It’s not just his personal opinion that this was one of the major studies of the past year, either. Analytic tools showed the Dutch report was one of the most frequently downloaded studies in 2020 by both clinical gastroenterologists and researchers, said Dr. Corley, director of delivery science and applied research at Kaiser Permanente of Northern California, Oakland, and a faculty gastroenterologist at the University of California, San Francisco.

The deep-learning system developed, evaluated, and externally validated by the Dutch investigators is designed to reduce the rate of failed detection of high-grade dysplasia and early adenocarcinoma in patients undergoing surveillance by general practice gastrointestinal endoscopists. The false-negative rate in looking for the sometimes subtle mucosal surface abnormalities indicative of early neoplasia is known to be higher among these general endoscopists than that among expert endoscopists, and yet it’s the general endoscopists who perform the majority of cancer surveillance in patients with Barrett’s esophagus.

The Dutch group developed the computer-aided detection system by applying artificial intelligence methods to analyze nearly one half-million endoscopic images of confirmed early neoplasia. Once the system was ready to go, they compared its diagnostic accuracy in 80 patients to that of 53 general, nonexpert endoscopists. The deep-learning system had 93% sensitivity and 83% specificity for identification of early neoplasia, significantly better than the 72% sensitivity and 74% specificity for the general endoscopists. The overall accuracy of the computer-assisted detection system was 88%, compared to 73% for the general endoscopists. Moreover, the deep-learning system achieved greater accuracy than did any single one of the endoscopists.

“I think this will be a really helpful addition, the equivalent of a second endoscopist raising a yellow flag to take a closer look at a particular area. It’ll be complementary,” Dr. Corley said at the Gastroenterology Updates, IBD, Liver Disease Conference.

An audience member said he’s aware that other computer-assisted detection systems have also shown outstanding performance for the detection of early neoplasia in Barrett’s esophagus. He asked, why aren’t these being deployed yet in routine clinical practice?

Two reasons, Dr. Corley replied. One is that some of those systems aren’t capable of working during real-time endoscopy. Also, industry seems to be taking a wait-and-see approach. The field of applied artificial intelligence is moving incredibly rapidly, and none of the endoscopic equipment manufacturers wants to incorporate a computer-assisted detection system into their gear when rumor has it that an even better system is going to be announced 6 months later. The manufacturers want to make sure they’re operationalizing the right one.

He suspects the major players in the endoscopic imaging industry are waiting to find a computer-assisted detection system that’s been published and widely accepted as clearly a winner. Then they’ll introduce it into their equipment.

“I do think we’re probably going to be seeing these increasingly. Some computer-assisted detection systems for colon cancer are starting to be put into equipment,” he observed.

Dr. Corley reported having no financial conflicts regarding his presentation.

bjancin@mdedge.com

This article was updated March 31, 2021.

One of the top publications in gastroenterology in 2020 was a Dutch study demonstrating that a computer-aided system suitable for real-time use in clinical practice detected early neoplasia in patients with Barrett’s esophagus with impressively greater accuracy than did a group of general endoscopists, according to Douglas A. Corley, MD, PhD.

It’s not just his personal opinion that this was one of the major studies of the past year, either. Analytic tools showed the Dutch report was one of the most frequently downloaded studies in 2020 by both clinical gastroenterologists and researchers, said Dr. Corley, director of delivery science and applied research at Kaiser Permanente of Northern California, Oakland, and a faculty gastroenterologist at the University of California, San Francisco.

The deep-learning system developed, evaluated, and externally validated by the Dutch investigators is designed to reduce the rate of failed detection of high-grade dysplasia and early adenocarcinoma in patients undergoing surveillance by general practice gastrointestinal endoscopists. The false-negative rate in looking for the sometimes subtle mucosal surface abnormalities indicative of early neoplasia is known to be higher among these general endoscopists than that among expert endoscopists, and yet it’s the general endoscopists who perform the majority of cancer surveillance in patients with Barrett’s esophagus.

The Dutch group developed the computer-aided detection system by applying artificial intelligence methods to analyze nearly one half-million endoscopic images of confirmed early neoplasia. Once the system was ready to go, they compared its diagnostic accuracy in 80 patients to that of 53 general, nonexpert endoscopists. The deep-learning system had 93% sensitivity and 83% specificity for identification of early neoplasia, significantly better than the 72% sensitivity and 74% specificity for the general endoscopists. The overall accuracy of the computer-assisted detection system was 88%, compared to 73% for the general endoscopists. Moreover, the deep-learning system achieved greater accuracy than did any single one of the endoscopists.

“I think this will be a really helpful addition, the equivalent of a second endoscopist raising a yellow flag to take a closer look at a particular area. It’ll be complementary,” Dr. Corley said at the Gastroenterology Updates, IBD, Liver Disease Conference.

An audience member said he’s aware that other computer-assisted detection systems have also shown outstanding performance for the detection of early neoplasia in Barrett’s esophagus. He asked, why aren’t these being deployed yet in routine clinical practice?

Two reasons, Dr. Corley replied. One is that some of those systems aren’t capable of working during real-time endoscopy. Also, industry seems to be taking a wait-and-see approach. The field of applied artificial intelligence is moving incredibly rapidly, and none of the endoscopic equipment manufacturers wants to incorporate a computer-assisted detection system into their gear when rumor has it that an even better system is going to be announced 6 months later. The manufacturers want to make sure they’re operationalizing the right one.

He suspects the major players in the endoscopic imaging industry are waiting to find a computer-assisted detection system that’s been published and widely accepted as clearly a winner. Then they’ll introduce it into their equipment.

“I do think we’re probably going to be seeing these increasingly. Some computer-assisted detection systems for colon cancer are starting to be put into equipment,” he observed.

Dr. Corley reported having no financial conflicts regarding his presentation.

bjancin@mdedge.com

This article was updated March 31, 2021.

Unknowns around the long-term effects of gender-affirming hormonal treatment on fertility in transgender individuals, especially adolescents, and what this means for fertility preservation, should be red flags for clinicians, according to one expert addressing the issue at the recent virtual ENDO 2021 meeting.

“One of the main concerns regarding fertility preservation in this population is that the decision to seek gender-affirming therapy is often made early in the reproductive lifespan, and for many patients this is well before the consideration of … child-bearing,” remarked Marie Menke, MD, an ob/gyn from University of Michigan, Ann Arbor, presenting in a session dedicated to state-of-the-art approaches to gamete preservation.

“These patients need to consider simultaneously their desire for gender-affirming therapy and their desire for child-bearing,” she added, explaining that gender-affirming therapy typically requires suppression of the hormonal axis that supports reproduction.

“This level of shared decision-making requires time and multidisciplinary involvement in the face of … limited data, and even with the best of counseling it can be quite overwhelming,” Dr. Menke stressed.

Specifically, the effects of gender-affirming therapy on both fertility and fertility preservation options in transgender individuals in comparison to the general population are areas that require much more research, she emphasized.

On the topic of adolescents specifically, she said they are “a special population,” as many seeking medical therapy for gender dysphoria have never considered long-term fertility goals or desires. Reports of such discussions during pediatric gender care vary greatly depending on the age of the patient and their geographic location.

And where such conversations have happened, “often there is no recollection by patients of such discussion prior to referral to endocrinology,” she emphasized.

Session co-moderator Irene Su, MD, a reproductive endocrinologist at the University of California, San Diego, said shared decisions with patients have to be made every day, even though data are limited.

“Little is known about both the adverse medical impact of gender-affirming hormonal therapy on fertility potential, as well as the psychosocial impact of interrupting/reversing gender-affirming hormonal therapy in the future to attempt fertility,” she told this news organization.

However, “because there are reasons to be concerned about an adverse impact on fertility, transgender individuals need access to fertility risk and preservation counseling,” she stressed.

Dr. Su has a special interest in improving reproductive health in young cancer survivors, and this involves similar discussions around fertility preservation – a medical subspecialty known as “oncofertility.”

There is a greater pool of knowledge in this field compared with fertility preservation and family planning in transgender patients, Dr. Su noted.

“While we need similar data in transgender individuals, what we’ve learned from the cancer survivor population is that they and their families want to know about known and unknown fertility risks and options, even if they ultimately do not choose to undertake fertility preservation procedures,” she explains.
 

Desire for future kids, but <10% currently preserve fertility

Dr. Menke said the estimated prevalence of individuals who identify as transgender is around 0.7% of the U.S. population, and she observed that, “by and large, fertility management involves tissue cryopreservation.”

She presented survey data showing that between 33%-54% of transgender and nonbinary individuals report a desire to have biological children currently, or in the future, and 94.6% are also strongly in support of transgender people having access to fertility preservation procedures.

Likewise, an online cross-sectional survey of over 1,100 people in the general population found that 76.2% agree that transgender individuals should be offered fertility preservation, and 60% support fertility preservation in minors.

Multiple professional societies support counseling in regard to options for fertility preservation and recommend that it should be offered to transgender individuals.

