Patients with metastatic breast cancer (MBC) face an elevated risk of severe illness or dying from COVID-19. Given the slow rollout of the Moderna and Pfizer COVID vaccines and new, more infectious viral variants circulating in the United States, oncologists will face a challenging balancing act for the foreseeable future: sustaining patients› MBC care while safeguarding them from COVID. The scale leans heavily toward continuing treatment, experts say.

“If we stop treatment for metastatic breast cancer, death will occur quickly,” Fatima F. Cardoso, MD, director of the breast unit at Champalimaud Clinical Centre in Lisbon, Portugal, stated this past August in a Medscape perspective.

Joanne Mortimer, MD, director of Women’s Cancer Programs at City of Hope, a comprehensive cancer center near Los Angeles, expressed a similar sentiment. “Having MBC is worse than getting COVID,” she told Medscape. “We can’t stop treating patients with MBC because of concerns of exposure.”

But maintaining treatment does not mean business as usual. Oncologists have had to modify their pre-pandemic practices to some degree, and that degree largely depends on local COVID conditions.

“Weighing the risk of treatment with the risk of contracting the virus means that many places have carried on treating metastatic breast cancer in a more thoughtful, careful way,” said Jill Dietz, MD, president of the American Society of Breast Surgeons. “That means focusing on high-value treatments for patients with the goal of maximizing their outcomes and quality of life while limiting in-person visits and potentially unnecessary elements of care.”

To guide this more careful approach, Dr. Dietz and colleagues from the recently formed COVID-19 Pandemic Breast Cancer Consortium published recommendations in April 2020 to account for different disease types and severities. These recommendations align closely with those from Cardoso and colleagues in Europe, also published last April.

Although issued early in the pandemic when there was greater uncertainty about viral transmission, adverse outcomes, and treatment for COVID-19, these recommendations still hold almost a year later.

“The framework has proven to be timeless in that it can help institutions where they are in the pandemic,” Dr. Dietz said.

The recommendations at play

For MBC, in particular, Dr. Dietz and colleagues focused on patients who need systemic care but whose treatment can be modified to keep them home more. The modifications include prescribing oral agents such as capecitabine, vinorelbine, and cyclophosphamide to minimize visits to the hospital or infusion suite.

To limit adverse events associated with these oral drugs, Dr. Dietz and colleagues also recommended reducing the dose when possible. For instance, research shows that lowering the dose of the CDK4/6 inhibitor palbociclib in patients with HR+/HER2-negative MBC does not diminish efficacy.

When oral agents are not an option, Dr. Dietz and colleagues suggested stretching out the intervals for chemotherapy infusions or injections. Data show that trastuzumab and pertuzumab injections for metastatic HER2-positive tumors «may reasonably be administered at longer intervals,» such as 4 weeks instead of 3 weeks.

The extent to which oncologists have applied these recommendations hinges on two factors: the local severity of COVID-19 cases and institution-specific policies.

For some oncologists, the pandemic has largely left treatment decisions untouched. “COVID-19 has only minimally impacted my practice,” said Rita Nanda, MD, director of the Breast Oncology Program and associate professor of medicine at University of Chicago Medicine.

Dr. Nanda recalled her concerns in the early days of the pandemic. As the nation watched COVID cases surge across New York City, Chicagoans prepared for the worst, fashioning the McCormick Place Convention Center into a field hospital for COVID patients.

“But fortunately, we were never overwhelmed at the University of Chicago and never needed to use the convention center,” Dr. Nanda said. “We did not have to alter or limit the type of therapy patients with MBC could receive.”

The main changes described by Dr. Nanda at the University of Chicago have centered around limiting the flow of traffic within the infusion suite or hospital by implementing prescreening checks to catch patients with COVID symptoms, keeping waiting rooms empty and infusion centers socially distanced, and having patients come in for appointments solo. The university’s home phlebotomy service also came in handy. Implemented before the pandemic, this service allowed patients with MBC to get their labs done at home before coming in for treatment.

“Overall, with social distancing, mask wearing, and limiting who comes in to the clinic, we have been able to keep patients and staff safe without altering treatment-specific decisions,” Dr. Nanda said.

Streamlining the foot traffic in the cancer center also worked well for Lisa A. Carey, MD, chief of the Division of Hematology/Oncology and deputy director of clinical sciences at University of North Carolina-Chapel Hill. “The truth is, oncological principles of care are still in place,” said Dr. Carey, the Richardson and Marilyn Jacobs Preyer Distinguished Professor in Breast Cancer Research. “COVID hasn’t altered those; it has only thrown a little wrench in how we deliver that care.”

Kelly McCann, MD, PhD, a hematologist/oncologist in the Department of Medicine at the David Geffen School of Medicine, University of California, Los Angeles, has had to walk a tighter rope to protect her patients with MBC, as COVID cases began to soar in LA county last fall.

To keep patients with MBC home more, Dr. McCann said many chose oral cytotoxic chemotherapies over infusional therapies. Some patients with HER2-positive MBC, for instance, opted for the oral combination neratinib + capecitabine over a trastuzumab-deruxtecan infusion, and others with triple-negative tumors chose capecitabine over a taxane.

At City of Hope, Mortimer has had a different experience of LA county’s COVID surge. Because the center only treats patients with cancer, “we have not had huge numbers of patients with COVID or had to significantly modify our practice outside of screening patients who come in and doing fewer scans compared to pre-COVID,” she said. With these precautions, “we have had no internal transmission of COVID within our institution.”

Still, patients with MBC have gotten COVID, and treating both illnesses does complicate decision-making. In some cases, Mortimer has postponed cancer treatment for patients who can delay for a few weeks while they recover from COVID. But patients who need to continue MBC treatment receive care in a separate unit, and Mortimer considers prescribing Eli Lilly’s recently approved antibody therapy bamlanivimab to treat COVID symptoms. “For each situation, we can always page our infectious disease experts to address any concerns or questions,” Dr. Mortimer said.

The MBC and COVID toll

The biggest hurdle for patients with MBC has been less about treatment decisions and more about handling the psychological toll of the pandemic, according to Charles Shapiro, MD, medical oncologist, Icahn School of Medicine at Mount Sinai in New York City.

“These are my personal observations, but I’ve seen how much more stressful it is to have metastatic breast cancer during the pandemic,” said Dr. Shapiro, who worries that fear of COVID may fuel or exacerbate patients’ depression and anxiety. “Patients can’t have family and friends by their side during infusions or appointments, and many feel isolated because of the risk of exposure.”

Because most patients with MBC still need in-person care such as exams, blood draws, or chemotherapy infusions, Dr. McCann has found that many of her patients “are afraid to come to a medical center and have been delaying appointments, imaging, and procedures.”

The psychological toll of treating breast cancer during the pandemic has touched oncologists as well. A recent survey found that burnout scores were significantly higher among physicians whose patients experienced delays in care, including chemotherapy or specialty consultations.

Getting patients vaccinated will improve protection and hopefully lessen fears surrounding COVID infection and transmission. Preliminary recommendations from the National Comprehensive Cancer Network›s COVID-19 Vaccination Advisory Committee state that patients with cancer «should be prioritized for vaccination.»

Dr. McCann agreed. “I’ve recommended COVID-19 vaccination to all of my patients with MBC,” she said. But because a lot of these therapies suppress the immune system to some degree, “I’ll recommend a period of time for vaccination in which the immune system is expected to have recovered, such as in the days prior to a dose of chemotherapy.”

Overall, according to Dr. Carey, institutional responses to treating MBC during the pandemic have been very similar: The key has been that “no one is keeping secrets,” she said. “Our global oncology community is sharing and adopting best practices. Our focus has been doing right by our patients.”

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

Patients with metastatic breast cancer (MBC) face an elevated risk of severe illness or dying from COVID-19. Given the slow rollout of the Moderna and Pfizer COVID vaccines and new, more infectious viral variants circulating in the United States, oncologists will face a challenging balancing act for the foreseeable future: sustaining patients› MBC care while safeguarding them from COVID. The scale leans heavily toward continuing treatment, experts say.

“If we stop treatment for metastatic breast cancer, death will occur quickly,” Fatima F. Cardoso, MD, director of the breast unit at Champalimaud Clinical Centre in Lisbon, Portugal, stated this past August in a Medscape perspective.

Joanne Mortimer, MD, director of Women’s Cancer Programs at City of Hope, a comprehensive cancer center near Los Angeles, expressed a similar sentiment. “Having MBC is worse than getting COVID,” she told Medscape. “We can’t stop treating patients with MBC because of concerns of exposure.”

But maintaining treatment does not mean business as usual. Oncologists have had to modify their pre-pandemic practices to some degree, and that degree largely depends on local COVID conditions.

“Weighing the risk of treatment with the risk of contracting the virus means that many places have carried on treating metastatic breast cancer in a more thoughtful, careful way,” said Jill Dietz, MD, president of the American Society of Breast Surgeons. “That means focusing on high-value treatments for patients with the goal of maximizing their outcomes and quality of life while limiting in-person visits and potentially unnecessary elements of care.”

To guide this more careful approach, Dr. Dietz and colleagues from the recently formed COVID-19 Pandemic Breast Cancer Consortium published recommendations in April 2020 to account for different disease types and severities. These recommendations align closely with those from Cardoso and colleagues in Europe, also published last April.

Although issued early in the pandemic when there was greater uncertainty about viral transmission, adverse outcomes, and treatment for COVID-19, these recommendations still hold almost a year later.

“The framework has proven to be timeless in that it can help institutions where they are in the pandemic,” Dr. Dietz said.

The recommendations at play

For MBC, in particular, Dr. Dietz and colleagues focused on patients who need systemic care but whose treatment can be modified to keep them home more. The modifications include prescribing oral agents such as capecitabine, vinorelbine, and cyclophosphamide to minimize visits to the hospital or infusion suite.

To limit adverse events associated with these oral drugs, Dr. Dietz and colleagues also recommended reducing the dose when possible. For instance, research shows that lowering the dose of the CDK4/6 inhibitor palbociclib in patients with HR+/HER2-negative MBC does not diminish efficacy.

When oral agents are not an option, Dr. Dietz and colleagues suggested stretching out the intervals for chemotherapy infusions or injections. Data show that trastuzumab and pertuzumab injections for metastatic HER2-positive tumors «may reasonably be administered at longer intervals,» such as 4 weeks instead of 3 weeks.

The extent to which oncologists have applied these recommendations hinges on two factors: the local severity of COVID-19 cases and institution-specific policies.

For some oncologists, the pandemic has largely left treatment decisions untouched. “COVID-19 has only minimally impacted my practice,” said Rita Nanda, MD, director of the Breast Oncology Program and associate professor of medicine at University of Chicago Medicine.

Dr. Nanda recalled her concerns in the early days of the pandemic. As the nation watched COVID cases surge across New York City, Chicagoans prepared for the worst, fashioning the McCormick Place Convention Center into a field hospital for COVID patients.

“But fortunately, we were never overwhelmed at the University of Chicago and never needed to use the convention center,” Dr. Nanda said. “We did not have to alter or limit the type of therapy patients with MBC could receive.”

The main changes described by Dr. Nanda at the University of Chicago have centered around limiting the flow of traffic within the infusion suite or hospital by implementing prescreening checks to catch patients with COVID symptoms, keeping waiting rooms empty and infusion centers socially distanced, and having patients come in for appointments solo. The university’s home phlebotomy service also came in handy. Implemented before the pandemic, this service allowed patients with MBC to get their labs done at home before coming in for treatment.

“Overall, with social distancing, mask wearing, and limiting who comes in to the clinic, we have been able to keep patients and staff safe without altering treatment-specific decisions,” Dr. Nanda said.

Streamlining the foot traffic in the cancer center also worked well for Lisa A. Carey, MD, chief of the Division of Hematology/Oncology and deputy director of clinical sciences at University of North Carolina-Chapel Hill. “The truth is, oncological principles of care are still in place,” said Dr. Carey, the Richardson and Marilyn Jacobs Preyer Distinguished Professor in Breast Cancer Research. “COVID hasn’t altered those; it has only thrown a little wrench in how we deliver that care.”

Kelly McCann, MD, PhD, a hematologist/oncologist in the Department of Medicine at the David Geffen School of Medicine, University of California, Los Angeles, has had to walk a tighter rope to protect her patients with MBC, as COVID cases began to soar in LA county last fall.

To keep patients with MBC home more, Dr. McCann said many chose oral cytotoxic chemotherapies over infusional therapies. Some patients with HER2-positive MBC, for instance, opted for the oral combination neratinib + capecitabine over a trastuzumab-deruxtecan infusion, and others with triple-negative tumors chose capecitabine over a taxane.

At City of Hope, Mortimer has had a different experience of LA county’s COVID surge. Because the center only treats patients with cancer, “we have not had huge numbers of patients with COVID or had to significantly modify our practice outside of screening patients who come in and doing fewer scans compared to pre-COVID,” she said. With these precautions, “we have had no internal transmission of COVID within our institution.”

Still, patients with MBC have gotten COVID, and treating both illnesses does complicate decision-making. In some cases, Mortimer has postponed cancer treatment for patients who can delay for a few weeks while they recover from COVID. But patients who need to continue MBC treatment receive care in a separate unit, and Mortimer considers prescribing Eli Lilly’s recently approved antibody therapy bamlanivimab to treat COVID symptoms. “For each situation, we can always page our infectious disease experts to address any concerns or questions,” Dr. Mortimer said.

The MBC and COVID toll

The biggest hurdle for patients with MBC has been less about treatment decisions and more about handling the psychological toll of the pandemic, according to Charles Shapiro, MD, medical oncologist, Icahn School of Medicine at Mount Sinai in New York City.

“These are my personal observations, but I’ve seen how much more stressful it is to have metastatic breast cancer during the pandemic,” said Dr. Shapiro, who worries that fear of COVID may fuel or exacerbate patients’ depression and anxiety. “Patients can’t have family and friends by their side during infusions or appointments, and many feel isolated because of the risk of exposure.”

Because most patients with MBC still need in-person care such as exams, blood draws, or chemotherapy infusions, Dr. McCann has found that many of her patients “are afraid to come to a medical center and have been delaying appointments, imaging, and procedures.”

The psychological toll of treating breast cancer during the pandemic has touched oncologists as well. A recent survey found that burnout scores were significantly higher among physicians whose patients experienced delays in care, including chemotherapy or specialty consultations.

Getting patients vaccinated will improve protection and hopefully lessen fears surrounding COVID infection and transmission. Preliminary recommendations from the National Comprehensive Cancer Network›s COVID-19 Vaccination Advisory Committee state that patients with cancer «should be prioritized for vaccination.»

Dr. McCann agreed. “I’ve recommended COVID-19 vaccination to all of my patients with MBC,” she said. But because a lot of these therapies suppress the immune system to some degree, “I’ll recommend a period of time for vaccination in which the immune system is expected to have recovered, such as in the days prior to a dose of chemotherapy.”

Overall, according to Dr. Carey, institutional responses to treating MBC during the pandemic have been very similar: The key has been that “no one is keeping secrets,” she said. “Our global oncology community is sharing and adopting best practices. Our focus has been doing right by our patients.”

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

Patients with metastatic breast cancer (MBC) face an elevated risk of severe illness or dying from COVID-19. Given the slow rollout of the Moderna and Pfizer COVID vaccines and new, more infectious viral variants circulating in the United States, oncologists will face a challenging balancing act for the foreseeable future: sustaining patients› MBC care while safeguarding them from COVID. The scale leans heavily toward continuing treatment, experts say.

“If we stop treatment for metastatic breast cancer, death will occur quickly,” Fatima F. Cardoso, MD, director of the breast unit at Champalimaud Clinical Centre in Lisbon, Portugal, stated this past August in a Medscape perspective.