The American Society for Reproductive Medicine (ASRM), the American College of Obstetricians and Gynecologists (ACOG), the World Professional Association for Transgender Health (WPATH), and the Endocrine Society all advocate that individuals seeking gender-affirming medical treatment should receive multidisciplinary counseling regarding fertility preservation prior to puberty suppression in adolescents, and prior to cross-sex hormone treatment in both adolescents and adults.

But despite all of these recommendations and the survey findings, fertility preservation rates in transgender patients are low, “at less than 10%,” reported Dr. Menke.

Fertility preservation counseling and management ideally needs to begin prior to initiation of hormone therapy, stressed Dr. Menke.

Given the limited data on the long-term effects of gender-affirming therapy on fertility and its preservation, such counseling often leads to a myriad of questions, she further explained.

“Patients ask ‘What are the chances of having biological children if I don’t pursue fertility preservation?’, and ‘How likely am I to have a biological child if I do pursue fertility preservation?’, as well as issues around access to care, with patients asking, ‘Will I be able to pursue this option [of fertility preservation]?’”

“The chance of having a biological child if fertility preservation is pursued is similar to those [patients with cancer] who receive ‘oncofertility’ care, which has a good prognosis,” she explained.

However, issues around access to care, and the cost of it, can be barriers.
 

What does a transgender male, born female, need to do?

For transgender males, options for fertility preservation include the recommended option of cryopreservation of the eggs (oocytes), although freezing of embryos and/or ovarian tissue are also possible.

The latter would be required in a prepubertal individual if they wanted to start puberty blockers and then go straight onto cross-sex hormones, Dr. Menke noted, although she said it’s not definitively known if prepubertal ovarian tissue is capable of being stimulated in the future to produce viable mature oocytes.

In someone who has gone through puberty, the ideal time to freeze eggs is before beginning gender-affirming hormone therapy, Dr. Menke explained. This is because it is not known whether testosterone has any adverse impact on oocyte development.

“We just don’t have definitive data that long-term testosterone isn’t gonadotoxic,” she said in response to a question about this after her talk.

Assessment of the reproductive consequences of gender-affirming therapy in transgender males can also be complicated by coexisting conditions, Dr. Menke explained.

For example, up to 58% of transgender males have polycystic ovary syndrome (PCOS) prior to transitioning, she noted. PCOS itself, and/or the gender-affirming therapy, may cause histologic changes of the ovarian tissue – for example, hyperplasia of ovarian stroma – and it’s not yet known to what extent this may impact future fertility, if present, she noted.

For oocyte preservation in female-to-male transgender individuals, stimulation with gonadotropins for 2-3 weeks is needed, and the procedure is invasive, requiring repeated vaginal ultrasounds. During this period, estradiol levels are supraphysiologic, and there is potential for breast development and vaginal bleeding post-retrieval, which individuals will need to be counseled about, Dr. Menke noted.

The cost of this also needs to be factored into the equation. Depending on insurance coverage, costs may be covered – and where there is no precedent, individuals can try referring their insurance companies to the ‘oncofertility consortium access-to-care model’, Dr. Menke advised.

If there is no coverage, the average cost for one egg-freezing cycle ranges from $10,000-$17,000 in the U.S., and often two to three cycles are needed to generate sufficient oocytes to be sure of a pregnancy. In addition, there are storage costs. Plus, there will be the cost of any future intervention to achieve a pregnancy, she stressed.

How long frozen oocytes remain viable is also still a matter of scientific debate, although “as the technology changes from slow-freeze to vitrification,” this time period should lengthen, Dr. Menke said.

In transgender males who have not preserved oocytes or embryos prior to transitioning, it’s necessary to stop testosterone to have the best chance of harvesting viable gametes, Dr. Menke said. Furthermore, individuals undertaking this procedure need to take into account all of the above-mentioned side effects of egg harvesting.

Although there have been reports of successful pregnancies with eggs retrieved from transgender males who have temporarily stopped testosterone, fertilization and embryo development following discontinuation of testosterone still require “additional investigation,” she observed.

Furthermore, “there are case reports of oocyte stimulation and retrieval of mature oocytes while patients continue testosterone therapy, and this may be an option in the future,” she noted, again stressing that it’s not known if excess testosterone is gonadotoxic.

Other options for fertility preservation in the transgender male include embryo cryopreservation, but this still involves hormonal stimulation and invasive procedures and would require the use of a sperm donor in a person who doesn’t currently have a partner (or who has one, but not necessarily one with whom they want to create a child).

For transgender males there is also the possibility of using a surrogate mother for the pregnancy, she noted.
 

What about transgender women, assigned male at birth?

For those assigned male at birth who wish to take puberty blockers, fertility preservation would require cryopreservation of testicular tissue, although Dr. Menke stressed that this is still considered “experimental.”

In the postpubertal period, the simplest option is to cryopreserve semen, with this ideally being performed prior to the individual commencing gender-affirming hormone therapy, Dr. Menke said.

If this is not done prior to beginning hormonal treatment, estrogen will need to be discontinued for fertility preservation, she noted.

Return of sperm function following cessation of estrogen may be limited – “expect at least 3 months before return of reproductive function,” Dr. Menke said. And even this may not be sufficient to restore normal spermatogenesis, she cautioned. “Absent or reduced spermatogenesis or morphological changes to Sertoli cells [have been reported in transgender women].”

Also, “there are needs for multiple attempts at ejaculation and storage requirements” for this approach. Cost for freezing sperm in the U.S., if not covered by insurance, is around $400, she noted, with storage costs ranging from $100 to up to $800 a year.

“Case reports using cryopreserved sperm [in transgender individuals] are promising overall … with clinical pregnancy rates following [in vitro fertilization] (IVF) with cryopreserved sperm … equivalent to patients without evidence of male factor fertility,” Dr. Menke reported.

However, she emphasized the fact that IVF, or intracytoplasmic sperm injection (ICSI), will still be necessary for conception, with potential additional costs.

Some individuals may also need to undergo surgical removal of sperm postpuberty; this is typically performed where there is evidence of male factor infertility, for example.

Embryo cryopreservation requires a partner or use of donor oocytes and, again, will have cost implications.

In conclusion, Dr. Menke reiterated that the use of fertility preservation techniques among transgender people is low, and it is more frequently accessed by transgender females. Among the identified barriers to fertility preservation are cost, lack of information, invasiveness of procedures, and desire not to delay medical transition.

Dr. Menke has disclosed no relevant financial relationships. Dr. Su has received a speaker honorarium from Ferring Pharmaceuticals. 

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

Unknowns around the long-term effects of gender-affirming hormonal treatment on fertility in transgender individuals, especially adolescents, and what this means for fertility preservation, should be red flags for clinicians, according to one expert addressing the issue at the recent virtual ENDO 2021 meeting.

“One of the main concerns regarding fertility preservation in this population is that the decision to seek gender-affirming therapy is often made early in the reproductive lifespan, and for many patients this is well before the consideration of … child-bearing,” remarked Marie Menke, MD, an ob/gyn from University of Michigan, Ann Arbor, presenting in a session dedicated to state-of-the-art approaches to gamete preservation.

“These patients need to consider simultaneously their desire for gender-affirming therapy and their desire for child-bearing,” she added, explaining that gender-affirming therapy typically requires suppression of the hormonal axis that supports reproduction.

“This level of shared decision-making requires time and multidisciplinary involvement in the face of … limited data, and even with the best of counseling it can be quite overwhelming,” Dr. Menke stressed.

Specifically, the effects of gender-affirming therapy on both fertility and fertility preservation options in transgender individuals in comparison to the general population are areas that require much more research, she emphasized.

On the topic of adolescents specifically, she said they are “a special population,” as many seeking medical therapy for gender dysphoria have never considered long-term fertility goals or desires. Reports of such discussions during pediatric gender care vary greatly depending on the age of the patient and their geographic location.

And where such conversations have happened, “often there is no recollection by patients of such discussion prior to referral to endocrinology,” she emphasized.

Session co-moderator Irene Su, MD, a reproductive endocrinologist at the University of California, San Diego, said shared decisions with patients have to be made every day, even though data are limited.

“Little is known about both the adverse medical impact of gender-affirming hormonal therapy on fertility potential, as well as the psychosocial impact of interrupting/reversing gender-affirming hormonal therapy in the future to attempt fertility,” she told this news organization.

However, “because there are reasons to be concerned about an adverse impact on fertility, transgender individuals need access to fertility risk and preservation counseling,” she stressed.

Dr. Su has a special interest in improving reproductive health in young cancer survivors, and this involves similar discussions around fertility preservation – a medical subspecialty known as “oncofertility.”

There is a greater pool of knowledge in this field compared with fertility preservation and family planning in transgender patients, Dr. Su noted.

“While we need similar data in transgender individuals, what we’ve learned from the cancer survivor population is that they and their families want to know about known and unknown fertility risks and options, even if they ultimately do not choose to undertake fertility preservation procedures,” she explains.
 

Desire for future kids, but <10% currently preserve fertility

Dr. Menke said the estimated prevalence of individuals who identify as transgender is around 0.7% of the U.S. population, and she observed that, “by and large, fertility management involves tissue cryopreservation.”

She presented survey data showing that between 33%-54% of transgender and nonbinary individuals report a desire to have biological children currently, or in the future, and 94.6% are also strongly in support of transgender people having access to fertility preservation procedures.

Likewise, an online cross-sectional survey of over 1,100 people in the general population found that 76.2% agree that transgender individuals should be offered fertility preservation, and 60% support fertility preservation in minors.

Multiple professional societies support counseling in regard to options for fertility preservation and recommend that it should be offered to transgender individuals.

The American Society for Reproductive Medicine (ASRM), the American College of Obstetricians and Gynecologists (ACOG), the World Professional Association for Transgender Health (WPATH), and the Endocrine Society all advocate that individuals seeking gender-affirming medical treatment should receive multidisciplinary counseling regarding fertility preservation prior to puberty suppression in adolescents, and prior to cross-sex hormone treatment in both adolescents and adults.

But despite all of these recommendations and the survey findings, fertility preservation rates in transgender patients are low, “at less than 10%,” reported Dr. Menke.

Fertility preservation counseling and management ideally needs to begin prior to initiation of hormone therapy, stressed Dr. Menke.

Given the limited data on the long-term effects of gender-affirming therapy on fertility and its preservation, such counseling often leads to a myriad of questions, she further explained.

“Patients ask ‘What are the chances of having biological children if I don’t pursue fertility preservation?’, and ‘How likely am I to have a biological child if I do pursue fertility preservation?’, as well as issues around access to care, with patients asking, ‘Will I be able to pursue this option [of fertility preservation]?’”

“The chance of having a biological child if fertility preservation is pursued is similar to those [patients with cancer] who receive ‘oncofertility’ care, which has a good prognosis,” she explained.

However, issues around access to care, and the cost of it, can be barriers.
 

What does a transgender male, born female, need to do?

For transgender males, options for fertility preservation include the recommended option of cryopreservation of the eggs (oocytes), although freezing of embryos and/or ovarian tissue are also possible.

The latter would be required in a prepubertal individual if they wanted to start puberty blockers and then go straight onto cross-sex hormones, Dr. Menke noted, although she said it’s not definitively known if prepubertal ovarian tissue is capable of being stimulated in the future to produce viable mature oocytes.

In someone who has gone through puberty, the ideal time to freeze eggs is before beginning gender-affirming hormone therapy, Dr. Menke explained. This is because it is not known whether testosterone has any adverse impact on oocyte development.

“We just don’t have definitive data that long-term testosterone isn’t gonadotoxic,” she said in response to a question about this after her talk.

Assessment of the reproductive consequences of gender-affirming therapy in transgender males can also be complicated by coexisting conditions, Dr. Menke explained.

For example, up to 58% of transgender males have polycystic ovary syndrome (PCOS) prior to transitioning, she noted. PCOS itself, and/or the gender-affirming therapy, may cause histologic changes of the ovarian tissue – for example, hyperplasia of ovarian stroma – and it’s not yet known to what extent this may impact future fertility, if present, she noted.

For oocyte preservation in female-to-male transgender individuals, stimulation with gonadotropins for 2-3 weeks is needed, and the procedure is invasive, requiring repeated vaginal ultrasounds. During this period, estradiol levels are supraphysiologic, and there is potential for breast development and vaginal bleeding post-retrieval, which individuals will need to be counseled about, Dr. Menke noted.

The cost of this also needs to be factored into the equation. Depending on insurance coverage, costs may be covered – and where there is no precedent, individuals can try referring their insurance companies to the ‘oncofertility consortium access-to-care model’, Dr. Menke advised.

If there is no coverage, the average cost for one egg-freezing cycle ranges from $10,000-$17,000 in the U.S., and often two to three cycles are needed to generate sufficient oocytes to be sure of a pregnancy. In addition, there are storage costs. Plus, there will be the cost of any future intervention to achieve a pregnancy, she stressed.

How long frozen oocytes remain viable is also still a matter of scientific debate, although “as the technology changes from slow-freeze to vitrification,” this time period should lengthen, Dr. Menke said.

In transgender males who have not preserved oocytes or embryos prior to transitioning, it’s necessary to stop testosterone to have the best chance of harvesting viable gametes, Dr. Menke said. Furthermore, individuals undertaking this procedure need to take into account all of the above-mentioned side effects of egg harvesting.

Although there have been reports of successful pregnancies with eggs retrieved from transgender males who have temporarily stopped testosterone, fertilization and embryo development following discontinuation of testosterone still require “additional investigation,” she observed.

Furthermore, “there are case reports of oocyte stimulation and retrieval of mature oocytes while patients continue testosterone therapy, and this may be an option in the future,” she noted, again stressing that it’s not known if excess testosterone is gonadotoxic.

Other options for fertility preservation in the transgender male include embryo cryopreservation, but this still involves hormonal stimulation and invasive procedures and would require the use of a sperm donor in a person who doesn’t currently have a partner (or who has one, but not necessarily one with whom they want to create a child).

For transgender males there is also the possibility of using a surrogate mother for the pregnancy, she noted.
 

What about transgender women, assigned male at birth?

For those assigned male at birth who wish to take puberty blockers, fertility preservation would require cryopreservation of testicular tissue, although Dr. Menke stressed that this is still considered “experimental.”

In the postpubertal period, the simplest option is to cryopreserve semen, with this ideally being performed prior to the individual commencing gender-affirming hormone therapy, Dr. Menke said.

If this is not done prior to beginning hormonal treatment, estrogen will need to be discontinued for fertility preservation, she noted.

Return of sperm function following cessation of estrogen may be limited – “expect at least 3 months before return of reproductive function,” Dr. Menke said. And even this may not be sufficient to restore normal spermatogenesis, she cautioned. “Absent or reduced spermatogenesis or morphological changes to Sertoli cells [have been reported in transgender women].”

Also, “there are needs for multiple attempts at ejaculation and storage requirements” for this approach. Cost for freezing sperm in the U.S., if not covered by insurance, is around $400, she noted, with storage costs ranging from $100 to up to $800 a year.

“Case reports using cryopreserved sperm [in transgender individuals] are promising overall … with clinical pregnancy rates following [in vitro fertilization] (IVF) with cryopreserved sperm … equivalent to patients without evidence of male factor fertility,” Dr. Menke reported.

However, she emphasized the fact that IVF, or intracytoplasmic sperm injection (ICSI), will still be necessary for conception, with potential additional costs.

Some individuals may also need to undergo surgical removal of sperm postpuberty; this is typically performed where there is evidence of male factor infertility, for example.

Embryo cryopreservation requires a partner or use of donor oocytes and, again, will have cost implications.

In conclusion, Dr. Menke reiterated that the use of fertility preservation techniques among transgender people is low, and it is more frequently accessed by transgender females. Among the identified barriers to fertility preservation are cost, lack of information, invasiveness of procedures, and desire not to delay medical transition.

Dr. Menke has disclosed no relevant financial relationships. Dr. Su has received a speaker honorarium from Ferring Pharmaceuticals. 

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

Unknowns around the long-term effects of gender-affirming hormonal treatment on fertility in transgender individuals, especially adolescents, and what this means for fertility preservation, should be red flags for clinicians, according to one expert addressing the issue at the recent virtual ENDO 2021 meeting.

“One of the main concerns regarding fertility preservation in this population is that the decision to seek gender-affirming therapy is often made early in the reproductive lifespan, and for many patients this is well before the consideration of … child-bearing,” remarked Marie Menke, MD, an ob/gyn from University of Michigan, Ann Arbor, presenting in a session dedicated to state-of-the-art approaches to gamete preservation.

“These patients need to consider simultaneously their desire for gender-affirming therapy and their desire for child-bearing,” she added, explaining that gender-affirming therapy typically requires suppression of the hormonal axis that supports reproduction.

“This level of shared decision-making requires time and multidisciplinary involvement in the face of … limited data, and even with the best of counseling it can be quite overwhelming,” Dr. Menke stressed.

Specifically, the effects of gender-affirming therapy on both fertility and fertility preservation options in transgender individuals in comparison to the general population are areas that require much more research, she emphasized.

On the topic of adolescents specifically, she said they are “a special population,” as many seeking medical therapy for gender dysphoria have never considered long-term fertility goals or desires. Reports of such discussions during pediatric gender care vary greatly depending on the age of the patient and their geographic location.

And where such conversations have happened, “often there is no recollection by patients of such discussion prior to referral to endocrinology,” she emphasized.

Session co-moderator Irene Su, MD, a reproductive endocrinologist at the University of California, San Diego, said shared decisions with patients have to be made every day, even though data are limited.

“Little is known about both the adverse medical impact of gender-affirming hormonal therapy on fertility potential, as well as the psychosocial impact of interrupting/reversing gender-affirming hormonal therapy in the future to attempt fertility,” she told this news organization.

However, “because there are reasons to be concerned about an adverse impact on fertility, transgender individuals need access to fertility risk and preservation counseling,” she stressed.

Dr. Su has a special interest in improving reproductive health in young cancer survivors, and this involves similar discussions around fertility preservation – a medical subspecialty known as “oncofertility.”