Joanne Mortimer, MD, director of Women’s Cancer Programs at City of Hope, a comprehensive cancer center near Los Angeles, expressed a similar sentiment. “Having MBC is worse than getting COVID,” she told Medscape. “We can’t stop treating patients with MBC because of concerns of exposure.”

But maintaining treatment does not mean business as usual. Oncologists have had to modify their pre-pandemic practices to some degree, and that degree largely depends on local COVID conditions.

“Weighing the risk of treatment with the risk of contracting the virus means that many places have carried on treating metastatic breast cancer in a more thoughtful, careful way,” said Jill Dietz, MD, president of the American Society of Breast Surgeons. “That means focusing on high-value treatments for patients with the goal of maximizing their outcomes and quality of life while limiting in-person visits and potentially unnecessary elements of care.”

To guide this more careful approach, Dr. Dietz and colleagues from the recently formed COVID-19 Pandemic Breast Cancer Consortium published recommendations in April 2020 to account for different disease types and severities. These recommendations align closely with those from Cardoso and colleagues in Europe, also published last April.

Although issued early in the pandemic when there was greater uncertainty about viral transmission, adverse outcomes, and treatment for COVID-19, these recommendations still hold almost a year later.

“The framework has proven to be timeless in that it can help institutions where they are in the pandemic,” Dr. Dietz said.

The recommendations at play

For MBC, in particular, Dr. Dietz and colleagues focused on patients who need systemic care but whose treatment can be modified to keep them home more. The modifications include prescribing oral agents such as capecitabine, vinorelbine, and cyclophosphamide to minimize visits to the hospital or infusion suite.

To limit adverse events associated with these oral drugs, Dr. Dietz and colleagues also recommended reducing the dose when possible. For instance, research shows that lowering the dose of the CDK4/6 inhibitor palbociclib in patients with HR+/HER2-negative MBC does not diminish efficacy.

When oral agents are not an option, Dr. Dietz and colleagues suggested stretching out the intervals for chemotherapy infusions or injections. Data show that trastuzumab and pertuzumab injections for metastatic HER2-positive tumors «may reasonably be administered at longer intervals,» such as 4 weeks instead of 3 weeks.

The extent to which oncologists have applied these recommendations hinges on two factors: the local severity of COVID-19 cases and institution-specific policies.

For some oncologists, the pandemic has largely left treatment decisions untouched. “COVID-19 has only minimally impacted my practice,” said Rita Nanda, MD, director of the Breast Oncology Program and associate professor of medicine at University of Chicago Medicine.

Dr. Nanda recalled her concerns in the early days of the pandemic. As the nation watched COVID cases surge across New York City, Chicagoans prepared for the worst, fashioning the McCormick Place Convention Center into a field hospital for COVID patients.

“But fortunately, we were never overwhelmed at the University of Chicago and never needed to use the convention center,” Dr. Nanda said. “We did not have to alter or limit the type of therapy patients with MBC could receive.”

The main changes described by Dr. Nanda at the University of Chicago have centered around limiting the flow of traffic within the infusion suite or hospital by implementing prescreening checks to catch patients with COVID symptoms, keeping waiting rooms empty and infusion centers socially distanced, and having patients come in for appointments solo. The university’s home phlebotomy service also came in handy. Implemented before the pandemic, this service allowed patients with MBC to get their labs done at home before coming in for treatment.

“Overall, with social distancing, mask wearing, and limiting who comes in to the clinic, we have been able to keep patients and staff safe without altering treatment-specific decisions,” Dr. Nanda said.

Streamlining the foot traffic in the cancer center also worked well for Lisa A. Carey, MD, chief of the Division of Hematology/Oncology and deputy director of clinical sciences at University of North Carolina-Chapel Hill. “The truth is, oncological principles of care are still in place,” said Dr. Carey, the Richardson and Marilyn Jacobs Preyer Distinguished Professor in Breast Cancer Research. “COVID hasn’t altered those; it has only thrown a little wrench in how we deliver that care.”

Kelly McCann, MD, PhD, a hematologist/oncologist in the Department of Medicine at the David Geffen School of Medicine, University of California, Los Angeles, has had to walk a tighter rope to protect her patients with MBC, as COVID cases began to soar in LA county last fall.

To keep patients with MBC home more, Dr. McCann said many chose oral cytotoxic chemotherapies over infusional therapies. Some patients with HER2-positive MBC, for instance, opted for the oral combination neratinib + capecitabine over a trastuzumab-deruxtecan infusion, and others with triple-negative tumors chose capecitabine over a taxane.

At City of Hope, Mortimer has had a different experience of LA county’s COVID surge. Because the center only treats patients with cancer, “we have not had huge numbers of patients with COVID or had to significantly modify our practice outside of screening patients who come in and doing fewer scans compared to pre-COVID,” she said. With these precautions, “we have had no internal transmission of COVID within our institution.”

Still, patients with MBC have gotten COVID, and treating both illnesses does complicate decision-making. In some cases, Mortimer has postponed cancer treatment for patients who can delay for a few weeks while they recover from COVID. But patients who need to continue MBC treatment receive care in a separate unit, and Mortimer considers prescribing Eli Lilly’s recently approved antibody therapy bamlanivimab to treat COVID symptoms. “For each situation, we can always page our infectious disease experts to address any concerns or questions,” Dr. Mortimer said.

The MBC and COVID toll

The biggest hurdle for patients with MBC has been less about treatment decisions and more about handling the psychological toll of the pandemic, according to Charles Shapiro, MD, medical oncologist, Icahn School of Medicine at Mount Sinai in New York City.

“These are my personal observations, but I’ve seen how much more stressful it is to have metastatic breast cancer during the pandemic,” said Dr. Shapiro, who worries that fear of COVID may fuel or exacerbate patients’ depression and anxiety. “Patients can’t have family and friends by their side during infusions or appointments, and many feel isolated because of the risk of exposure.”

Because most patients with MBC still need in-person care such as exams, blood draws, or chemotherapy infusions, Dr. McCann has found that many of her patients “are afraid to come to a medical center and have been delaying appointments, imaging, and procedures.”

The psychological toll of treating breast cancer during the pandemic has touched oncologists as well. A recent survey found that burnout scores were significantly higher among physicians whose patients experienced delays in care, including chemotherapy or specialty consultations.

Getting patients vaccinated will improve protection and hopefully lessen fears surrounding COVID infection and transmission. Preliminary recommendations from the National Comprehensive Cancer Network›s COVID-19 Vaccination Advisory Committee state that patients with cancer «should be prioritized for vaccination.»

Dr. McCann agreed. “I’ve recommended COVID-19 vaccination to all of my patients with MBC,” she said. But because a lot of these therapies suppress the immune system to some degree, “I’ll recommend a period of time for vaccination in which the immune system is expected to have recovered, such as in the days prior to a dose of chemotherapy.”

Overall, according to Dr. Carey, institutional responses to treating MBC during the pandemic have been very similar: The key has been that “no one is keeping secrets,” she said. “Our global oncology community is sharing and adopting best practices. Our focus has been doing right by our patients.”

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

Neoadjuvant chemoradiation plus esophagectomy can be performed safely in well-selected older patients with locally advanced esophageal or esophagogastric junction cancer, according to a review 282 patients treated from 2004 through 2019 at Ochsner Medical Center, New Orleans.

Although guidelines recommend curative-intent neoadjuvant chemoradiation (NACR) followed by surgical resection, it’s been demonstrated in several studies that “older patients with potentially curable stage II and III disease are often not considered” for the approach out of concern that they will not tolerate it, said investigators led by W. Peter Sawyer, MD, a surgery resident at Ochsner.

Outcomes, however, were comparable in the study when 188 patients aged younger than 70 years were compared with 94 patients aged 70 years or older, including 4 who were over 80 years old. “Patients 70 years and older should be evaluated for optimal curative therapy including neoadjuvant chemoradiotherapy and surgical resection,” the investigators concluded.

The patients had NACR followed by esophagectomy mostly for stage 2 disease. The average age was 59 years in the younger group and 74 years in the older group.

Older patients had a higher prevalence of cardiac, vascular, and pulmonary comorbidities and were more likely to have postoperative atrial arrhythmia and urinary retention.

However, there were no statistically significant differences in hospital length of stay (about 10 days in both groups), operative mortality (4.3% in the older group versus 3.8% in the younger group), or the incidence of postoperative grade 3 or higher complications (27.7% older versus 38.3% younger). Age-adjusted survival was 44.8% at 5 years among patients 70 years and older versus 39% among younger patients.

Comorbidity scores, clinically positive nodes, and clinical T3 tumors predicted worse survival on multivariate analysis, but age did not.

“Age itself doesn’t represent a contraindication to aggressive treatment. It is the patient’s comorbidities and functional status which are more important to predict the risk of complications after esophagectomy,” said Daniela Molena, MD, director of the esophageal surgery program at Memorial Sloan Kettering Cancer Center, New York, when asked for a comment.

The team noted that the results “reflect careful patient selection as well as thorough preoperative evaluation and preparation.” Patients with unstable or severe chronic heart disease, moderate to severe chronic liver disease, or severe chronic pulmonary disease were ineligible for surgery. Eligible patients had cardiac stress testing and were strongly encouraged to begin daily exercise. Nutritional deficiencies were addressed before surgery.

The Ochsner team is one of several in recent years that have pushed back on age limits for aggressive esophageal cancer treatment.

A British team, for example, reviewed 992 transthoracic esophagectomies, including 330 in patients 70 years or older, and found lower in-hospital mortality and pulmonary and cardiac morbidity for older patients than previously reported.

They concluded that “age should not be a discriminating factor when determining the treatment strategy for patients presenting with curative esophageal cancer.”

Even so, undertreatment remains “a big problem for elderly patients, and since the median age at diagnoses is 68 years, this is a problem for a large portion of patients with esophageal cancer,” Dr. Molena said.

“Patients can be cured of this disease” with aggressive treatment, but “unfortunately, patients often are not evaluated by a surgeon or referred to a high-volume center and are discouraged from undergoing surgery after an apparent good response to chemoradiation,” partly because esophagectomy has “unfairly gained a bad reputation over the years,” she said.

“There are clear data that outcomes of esophagectomy are very good at high volume centers with minimally invasive techniques and the ability to promptly identify and treat complications,” Dr. Molena said.

Overall, 52% of patients aged 70 years or older with stage II and III disease underwent NACR plus surgery at Ochsner, suggesting that “optimal, curative intent triple modality therapy [chemo, radiation, and esophagectomy] can be used successfully in a sizable segment of the elderly population,” the investigators said.

Treatment has changed significantly at Ochsner since the start of the review period in 2004, including a shift away from a fluorouracil and cisplatin doublet in favor of carboplatin and paclitaxel, which is less toxic, and greater use of minimally invasive surgery. The proportion of people 70 years or older undergoing triple modality treatment has been steadily increasing.

There was no outside funding. Investigator disclosures weren’t reported. Dr. Molena had no relevant disclosures.
 

aotto@mdedge.com

Neoadjuvant chemoradiation plus esophagectomy can be performed safely in well-selected older patients with locally advanced esophageal or esophagogastric junction cancer, according to a review 282 patients treated from 2004 through 2019 at Ochsner Medical Center, New Orleans.

Although guidelines recommend curative-intent neoadjuvant chemoradiation (NACR) followed by surgical resection, it’s been demonstrated in several studies that “older patients with potentially curable stage II and III disease are often not considered” for the approach out of concern that they will not tolerate it, said investigators led by W. Peter Sawyer, MD, a surgery resident at Ochsner.

Outcomes, however, were comparable in the study when 188 patients aged younger than 70 years were compared with 94 patients aged 70 years or older, including 4 who were over 80 years old. “Patients 70 years and older should be evaluated for optimal curative therapy including neoadjuvant chemoradiotherapy and surgical resection,” the investigators concluded.

The patients had NACR followed by esophagectomy mostly for stage 2 disease. The average age was 59 years in the younger group and 74 years in the older group.

Older patients had a higher prevalence of cardiac, vascular, and pulmonary comorbidities and were more likely to have postoperative atrial arrhythmia and urinary retention.

However, there were no statistically significant differences in hospital length of stay (about 10 days in both groups), operative mortality (4.3% in the older group versus 3.8% in the younger group), or the incidence of postoperative grade 3 or higher complications (27.7% older versus 38.3% younger). Age-adjusted survival was 44.8% at 5 years among patients 70 years and older versus 39% among younger patients.

Comorbidity scores, clinically positive nodes, and clinical T3 tumors predicted worse survival on multivariate analysis, but age did not.

“Age itself doesn’t represent a contraindication to aggressive treatment. It is the patient’s comorbidities and functional status which are more important to predict the risk of complications after esophagectomy,” said Daniela Molena, MD, director of the esophageal surgery program at Memorial Sloan Kettering Cancer Center, New York, when asked for a comment.

The team noted that the results “reflect careful patient selection as well as thorough preoperative evaluation and preparation.” Patients with unstable or severe chronic heart disease, moderate to severe chronic liver disease, or severe chronic pulmonary disease were ineligible for surgery. Eligible patients had cardiac stress testing and were strongly encouraged to begin daily exercise. Nutritional deficiencies were addressed before surgery.

The Ochsner team is one of several in recent years that have pushed back on age limits for aggressive esophageal cancer treatment.

A British team, for example, reviewed 992 transthoracic esophagectomies, including 330 in patients 70 years or older, and found lower in-hospital mortality and pulmonary and cardiac morbidity for older patients than previously reported.

They concluded that “age should not be a discriminating factor when determining the treatment strategy for patients presenting with curative esophageal cancer.”

Even so, undertreatment remains “a big problem for elderly patients, and since the median age at diagnoses is 68 years, this is a problem for a large portion of patients with esophageal cancer,” Dr. Molena said.

“Patients can be cured of this disease” with aggressive treatment, but “unfortunately, patients often are not evaluated by a surgeon or referred to a high-volume center and are discouraged from undergoing surgery after an apparent good response to chemoradiation,” partly because esophagectomy has “unfairly gained a bad reputation over the years,” she said.

“There are clear data that outcomes of esophagectomy are very good at high volume centers with minimally invasive techniques and the ability to promptly identify and treat complications,” Dr. Molena said.

Overall, 52% of patients aged 70 years or older with stage II and III disease underwent NACR plus surgery at Ochsner, suggesting that “optimal, curative intent triple modality therapy [chemo, radiation, and esophagectomy] can be used successfully in a sizable segment of the elderly population,” the investigators said.

Treatment has changed significantly at Ochsner since the start of the review period in 2004, including a shift away from a fluorouracil and cisplatin doublet in favor of carboplatin and paclitaxel, which is less toxic, and greater use of minimally invasive surgery. The proportion of people 70 years or older undergoing triple modality treatment has been steadily increasing.

There was no outside funding. Investigator disclosures weren’t reported. Dr. Molena had no relevant disclosures.
 

aotto@mdedge.com

Neoadjuvant chemoradiation plus esophagectomy can be performed safely in well-selected older patients with locally advanced esophageal or esophagogastric junction cancer, according to a review 282 patients treated from 2004 through 2019 at Ochsner Medical Center, New Orleans.

Although guidelines recommend curative-intent neoadjuvant chemoradiation (NACR) followed by surgical resection, it’s been demonstrated in several studies that “older patients with potentially curable stage II and III disease are often not considered” for the approach out of concern that they will not tolerate it, said investigators led by W. Peter Sawyer, MD, a surgery resident at Ochsner.