There is a greater pool of knowledge in this field compared with fertility preservation and family planning in transgender patients, Dr. Su noted.

“While we need similar data in transgender individuals, what we’ve learned from the cancer survivor population is that they and their families want to know about known and unknown fertility risks and options, even if they ultimately do not choose to undertake fertility preservation procedures,” she explains.
 

Desire for future kids, but <10% currently preserve fertility

Dr. Menke said the estimated prevalence of individuals who identify as transgender is around 0.7% of the U.S. population, and she observed that, “by and large, fertility management involves tissue cryopreservation.”

She presented survey data showing that between 33%-54% of transgender and nonbinary individuals report a desire to have biological children currently, or in the future, and 94.6% are also strongly in support of transgender people having access to fertility preservation procedures.

Likewise, an online cross-sectional survey of over 1,100 people in the general population found that 76.2% agree that transgender individuals should be offered fertility preservation, and 60% support fertility preservation in minors.

Multiple professional societies support counseling in regard to options for fertility preservation and recommend that it should be offered to transgender individuals.

The American Society for Reproductive Medicine (ASRM), the American College of Obstetricians and Gynecologists (ACOG), the World Professional Association for Transgender Health (WPATH), and the Endocrine Society all advocate that individuals seeking gender-affirming medical treatment should receive multidisciplinary counseling regarding fertility preservation prior to puberty suppression in adolescents, and prior to cross-sex hormone treatment in both adolescents and adults.

But despite all of these recommendations and the survey findings, fertility preservation rates in transgender patients are low, “at less than 10%,” reported Dr. Menke.

Fertility preservation counseling and management ideally needs to begin prior to initiation of hormone therapy, stressed Dr. Menke.

Given the limited data on the long-term effects of gender-affirming therapy on fertility and its preservation, such counseling often leads to a myriad of questions, she further explained.

“Patients ask ‘What are the chances of having biological children if I don’t pursue fertility preservation?’, and ‘How likely am I to have a biological child if I do pursue fertility preservation?’, as well as issues around access to care, with patients asking, ‘Will I be able to pursue this option [of fertility preservation]?’”

“The chance of having a biological child if fertility preservation is pursued is similar to those [patients with cancer] who receive ‘oncofertility’ care, which has a good prognosis,” she explained.

However, issues around access to care, and the cost of it, can be barriers.
 

What does a transgender male, born female, need to do?

For transgender males, options for fertility preservation include the recommended option of cryopreservation of the eggs (oocytes), although freezing of embryos and/or ovarian tissue are also possible.

The latter would be required in a prepubertal individual if they wanted to start puberty blockers and then go straight onto cross-sex hormones, Dr. Menke noted, although she said it’s not definitively known if prepubertal ovarian tissue is capable of being stimulated in the future to produce viable mature oocytes.

In someone who has gone through puberty, the ideal time to freeze eggs is before beginning gender-affirming hormone therapy, Dr. Menke explained. This is because it is not known whether testosterone has any adverse impact on oocyte development.

“We just don’t have definitive data that long-term testosterone isn’t gonadotoxic,” she said in response to a question about this after her talk.

Assessment of the reproductive consequences of gender-affirming therapy in transgender males can also be complicated by coexisting conditions, Dr. Menke explained.

For example, up to 58% of transgender males have polycystic ovary syndrome (PCOS) prior to transitioning, she noted. PCOS itself, and/or the gender-affirming therapy, may cause histologic changes of the ovarian tissue – for example, hyperplasia of ovarian stroma – and it’s not yet known to what extent this may impact future fertility, if present, she noted.

For oocyte preservation in female-to-male transgender individuals, stimulation with gonadotropins for 2-3 weeks is needed, and the procedure is invasive, requiring repeated vaginal ultrasounds. During this period, estradiol levels are supraphysiologic, and there is potential for breast development and vaginal bleeding post-retrieval, which individuals will need to be counseled about, Dr. Menke noted.

The cost of this also needs to be factored into the equation. Depending on insurance coverage, costs may be covered – and where there is no precedent, individuals can try referring their insurance companies to the ‘oncofertility consortium access-to-care model’, Dr. Menke advised.

If there is no coverage, the average cost for one egg-freezing cycle ranges from $10,000-$17,000 in the U.S., and often two to three cycles are needed to generate sufficient oocytes to be sure of a pregnancy. In addition, there are storage costs. Plus, there will be the cost of any future intervention to achieve a pregnancy, she stressed.

How long frozen oocytes remain viable is also still a matter of scientific debate, although “as the technology changes from slow-freeze to vitrification,” this time period should lengthen, Dr. Menke said.

In transgender males who have not preserved oocytes or embryos prior to transitioning, it’s necessary to stop testosterone to have the best chance of harvesting viable gametes, Dr. Menke said. Furthermore, individuals undertaking this procedure need to take into account all of the above-mentioned side effects of egg harvesting.

Although there have been reports of successful pregnancies with eggs retrieved from transgender males who have temporarily stopped testosterone, fertilization and embryo development following discontinuation of testosterone still require “additional investigation,” she observed.

Furthermore, “there are case reports of oocyte stimulation and retrieval of mature oocytes while patients continue testosterone therapy, and this may be an option in the future,” she noted, again stressing that it’s not known if excess testosterone is gonadotoxic.

Other options for fertility preservation in the transgender male include embryo cryopreservation, but this still involves hormonal stimulation and invasive procedures and would require the use of a sperm donor in a person who doesn’t currently have a partner (or who has one, but not necessarily one with whom they want to create a child).

For transgender males there is also the possibility of using a surrogate mother for the pregnancy, she noted.
 

What about transgender women, assigned male at birth?

For those assigned male at birth who wish to take puberty blockers, fertility preservation would require cryopreservation of testicular tissue, although Dr. Menke stressed that this is still considered “experimental.”

In the postpubertal period, the simplest option is to cryopreserve semen, with this ideally being performed prior to the individual commencing gender-affirming hormone therapy, Dr. Menke said.

If this is not done prior to beginning hormonal treatment, estrogen will need to be discontinued for fertility preservation, she noted.

Return of sperm function following cessation of estrogen may be limited – “expect at least 3 months before return of reproductive function,” Dr. Menke said. And even this may not be sufficient to restore normal spermatogenesis, she cautioned. “Absent or reduced spermatogenesis or morphological changes to Sertoli cells [have been reported in transgender women].”

Also, “there are needs for multiple attempts at ejaculation and storage requirements” for this approach. Cost for freezing sperm in the U.S., if not covered by insurance, is around $400, she noted, with storage costs ranging from $100 to up to $800 a year.

“Case reports using cryopreserved sperm [in transgender individuals] are promising overall … with clinical pregnancy rates following [in vitro fertilization] (IVF) with cryopreserved sperm … equivalent to patients without evidence of male factor fertility,” Dr. Menke reported.

However, she emphasized the fact that IVF, or intracytoplasmic sperm injection (ICSI), will still be necessary for conception, with potential additional costs.

Some individuals may also need to undergo surgical removal of sperm postpuberty; this is typically performed where there is evidence of male factor infertility, for example.

Embryo cryopreservation requires a partner or use of donor oocytes and, again, will have cost implications.

In conclusion, Dr. Menke reiterated that the use of fertility preservation techniques among transgender people is low, and it is more frequently accessed by transgender females. Among the identified barriers to fertility preservation are cost, lack of information, invasiveness of procedures, and desire not to delay medical transition.

Dr. Menke has disclosed no relevant financial relationships. Dr. Su has received a speaker honorarium from Ferring Pharmaceuticals. 

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

Physicians are active on social media with contact dermatitis content, but they can take more advantage of this opportunity to educate patients, according to a review of posts on YouTube, Facebook, Instagram, Google, Twitter, and Reddit.

Data on social media use suggest that approximately 65% of U.S. adults regularly use social media, and 40% of individuals use it in making medical decisions, Morgan Nguyen, a medical student at Northwestern University, Chicago, said at the annual meeting of the American Contact Dermatitis Society, held virtually this year.

“Dermatologists’ awareness of social media discussions can further their understanding of where patients go for information and what they might encounter,” she said. In particular, “contact dermatitis practitioners can tailor their counseling by knowing what their patients are seeing online.”

To characterize the social media landscape for content related to allergic contact dermatitis (ACD), Ms. Nguyen and colleagues assessed metrics on content and authorship on six different platforms.

For YouTube, the authors reviewed 15 videos related to ACD with views ranging from 24,262 to 232,300. Of these videos, two were produced as medical education, four were produced by patients, and nine were produced by physicians. The content of many videos was poor quality, with an average QUEST score of 7.4/28 overall and 8.7 for physician videos. Video quality was not associated with increased views. Video titles included “What to do if you have a rash on your face,” and “Contact dermatitis on lips!”

Overall, Instagram was more popular than Twitter, particularly among patients. The investigators searched using the hashtags #ContactDermatitis, #AllergicContactDermatitis, and #ContactDerm and reviewed the 100 most recent posts for authorship. The most recent 100 posts occurred over 16 days; physicians, patients, and companies each contributed approximately one-third of the content, but patient content was more focused on symptoms, treatment progress, and advice.

For Instagram, the hashtag search phrase made a notable difference in authorship, Ms. Nguyen said. Physicians were disproportionately more likely to use #AllergicContactDermatitis (43%) compared with patients (22%).

On Twitter, the most recent 100 posts were spread over 152 days, and professional organizations and companies generated approximately two-thirds of the posts. The #ContactDermatitis hashtag was the most common, and accounted for 94% of tweets.

Although patient support groups specific to ACD exist on Facebook, the researchers found none on Reddit. These two venues are designed for creating online communities, rather than simply providing information, and the researchers searched for support groups related to contact dermatitis. One of the main differences between the two is that Facebook allows for the creation of private groups, while Reddit is an open forum.

The largest contact dermatitis Facebook group, the “Eczema, Contact Dermatitis and Patch Testing Alliance,” had 4,665 members at the time of the study, and most groups were private. Although no support groups existed on Reddit, titles of Reddit forums discussing ACD included allergies, askdoctors, fragrance, haircarescience, legaladvice, skincareaddicts, beauty, dermatologyquestions, medical_advice, skincare_addiction, tretinoin, and vulvodynia.

For Google, the researchers used terms similar to “contact dermatitis” as generated by the Google Keyword Planner tool, and used Google Adwords data to estimate monthly searches. The top estimated term was “contact dermatitis,” with 8,322 searches, followed by “contact dermatitis pictures,” with 1,666 searches, and “contact dermatitis treatment” with 595 searches. By contrast, “allergic dermatitis” had an estimated 346 monthly searches, and “allergic contact dermatitis” had 194.

Overall, approximately 9,000 searches each month involve “contact dermatitis,” “allergic contact dermatitis,” or “allergic dermatitis,” said Ms. Nguyen. However, these estimated searches seemed comparatively low, given the high burden of ACD, she said. Although ACD ranks eighth among skin diseases based on health care costs, psoriasis (fourteenth based on health care costs) shows an estimated monthly Google search volume of 600,462, she pointed out.

The study findings were limited by several factors including the potential impact of the COVID-19 pandemic on social media use, and by the lack of specificity associated with the search term “contact dermatitis,” which is not unique to ACD, Ms. Nguyen said.

Although more research on quality assessment is needed, the results suggest that social media is a popular venue for ACD patients to seek and share information, Ms. Nguyen emphasized. There is an opportunity for patch testing physicians to create and disperse educational content for patients using these sites, she concluded.
 

Study highlights education opportunities

“Due to the pandemic, patients have been increasingly interacting with online resources in lieu of coming to a physician’s office,” corresponding author Walter J. Liszewski, MD, of the department of dermatology, Northwestern University, Chicago, said in an interview. “As social media is increasingly used by patients and physicians, it is important to get a sense of its footprint,” he said.

He and Ms. Nguyen were surprised by several of their findings: First, searches for ACD on Google were not particularly common given its relatively high prevalence and economic cost to society. In addition, they found that physicians often used different language than that of patients to describe ACD on Twitter and Instagram. They were also surprised at how often ACD appeared in Reddit posts, which they noted highlights that ACD impacts multiple sections of society.

The greatest challenge in studying social media and medicine is the quality of material available, Dr. Liszewski and Ms. Nguyen observed, emphasizing that while there are numerous videos on ACD on YouTube, the quality is highly variable, and there is a need for more patient-centered, educational materials. However, the results of their study highlight the opportunity for physicians and industry to create medically-accurate educational materials, they added.

Ms. Nguyen and Dr. Liszewski had no financial conflicts to disclose.

Physicians are active on social media with contact dermatitis content, but they can take more advantage of this opportunity to educate patients, according to a review of posts on YouTube, Facebook, Instagram, Google, Twitter, and Reddit.

Data on social media use suggest that approximately 65% of U.S. adults regularly use social media, and 40% of individuals use it in making medical decisions, Morgan Nguyen, a medical student at Northwestern University, Chicago, said at the annual meeting of the American Contact Dermatitis Society, held virtually this year.

“Dermatologists’ awareness of social media discussions can further their understanding of where patients go for information and what they might encounter,” she said. In particular, “contact dermatitis practitioners can tailor their counseling by knowing what their patients are seeing online.”

To characterize the social media landscape for content related to allergic contact dermatitis (ACD), Ms. Nguyen and colleagues assessed metrics on content and authorship on six different platforms.

For YouTube, the authors reviewed 15 videos related to ACD with views ranging from 24,262 to 232,300. Of these videos, two were produced as medical education, four were produced by patients, and nine were produced by physicians. The content of many videos was poor quality, with an average QUEST score of 7.4/28 overall and 8.7 for physician videos. Video quality was not associated with increased views. Video titles included “What to do if you have a rash on your face,” and “Contact dermatitis on lips!”

Overall, Instagram was more popular than Twitter, particularly among patients. The investigators searched using the hashtags #ContactDermatitis, #AllergicContactDermatitis, and #ContactDerm and reviewed the 100 most recent posts for authorship. The most recent 100 posts occurred over 16 days; physicians, patients, and companies each contributed approximately one-third of the content, but patient content was more focused on symptoms, treatment progress, and advice.

For Instagram, the hashtag search phrase made a notable difference in authorship, Ms. Nguyen said. Physicians were disproportionately more likely to use #AllergicContactDermatitis (43%) compared with patients (22%).

On Twitter, the most recent 100 posts were spread over 152 days, and professional organizations and companies generated approximately two-thirds of the posts. The #ContactDermatitis hashtag was the most common, and accounted for 94% of tweets.

Although patient support groups specific to ACD exist on Facebook, the researchers found none on Reddit. These two venues are designed for creating online communities, rather than simply providing information, and the researchers searched for support groups related to contact dermatitis. One of the main differences between the two is that Facebook allows for the creation of private groups, while Reddit is an open forum.

The largest contact dermatitis Facebook group, the “Eczema, Contact Dermatitis and Patch Testing Alliance,” had 4,665 members at the time of the study, and most groups were private. Although no support groups existed on Reddit, titles of Reddit forums discussing ACD included allergies, askdoctors, fragrance, haircarescience, legaladvice, skincareaddicts, beauty, dermatologyquestions, medical_advice, skincare_addiction, tretinoin, and vulvodynia.

For Google, the researchers used terms similar to “contact dermatitis” as generated by the Google Keyword Planner tool, and used Google Adwords data to estimate monthly searches. The top estimated term was “contact dermatitis,” with 8,322 searches, followed by “contact dermatitis pictures,” with 1,666 searches, and “contact dermatitis treatment” with 595 searches. By contrast, “allergic dermatitis” had an estimated 346 monthly searches, and “allergic contact dermatitis” had 194.

Overall, approximately 9,000 searches each month involve “contact dermatitis,” “allergic contact dermatitis,” or “allergic dermatitis,” said Ms. Nguyen. However, these estimated searches seemed comparatively low, given the high burden of ACD, she said. Although ACD ranks eighth among skin diseases based on health care costs, psoriasis (fourteenth based on health care costs) shows an estimated monthly Google search volume of 600,462, she pointed out.

The study findings were limited by several factors including the potential impact of the COVID-19 pandemic on social media use, and by the lack of specificity associated with the search term “contact dermatitis,” which is not unique to ACD, Ms. Nguyen said.

Although more research on quality assessment is needed, the results suggest that social media is a popular venue for ACD patients to seek and share information, Ms. Nguyen emphasized. There is an opportunity for patch testing physicians to create and disperse educational content for patients using these sites, she concluded.
 

Study highlights education opportunities

“Due to the pandemic, patients have been increasingly interacting with online resources in lieu of coming to a physician’s office,” corresponding author Walter J. Liszewski, MD, of the department of dermatology, Northwestern University, Chicago, said in an interview. “As social media is increasingly used by patients and physicians, it is important to get a sense of its footprint,” he said.

He and Ms. Nguyen were surprised by several of their findings: First, searches for ACD on Google were not particularly common given its relatively high prevalence and economic cost to society. In addition, they found that physicians often used different language than that of patients to describe ACD on Twitter and Instagram. They were also surprised at how often ACD appeared in Reddit posts, which they noted highlights that ACD impacts multiple sections of society.

The greatest challenge in studying social media and medicine is the quality of material available, Dr. Liszewski and Ms. Nguyen observed, emphasizing that while there are numerous videos on ACD on YouTube, the quality is highly variable, and there is a need for more patient-centered, educational materials. However, the results of their study highlight the opportunity for physicians and industry to create medically-accurate educational materials, they added.

Ms. Nguyen and Dr. Liszewski had no financial conflicts to disclose.

Physicians are active on social media with contact dermatitis content, but they can take more advantage of this opportunity to educate patients, according to a review of posts on YouTube, Facebook, Instagram, Google, Twitter, and Reddit.

Data on social media use suggest that approximately 65% of U.S. adults regularly use social media, and 40% of individuals use it in making medical decisions, Morgan Nguyen, a medical student at Northwestern University, Chicago, said at the annual meeting of the American Contact Dermatitis Society, held virtually this year.