Outcomes, however, were comparable in the study when 188 patients aged younger than 70 years were compared with 94 patients aged 70 years or older, including 4 who were over 80 years old. “Patients 70 years and older should be evaluated for optimal curative therapy including neoadjuvant chemoradiotherapy and surgical resection,” the investigators concluded.

The patients had NACR followed by esophagectomy mostly for stage 2 disease. The average age was 59 years in the younger group and 74 years in the older group.

Older patients had a higher prevalence of cardiac, vascular, and pulmonary comorbidities and were more likely to have postoperative atrial arrhythmia and urinary retention.

However, there were no statistically significant differences in hospital length of stay (about 10 days in both groups), operative mortality (4.3% in the older group versus 3.8% in the younger group), or the incidence of postoperative grade 3 or higher complications (27.7% older versus 38.3% younger). Age-adjusted survival was 44.8% at 5 years among patients 70 years and older versus 39% among younger patients.

Comorbidity scores, clinically positive nodes, and clinical T3 tumors predicted worse survival on multivariate analysis, but age did not.

“Age itself doesn’t represent a contraindication to aggressive treatment. It is the patient’s comorbidities and functional status which are more important to predict the risk of complications after esophagectomy,” said Daniela Molena, MD, director of the esophageal surgery program at Memorial Sloan Kettering Cancer Center, New York, when asked for a comment.

The team noted that the results “reflect careful patient selection as well as thorough preoperative evaluation and preparation.” Patients with unstable or severe chronic heart disease, moderate to severe chronic liver disease, or severe chronic pulmonary disease were ineligible for surgery. Eligible patients had cardiac stress testing and were strongly encouraged to begin daily exercise. Nutritional deficiencies were addressed before surgery.

The Ochsner team is one of several in recent years that have pushed back on age limits for aggressive esophageal cancer treatment.

A British team, for example, reviewed 992 transthoracic esophagectomies, including 330 in patients 70 years or older, and found lower in-hospital mortality and pulmonary and cardiac morbidity for older patients than previously reported.

They concluded that “age should not be a discriminating factor when determining the treatment strategy for patients presenting with curative esophageal cancer.”

Even so, undertreatment remains “a big problem for elderly patients, and since the median age at diagnoses is 68 years, this is a problem for a large portion of patients with esophageal cancer,” Dr. Molena said.

“Patients can be cured of this disease” with aggressive treatment, but “unfortunately, patients often are not evaluated by a surgeon or referred to a high-volume center and are discouraged from undergoing surgery after an apparent good response to chemoradiation,” partly because esophagectomy has “unfairly gained a bad reputation over the years,” she said.

“There are clear data that outcomes of esophagectomy are very good at high volume centers with minimally invasive techniques and the ability to promptly identify and treat complications,” Dr. Molena said.

Overall, 52% of patients aged 70 years or older with stage II and III disease underwent NACR plus surgery at Ochsner, suggesting that “optimal, curative intent triple modality therapy [chemo, radiation, and esophagectomy] can be used successfully in a sizable segment of the elderly population,” the investigators said.

Treatment has changed significantly at Ochsner since the start of the review period in 2004, including a shift away from a fluorouracil and cisplatin doublet in favor of carboplatin and paclitaxel, which is less toxic, and greater use of minimally invasive surgery. The proportion of people 70 years or older undergoing triple modality treatment has been steadily increasing.

There was no outside funding. Investigator disclosures weren’t reported. Dr. Molena had no relevant disclosures.
 

aotto@mdedge.com

Globally, some 700,000 people die from antibiotic-resistant infections ever year; by 2050, that number could be 10 million, according to the United Nations. To find new ways to fight pathogenic microorganisms, scientists are looking to Crispr, the gene-editing tool, according to the New York Times.

“Crispr is a specialized region of DNA that creates what amount to genetic scissors – enzymes that allow the cell (or a scientist) to precisely edit other DNA or its sister molecule, RNA…Crispr was originally discovered in bacteria, where it helps keep track of past injury. When a virus attacks, the bacterium stores small chunks of the viral genome within its own DNA. This helps the bacterium recognize viral infections when they occur again. Then, using Crispr-associated enzymes, it can disarm the virus and prevent the infection from spreading…today researchers are looking to Crispr to edit bacteria and viruses that infect humans and create new treatments.”

In a recent study, researchers successfully used a Crispr-associated enzyme called Cas9 to eliminate a species of Salmonella. They programmed the Cas9 to view the bacterium as the enemy and forced Salmonella to make lethal cuts to its own genome.

Some companies are now exploring Crispr-based antibiotics that might be delivered through viruses engineered so that they cannot reproduce or cause infections themselves, to name just one approach.

“Now researchers face the challenge of demonstrating that Crispr antibacterial and antiviral drugs are effective in living animals and in humans, not just in the lab, and that they will be cheaper than conventional therapies.”
 

Reference

1. Sheikh K. Is Crispr the Next Antibiotic? The New York Times. Oct 28, 2019.

https://www.nytimes.com/2019/10/28/health/crispr-genetics-antibiotic-resistance.html. Accessed Dec 3, 2019.

Globally, some 700,000 people die from antibiotic-resistant infections ever year; by 2050, that number could be 10 million, according to the United Nations. To find new ways to fight pathogenic microorganisms, scientists are looking to Crispr, the gene-editing tool, according to the New York Times.

“Crispr is a specialized region of DNA that creates what amount to genetic scissors – enzymes that allow the cell (or a scientist) to precisely edit other DNA or its sister molecule, RNA…Crispr was originally discovered in bacteria, where it helps keep track of past injury. When a virus attacks, the bacterium stores small chunks of the viral genome within its own DNA. This helps the bacterium recognize viral infections when they occur again. Then, using Crispr-associated enzymes, it can disarm the virus and prevent the infection from spreading…today researchers are looking to Crispr to edit bacteria and viruses that infect humans and create new treatments.”

In a recent study, researchers successfully used a Crispr-associated enzyme called Cas9 to eliminate a species of Salmonella. They programmed the Cas9 to view the bacterium as the enemy and forced Salmonella to make lethal cuts to its own genome.

Some companies are now exploring Crispr-based antibiotics that might be delivered through viruses engineered so that they cannot reproduce or cause infections themselves, to name just one approach.

“Now researchers face the challenge of demonstrating that Crispr antibacterial and antiviral drugs are effective in living animals and in humans, not just in the lab, and that they will be cheaper than conventional therapies.”
 

Reference

1. Sheikh K. Is Crispr the Next Antibiotic? The New York Times. Oct 28, 2019.

https://www.nytimes.com/2019/10/28/health/crispr-genetics-antibiotic-resistance.html. Accessed Dec 3, 2019.

Globally, some 700,000 people die from antibiotic-resistant infections ever year; by 2050, that number could be 10 million, according to the United Nations. To find new ways to fight pathogenic microorganisms, scientists are looking to Crispr, the gene-editing tool, according to the New York Times.

“Crispr is a specialized region of DNA that creates what amount to genetic scissors – enzymes that allow the cell (or a scientist) to precisely edit other DNA or its sister molecule, RNA…Crispr was originally discovered in bacteria, where it helps keep track of past injury. When a virus attacks, the bacterium stores small chunks of the viral genome within its own DNA. This helps the bacterium recognize viral infections when they occur again. Then, using Crispr-associated enzymes, it can disarm the virus and prevent the infection from spreading…today researchers are looking to Crispr to edit bacteria and viruses that infect humans and create new treatments.”

In a recent study, researchers successfully used a Crispr-associated enzyme called Cas9 to eliminate a species of Salmonella. They programmed the Cas9 to view the bacterium as the enemy and forced Salmonella to make lethal cuts to its own genome.

Some companies are now exploring Crispr-based antibiotics that might be delivered through viruses engineered so that they cannot reproduce or cause infections themselves, to name just one approach.

“Now researchers face the challenge of demonstrating that Crispr antibacterial and antiviral drugs are effective in living animals and in humans, not just in the lab, and that they will be cheaper than conventional therapies.”
 

Reference

1. Sheikh K. Is Crispr the Next Antibiotic? The New York Times. Oct 28, 2019.

https://www.nytimes.com/2019/10/28/health/crispr-genetics-antibiotic-resistance.html. Accessed Dec 3, 2019.

The pandemic has affected reproductive health because of barriers to contraception access, potentially increasing unwanted pregnancies, reported Tracy Kuo Lin, PhD, of the University of California, San Francisco, and associates.

During the pandemic, women have experienced an increased desire to avoid pregnancy, and when that desire is coupled with loss of income, accessing contraception becomes more difficult, Dr. Lin and colleagues observed in a cross-sectional survey published in the journal Contraception.

The study aimed to quantify the effect of COVID-19 on women’s economic status and reproductive health decisions related to childbearing and pregnancy. Women aged 18-49 who resided in the U.S. were targeted via Facebook and Instagram advertisements from May 16 to June 16, 2020. In all, 554 racially diverse respondents from 43 states were selected: 41% aged 18-24, 37% aged 25-34, and 23% aged 35-49.
 

Income losses affect nearly half of respondents

In determining risk of unwanted pregnancy, the researchers considered the influence of COVID-19 on a number of factors related to economic well-being as well as respondents’ sexual activity, intimate partner violence, overall desire for pregnancy, and access to contraception as issues affecting their interest in becoming pregnant and their ability to access medical care and contraception. Overall, 46% experienced a reduction in income, 43% reported no change, and 10% experienced an increase in income.

Difficulty in being able to afford food, transportation, and housing doubled among respondents from 8% to 16% as a result of the pandemic. The study authors cited education, race/ethnicity, federal poverty level, and change in income as predictors of inability to provide for these basic needs.

A total of 83% of respondents reported having sex within the past month; 54% of those had sex with someone they lived with, compared with 29% who had sex with someone they did not live with. The pandemic had no impact on sexual desire for 37% of respondents, compared with 32% who experienced a decrease in desire, and 29% who experienced more desire for sex. The presence of shelter-in-place orders had no effect on frequency of or desire for sex. Among the respondents, 4% noted intimate partner violence, which increased slightly from 3% before the pandemic.

Among respondents using contraception, the study authors noted that 17% reported greater difficulty accessing birth control during the pandemic compared with 4% who felt access had become easier. Of those citing increased difficulties, 9% noted increasing challenges getting to a pharmacy, 4% were less able to afford birth control, 3% said it had become harder to obtain a prescription, and 1% cited difficulties having long-acting reversible contraceptives removed.

Despite the pandemic’s overall impact on quality of life, 41% of respondents reported a stronger desire to become pregnant, compared with 25% who had a reduced desire, and 34% whose interest in pregnancy was unchanged by the pandemic.

More than one-third of respondents (37%) admitted that COVID-19 contributed to their fears of becoming pregnant while 13% indicated their fear of pregnancy stemmed from concerns over being able to afford the cost of having a child. Not surprisingly, the decrease in desire for pregnancy was twice as high in those who reported they were unable to afford food, transportation, and/or housing compared with those who saw no change in their ability to afford basic needs.

“In these uncertain economic times, it is of utmost importance to create policies that will ensure access to and comprehensive coverage of core sexual and reproductive health services,” Dr. Lin and colleagues urged. “By doing so, we safeguard people’s ability to make decisions that support their reproductive health goals.”
 

Will COVID-19 drive needed practice and policy changes?

“This study highlights the economic and reproductive health toll of COVID-19 and the pressing need for improved contraception access,” Eve Espey, MD, MPH, said in an interview.

“Ob.gyns. and other practitioners can use this information to consider evidence-based practice changes that incorporate telemedicine visits, extended refills on contraceptive methods, and a focus on postpartum and postabortion initiation of contraception,” noted Dr. Espey, of the University of New Mexico, Albuquerque. For women who are experiencing economic hardship, consulting with state-based programs that offer pharmacy access and online access to contraceptives may offer a reasonable alternative, she added.

The study was funded by the University of California, San Francisco’s National Center of Excellence in Women’s Health. Dr. Lin received funding from Lazarex Cancer Foundation. The remaining authors had no conflicts of interest and reported no disclosures.

The pandemic has affected reproductive health because of barriers to contraception access, potentially increasing unwanted pregnancies, reported Tracy Kuo Lin, PhD, of the University of California, San Francisco, and associates.

During the pandemic, women have experienced an increased desire to avoid pregnancy, and when that desire is coupled with loss of income, accessing contraception becomes more difficult, Dr. Lin and colleagues observed in a cross-sectional survey published in the journal Contraception.

The study aimed to quantify the effect of COVID-19 on women’s economic status and reproductive health decisions related to childbearing and pregnancy. Women aged 18-49 who resided in the U.S. were targeted via Facebook and Instagram advertisements from May 16 to June 16, 2020. In all, 554 racially diverse respondents from 43 states were selected: 41% aged 18-24, 37% aged 25-34, and 23% aged 35-49.
 

Income losses affect nearly half of respondents

In determining risk of unwanted pregnancy, the researchers considered the influence of COVID-19 on a number of factors related to economic well-being as well as respondents’ sexual activity, intimate partner violence, overall desire for pregnancy, and access to contraception as issues affecting their interest in becoming pregnant and their ability to access medical care and contraception. Overall, 46% experienced a reduction in income, 43% reported no change, and 10% experienced an increase in income.

Difficulty in being able to afford food, transportation, and housing doubled among respondents from 8% to 16% as a result of the pandemic. The study authors cited education, race/ethnicity, federal poverty level, and change in income as predictors of inability to provide for these basic needs.

A total of 83% of respondents reported having sex within the past month; 54% of those had sex with someone they lived with, compared with 29% who had sex with someone they did not live with. The pandemic had no impact on sexual desire for 37% of respondents, compared with 32% who experienced a decrease in desire, and 29% who experienced more desire for sex. The presence of shelter-in-place orders had no effect on frequency of or desire for sex. Among the respondents, 4% noted intimate partner violence, which increased slightly from 3% before the pandemic.

Among respondents using contraception, the study authors noted that 17% reported greater difficulty accessing birth control during the pandemic compared with 4% who felt access had become easier. Of those citing increased difficulties, 9% noted increasing challenges getting to a pharmacy, 4% were less able to afford birth control, 3% said it had become harder to obtain a prescription, and 1% cited difficulties having long-acting reversible contraceptives removed.

Despite the pandemic’s overall impact on quality of life, 41% of respondents reported a stronger desire to become pregnant, compared with 25% who had a reduced desire, and 34% whose interest in pregnancy was unchanged by the pandemic.

More than one-third of respondents (37%) admitted that COVID-19 contributed to their fears of becoming pregnant while 13% indicated their fear of pregnancy stemmed from concerns over being able to afford the cost of having a child. Not surprisingly, the decrease in desire for pregnancy was twice as high in those who reported they were unable to afford food, transportation, and/or housing compared with those who saw no change in their ability to afford basic needs.

“In these uncertain economic times, it is of utmost importance to create policies that will ensure access to and comprehensive coverage of core sexual and reproductive health services,” Dr. Lin and colleagues urged. “By doing so, we safeguard people’s ability to make decisions that support their reproductive health goals.”
 

Will COVID-19 drive needed practice and policy changes?

“This study highlights the economic and reproductive health toll of COVID-19 and the pressing need for improved contraception access,” Eve Espey, MD, MPH, said in an interview.

“Ob.gyns. and other practitioners can use this information to consider evidence-based practice changes that incorporate telemedicine visits, extended refills on contraceptive methods, and a focus on postpartum and postabortion initiation of contraception,” noted Dr. Espey, of the University of New Mexico, Albuquerque. For women who are experiencing economic hardship, consulting with state-based programs that offer pharmacy access and online access to contraceptives may offer a reasonable alternative, she added.

The study was funded by the University of California, San Francisco’s National Center of Excellence in Women’s Health. Dr. Lin received funding from Lazarex Cancer Foundation. The remaining authors had no conflicts of interest and reported no disclosures.