“Dermatologists’ awareness of social media discussions can further their understanding of where patients go for information and what they might encounter,” she said. In particular, “contact dermatitis practitioners can tailor their counseling by knowing what their patients are seeing online.”

To characterize the social media landscape for content related to allergic contact dermatitis (ACD), Ms. Nguyen and colleagues assessed metrics on content and authorship on six different platforms.

For YouTube, the authors reviewed 15 videos related to ACD with views ranging from 24,262 to 232,300. Of these videos, two were produced as medical education, four were produced by patients, and nine were produced by physicians. The content of many videos was poor quality, with an average QUEST score of 7.4/28 overall and 8.7 for physician videos. Video quality was not associated with increased views. Video titles included “What to do if you have a rash on your face,” and “Contact dermatitis on lips!”

Overall, Instagram was more popular than Twitter, particularly among patients. The investigators searched using the hashtags #ContactDermatitis, #AllergicContactDermatitis, and #ContactDerm and reviewed the 100 most recent posts for authorship. The most recent 100 posts occurred over 16 days; physicians, patients, and companies each contributed approximately one-third of the content, but patient content was more focused on symptoms, treatment progress, and advice.

For Instagram, the hashtag search phrase made a notable difference in authorship, Ms. Nguyen said. Physicians were disproportionately more likely to use #AllergicContactDermatitis (43%) compared with patients (22%).

On Twitter, the most recent 100 posts were spread over 152 days, and professional organizations and companies generated approximately two-thirds of the posts. The #ContactDermatitis hashtag was the most common, and accounted for 94% of tweets.

Although patient support groups specific to ACD exist on Facebook, the researchers found none on Reddit. These two venues are designed for creating online communities, rather than simply providing information, and the researchers searched for support groups related to contact dermatitis. One of the main differences between the two is that Facebook allows for the creation of private groups, while Reddit is an open forum.

The largest contact dermatitis Facebook group, the “Eczema, Contact Dermatitis and Patch Testing Alliance,” had 4,665 members at the time of the study, and most groups were private. Although no support groups existed on Reddit, titles of Reddit forums discussing ACD included allergies, askdoctors, fragrance, haircarescience, legaladvice, skincareaddicts, beauty, dermatologyquestions, medical_advice, skincare_addiction, tretinoin, and vulvodynia.

For Google, the researchers used terms similar to “contact dermatitis” as generated by the Google Keyword Planner tool, and used Google Adwords data to estimate monthly searches. The top estimated term was “contact dermatitis,” with 8,322 searches, followed by “contact dermatitis pictures,” with 1,666 searches, and “contact dermatitis treatment” with 595 searches. By contrast, “allergic dermatitis” had an estimated 346 monthly searches, and “allergic contact dermatitis” had 194.

Overall, approximately 9,000 searches each month involve “contact dermatitis,” “allergic contact dermatitis,” or “allergic dermatitis,” said Ms. Nguyen. However, these estimated searches seemed comparatively low, given the high burden of ACD, she said. Although ACD ranks eighth among skin diseases based on health care costs, psoriasis (fourteenth based on health care costs) shows an estimated monthly Google search volume of 600,462, she pointed out.

The study findings were limited by several factors including the potential impact of the COVID-19 pandemic on social media use, and by the lack of specificity associated with the search term “contact dermatitis,” which is not unique to ACD, Ms. Nguyen said.

Although more research on quality assessment is needed, the results suggest that social media is a popular venue for ACD patients to seek and share information, Ms. Nguyen emphasized. There is an opportunity for patch testing physicians to create and disperse educational content for patients using these sites, she concluded.
 

Study highlights education opportunities

“Due to the pandemic, patients have been increasingly interacting with online resources in lieu of coming to a physician’s office,” corresponding author Walter J. Liszewski, MD, of the department of dermatology, Northwestern University, Chicago, said in an interview. “As social media is increasingly used by patients and physicians, it is important to get a sense of its footprint,” he said.

He and Ms. Nguyen were surprised by several of their findings: First, searches for ACD on Google were not particularly common given its relatively high prevalence and economic cost to society. In addition, they found that physicians often used different language than that of patients to describe ACD on Twitter and Instagram. They were also surprised at how often ACD appeared in Reddit posts, which they noted highlights that ACD impacts multiple sections of society.

The greatest challenge in studying social media and medicine is the quality of material available, Dr. Liszewski and Ms. Nguyen observed, emphasizing that while there are numerous videos on ACD on YouTube, the quality is highly variable, and there is a need for more patient-centered, educational materials. However, the results of their study highlight the opportunity for physicians and industry to create medically-accurate educational materials, they added.

Ms. Nguyen and Dr. Liszewski had no financial conflicts to disclose.

The combination of ixabepilone and bevacizumab demonstrated efficacy in patients with platinum-resistant or refractory epithelial ovarian, fallopian tube, or primary peritoneal cancer in a phase 2 trial.

The median progression-free survival (PFS) was 5.5 months for patients randomized to receive ixabepilone and bevacizumab, versus 2.2 months for patients assigned to ixabepilone alone (P < .001). The median overall survival (OS) was 10 months and 6 months, respectively (P = .006), although the trial was underpowered to detect OS differences.

These results were presented in a late-breaking abstract session at the Society of Gynecologic Oncology’s Virtual Annual Meeting on Women’s Cancer (Abstract 11570).

“Therapeutic options for platinum- and taxane-resistant ovarian cancer are limited, and, unfortunately, median overall survival in this population is only approximately 12 months. It’s obvious that additional treatment strategies are warranted,” Dana M. Roque, MD, of the University of Maryland in Baltimore, said when presenting the results.
 

Study rationale and details

Dr. Roque explained that ixabepilone is an epothilone B analog that may retain activity in patients with taxane-resistant disease. She and her colleagues previously found, in a retrospective study, that ixabepilone, with or without bevacizumab, showed “promising” activity with acceptable toxicity in patients with recurrent uterine or ovarian/primary peritoneal/fallopian tube cancers.

At SGO 2021, Dr. Roque reported results of a prospective, phase 2 trial of 76 patients randomized to ixabepilone alone or in combination with bevacizumab.

Patients with measurable recurrent or persistent platinum-resistant or refractory epithelial nonmucinous ovarian, fallopian tube, or primary peritoneal cancers were enrolled. The patients had to have received at least three prior cycles of paclitaxel, but there was no upper limit on prior lines of therapy, including bevacizumab.

After stratification by prior bevacizumab and study site, the patients were randomly assigned to either ixabepilone monotherapy at a dose of 20 mg/m² on days 1, 8, and 15 of every 28-day cycle (n = 37), or the same dose of ixabepilone plus bevacizumab at 10 mg/kg on days 1 and 15 every 28 days (n = 39).

Most patients in each arm – 78% in the monotherapy arm and 87% in the combination arm – had serous tumors, with the remaining patients having carcinosarcomas or other, unspecified histologies.
 

Efficacy and safety

The overall response rate was 33% with the combination and 8% with ixabepilone monotherapy. There were no correlations between TUBB3 staining and either responses or durable disease control.

As noted before, PFS and OS were significantly better with the combination. Neither PFS nor OS were influenced by prior bevacizumab use, heavy pretreatment, poor performance status, nonserous histology, or age.

Dose-limiting toxicities with the combination included peripheral neuropathy, neutropenia, and fatigue. There was one bowel perforation in a patient on the combination.

Patients assigned to the combination were significantly more likely to experience hypertension (36% vs. 8%, P = .005) and peripheral neuropathy (51% vs. 19%, P = .004). However, there were no differences in serious adverse events between the treatment arms.

Dr. Roque acknowledged that this study was limited by incomplete immunohistochemistry data, a lack of stratification by extent of prior taxane exposure in the recurrent setting, a lack of a bevacizumab control arm, and underpowering to detect OS differences.
 

Comparison with AURELIA

Dr. Roque and the invited discussant, Thomas J. Herzog, MD, of the University of Cincinnati Cancer Center in Ohio, both compared results of the current trial to results from the AURELIA trial, in which patients with platinum-resistant ovarian cancers were randomized to chemotherapy with or without bevacizumab.

According to AURELIA data published in 2014, the ORR with the bevacizumab-chemotherapy combination was 27%, compared with 33% with ixabepilone-bevacizumab in the current trial. The median PFS was 6.7 months and 5.5 months, respectively, and the median OS was 16.6 months and 10 months, respectively.

An analysis of AURELIA data published in 2015 suggested that outcomes were even better for patients who received paclitaxel plus bevacizumab. This group had an ORR of 53.3%, a median PFS of 10.4 months, and a median OS of 22.4 months.

Though the current study’s results don’t appear to measure up to results from AURELIA, Dr. Herzog called the current study “very exciting.”

“The efficacy looks very promising,” he said. “They even showed efficacy for OS that looked very interesting, even though that was underpowered.”