The pandemic has affected reproductive health because of barriers to contraception access, potentially increasing unwanted pregnancies, reported Tracy Kuo Lin, PhD, of the University of California, San Francisco, and associates.

During the pandemic, women have experienced an increased desire to avoid pregnancy, and when that desire is coupled with loss of income, accessing contraception becomes more difficult, Dr. Lin and colleagues observed in a cross-sectional survey published in the journal Contraception.

The study aimed to quantify the effect of COVID-19 on women’s economic status and reproductive health decisions related to childbearing and pregnancy. Women aged 18-49 who resided in the U.S. were targeted via Facebook and Instagram advertisements from May 16 to June 16, 2020. In all, 554 racially diverse respondents from 43 states were selected: 41% aged 18-24, 37% aged 25-34, and 23% aged 35-49.
 

Income losses affect nearly half of respondents

In determining risk of unwanted pregnancy, the researchers considered the influence of COVID-19 on a number of factors related to economic well-being as well as respondents’ sexual activity, intimate partner violence, overall desire for pregnancy, and access to contraception as issues affecting their interest in becoming pregnant and their ability to access medical care and contraception. Overall, 46% experienced a reduction in income, 43% reported no change, and 10% experienced an increase in income.

Difficulty in being able to afford food, transportation, and housing doubled among respondents from 8% to 16% as a result of the pandemic. The study authors cited education, race/ethnicity, federal poverty level, and change in income as predictors of inability to provide for these basic needs.

A total of 83% of respondents reported having sex within the past month; 54% of those had sex with someone they lived with, compared with 29% who had sex with someone they did not live with. The pandemic had no impact on sexual desire for 37% of respondents, compared with 32% who experienced a decrease in desire, and 29% who experienced more desire for sex. The presence of shelter-in-place orders had no effect on frequency of or desire for sex. Among the respondents, 4% noted intimate partner violence, which increased slightly from 3% before the pandemic.

Among respondents using contraception, the study authors noted that 17% reported greater difficulty accessing birth control during the pandemic compared with 4% who felt access had become easier. Of those citing increased difficulties, 9% noted increasing challenges getting to a pharmacy, 4% were less able to afford birth control, 3% said it had become harder to obtain a prescription, and 1% cited difficulties having long-acting reversible contraceptives removed.

Despite the pandemic’s overall impact on quality of life, 41% of respondents reported a stronger desire to become pregnant, compared with 25% who had a reduced desire, and 34% whose interest in pregnancy was unchanged by the pandemic.

More than one-third of respondents (37%) admitted that COVID-19 contributed to their fears of becoming pregnant while 13% indicated their fear of pregnancy stemmed from concerns over being able to afford the cost of having a child. Not surprisingly, the decrease in desire for pregnancy was twice as high in those who reported they were unable to afford food, transportation, and/or housing compared with those who saw no change in their ability to afford basic needs.

“In these uncertain economic times, it is of utmost importance to create policies that will ensure access to and comprehensive coverage of core sexual and reproductive health services,” Dr. Lin and colleagues urged. “By doing so, we safeguard people’s ability to make decisions that support their reproductive health goals.”
 

Will COVID-19 drive needed practice and policy changes?

“This study highlights the economic and reproductive health toll of COVID-19 and the pressing need for improved contraception access,” Eve Espey, MD, MPH, said in an interview.

“Ob.gyns. and other practitioners can use this information to consider evidence-based practice changes that incorporate telemedicine visits, extended refills on contraceptive methods, and a focus on postpartum and postabortion initiation of contraception,” noted Dr. Espey, of the University of New Mexico, Albuquerque. For women who are experiencing economic hardship, consulting with state-based programs that offer pharmacy access and online access to contraceptives may offer a reasonable alternative, she added.

The study was funded by the University of California, San Francisco’s National Center of Excellence in Women’s Health. Dr. Lin received funding from Lazarex Cancer Foundation. The remaining authors had no conflicts of interest and reported no disclosures.

Restoring movement following a stroke can be challenging, but recent proof-of-concept research may offer an effective way to do just that. Researchers behind the ongoing Cortimo trial successfully performed a procedure on a patient 2 years removed from a stroke, in which microelectrode arrays were implanted into his brain to decode signals driving motor function. These signals then allowed him to operate a powered brace worn on his paralyzed arm.

This news organization spoke with the trial’s principal investigator, Mijail D. Serruya, MD, PhD, an assistant professor of neurology at Thomas Jefferson University Hospital, Philadelphia, about the trial’s initial findings, what this technology may ultimately look like, and the implications for stroke patients in knowing that restorative interventions may be on the horizon.
 

How did you first get involved with implanting electrodes to help stroke patients with recovery?

I was involved in the first human application of a microelectrode array in a young man who had quadriplegia because of a spinal cord injury. We showed that we could record signal directly from his motor cortex and use it to move a cursor on the screen, and open and close a prosthetic hand and arm.

I was naive and thought that this would soon be a widely available clinical medical device. Now it’s nearly 15 years later, and while it certainly has been safely used in multiple labs to record signals from people with spinal cord injury, amyotrophic lateral sclerosis (ALS), or locked-in syndrome from a brain stem stroke, it still requires a team of technicians and a percutaneous connector. It really has not gotten out of the university.

A few years ago I spoke with Robert Rosenwasser, MD, chairman of the department of neurosurgery at Thomas Jefferson, who runs a very busy stroke center and performed the surgery in this trial. We put our heads together and said: “Maybe the time is now to see whether we can move this technology to this much more prevalent condition of a hemispheric stroke.” And that’s what we did.
 

How did the idea of using computer brain electrode interfaces begin?

Around 20 years ago, if you had someone who had severe paralysis and you wanted to restore movement, the question was, where can you get a good control signal from? Obviously, if someone can talk, they can use a voice-actuated system with speech recognition and maybe you can track their eye gaze. But if they’re trying to move their limbs, you want a motor control signal.

In someone who has end-stage ALS or a brain stem stroke, you can’t even record residual muscle activity; you have almost nothing to work with. The only thing left is to try to record directly from the brain itself.

It’s important to clarify that brain-computer interfaces are not necessarily stimulating the brain to inject the signal. They’re just recording the endogenous activity that the brain makes. In comparison, a deep brain stimulator is usually not recording anything; it’s just delivering energy to the brain and hoping for the best.

But what we’re doing is asking, if the person is trying to move the paralyzed limb but can’t, can we get to the source of the signal and then do something with it?
 

What’s the process for measuring that in, for example, someone who has a localized lesion in the motor cortex?

The first step is a scan. People have been doing functional MRI on patients who have had a stroke as long as we’ve had fMRI. We know that people can actually activate on MRI areas of their brain around the stroke, but obviously not in the stroke because it’s been lesioned. However, we do know that the circuit adjacent to it and other regions do appear able to be modulated.

So by having a person either imagine trying to do what they want to do or doing what they can do, if they have some tiny residual movement, you can then identify a kind of hot spot on the fMRI where the brain gobbles up all the oxygen because it’s so active. Then that gives you an anatomical target for the surgeon to place the electrode arrays.
 

The Cortimo trial’s enticing findings

What are the most striking results that you’ve seen so far with the device?

The first thing is that we were able to get such recordings at all. We knew from fMRIs that there were fluctuations in oxygen changing when the person was trying to do something they couldn’t do. But nobody knew that you would see this whole population of individual neurons chattering away when you place these electrode arrays in the motor cortex right next to the stroke, and make sense of what we’re recording.

Obviously, that’s very encouraging and gives us hope that many months or years after a stroke, people’s brains are able to maintain this representation of all these different movements and plans. It’s almost like it’s trapped on the other side of the stroke and some of the signals can’t get out.

The other discovery we’re pleased with is that we can actually decode signals in real time and the person can use it to do something, such as trigger the brain to open and close the hand. That’s very different from all the prior research with brain array interfaces.

Furthermore, the gentleman who participated actually had strokes in other parts of his brain affecting his vision; he had homonymous hemianopia. That raised the question of what happens if you affect parts of the brain that have to do with attention and visual processing. Could a system like this work? And again, the answer appears to be yes.
 

What are the next steps for this technology before it can potentially become available in the clinic?

For this to work, the system clearly has to be fully implantable. What we used was percutaneous. The risk-benefit may be acceptable for someone who has quadriplegia because of, for example, spinal cord injury or end-stage ALS who may already have a tracheostomy and a percutaneous endoscopic gastrostomy. But for someone who is hemiparetic and ambulatory, that may not be acceptable. And a fully implantable system would also have much better patient compliance.

Also, when you’re recording from lots and lots of individual brain cells at many, many samples a second on many, many channels, it’s certainly an engineering challenge. It’s not just a single channel that you occasionally query; it’s hundreds of thousands of channels of this complicated data stream.

But these are solvable challenges. People have been making a lot of progress. It’s really a matter of funding and the engineering expertise, rather than some sort of fundamental scientific breakthrough.

With that said, I think it could be within the next 5-10 years that we could actually have a product that expands the toolbox of what can be done for patients who’ve had a stroke, if they’re motivated and there’s no real contraindication.
 

Creating a novel device

On that point, are you partnering with engineering and technology companies?

The hope is that we and other groups working on this can do for the interface sort of what Celera Genomics did for the Human Genome Project. By having enough interest and investment, you may be able to propel the field forward to widespread use rather than just a purely academic, lab-science type of project.

We are in discussion with different companies to see how we can move ahead with this, and we would be pleased to work with whomever is interested. It may be that different companies have different pieces of the puzzle – a better sensor or a better wireless transmitter.

The plan is to move as quickly as we can to a fully implantable system. And then the benchmark for any kind of clinical advancement is to do a prospective trial. With devices, if you can get a big enough effect size, then you sometimes don’t need quite as many patients to prove it. If paralysis is striking enough and you can reverse that, then you can convince the Food and Drug Administration of its safety and efficacy, and the various insurance companies, that it’s actually reasonable and necessary.
 

How long will an implantable device last?

That’s a key question and concern. If you have someone like our participant, who’s in his early 40s, will it keep working 10, 20, 30, 40 years? For the rest of his life? Deep brain stimulators and cochlear implants do function for those long durations, but their designs are quite different. There’s a macroelectrode that’s just delivering current, which is very different from listening in on this microscopic scale. There are different technical considerations.

One possible solution is to make the device out of living tissue, which is something I just wrote about with my colleague D. Kacy Cullen. Living electrodes and amplifiers may seem a bit like science fiction, but on the other hand, we have over a century of plastic surgeons, neurosurgeons, and orthopedic surgeons doing all kinds of complicated modifications of the body, moving nerves and vessels around. It makes you realize that, in a sense, they’ve already done living electrodes by doing a nerve transfer. So the question becomes whether we can refine that living electrode technology, which could then open up more possibilities.
 

Are there any final messages you’d like to share with clinician audience of this news organization?

Regardless of our specialty, we’re always telling our patients about the benefits of things like eating healthy, exercise, and sleep. Now we can point to the fact that, 2 years after stroke, all of these brain areas are still active, and devices that can potentially reverse and unparalyze your limbs may be available in the coming 5- or 10-plus years. That gives clinicians more justification to tell their patients to really stay on top of those things so that they can be in as optimal brain-mind health as possible to someday benefit from them.

Patients and their families need to be part of the conversation of where this is all going. That’s one thing that’s totally different for brain devices versus other devices, where a person’s psychological state doesn’t necessarily matter. But with a brain device, your mental state, psychosocial situation, exercise, sleep – the way you think about and approach it – actually changes to the structure of the brain pretty dramatically.

I don’t want to cause unreasonable hope that we’re going to snap our fingers and it’s going to be cured. But I do think it’s fair to raise a possibility as a way to say that keeping oneself really healthy is justified.

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

Restoring movement following a stroke can be challenging, but recent proof-of-concept research may offer an effective way to do just that. Researchers behind the ongoing Cortimo trial successfully performed a procedure on a patient 2 years removed from a stroke, in which microelectrode arrays were implanted into his brain to decode signals driving motor function. These signals then allowed him to operate a powered brace worn on his paralyzed arm.

This news organization spoke with the trial’s principal investigator, Mijail D. Serruya, MD, PhD, an assistant professor of neurology at Thomas Jefferson University Hospital, Philadelphia, about the trial’s initial findings, what this technology may ultimately look like, and the implications for stroke patients in knowing that restorative interventions may be on the horizon.
 

How did you first get involved with implanting electrodes to help stroke patients with recovery?

I was involved in the first human application of a microelectrode array in a young man who had quadriplegia because of a spinal cord injury. We showed that we could record signal directly from his motor cortex and use it to move a cursor on the screen, and open and close a prosthetic hand and arm.

I was naive and thought that this would soon be a widely available clinical medical device. Now it’s nearly 15 years later, and while it certainly has been safely used in multiple labs to record signals from people with spinal cord injury, amyotrophic lateral sclerosis (ALS), or locked-in syndrome from a brain stem stroke, it still requires a team of technicians and a percutaneous connector. It really has not gotten out of the university.

A few years ago I spoke with Robert Rosenwasser, MD, chairman of the department of neurosurgery at Thomas Jefferson, who runs a very busy stroke center and performed the surgery in this trial. We put our heads together and said: “Maybe the time is now to see whether we can move this technology to this much more prevalent condition of a hemispheric stroke.” And that’s what we did.
 

How did the idea of using computer brain electrode interfaces begin?

Around 20 years ago, if you had someone who had severe paralysis and you wanted to restore movement, the question was, where can you get a good control signal from? Obviously, if someone can talk, they can use a voice-actuated system with speech recognition and maybe you can track their eye gaze. But if they’re trying to move their limbs, you want a motor control signal.

In someone who has end-stage ALS or a brain stem stroke, you can’t even record residual muscle activity; you have almost nothing to work with. The only thing left is to try to record directly from the brain itself.

It’s important to clarify that brain-computer interfaces are not necessarily stimulating the brain to inject the signal. They’re just recording the endogenous activity that the brain makes. In comparison, a deep brain stimulator is usually not recording anything; it’s just delivering energy to the brain and hoping for the best.

But what we’re doing is asking, if the person is trying to move the paralyzed limb but can’t, can we get to the source of the signal and then do something with it?
 

What’s the process for measuring that in, for example, someone who has a localized lesion in the motor cortex?

The first step is a scan. People have been doing functional MRI on patients who have had a stroke as long as we’ve had fMRI. We know that people can actually activate on MRI areas of their brain around the stroke, but obviously not in the stroke because it’s been lesioned. However, we do know that the circuit adjacent to it and other regions do appear able to be modulated.

So by having a person either imagine trying to do what they want to do or doing what they can do, if they have some tiny residual movement, you can then identify a kind of hot spot on the fMRI where the brain gobbles up all the oxygen because it’s so active. Then that gives you an anatomical target for the surgeon to place the electrode arrays.
 

The Cortimo trial’s enticing findings

What are the most striking results that you’ve seen so far with the device?

The first thing is that we were able to get such recordings at all. We knew from fMRIs that there were fluctuations in oxygen changing when the person was trying to do something they couldn’t do. But nobody knew that you would see this whole population of individual neurons chattering away when you place these electrode arrays in the motor cortex right next to the stroke, and make sense of what we’re recording.

Obviously, that’s very encouraging and gives us hope that many months or years after a stroke, people’s brains are able to maintain this representation of all these different movements and plans. It’s almost like it’s trapped on the other side of the stroke and some of the signals can’t get out.

The other discovery we’re pleased with is that we can actually decode signals in real time and the person can use it to do something, such as trigger the brain to open and close the hand. That’s very different from all the prior research with brain array interfaces.

Furthermore, the gentleman who participated actually had strokes in other parts of his brain affecting his vision; he had homonymous hemianopia. That raised the question of what happens if you affect parts of the brain that have to do with attention and visual processing. Could a system like this work? And again, the answer appears to be yes.
 

What are the next steps for this technology before it can potentially become available in the clinic?

For this to work, the system clearly has to be fully implantable. What we used was percutaneous. The risk-benefit may be acceptable for someone who has quadriplegia because of, for example, spinal cord injury or end-stage ALS who may already have a tracheostomy and a percutaneous endoscopic gastrostomy. But for someone who is hemiparetic and ambulatory, that may not be acceptable. And a fully implantable system would also have much better patient compliance.

Also, when you’re recording from lots and lots of individual brain cells at many, many samples a second on many, many channels, it’s certainly an engineering challenge. It’s not just a single channel that you occasionally query; it’s hundreds of thousands of channels of this complicated data stream.

But these are solvable challenges. People have been making a lot of progress. It’s really a matter of funding and the engineering expertise, rather than some sort of fundamental scientific breakthrough.

With that said, I think it could be within the next 5-10 years that we could actually have a product that expands the toolbox of what can be done for patients who’ve had a stroke, if they’re motivated and there’s no real contraindication.
 

Creating a novel device

On that point, are you partnering with engineering and technology companies?

The hope is that we and other groups working on this can do for the interface sort of what Celera Genomics did for the Human Genome Project. By having enough interest and investment, you may be able to propel the field forward to widespread use rather than just a purely academic, lab-science type of project.

We are in discussion with different companies to see how we can move ahead with this, and we would be pleased to work with whomever is interested. It may be that different companies have different pieces of the puzzle – a better sensor or a better wireless transmitter.

The plan is to move as quickly as we can to a fully implantable system. And then the benchmark for any kind of clinical advancement is to do a prospective trial. With devices, if you can get a big enough effect size, then you sometimes don’t need quite as many patients to prove it. If paralysis is striking enough and you can reverse that, then you can convince the Food and Drug Administration of its safety and efficacy, and the various insurance companies, that it’s actually reasonable and necessary.
 

How long will an implantable device last?

That’s a key question and concern. If you have someone like our participant, who’s in his early 40s, will it keep working 10, 20, 30, 40 years? For the rest of his life? Deep brain stimulators and cochlear implants do function for those long durations, but their designs are quite different. There’s a macroelectrode that’s just delivering current, which is very different from listening in on this microscopic scale. There are different technical considerations.

One possible solution is to make the device out of living tissue, which is something I just wrote about with my colleague D. Kacy Cullen. Living electrodes and amplifiers may seem a bit like science fiction, but on the other hand, we have over a century of plastic surgeons, neurosurgeons, and orthopedic surgeons doing all kinds of complicated modifications of the body, moving nerves and vessels around. It makes you realize that, in a sense, they’ve already done living electrodes by doing a nerve transfer. So the question becomes whether we can refine that living electrode technology, which could then open up more possibilities.
 

Are there any final messages you’d like to share with clinician audience of this news organization?

Regardless of our specialty, we’re always telling our patients about the benefits of things like eating healthy, exercise, and sleep. Now we can point to the fact that, 2 years after stroke, all of these brain areas are still active, and devices that can potentially reverse and unparalyze your limbs may be available in the coming 5- or 10-plus years. That gives clinicians more justification to tell their patients to really stay on top of those things so that they can be in as optimal brain-mind health as possible to someday benefit from them.

Patients and their families need to be part of the conversation of where this is all going. That’s one thing that’s totally different for brain devices versus other devices, where a person’s psychological state doesn’t necessarily matter. But with a brain device, your mental state, psychosocial situation, exercise, sleep – the way you think about and approach it – actually changes to the structure of the brain pretty dramatically.

I don’t want to cause unreasonable hope that we’re going to snap our fingers and it’s going to be cured. But I do think it’s fair to raise a possibility as a way to say that keeping oneself really healthy is justified.

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

Restoring movement following a stroke can be challenging, but recent proof-of-concept research may offer an effective way to do just that. Researchers behind the ongoing Cortimo trial successfully performed a procedure on a patient 2 years removed from a stroke, in which microelectrode arrays were implanted into his brain to decode signals driving motor function. These signals then allowed him to operate a powered brace worn on his paralyzed arm.

This news organization spoke with the trial’s principal investigator, Mijail D. Serruya, MD, PhD, an assistant professor of neurology at Thomas Jefferson University Hospital, Philadelphia, about the trial’s initial findings, what this technology may ultimately look like, and the implications for stroke patients in knowing that restorative interventions may be on the horizon.
 

How did you first get involved with implanting electrodes to help stroke patients with recovery?

I was involved in the first human application of a microelectrode array in a young man who had quadriplegia because of a spinal cord injury. We showed that we could record signal directly from his motor cortex and use it to move a cursor on the screen, and open and close a prosthetic hand and arm.

I was naive and thought that this would soon be a widely available clinical medical device. Now it’s nearly 15 years later, and while it certainly has been safely used in multiple labs to record signals from people with spinal cord injury, amyotrophic lateral sclerosis (ALS), or locked-in syndrome from a brain stem stroke, it still requires a team of technicians and a percutaneous connector. It really has not gotten out of the university.

A few years ago I spoke with Robert Rosenwasser, MD, chairman of the department of neurosurgery at Thomas Jefferson, who runs a very busy stroke center and performed the surgery in this trial. We put our heads together and said: “Maybe the time is now to see whether we can move this technology to this much more prevalent condition of a hemispheric stroke.” And that’s what we did.
 

How did the idea of using computer brain electrode interfaces begin?

Around 20 years ago, if you had someone who had severe paralysis and you wanted to restore movement, the question was, where can you get a good control signal from? Obviously, if someone can talk, they can use a voice-actuated system with speech recognition and maybe you can track their eye gaze. But if they’re trying to move their limbs, you want a motor control signal.

In someone who has end-stage ALS or a brain stem stroke, you can’t even record residual muscle activity; you have almost nothing to work with. The only thing left is to try to record directly from the brain itself.

It’s important to clarify that brain-computer interfaces are not necessarily stimulating the brain to inject the signal. They’re just recording the endogenous activity that the brain makes. In comparison, a deep brain stimulator is usually not recording anything; it’s just delivering energy to the brain and hoping for the best.

But what we’re doing is asking, if the person is trying to move the paralyzed limb but can’t, can we get to the source of the signal and then do something with it?
 

What’s the process for measuring that in, for example, someone who has a localized lesion in the motor cortex?

The first step is a scan. People have been doing functional MRI on patients who have had a stroke as long as we’ve had fMRI. We know that people can actually activate on MRI areas of their brain around the stroke, but obviously not in the stroke because it’s been lesioned. However, we do know that the circuit adjacent to it and other regions do appear able to be modulated.

So by having a person either imagine trying to do what they want to do or doing what they can do, if they have some tiny residual movement, you can then identify a kind of hot spot on the fMRI where the brain gobbles up all the oxygen because it’s so active. Then that gives you an anatomical target for the surgeon to place the electrode arrays.
 

The Cortimo trial’s enticing findings

What are the most striking results that you’ve seen so far with the device?

The first thing is that we were able to get such recordings at all. We knew from fMRIs that there were fluctuations in oxygen changing when the person was trying to do something they couldn’t do. But nobody knew that you would see this whole population of individual neurons chattering away when you place these electrode arrays in the motor cortex right next to the stroke, and make sense of what we’re recording.

Obviously, that’s very encouraging and gives us hope that many months or years after a stroke, people’s brains are able to maintain this representation of all these different movements and plans. It’s almost like it’s trapped on the other side of the stroke and some of the signals can’t get out.

The other discovery we’re pleased with is that we can actually decode signals in real time and the person can use it to do something, such as trigger the brain to open and close the hand. That’s very different from all the prior research with brain array interfaces.

Furthermore, the gentleman who participated actually had strokes in other parts of his brain affecting his vision; he had homonymous hemianopia. That raised the question of what happens if you affect parts of the brain that have to do with attention and visual processing. Could a system like this work? And again, the answer appears to be yes.
 

What are the next steps for this technology before it can potentially become available in the clinic?

For this to work, the system clearly has to be fully implantable. What we used was percutaneous. The risk-benefit may be acceptable for someone who has quadriplegia because of, for example, spinal cord injury or end-stage ALS who may already have a tracheostomy and a percutaneous endoscopic gastrostomy. But for someone who is hemiparetic and ambulatory, that may not be acceptable. And a fully implantable system would also have much better patient compliance.

Also, when you’re recording from lots and lots of individual brain cells at many, many samples a second on many, many channels, it’s certainly an engineering challenge. It’s not just a single channel that you occasionally query; it’s hundreds of thousands of channels of this complicated data stream.

But these are solvable challenges. People have been making a lot of progress. It’s really a matter of funding and the engineering expertise, rather than some sort of fundamental scientific breakthrough.

With that said, I think it could be within the next 5-10 years that we could actually have a product that expands the toolbox of what can be done for patients who’ve had a stroke, if they’re motivated and there’s no real contraindication.
 

Creating a novel device

On that point, are you partnering with engineering and technology companies?

The hope is that we and other groups working on this can do for the interface sort of what Celera Genomics did for the Human Genome Project. By having enough interest and investment, you may be able to propel the field forward to widespread use rather than just a purely academic, lab-science type of project.

We are in discussion with different companies to see how we can move ahead with this, and we would be pleased to work with whomever is interested. It may be that different companies have different pieces of the puzzle – a better sensor or a better wireless transmitter.

The plan is to move as quickly as we can to a fully implantable system. And then the benchmark for any kind of clinical advancement is to do a prospective trial. With devices, if you can get a big enough effect size, then you sometimes don’t need quite as many patients to prove it. If paralysis is striking enough and you can reverse that, then you can convince the Food and Drug Administration of its safety and efficacy, and the various insurance companies, that it’s actually reasonable and necessary.
 

How long will an implantable device last?

That’s a key question and concern. If you have someone like our participant, who’s in his early 40s, will it keep working 10, 20, 30, 40 years? For the rest of his life? Deep brain stimulators and cochlear implants do function for those long durations, but their designs are quite different. There’s a macroelectrode that’s just delivering current, which is very different from listening in on this microscopic scale. There are different technical considerations.

One possible solution is to make the device out of living tissue, which is something I just wrote about with my colleague D. Kacy Cullen. Living electrodes and amplifiers may seem a bit like science fiction, but on the other hand, we have over a century of plastic surgeons, neurosurgeons, and orthopedic surgeons doing all kinds of complicated modifications of the body, moving nerves and vessels around. It makes you realize that, in a sense, they’ve already done living electrodes by doing a nerve transfer. So the question becomes whether we can refine that living electrode technology, which could then open up more possibilities.
 

Are there any final messages you’d like to share with clinician audience of this news organization?

Regardless of our specialty, we’re always telling our patients about the benefits of things like eating healthy, exercise, and sleep. Now we can point to the fact that, 2 years after stroke, all of these brain areas are still active, and devices that can potentially reverse and unparalyze your limbs may be available in the coming 5- or 10-plus years. That gives clinicians more justification to tell their patients to really stay on top of those things so that they can be in as optimal brain-mind health as possible to someday benefit from them.

Patients and their families need to be part of the conversation of where this is all going. That’s one thing that’s totally different for brain devices versus other devices, where a person’s psychological state doesn’t necessarily matter. But with a brain device, your mental state, psychosocial situation, exercise, sleep – the way you think about and approach it – actually changes to the structure of the brain pretty dramatically.

I don’t want to cause unreasonable hope that we’re going to snap our fingers and it’s going to be cured. But I do think it’s fair to raise a possibility as a way to say that keeping oneself really healthy is justified.

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

I got an interesting fax recently.

It started with how tough things have been for small practices during the pandemic (like I need reminding) and suggests it has solutions for my practice to stay afloat.

Dr. Block has a solo neurology practice in Scottsdale, Ariz.

I got an interesting fax recently.

It started with how tough things have been for small practices during the pandemic (like I need reminding) and suggests it has solutions for my practice to stay afloat.

Dr. Block has a solo neurology practice in Scottsdale, Ariz.

I got an interesting fax recently.

It started with how tough things have been for small practices during the pandemic (like I need reminding) and suggests it has solutions for my practice to stay afloat.

Dr. Block has a solo neurology practice in Scottsdale, Ariz.

The Food and Drug Administration has approved the antisense oligonucleotide casimersen (Amondys 45, Sarepta Therapeutics) injection for the treatment of patients with Duchenne muscular dystrophy (DMD) plus a rare DMD mutation, the agency has announced. 

This particular mutation of the DMD gene “is amenable to exon 45 skipping,” the FDA noted in a press release. The agency added that this is its first approval of a targeted treatment for patients with the mutation.

“Developing drugs designed for patients with specific mutations is a critical part of personalized medicine,” Eric Bastings, MD, deputy director of the Office of Neuroscience at the FDA’s Center for Drug Evaluation and Research, said in a statement.

The approval was based on results from a 43-person randomized controlled trial. Patients who received casimersen had a greater increase in production of the muscle-fiber protein dystrophin compared with their counterparts who received placebo.
 

Approved – with cautions

The FDA noted that DMD prevalence worldwide is about 1 in 3,600 boys – although it can also affect girls in rare cases. Symptoms of the disorder are commonly first observed around age 3 years but worsen steadily over time. DMD gene mutations lead to a decrease in dystrophin.

As reported by Medscape Medical News in August, the FDA approved viltolarsen (Viltepso, NS Pharma) for the treatment of DMD in patients with a confirmed mutation amenable to exon 53 skipping, following approval of golodirsen injection (Vyondys 53, Sarepta Therapeutics) for the same indication in December 2019.  

The DMD gene mutation that is amenable to exon 45 skipping is present in about 8% of patients with DMD.

The trial that carried weight with the FDA included 43 male participants with DMD aged 7-20 years. All were confirmed to have the exon 45-skipping gene mutation and all were randomly assigned 2:1 to received IV casimersen 30 mg/kg or matching placebo.

Results showed that, between baseline and 48 weeks post treatment, the casimersen group showed a significantly higher increase in levels of dystrophin protein than in the placebo group.

Upper respiratory tract infections, fever, joint and throat pain, headache, and cough were the most common adverse events experienced by the active-treatment group.

Although the clinical studies assessing casimersen did not show any reports of kidney toxicity, the adverse event was observed in some nonclinical studies. Therefore, clinicians should monitor kidney function in any patient receiving this treatment, the FDA recommended.

Overall, “the FDA has concluded that the data submitted by the applicant demonstrated an increase in dystrophin production that is reasonably likely to predict clinical benefit” in this patient population, the agency said in its press release.

However, it noted that definitive clinical benefits such as improved motor function were not “established.”

“In making this decision, the FDA considered the potential risks associated with the drug, the life-threatening and debilitating nature of the disease, and the lack of [other] available therapy,” the agency said.

It added that the manufacturer is currently conducting a multicenter study focused on the safety and efficacy of the drug in ambulatory patients with DMD.

The FDA approved casimersen using its Accelerated Approval pathway, granted Fast Track and Priority Review designations to its applications, and gave the treatment Orphan Drug designation.

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

The Food and Drug Administration has approved the antisense oligonucleotide casimersen (Amondys 45, Sarepta Therapeutics) injection for the treatment of patients with Duchenne muscular dystrophy (DMD) plus a rare DMD mutation, the agency has announced. 

This particular mutation of the DMD gene “is amenable to exon 45 skipping,” the FDA noted in a press release. The agency added that this is its first approval of a targeted treatment for patients with the mutation.