Dr. Herzog did note the lack of a companion diagnostic because the TUBB3 staining did not correlate with response. He also said the trial was limited by the lack of a bevacizumab control arm. Furthermore, because of the relatively small sample size in the combination group (n = 39), the lower bound of the confidence interval for ORR includes response rates typically seen with conventional therapies.

“I do think that the combination does make sense biologically, so I’d like to see more data on that,” he concluded.

The trial was sponsored by Yale University, with study drug supplied by R-Pharm-US. Dr. Roque reported no conflicts of interest. Dr. Herzog disclosed serving as a scientific advisor to several companies, including Genentech, maker of bevacizumab.

The combination of ixabepilone and bevacizumab demonstrated efficacy in patients with platinum-resistant or refractory epithelial ovarian, fallopian tube, or primary peritoneal cancer in a phase 2 trial.

The median progression-free survival (PFS) was 5.5 months for patients randomized to receive ixabepilone and bevacizumab, versus 2.2 months for patients assigned to ixabepilone alone (P < .001). The median overall survival (OS) was 10 months and 6 months, respectively (P = .006), although the trial was underpowered to detect OS differences.

These results were presented in a late-breaking abstract session at the Society of Gynecologic Oncology’s Virtual Annual Meeting on Women’s Cancer (Abstract 11570).

“Therapeutic options for platinum- and taxane-resistant ovarian cancer are limited, and, unfortunately, median overall survival in this population is only approximately 12 months. It’s obvious that additional treatment strategies are warranted,” Dana M. Roque, MD, of the University of Maryland in Baltimore, said when presenting the results.
 

Study rationale and details

Dr. Roque explained that ixabepilone is an epothilone B analog that may retain activity in patients with taxane-resistant disease. She and her colleagues previously found, in a retrospective study, that ixabepilone, with or without bevacizumab, showed “promising” activity with acceptable toxicity in patients with recurrent uterine or ovarian/primary peritoneal/fallopian tube cancers.

At SGO 2021, Dr. Roque reported results of a prospective, phase 2 trial of 76 patients randomized to ixabepilone alone or in combination with bevacizumab.

Patients with measurable recurrent or persistent platinum-resistant or refractory epithelial nonmucinous ovarian, fallopian tube, or primary peritoneal cancers were enrolled. The patients had to have received at least three prior cycles of paclitaxel, but there was no upper limit on prior lines of therapy, including bevacizumab.

After stratification by prior bevacizumab and study site, the patients were randomly assigned to either ixabepilone monotherapy at a dose of 20 mg/m² on days 1, 8, and 15 of every 28-day cycle (n = 37), or the same dose of ixabepilone plus bevacizumab at 10 mg/kg on days 1 and 15 every 28 days (n = 39).

Most patients in each arm – 78% in the monotherapy arm and 87% in the combination arm – had serous tumors, with the remaining patients having carcinosarcomas or other, unspecified histologies.
 

Efficacy and safety

The overall response rate was 33% with the combination and 8% with ixabepilone monotherapy. There were no correlations between TUBB3 staining and either responses or durable disease control.

As noted before, PFS and OS were significantly better with the combination. Neither PFS nor OS were influenced by prior bevacizumab use, heavy pretreatment, poor performance status, nonserous histology, or age.

Dose-limiting toxicities with the combination included peripheral neuropathy, neutropenia, and fatigue. There was one bowel perforation in a patient on the combination.

Patients assigned to the combination were significantly more likely to experience hypertension (36% vs. 8%, P = .005) and peripheral neuropathy (51% vs. 19%, P = .004). However, there were no differences in serious adverse events between the treatment arms.

Dr. Roque acknowledged that this study was limited by incomplete immunohistochemistry data, a lack of stratification by extent of prior taxane exposure in the recurrent setting, a lack of a bevacizumab control arm, and underpowering to detect OS differences.
 

Comparison with AURELIA

Dr. Roque and the invited discussant, Thomas J. Herzog, MD, of the University of Cincinnati Cancer Center in Ohio, both compared results of the current trial to results from the AURELIA trial, in which patients with platinum-resistant ovarian cancers were randomized to chemotherapy with or without bevacizumab.

According to AURELIA data published in 2014, the ORR with the bevacizumab-chemotherapy combination was 27%, compared with 33% with ixabepilone-bevacizumab in the current trial. The median PFS was 6.7 months and 5.5 months, respectively, and the median OS was 16.6 months and 10 months, respectively.

An analysis of AURELIA data published in 2015 suggested that outcomes were even better for patients who received paclitaxel plus bevacizumab. This group had an ORR of 53.3%, a median PFS of 10.4 months, and a median OS of 22.4 months.

Though the current study’s results don’t appear to measure up to results from AURELIA, Dr. Herzog called the current study “very exciting.”

“The efficacy looks very promising,” he said. “They even showed efficacy for OS that looked very interesting, even though that was underpowered.”

Dr. Herzog did note the lack of a companion diagnostic because the TUBB3 staining did not correlate with response. He also said the trial was limited by the lack of a bevacizumab control arm. Furthermore, because of the relatively small sample size in the combination group (n = 39), the lower bound of the confidence interval for ORR includes response rates typically seen with conventional therapies.

“I do think that the combination does make sense biologically, so I’d like to see more data on that,” he concluded.

The trial was sponsored by Yale University, with study drug supplied by R-Pharm-US. Dr. Roque reported no conflicts of interest. Dr. Herzog disclosed serving as a scientific advisor to several companies, including Genentech, maker of bevacizumab.

The combination of ixabepilone and bevacizumab demonstrated efficacy in patients with platinum-resistant or refractory epithelial ovarian, fallopian tube, or primary peritoneal cancer in a phase 2 trial.

The median progression-free survival (PFS) was 5.5 months for patients randomized to receive ixabepilone and bevacizumab, versus 2.2 months for patients assigned to ixabepilone alone (P < .001). The median overall survival (OS) was 10 months and 6 months, respectively (P = .006), although the trial was underpowered to detect OS differences.

These results were presented in a late-breaking abstract session at the Society of Gynecologic Oncology’s Virtual Annual Meeting on Women’s Cancer (Abstract 11570).

“Therapeutic options for platinum- and taxane-resistant ovarian cancer are limited, and, unfortunately, median overall survival in this population is only approximately 12 months. It’s obvious that additional treatment strategies are warranted,” Dana M. Roque, MD, of the University of Maryland in Baltimore, said when presenting the results.
 

Study rationale and details

Dr. Roque explained that ixabepilone is an epothilone B analog that may retain activity in patients with taxane-resistant disease. She and her colleagues previously found, in a retrospective study, that ixabepilone, with or without bevacizumab, showed “promising” activity with acceptable toxicity in patients with recurrent uterine or ovarian/primary peritoneal/fallopian tube cancers.

At SGO 2021, Dr. Roque reported results of a prospective, phase 2 trial of 76 patients randomized to ixabepilone alone or in combination with bevacizumab.

Patients with measurable recurrent or persistent platinum-resistant or refractory epithelial nonmucinous ovarian, fallopian tube, or primary peritoneal cancers were enrolled. The patients had to have received at least three prior cycles of paclitaxel, but there was no upper limit on prior lines of therapy, including bevacizumab.

After stratification by prior bevacizumab and study site, the patients were randomly assigned to either ixabepilone monotherapy at a dose of 20 mg/m² on days 1, 8, and 15 of every 28-day cycle (n = 37), or the same dose of ixabepilone plus bevacizumab at 10 mg/kg on days 1 and 15 every 28 days (n = 39).

Most patients in each arm – 78% in the monotherapy arm and 87% in the combination arm – had serous tumors, with the remaining patients having carcinosarcomas or other, unspecified histologies.
 

Efficacy and safety

The overall response rate was 33% with the combination and 8% with ixabepilone monotherapy. There were no correlations between TUBB3 staining and either responses or durable disease control.

As noted before, PFS and OS were significantly better with the combination. Neither PFS nor OS were influenced by prior bevacizumab use, heavy pretreatment, poor performance status, nonserous histology, or age.

Dose-limiting toxicities with the combination included peripheral neuropathy, neutropenia, and fatigue. There was one bowel perforation in a patient on the combination.

Patients assigned to the combination were significantly more likely to experience hypertension (36% vs. 8%, P = .005) and peripheral neuropathy (51% vs. 19%, P = .004). However, there were no differences in serious adverse events between the treatment arms.

Dr. Roque acknowledged that this study was limited by incomplete immunohistochemistry data, a lack of stratification by extent of prior taxane exposure in the recurrent setting, a lack of a bevacizumab control arm, and underpowering to detect OS differences.
 

Comparison with AURELIA

Dr. Roque and the invited discussant, Thomas J. Herzog, MD, of the University of Cincinnati Cancer Center in Ohio, both compared results of the current trial to results from the AURELIA trial, in which patients with platinum-resistant ovarian cancers were randomized to chemotherapy with or without bevacizumab.

According to AURELIA data published in 2014, the ORR with the bevacizumab-chemotherapy combination was 27%, compared with 33% with ixabepilone-bevacizumab in the current trial. The median PFS was 6.7 months and 5.5 months, respectively, and the median OS was 16.6 months and 10 months, respectively.