“Developing drugs designed for patients with specific mutations is a critical part of personalized medicine,” Eric Bastings, MD, deputy director of the Office of Neuroscience at the FDA’s Center for Drug Evaluation and Research, said in a statement.

The approval was based on results from a 43-person randomized controlled trial. Patients who received casimersen had a greater increase in production of the muscle-fiber protein dystrophin compared with their counterparts who received placebo.
 

Approved – with cautions

The FDA noted that DMD prevalence worldwide is about 1 in 3,600 boys – although it can also affect girls in rare cases. Symptoms of the disorder are commonly first observed around age 3 years but worsen steadily over time. DMD gene mutations lead to a decrease in dystrophin.

As reported by Medscape Medical News in August, the FDA approved viltolarsen (Viltepso, NS Pharma) for the treatment of DMD in patients with a confirmed mutation amenable to exon 53 skipping, following approval of golodirsen injection (Vyondys 53, Sarepta Therapeutics) for the same indication in December 2019.  

The DMD gene mutation that is amenable to exon 45 skipping is present in about 8% of patients with DMD.

The trial that carried weight with the FDA included 43 male participants with DMD aged 7-20 years. All were confirmed to have the exon 45-skipping gene mutation and all were randomly assigned 2:1 to received IV casimersen 30 mg/kg or matching placebo.

Results showed that, between baseline and 48 weeks post treatment, the casimersen group showed a significantly higher increase in levels of dystrophin protein than in the placebo group.

Upper respiratory tract infections, fever, joint and throat pain, headache, and cough were the most common adverse events experienced by the active-treatment group.

Although the clinical studies assessing casimersen did not show any reports of kidney toxicity, the adverse event was observed in some nonclinical studies. Therefore, clinicians should monitor kidney function in any patient receiving this treatment, the FDA recommended.

Overall, “the FDA has concluded that the data submitted by the applicant demonstrated an increase in dystrophin production that is reasonably likely to predict clinical benefit” in this patient population, the agency said in its press release.

However, it noted that definitive clinical benefits such as improved motor function were not “established.”

“In making this decision, the FDA considered the potential risks associated with the drug, the life-threatening and debilitating nature of the disease, and the lack of [other] available therapy,” the agency said.

It added that the manufacturer is currently conducting a multicenter study focused on the safety and efficacy of the drug in ambulatory patients with DMD.

The FDA approved casimersen using its Accelerated Approval pathway, granted Fast Track and Priority Review designations to its applications, and gave the treatment Orphan Drug designation.

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

The Food and Drug Administration has approved the antisense oligonucleotide casimersen (Amondys 45, Sarepta Therapeutics) injection for the treatment of patients with Duchenne muscular dystrophy (DMD) plus a rare DMD mutation, the agency has announced. 

This particular mutation of the DMD gene “is amenable to exon 45 skipping,” the FDA noted in a press release. The agency added that this is its first approval of a targeted treatment for patients with the mutation.

“Developing drugs designed for patients with specific mutations is a critical part of personalized medicine,” Eric Bastings, MD, deputy director of the Office of Neuroscience at the FDA’s Center for Drug Evaluation and Research, said in a statement.

The approval was based on results from a 43-person randomized controlled trial. Patients who received casimersen had a greater increase in production of the muscle-fiber protein dystrophin compared with their counterparts who received placebo.
 

Approved – with cautions

The FDA noted that DMD prevalence worldwide is about 1 in 3,600 boys – although it can also affect girls in rare cases. Symptoms of the disorder are commonly first observed around age 3 years but worsen steadily over time. DMD gene mutations lead to a decrease in dystrophin.

As reported by Medscape Medical News in August, the FDA approved viltolarsen (Viltepso, NS Pharma) for the treatment of DMD in patients with a confirmed mutation amenable to exon 53 skipping, following approval of golodirsen injection (Vyondys 53, Sarepta Therapeutics) for the same indication in December 2019.  

The DMD gene mutation that is amenable to exon 45 skipping is present in about 8% of patients with DMD.

The trial that carried weight with the FDA included 43 male participants with DMD aged 7-20 years. All were confirmed to have the exon 45-skipping gene mutation and all were randomly assigned 2:1 to received IV casimersen 30 mg/kg or matching placebo.

Results showed that, between baseline and 48 weeks post treatment, the casimersen group showed a significantly higher increase in levels of dystrophin protein than in the placebo group.

Upper respiratory tract infections, fever, joint and throat pain, headache, and cough were the most common adverse events experienced by the active-treatment group.

Although the clinical studies assessing casimersen did not show any reports of kidney toxicity, the adverse event was observed in some nonclinical studies. Therefore, clinicians should monitor kidney function in any patient receiving this treatment, the FDA recommended.

Overall, “the FDA has concluded that the data submitted by the applicant demonstrated an increase in dystrophin production that is reasonably likely to predict clinical benefit” in this patient population, the agency said in its press release.

However, it noted that definitive clinical benefits such as improved motor function were not “established.”

“In making this decision, the FDA considered the potential risks associated with the drug, the life-threatening and debilitating nature of the disease, and the lack of [other] available therapy,” the agency said.

It added that the manufacturer is currently conducting a multicenter study focused on the safety and efficacy of the drug in ambulatory patients with DMD.

The FDA approved casimersen using its Accelerated Approval pathway, granted Fast Track and Priority Review designations to its applications, and gave the treatment Orphan Drug designation.

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

New onset atrial fibrillation or flutter (AF/AFL) is uncommon in patients hospitalized with COVID-19 and occurs at a rate similar to that seen in patients hospitalized with influenza.

Mitchel L. Zoler/MDedge News

Among 3,970 patients treated during the early months of the pandemic, new onset AF/AFL was seen in 4%, matching the 4% incidence found in a historic cohort of patients hospitalized with influenza.

On the other hand, mortality was similarly high in both groups of patients studied with AF/AFL, showing a 77% increased risk of death in COVID-19 and a 78% increased risk in influenza, a team from Icahn School of Medicine at Mount Sinai in New York reported.

“We saw new onset Afib and flutter in a minority of patients and it was associated with much higher mortality, but the point is that this increase is basically the same as what you see in influenza, which we feel is an indication that this is more of a generalized response to the inflammatory milieu of such a severe viral illness, as opposed to something specific to COVID,” Vivek Y. Reddy, MD, said in the report, published online Feb. 25 in JACC: Clinical Electrophysiology.

“Here we see, with a similar respiratory virus used as controls, that the results are exactly what I would have expected to see, which is that where there is a lot of inflammation, we see Afib,” said John Mandrola, MD, of Baptist Medical Associates, Louisville, Ky., who was not involved with the study.

“We need more studies like this one because we know SARS-CoV-2 is a bad virus that may have important effects on the heart, but all the of research done so far has been problematic because it didn’t include controls.”
 

Atrial arrhythmias in COVID and flu

Dr. Reddy and coinvestigators performed a retrospective analysis of a large cohort of patients admitted with laboratory-confirmed COVID-19 during Feb. 4-April 22, 2020, to one of five hospitals within the Mount Sinai Health System.

Their comparator arm included 1,420 patients with confirmed influenza A or B hospitalized between Jan. 1, 2017, and Jan. 1, 2020. For both cohorts, automated electronic record abstraction was used and all patient data were de-identified prior to analysis. In the COVID-19 cohort, a manual review of 1,110 charts was also performed.

Compared with those who did not develop AF/AFL, COVID-19 patients with newly detected AF/AFL and COVID-19 were older (74 vs. 66 years; P < .01) and had higher levels of inflammatory markers, including C-reactive protein and interleukin-6, and higher troponin and D-dimer levels (all P < .01).

Overall, including those with a history of atrial arrhythmias, 10% of patients with hospitalized COVID-19 (13% in the manual review) and 12% of those with influenza had AF/AFL detected during their hospitalization.

Mortality at 30 days was higher in COVID-19 patients with AF/AFL compared to those without (46% vs. 26%; P < .01), as were the rates of intubation (27% vs. 15%; relative risk, 1.8; P < .01), and stroke (1.6% vs. 0.6%, RR, 2.7; P = .05).

Despite having more comorbidities, in-hospital mortality was significantly lower in the influenza cohort overall, compared to the COVID-19 cohort (9% vs. 29%; P < .01), reflecting the higher case fatality rate in COVID-19, Dr. Reddy, director of cardiac arrhythmia services at Mount Sinai Hospital, said in an interview.

But as with COVID-19, those influenza patients who had in-hospital AF/AFL were more likely to require intubation (14% vs. 7%; P = .004) or die (16% vs. 10%; P = .003).

“The data are not perfect and there are always limitations when doing an observational study using historic controls, but my guess would be that if we looked at other databases and other populations hospitalized for severe illness, we’d likely see something similar because when the body is inflamed, you’re more likely to see Afib,” said Dr. Mandrola.

Dr. Reddy concurred, noting that they considered comparing other populations to COVID-19 patients, including those with “just generalized severe illness,” but in the end felt there were many similarities between influenza and COVID-19, even though mortality in the latter is higher.

“It would be interesting for people to look at other illnesses and see if they find the same thing,” he said.

Dr. Reddy reported having no disclosures relevant to COVID-19. Dr. Mandrola is chief cardiology correspondent for Medscape.com. He reported having no relevant disclosures. MDedge is a member of the Medscape Professional Network.

New onset atrial fibrillation or flutter (AF/AFL) is uncommon in patients hospitalized with COVID-19 and occurs at a rate similar to that seen in patients hospitalized with influenza.

Mitchel L. Zoler/MDedge News

Among 3,970 patients treated during the early months of the pandemic, new onset AF/AFL was seen in 4%, matching the 4% incidence found in a historic cohort of patients hospitalized with influenza.

On the other hand, mortality was similarly high in both groups of patients studied with AF/AFL, showing a 77% increased risk of death in COVID-19 and a 78% increased risk in influenza, a team from Icahn School of Medicine at Mount Sinai in New York reported.

“We saw new onset Afib and flutter in a minority of patients and it was associated with much higher mortality, but the point is that this increase is basically the same as what you see in influenza, which we feel is an indication that this is more of a generalized response to the inflammatory milieu of such a severe viral illness, as opposed to something specific to COVID,” Vivek Y. Reddy, MD, said in the report, published online Feb. 25 in JACC: Clinical Electrophysiology.

“Here we see, with a similar respiratory virus used as controls, that the results are exactly what I would have expected to see, which is that where there is a lot of inflammation, we see Afib,” said John Mandrola, MD, of Baptist Medical Associates, Louisville, Ky., who was not involved with the study.

“We need more studies like this one because we know SARS-CoV-2 is a bad virus that may have important effects on the heart, but all the of research done so far has been problematic because it didn’t include controls.”
 

Atrial arrhythmias in COVID and flu

Dr. Reddy and coinvestigators performed a retrospective analysis of a large cohort of patients admitted with laboratory-confirmed COVID-19 during Feb. 4-April 22, 2020, to one of five hospitals within the Mount Sinai Health System.

Their comparator arm included 1,420 patients with confirmed influenza A or B hospitalized between Jan. 1, 2017, and Jan. 1, 2020. For both cohorts, automated electronic record abstraction was used and all patient data were de-identified prior to analysis. In the COVID-19 cohort, a manual review of 1,110 charts was also performed.

Compared with those who did not develop AF/AFL, COVID-19 patients with newly detected AF/AFL and COVID-19 were older (74 vs. 66 years; P < .01) and had higher levels of inflammatory markers, including C-reactive protein and interleukin-6, and higher troponin and D-dimer levels (all P < .01).

Overall, including those with a history of atrial arrhythmias, 10% of patients with hospitalized COVID-19 (13% in the manual review) and 12% of those with influenza had AF/AFL detected during their hospitalization.

Mortality at 30 days was higher in COVID-19 patients with AF/AFL compared to those without (46% vs. 26%; P < .01), as were the rates of intubation (27% vs. 15%; relative risk, 1.8; P < .01), and stroke (1.6% vs. 0.6%, RR, 2.7; P = .05).

Despite having more comorbidities, in-hospital mortality was significantly lower in the influenza cohort overall, compared to the COVID-19 cohort (9% vs. 29%; P < .01), reflecting the higher case fatality rate in COVID-19, Dr. Reddy, director of cardiac arrhythmia services at Mount Sinai Hospital, said in an interview.

But as with COVID-19, those influenza patients who had in-hospital AF/AFL were more likely to require intubation (14% vs. 7%; P = .004) or die (16% vs. 10%; P = .003).

“The data are not perfect and there are always limitations when doing an observational study using historic controls, but my guess would be that if we looked at other databases and other populations hospitalized for severe illness, we’d likely see something similar because when the body is inflamed, you’re more likely to see Afib,” said Dr. Mandrola.

Dr. Reddy concurred, noting that they considered comparing other populations to COVID-19 patients, including those with “just generalized severe illness,” but in the end felt there were many similarities between influenza and COVID-19, even though mortality in the latter is higher.

“It would be interesting for people to look at other illnesses and see if they find the same thing,” he said.

Dr. Reddy reported having no disclosures relevant to COVID-19. Dr. Mandrola is chief cardiology correspondent for Medscape.com. He reported having no relevant disclosures. MDedge is a member of the Medscape Professional Network.

New onset atrial fibrillation or flutter (AF/AFL) is uncommon in patients hospitalized with COVID-19 and occurs at a rate similar to that seen in patients hospitalized with influenza.

Mitchel L. Zoler/MDedge News

Among 3,970 patients treated during the early months of the pandemic, new onset AF/AFL was seen in 4%, matching the 4% incidence found in a historic cohort of patients hospitalized with influenza.

On the other hand, mortality was similarly high in both groups of patients studied with AF/AFL, showing a 77% increased risk of death in COVID-19 and a 78% increased risk in influenza, a team from Icahn School of Medicine at Mount Sinai in New York reported.

“We saw new onset Afib and flutter in a minority of patients and it was associated with much higher mortality, but the point is that this increase is basically the same as what you see in influenza, which we feel is an indication that this is more of a generalized response to the inflammatory milieu of such a severe viral illness, as opposed to something specific to COVID,” Vivek Y. Reddy, MD, said in the report, published online Feb. 25 in JACC: Clinical Electrophysiology.

“Here we see, with a similar respiratory virus used as controls, that the results are exactly what I would have expected to see, which is that where there is a lot of inflammation, we see Afib,” said John Mandrola, MD, of Baptist Medical Associates, Louisville, Ky., who was not involved with the study.

“We need more studies like this one because we know SARS-CoV-2 is a bad virus that may have important effects on the heart, but all the of research done so far has been problematic because it didn’t include controls.”
 

Atrial arrhythmias in COVID and flu

Dr. Reddy and coinvestigators performed a retrospective analysis of a large cohort of patients admitted with laboratory-confirmed COVID-19 during Feb. 4-April 22, 2020, to one of five hospitals within the Mount Sinai Health System.

Their comparator arm included 1,420 patients with confirmed influenza A or B hospitalized between Jan. 1, 2017, and Jan. 1, 2020. For both cohorts, automated electronic record abstraction was used and all patient data were de-identified prior to analysis. In the COVID-19 cohort, a manual review of 1,110 charts was also performed.

Compared with those who did not develop AF/AFL, COVID-19 patients with newly detected AF/AFL and COVID-19 were older (74 vs. 66 years; P < .01) and had higher levels of inflammatory markers, including C-reactive protein and interleukin-6, and higher troponin and D-dimer levels (all P < .01).

Overall, including those with a history of atrial arrhythmias, 10% of patients with hospitalized COVID-19 (13% in the manual review) and 12% of those with influenza had AF/AFL detected during their hospitalization.

Mortality at 30 days was higher in COVID-19 patients with AF/AFL compared to those without (46% vs. 26%; P < .01), as were the rates of intubation (27% vs. 15%; relative risk, 1.8; P < .01), and stroke (1.6% vs. 0.6%, RR, 2.7; P = .05).

Despite having more comorbidities, in-hospital mortality was significantly lower in the influenza cohort overall, compared to the COVID-19 cohort (9% vs. 29%; P < .01), reflecting the higher case fatality rate in COVID-19, Dr. Reddy, director of cardiac arrhythmia services at Mount Sinai Hospital, said in an interview.

But as with COVID-19, those influenza patients who had in-hospital AF/AFL were more likely to require intubation (14% vs. 7%; P = .004) or die (16% vs. 10%; P = .003).

“The data are not perfect and there are always limitations when doing an observational study using historic controls, but my guess would be that if we looked at other databases and other populations hospitalized for severe illness, we’d likely see something similar because when the body is inflamed, you’re more likely to see Afib,” said Dr. Mandrola.

Dr. Reddy concurred, noting that they considered comparing other populations to COVID-19 patients, including those with “just generalized severe illness,” but in the end felt there were many similarities between influenza and COVID-19, even though mortality in the latter is higher.

“It would be interesting for people to look at other illnesses and see if they find the same thing,” he said.

Dr. Reddy reported having no disclosures relevant to COVID-19. Dr. Mandrola is chief cardiology correspondent for Medscape.com. He reported having no relevant disclosures. MDedge is a member of the Medscape Professional Network.

Approximately half of all patients with locally advanced or metastatic urothelial cancer (la/mUC) are ineligible to receive cisplatin-based chemotherapy. They face poor outlooks and extremely limited treatment options.

A new study indicates that enfortumab vedotin (EV) can cause major, prolonged responses in most patients in that unfortunate setting.
 

EV is an antibody-drug conjugate directed against nectin-4, an immunoglobulin-like cell adhesion molecule that is highly expressed in UC, obviating the need for testing prior to treatment. It is internalized in malignant cells, with release of the active moiety (monomethyl auristatin E; MMAE). MMAE causes microtubule disruption, with resultant cell-cycle arrest and apoptosis.

EV received accelerated approval from the Food and Drug Administration in December 2019 after publication of the results from cohort 1 of the open-label, single-arm, phase 2 EV-201 study.

Arjun V. Balar, MD, of the Perlmutter Cancer Center at New York University Langone Health, presented results from cohort 2 of EV-201 – the cisplatin-ineligible cohort – at the 2021 Genitourinary Cancer Symposium (Abstract 394).
 

EV in patients ineligible for platinum-based therapy

Patients in cohort 2 of EV-201 had received immune checkpoint inhibitor therapy for la/mUC. They received EV in the FDA-approved dose for cohort 1: 1.25 mg/kg EV on days 1, 8, and 15 of a 28-day cycle.

Patients experienced disease progression during or following their most recent treatment. Patients with more than two neuropathies, active central nervous system metastases, and uncontrolled diabetes mellitus were excluded.

“Platinum ineligible” was defined as a creatinine clearance between 30-59 cm³/min, Eastern Cooperative Oncology Group performance status (ECOG PS) 2, or hearing loss of grade 2 or greater.

The primary endpoint for cohort 2 was confirmed overall response rate (ORR) per RECIST 1.1 by blinded independent central review. Secondary endpoints were duration of response, progression-free survival, overall survival, and safety.

There were 91 patients enrolled. Two patients never received EV treatment because of deterioration after registration. The median treatment duration among the remaining 89 patients was 6.0 months (range, 0.3-24.6).

Impressive results in poor-risk patients

The patients in EV-201 cohort 2 were elderly (median age, 75 years; range, 49-90) with comorbidities. The primary reasons for platinum-ineligibility were creatinine clearance less than 60 mL/min (66%), grade 2 or greater hearing loss (15%), and ECOG PS 2 (7%); 12% of patients met more than one criterion for platinum ineligibility.

The primary tumor site was in the upper urinary tract in 43% of patients, and 79% had visceral metastases, including 24% with liver involvement.

The confirmed ORR was 52% (95% confidence interval, 40.8-62.4), with 20% complete responses. There were responses in all subgroups, including patients with primary tumor sites in the upper tract (ORR, 61%), those with liver metastasis (ORR, 48%), and patients who had not responded to immune checkpoint inhibitors (ORR, 48%).

A total of 88% of patients had some decrease in measurable tumor diameters, generally within a few weeks of treatment initiation (median time to response, 1.8 months). The rapid response to treatment was especially important to patients having cancer-associated pain.

The median progression-free and overall survival durations were 5.8 months (95% CI, 5.0-8.3) and 14.7 months (95% CI, 10.5-18.2), respectively. The median response duration was 10.9 months (95% CI, 5.78-NR). More than 25% of responses extended beyond 12 months.

About 82% of patients in cohort 2 discontinued treatment, most commonly because of disease progression (51%). The second most common reason was the development of treatment-related adverse events (TRAE; 24%).
 

Drilling down on treatment-related adverse events

As might be expected for cisplatin-ineligible patients, adverse events were higher for patients in cohort 2 than for cohort 1 and led to treatment discontinuation in 16% of patients overall.

TRAEs over grade 3 occurred in 55% of patients. TRAEs of special interest included rash (61% overall; 17% ≥ grade 3), peripheral neuropathy (54% overall; 8% ≥ grade 3), and hyperglycemia (10% overall; 6% ≥ grade 3). Dose reductions, interruptions, and physical therapy were helpful.

Twenty percent of patients with TRAE hyperglycemia had hyperglycemia at baseline, and 30% of TRAEs were in patients with high body mass index (BMI).

There were four treatment-related deaths, all in patients 75 years or older with multiple comorbidities. Three of the four deaths occurred within 30 days of first EV dose in patients with BMI of 30 or greater (acute kidney injury, metabolic acidosis, and multiple organ dysfunction syndrome). The remaining death occurred more than 30 days after the last dose (pneumonitis).
 

Context and caution

The authors concluded that EV produced durable responses in platinum-ineligible patients with la/mUC, including 20% complete responses. Safety was felt to be as expected, given the known toxicities of the agent and the compromised medical condition of the patients studied.

The study discussant, Arlene O. Siefker-Radtke, MD, of the University of Texas MD Anderson Cancer Center, Houston, agreed that EV fills an unmet need, showing impressive responses in patients with visceral, liver, and bone metastases. She agreed that EV should be investigated across the spectrum of urothelial cancer.

Dr. Siefker-Radtke reminded attendees that the FDA package insert for EV described a 48% increase in the area under the concentration-time curve concentration of the MMAE active moiety in patients with mild hepatic impairment and that EV use should be avoided entirely in patients with moderate to severe liver disease.

She speculated whether augmented toxicity in patients with a high BMI could be attributable to clinically occult impaired hepatic function from fatty liver infiltration.

She indicated that clinicians should monitor closely patients with higher BMI and grade 3-4 hyperglycemia or elevated hemoglobin A1c levels and advised holding EV in patients who develop:

• Glucose levels above 250 mg/dL
• Peeling skin or bullous skin lesions. These lesions can be heralded by a diffuse erythematous or papillary rash in the preceding weeks.
• Grade 3 diarrhea or mucosal membrane toxicity of other types.

Notwithstanding concerns about toxicity and the need for monitoring, EV merits continued study in combination with other agents and in additional settings in the clinical spectrum of urothelial cancer. It is an important new option for oncologists caring for patients with urothelial cancer.

The EV-201 study was funded by Seagen. Dr. Balar and Dr. Siefker-Radtke disclosed relationships with Seagen and many other companies.

Dr. Lyss was a community-based medical oncologist and clinical researcher for more than 35 years before his recent retirement. His clinical and research interests were focused on breast and lung cancers, as well as expanding clinical trial access to medically underserved populations. He is based in St. Louis. He has no conflicts of interest.

Approximately half of all patients with locally advanced or metastatic urothelial cancer (la/mUC) are ineligible to receive cisplatin-based chemotherapy. They face poor outlooks and extremely limited treatment options.

A new study indicates that enfortumab vedotin (EV) can cause major, prolonged responses in most patients in that unfortunate setting.
 

EV is an antibody-drug conjugate directed against nectin-4, an immunoglobulin-like cell adhesion molecule that is highly expressed in UC, obviating the need for testing prior to treatment. It is internalized in malignant cells, with release of the active moiety (monomethyl auristatin E; MMAE). MMAE causes microtubule disruption, with resultant cell-cycle arrest and apoptosis.

EV received accelerated approval from the Food and Drug Administration in December 2019 after publication of the results from cohort 1 of the open-label, single-arm, phase 2 EV-201 study.

Arjun V. Balar, MD, of the Perlmutter Cancer Center at New York University Langone Health, presented results from cohort 2 of EV-201 – the cisplatin-ineligible cohort – at the 2021 Genitourinary Cancer Symposium (Abstract 394).
 

EV in patients ineligible for platinum-based therapy

Patients in cohort 2 of EV-201 had received immune checkpoint inhibitor therapy for la/mUC. They received EV in the FDA-approved dose for cohort 1: 1.25 mg/kg EV on days 1, 8, and 15 of a 28-day cycle.

Patients experienced disease progression during or following their most recent treatment. Patients with more than two neuropathies, active central nervous system metastases, and uncontrolled diabetes mellitus were excluded.

“Platinum ineligible” was defined as a creatinine clearance between 30-59 cm³/min, Eastern Cooperative Oncology Group performance status (ECOG PS) 2, or hearing loss of grade 2 or greater.

The primary endpoint for cohort 2 was confirmed overall response rate (ORR) per RECIST 1.1 by blinded independent central review. Secondary endpoints were duration of response, progression-free survival, overall survival, and safety.

There were 91 patients enrolled. Two patients never received EV treatment because of deterioration after registration. The median treatment duration among the remaining 89 patients was 6.0 months (range, 0.3-24.6).

Impressive results in poor-risk patients

The patients in EV-201 cohort 2 were elderly (median age, 75 years; range, 49-90) with comorbidities. The primary reasons for platinum-ineligibility were creatinine clearance less than 60 mL/min (66%), grade 2 or greater hearing loss (15%), and ECOG PS 2 (7%); 12% of patients met more than one criterion for platinum ineligibility.

The primary tumor site was in the upper urinary tract in 43% of patients, and 79% had visceral metastases, including 24% with liver involvement.

The confirmed ORR was 52% (95% confidence interval, 40.8-62.4), with 20% complete responses. There were responses in all subgroups, including patients with primary tumor sites in the upper tract (ORR, 61%), those with liver metastasis (ORR, 48%), and patients who had not responded to immune checkpoint inhibitors (ORR, 48%).

A total of 88% of patients had some decrease in measurable tumor diameters, generally within a few weeks of treatment initiation (median time to response, 1.8 months). The rapid response to treatment was especially important to patients having cancer-associated pain.

The median progression-free and overall survival durations were 5.8 months (95% CI, 5.0-8.3) and 14.7 months (95% CI, 10.5-18.2), respectively. The median response duration was 10.9 months (95% CI, 5.78-NR). More than 25% of responses extended beyond 12 months.

About 82% of patients in cohort 2 discontinued treatment, most commonly because of disease progression (51%). The second most common reason was the development of treatment-related adverse events (TRAE; 24%).
 

Drilling down on treatment-related adverse events

As might be expected for cisplatin-ineligible patients, adverse events were higher for patients in cohort 2 than for cohort 1 and led to treatment discontinuation in 16% of patients overall.

TRAEs over grade 3 occurred in 55% of patients. TRAEs of special interest included rash (61% overall; 17% ≥ grade 3), peripheral neuropathy (54% overall; 8% ≥ grade 3), and hyperglycemia (10% overall; 6% ≥ grade 3). Dose reductions, interruptions, and physical therapy were helpful.

Twenty percent of patients with TRAE hyperglycemia had hyperglycemia at baseline, and 30% of TRAEs were in patients with high body mass index (BMI).

There were four treatment-related deaths, all in patients 75 years or older with multiple comorbidities. Three of the four deaths occurred within 30 days of first EV dose in patients with BMI of 30 or greater (acute kidney injury, metabolic acidosis, and multiple organ dysfunction syndrome). The remaining death occurred more than 30 days after the last dose (pneumonitis).
 

Context and caution

The authors concluded that EV produced durable responses in platinum-ineligible patients with la/mUC, including 20% complete responses. Safety was felt to be as expected, given the known toxicities of the agent and the compromised medical condition of the patients studied.

The study discussant, Arlene O. Siefker-Radtke, MD, of the University of Texas MD Anderson Cancer Center, Houston, agreed that EV fills an unmet need, showing impressive responses in patients with visceral, liver, and bone metastases. She agreed that EV should be investigated across the spectrum of urothelial cancer.

Dr. Siefker-Radtke reminded attendees that the FDA package insert for EV described a 48% increase in the area under the concentration-time curve concentration of the MMAE active moiety in patients with mild hepatic impairment and that EV use should be avoided entirely in patients with moderate to severe liver disease.

She speculated whether augmented toxicity in patients with a high BMI could be attributable to clinically occult impaired hepatic function from fatty liver infiltration.

She indicated that clinicians should monitor closely patients with higher BMI and grade 3-4 hyperglycemia or elevated hemoglobin A1c levels and advised holding EV in patients who develop:

• Glucose levels above 250 mg/dL
• Peeling skin or bullous skin lesions. These lesions can be heralded by a diffuse erythematous or papillary rash in the preceding weeks.
• Grade 3 diarrhea or mucosal membrane toxicity of other types.

Notwithstanding concerns about toxicity and the need for monitoring, EV merits continued study in combination with other agents and in additional settings in the clinical spectrum of urothelial cancer. It is an important new option for oncologists caring for patients with urothelial cancer.

The EV-201 study was funded by Seagen. Dr. Balar and Dr. Siefker-Radtke disclosed relationships with Seagen and many other companies.

Dr. Lyss was a community-based medical oncologist and clinical researcher for more than 35 years before his recent retirement. His clinical and research interests were focused on breast and lung cancers, as well as expanding clinical trial access to medically underserved populations. He is based in St. Louis. He has no conflicts of interest.

Approximately half of all patients with locally advanced or metastatic urothelial cancer (la/mUC) are ineligible to receive cisplatin-based chemotherapy. They face poor outlooks and extremely limited treatment options.

A new study indicates that enfortumab vedotin (EV) can cause major, prolonged responses in most patients in that unfortunate setting.
 

EV is an antibody-drug conjugate directed against nectin-4, an immunoglobulin-like cell adhesion molecule that is highly expressed in UC, obviating the need for testing prior to treatment. It is internalized in malignant cells, with release of the active moiety (monomethyl auristatin E; MMAE). MMAE causes microtubule disruption, with resultant cell-cycle arrest and apoptosis.

EV received accelerated approval from the Food and Drug Administration in December 2019 after publication of the results from cohort 1 of the open-label, single-arm, phase 2 EV-201 study.

Arjun V. Balar, MD, of the Perlmutter Cancer Center at New York University Langone Health, presented results from cohort 2 of EV-201 – the cisplatin-ineligible cohort – at the 2021 Genitourinary Cancer Symposium (Abstract 394).
 

EV in patients ineligible for platinum-based therapy

Patients in cohort 2 of EV-201 had received immune checkpoint inhibitor therapy for la/mUC. They received EV in the FDA-approved dose for cohort 1: 1.25 mg/kg EV on days 1, 8, and 15 of a 28-day cycle.

Patients experienced disease progression during or following their most recent treatment. Patients with more than two neuropathies, active central nervous system metastases, and uncontrolled diabetes mellitus were excluded.

“Platinum ineligible” was defined as a creatinine clearance between 30-59 cm³/min, Eastern Cooperative Oncology Group performance status (ECOG PS) 2, or hearing loss of grade 2 or greater.