An analysis of AURELIA data published in 2015 suggested that outcomes were even better for patients who received paclitaxel plus bevacizumab. This group had an ORR of 53.3%, a median PFS of 10.4 months, and a median OS of 22.4 months.

Though the current study’s results don’t appear to measure up to results from AURELIA, Dr. Herzog called the current study “very exciting.”

“The efficacy looks very promising,” he said. “They even showed efficacy for OS that looked very interesting, even though that was underpowered.”

Dr. Herzog did note the lack of a companion diagnostic because the TUBB3 staining did not correlate with response. He also said the trial was limited by the lack of a bevacizumab control arm. Furthermore, because of the relatively small sample size in the combination group (n = 39), the lower bound of the confidence interval for ORR includes response rates typically seen with conventional therapies.

“I do think that the combination does make sense biologically, so I’d like to see more data on that,” he concluded.

The trial was sponsored by Yale University, with study drug supplied by R-Pharm-US. Dr. Roque reported no conflicts of interest. Dr. Herzog disclosed serving as a scientific advisor to several companies, including Genentech, maker of bevacizumab.

Approximately 20% of shoe allergens are not detected with the current screening series, according to a retrospective study of more than 30,000 patients.

Contact allergy to shoes remains a common but difficult problem for many reasons, including the limited information from shoe manufacturers, differences in shoe manufacturing processes, and changes in shoe trends, said Raina Bembry, MD, a dermatitis research fellow at Duke University, Durham, N.C., in a presentation at the annual meeting of the American Contact Dermatitis Society.

The North American Contact Dermatitis Group (NACDG) published data on shoe allergens from 2001-2004 in a 2007 review. To update this information to reflect changes in shoe manufacturing and trends, she and her coinvestigators characterized demographics, clinical characteristics, patch test results, and occupational data for NACDG patients with shoe contact allergy. They identified 33,661 patients who were patch tested with the standard series with or without a supplemental allergen between 2005 and 2018; over half were over aged 40.

The primary focus was individuals with a confirmed shoe (defined as shoes, boots, sandals, or slippers) as the source of a screening allergen or supplemental allergen, a positive patch test, and the foot as one of three sites of involvement. A total of 352 individuals met these criteria and had a confirmed final diagnosis of allergic contact dermatitis, Dr. Bembry said. Compared with individuals who had positive patch tests without a confirmed diagnosis, those with confirmed allergic dermatitis were significantly more likely to be male (odds ratio, 3.36) and less likely to be over aged 40 years (OR, 0.49).

The most common NACDG screening allergen, potassium dichromate, was found in 29.8% of the study population, followed by p-tert-butylphenol formaldehyde resin in 20.1%, thiuram mix (13.3%), mixed dialkyl thioureas (12.6%) and carba mix (12%).

Notably, 29.8% of the patients showed positive patch test reactions to supplemental allergens, and 12.2% only reacted to supplemental allergens, Dr. Bembry said.

The results were limited by several factors, including referral selection bias, reliance on clinical judgment for patch test interpretations, and lack of data on the specifics of the supplemental allergens other than the source code, she said. In addition, the study does not identify nonshoe sources of foot contact allergy, and six screening allergens were not testing during this study period.

Overall, the findings were similar to those from previous studies in that patients affected with contact dermatitis from shoe allergens tended to be younger and male, with no occupational relevance to the reaction, said Dr. Bembry.

The finding that almost 20% of allergens were not found with the screening series emphasizes the value of testing not only relevant supplemental allergens, but also patient products and shoe components, she concluded.

Dr. Bembry had no financial conflicts to disclose. Coauthor Amber Atwater, MD, the immediate past president of the ACDS, and associate professor of dermatology at Duke University, disclosed receiving the Pfizer Independent Grant for Learning & Change and consulting for Henkel.

Approximately 20% of shoe allergens are not detected with the current screening series, according to a retrospective study of more than 30,000 patients.

Contact allergy to shoes remains a common but difficult problem for many reasons, including the limited information from shoe manufacturers, differences in shoe manufacturing processes, and changes in shoe trends, said Raina Bembry, MD, a dermatitis research fellow at Duke University, Durham, N.C., in a presentation at the annual meeting of the American Contact Dermatitis Society.

The North American Contact Dermatitis Group (NACDG) published data on shoe allergens from 2001-2004 in a 2007 review. To update this information to reflect changes in shoe manufacturing and trends, she and her coinvestigators characterized demographics, clinical characteristics, patch test results, and occupational data for NACDG patients with shoe contact allergy. They identified 33,661 patients who were patch tested with the standard series with or without a supplemental allergen between 2005 and 2018; over half were over aged 40.

The primary focus was individuals with a confirmed shoe (defined as shoes, boots, sandals, or slippers) as the source of a screening allergen or supplemental allergen, a positive patch test, and the foot as one of three sites of involvement. A total of 352 individuals met these criteria and had a confirmed final diagnosis of allergic contact dermatitis, Dr. Bembry said. Compared with individuals who had positive patch tests without a confirmed diagnosis, those with confirmed allergic dermatitis were significantly more likely to be male (odds ratio, 3.36) and less likely to be over aged 40 years (OR, 0.49).

The most common NACDG screening allergen, potassium dichromate, was found in 29.8% of the study population, followed by p-tert-butylphenol formaldehyde resin in 20.1%, thiuram mix (13.3%), mixed dialkyl thioureas (12.6%) and carba mix (12%).

Notably, 29.8% of the patients showed positive patch test reactions to supplemental allergens, and 12.2% only reacted to supplemental allergens, Dr. Bembry said.

The results were limited by several factors, including referral selection bias, reliance on clinical judgment for patch test interpretations, and lack of data on the specifics of the supplemental allergens other than the source code, she said. In addition, the study does not identify nonshoe sources of foot contact allergy, and six screening allergens were not testing during this study period.

Overall, the findings were similar to those from previous studies in that patients affected with contact dermatitis from shoe allergens tended to be younger and male, with no occupational relevance to the reaction, said Dr. Bembry.

The finding that almost 20% of allergens were not found with the screening series emphasizes the value of testing not only relevant supplemental allergens, but also patient products and shoe components, she concluded.

Dr. Bembry had no financial conflicts to disclose. Coauthor Amber Atwater, MD, the immediate past president of the ACDS, and associate professor of dermatology at Duke University, disclosed receiving the Pfizer Independent Grant for Learning & Change and consulting for Henkel.

Approximately 20% of shoe allergens are not detected with the current screening series, according to a retrospective study of more than 30,000 patients.

Contact allergy to shoes remains a common but difficult problem for many reasons, including the limited information from shoe manufacturers, differences in shoe manufacturing processes, and changes in shoe trends, said Raina Bembry, MD, a dermatitis research fellow at Duke University, Durham, N.C., in a presentation at the annual meeting of the American Contact Dermatitis Society.

The North American Contact Dermatitis Group (NACDG) published data on shoe allergens from 2001-2004 in a 2007 review. To update this information to reflect changes in shoe manufacturing and trends, she and her coinvestigators characterized demographics, clinical characteristics, patch test results, and occupational data for NACDG patients with shoe contact allergy. They identified 33,661 patients who were patch tested with the standard series with or without a supplemental allergen between 2005 and 2018; over half were over aged 40.

The primary focus was individuals with a confirmed shoe (defined as shoes, boots, sandals, or slippers) as the source of a screening allergen or supplemental allergen, a positive patch test, and the foot as one of three sites of involvement. A total of 352 individuals met these criteria and had a confirmed final diagnosis of allergic contact dermatitis, Dr. Bembry said. Compared with individuals who had positive patch tests without a confirmed diagnosis, those with confirmed allergic dermatitis were significantly more likely to be male (odds ratio, 3.36) and less likely to be over aged 40 years (OR, 0.49).

The most common NACDG screening allergen, potassium dichromate, was found in 29.8% of the study population, followed by p-tert-butylphenol formaldehyde resin in 20.1%, thiuram mix (13.3%), mixed dialkyl thioureas (12.6%) and carba mix (12%).

Notably, 29.8% of the patients showed positive patch test reactions to supplemental allergens, and 12.2% only reacted to supplemental allergens, Dr. Bembry said.

The results were limited by several factors, including referral selection bias, reliance on clinical judgment for patch test interpretations, and lack of data on the specifics of the supplemental allergens other than the source code, she said. In addition, the study does not identify nonshoe sources of foot contact allergy, and six screening allergens were not testing during this study period.

Overall, the findings were similar to those from previous studies in that patients affected with contact dermatitis from shoe allergens tended to be younger and male, with no occupational relevance to the reaction, said Dr. Bembry.

The finding that almost 20% of allergens were not found with the screening series emphasizes the value of testing not only relevant supplemental allergens, but also patient products and shoe components, she concluded.

Dr. Bembry had no financial conflicts to disclose. Coauthor Amber Atwater, MD, the immediate past president of the ACDS, and associate professor of dermatology at Duke University, disclosed receiving the Pfizer Independent Grant for Learning & Change and consulting for Henkel.