The primary endpoint for cohort 2 was confirmed overall response rate (ORR) per RECIST 1.1 by blinded independent central review. Secondary endpoints were duration of response, progression-free survival, overall survival, and safety.

There were 91 patients enrolled. Two patients never received EV treatment because of deterioration after registration. The median treatment duration among the remaining 89 patients was 6.0 months (range, 0.3-24.6).

Impressive results in poor-risk patients

The patients in EV-201 cohort 2 were elderly (median age, 75 years; range, 49-90) with comorbidities. The primary reasons for platinum-ineligibility were creatinine clearance less than 60 mL/min (66%), grade 2 or greater hearing loss (15%), and ECOG PS 2 (7%); 12% of patients met more than one criterion for platinum ineligibility.

The primary tumor site was in the upper urinary tract in 43% of patients, and 79% had visceral metastases, including 24% with liver involvement.

The confirmed ORR was 52% (95% confidence interval, 40.8-62.4), with 20% complete responses. There were responses in all subgroups, including patients with primary tumor sites in the upper tract (ORR, 61%), those with liver metastasis (ORR, 48%), and patients who had not responded to immune checkpoint inhibitors (ORR, 48%).

A total of 88% of patients had some decrease in measurable tumor diameters, generally within a few weeks of treatment initiation (median time to response, 1.8 months). The rapid response to treatment was especially important to patients having cancer-associated pain.

The median progression-free and overall survival durations were 5.8 months (95% CI, 5.0-8.3) and 14.7 months (95% CI, 10.5-18.2), respectively. The median response duration was 10.9 months (95% CI, 5.78-NR). More than 25% of responses extended beyond 12 months.

About 82% of patients in cohort 2 discontinued treatment, most commonly because of disease progression (51%). The second most common reason was the development of treatment-related adverse events (TRAE; 24%).
 

Drilling down on treatment-related adverse events

As might be expected for cisplatin-ineligible patients, adverse events were higher for patients in cohort 2 than for cohort 1 and led to treatment discontinuation in 16% of patients overall.

TRAEs over grade 3 occurred in 55% of patients. TRAEs of special interest included rash (61% overall; 17% ≥ grade 3), peripheral neuropathy (54% overall; 8% ≥ grade 3), and hyperglycemia (10% overall; 6% ≥ grade 3). Dose reductions, interruptions, and physical therapy were helpful.

Twenty percent of patients with TRAE hyperglycemia had hyperglycemia at baseline, and 30% of TRAEs were in patients with high body mass index (BMI).

There were four treatment-related deaths, all in patients 75 years or older with multiple comorbidities. Three of the four deaths occurred within 30 days of first EV dose in patients with BMI of 30 or greater (acute kidney injury, metabolic acidosis, and multiple organ dysfunction syndrome). The remaining death occurred more than 30 days after the last dose (pneumonitis).
 

Context and caution

The authors concluded that EV produced durable responses in platinum-ineligible patients with la/mUC, including 20% complete responses. Safety was felt to be as expected, given the known toxicities of the agent and the compromised medical condition of the patients studied.

The study discussant, Arlene O. Siefker-Radtke, MD, of the University of Texas MD Anderson Cancer Center, Houston, agreed that EV fills an unmet need, showing impressive responses in patients with visceral, liver, and bone metastases. She agreed that EV should be investigated across the spectrum of urothelial cancer.

Dr. Siefker-Radtke reminded attendees that the FDA package insert for EV described a 48% increase in the area under the concentration-time curve concentration of the MMAE active moiety in patients with mild hepatic impairment and that EV use should be avoided entirely in patients with moderate to severe liver disease.

She speculated whether augmented toxicity in patients with a high BMI could be attributable to clinically occult impaired hepatic function from fatty liver infiltration.

She indicated that clinicians should monitor closely patients with higher BMI and grade 3-4 hyperglycemia or elevated hemoglobin A1c levels and advised holding EV in patients who develop:

• Glucose levels above 250 mg/dL
• Peeling skin or bullous skin lesions. These lesions can be heralded by a diffuse erythematous or papillary rash in the preceding weeks.
• Grade 3 diarrhea or mucosal membrane toxicity of other types.

Notwithstanding concerns about toxicity and the need for monitoring, EV merits continued study in combination with other agents and in additional settings in the clinical spectrum of urothelial cancer. It is an important new option for oncologists caring for patients with urothelial cancer.

The EV-201 study was funded by Seagen. Dr. Balar and Dr. Siefker-Radtke disclosed relationships with Seagen and many other companies.

Dr. Lyss was a community-based medical oncologist and clinical researcher for more than 35 years before his recent retirement. His clinical and research interests were focused on breast and lung cancers, as well as expanding clinical trial access to medically underserved populations. He is based in St. Louis. He has no conflicts of interest.

Loss-of-function mutations in the FLG gene are the strongest known genetic risk factor for developing atopic dermatitis (AD), according to Zelma Chiesa Fuxench, MD.

This gene codes for profilaggrin, a protein, which is then cleaved to form filaggrin, which helps to organize the cytoskeleton of the skin and is an important structural component of the skin. The understanding is that patients who have filaggrin mutations tend to have earlier onset and more persistent disease, Dr. Chiesa Fuxench, of the department of dermatology at the University of Pennsylvania, Philadelphia, said during the Revolutionizing Atopic Dermatitis virtual symposium.

“Prior studies have shown that mutations in the FLG gene can confer a risk of developed AD that is two- to sevenfold with variants R501X and the 22804del4 frequently described. It is important to note that most of these findings have been described primarily in populations of European descent, with other variants being found in populations of African nation descent, and seem to be more prevalent in populations with early onset disease.”
 

Environmental factors

Other AD-related risk factors that have been previously described in the literature include environmental factors such as climate, diet, breastfeeding, obesity, pollution, tobacco smoke, pet ownership, and microbiome or gut microflora. “The list of culprits is ever increasing,” she said. “However, it’s important to recognize that data to support some of these associations are lacking, and oftentimes, a lot of the results are contradictory.”

As part of the International Study of Asthma and Allergies in Childhood, researchers evaluated the association between climate factors with the 12-month period prevalence rates of symptoms of atopic eczema in children. They found that patients who lived at higher latitudes and those who lived in areas where there were lower mean outdoor temperatures tended to have a higher prevalence of eczema symptoms. Worldwide, they found that symptoms of eczema were also prevalent in areas where there was lower indoor humidity.

“The authors concluded that they can’t really demonstrate a cause and effect, and that while latitude and temperature changes appear to affect the prevalence of eczema, they may do so indirectly, perhaps to changes in behavior and differences in sun exposure,” said Dr. Chiesa Fuxench, who was not involved with the study. “For example, we know that vitamin D is a protective risk factor for AD. Low vitamin D has been associated with more severe disease in some studies. We also know that UV exposure leads to the conversion of filaggrin degradation products such as trans-urocanic acid into cis-urocanic acid, which has been demonstrated to have immunosuppressive effects.”

A systematic review and meta-analysis of nine articles found small associations, which were significant, between being born in the winter (odds ratio, 1.15) and fall (OR, 1.16) and the risk of developing AD, compared with being born in the spring and summer. However, an analysis of satellite-derived data on air temperature across the United States from 1993 to 2011 found that as ambient air temperature increases, so did the risk for an ambulatory visit for AD to physicians from the National Ambulatory Medical Care Survey.

In all areas but the south, the largest number of AD visits occur in the spring. In the south, more AD visits occur in the summer. “This raises the point that we don’t really know everything when it comes to the influence of temperature and climate change on AD,” Dr. Chiesa Fuxench said.

Several maternal and neonatal risk factors for AD have been described in the literature, including the effect of prenatal exposure to antibiotics. In one large analysis, investigators assessed the association among 18-month-old children in the Danish National Birth Cohort, which included 62,560 mother-child pairs. They found that prenatal antibiotic use was associated with an increased odds of AD among children born to atopic mothers but only when used during all three trimesters (adjusted OR, 1.45). When they further stratified these analyses by type of birth (vaginal versus C-section), the association persisted in both groups, but was stronger among those delivered by C-section.

 

Probiotics

The role of probiotics to reduce the risk for AD has also been investigated. “We do know that probiotics could potentially be helpful, and it is often a readily available intervention,” Dr. Chiesa Fuxench said. “But the question still is how and when to supplement.”

In a systematic review and meta-analysis, researchers examined supplementation with probiotics given to breastfeeding mothers, pregnant mothers, or directly given to infants, and the risk of developing AD up to 18 months of age. They found that overall, probiotic exposure resulted in decreased risk of developing AD. In stratified analyses, the strongest association was observed for those who received probiotics during their pregnancy, during breastfeeding, and as an infant, which conferred about a 25% reduced risk.
 

Antibiotic exposure

What about early-life exposure to antibiotics on one’s risk for developing AD? A meta-analysis of 22 studies found that children who had been exposed to antibiotics during the first 2 years of life had an increased risk of eczema (OR, 1.26), compared with children who had not been exposed during the same period of time. “Interesting hypotheses can be generated from this study,” she said. “Perhaps future steps should focus on the impact of antibiotic exposure, the gut microbiome, and maternal risk factors for AD.”

In a separate study that supported these findings, researchers evaluated the association between the use of acid-suppressive medications and antibiotics during infancy and the development of allergic disease in early childhood. They found that exposure to either of these medications during the first six months of infancy resulted in a mild increased risk of developing AD, and concluded that they should be used during infancy only in situations of clear clinical benefit. “We should be good stewards of antibiotic use, in particular due to concern for antibiotic resistance in the population overall,” Dr. Chiesa Fuxench said.
 

Prevention strategies

Several AD prevention strategies have also been described in the medical literature, including the use of daily emollients during infancy. In a multicenter trial carried out in the United Kingdom, researchers tested whether daily use of emollient in the first year of life could prevent eczema in high-risk children, which was defined as having at least one first-degree relative with parent-reported eczema, allergic rhinitis, or asthma. The primary outcome was eczema at age 2 years. The researchers found no evidence to suggest that daily emollient use during the first year of life prevents eczema.

Another study, the PreventADALL trial of 2,397 infants, consisted of four treatment arms: a control group advised to follow national guidelines on infant nutrition; a skin intervention group that was asked to use skin emollients, a food intervention group with early introduction of peanut, cow’s milk, wheat, and egg, and a combined skin and food intervention. The investigators found no difference in the risk reduction of developing AD among patients who were treated with skin emollients or early complementary feeding, and concluded that these types of interventions should not be considered as interventions to prevent AD in this cohort of patients.

However, Dr. Chiesa Fuxench emphasized that emollients and moisturizers are an important part of the treatment regimen for AD patients. A Cochrane systematic review of nearly 80 randomized, controlled trials evaluating the use of emollients in eczema found that most moisturizers showed some beneficial effects in addition to active treatment, including prolonging the time to flare, reducing the number of flares, and reducing the amount of topical corticosteroids used.

For treatment, Dr. Chiesa Fuxench recommends a proactive approach focused on short-term induction therapy with intensive topical anti-inflammatories until the affected area is almost healed, followed by maintenance therapy that involves use of a long-term, low- to mid-potency steroid or a topical calcineurin inhibitor to previously affected areas. “These interventions have been shown to decrease the risk of recurrence and can shorten the treatment duration in the event of a flare,” she said.

She also favors a time-contingent approach to treating patients with AD. “As physicians, we tend to do our visits more as symptom contingent, which means when a patient is flaring. This reinforces the view that this is a difficult disease to treat, and that there is no hope,” she pointed out. But for chronic diseases, she added, “a time-contingent approach with appointments at set intervals leads to a different perception. It can result in better compliance, because skin care might be performed more regularly. It’s analogous to when you know you’re going to see the dentist so you floss more regularly the week before your appointment. There also seems to be less pressure on physicians and patients because you are seeing each other more frequently; you can talk more openly about what’s working and what’s not.”

Dr. Chiesa Fuxench reported having no disclosures relevant to her presentation.

dbrunk@mdedge.com

Loss-of-function mutations in the FLG gene are the strongest known genetic risk factor for developing atopic dermatitis (AD), according to Zelma Chiesa Fuxench, MD.

This gene codes for profilaggrin, a protein, which is then cleaved to form filaggrin, which helps to organize the cytoskeleton of the skin and is an important structural component of the skin. The understanding is that patients who have filaggrin mutations tend to have earlier onset and more persistent disease, Dr. Chiesa Fuxench, of the department of dermatology at the University of Pennsylvania, Philadelphia, said during the Revolutionizing Atopic Dermatitis virtual symposium.

“Prior studies have shown that mutations in the FLG gene can confer a risk of developed AD that is two- to sevenfold with variants R501X and the 22804del4 frequently described. It is important to note that most of these findings have been described primarily in populations of European descent, with other variants being found in populations of African nation descent, and seem to be more prevalent in populations with early onset disease.”
 

Environmental factors

Other AD-related risk factors that have been previously described in the literature include environmental factors such as climate, diet, breastfeeding, obesity, pollution, tobacco smoke, pet ownership, and microbiome or gut microflora. “The list of culprits is ever increasing,” she said. “However, it’s important to recognize that data to support some of these associations are lacking, and oftentimes, a lot of the results are contradictory.”

As part of the International Study of Asthma and Allergies in Childhood, researchers evaluated the association between climate factors with the 12-month period prevalence rates of symptoms of atopic eczema in children. They found that patients who lived at higher latitudes and those who lived in areas where there were lower mean outdoor temperatures tended to have a higher prevalence of eczema symptoms. Worldwide, they found that symptoms of eczema were also prevalent in areas where there was lower indoor humidity.

“The authors concluded that they can’t really demonstrate a cause and effect, and that while latitude and temperature changes appear to affect the prevalence of eczema, they may do so indirectly, perhaps to changes in behavior and differences in sun exposure,” said Dr. Chiesa Fuxench, who was not involved with the study. “For example, we know that vitamin D is a protective risk factor for AD. Low vitamin D has been associated with more severe disease in some studies. We also know that UV exposure leads to the conversion of filaggrin degradation products such as trans-urocanic acid into cis-urocanic acid, which has been demonstrated to have immunosuppressive effects.”

A systematic review and meta-analysis of nine articles found small associations, which were significant, between being born in the winter (odds ratio, 1.15) and fall (OR, 1.16) and the risk of developing AD, compared with being born in the spring and summer. However, an analysis of satellite-derived data on air temperature across the United States from 1993 to 2011 found that as ambient air temperature increases, so did the risk for an ambulatory visit for AD to physicians from the National Ambulatory Medical Care Survey.

In all areas but the south, the largest number of AD visits occur in the spring. In the south, more AD visits occur in the summer. “This raises the point that we don’t really know everything when it comes to the influence of temperature and climate change on AD,” Dr. Chiesa Fuxench said.

Several maternal and neonatal risk factors for AD have been described in the literature, including the effect of prenatal exposure to antibiotics. In one large analysis, investigators assessed the association among 18-month-old children in the Danish National Birth Cohort, which included 62,560 mother-child pairs. They found that prenatal antibiotic use was associated with an increased odds of AD among children born to atopic mothers but only when used during all three trimesters (adjusted OR, 1.45). When they further stratified these analyses by type of birth (vaginal versus C-section), the association persisted in both groups, but was stronger among those delivered by C-section.

 

Probiotics

The role of probiotics to reduce the risk for AD has also been investigated. “We do know that probiotics could potentially be helpful, and it is often a readily available intervention,” Dr. Chiesa Fuxench said. “But the question still is how and when to supplement.”

In a systematic review and meta-analysis, researchers examined supplementation with probiotics given to breastfeeding mothers, pregnant mothers, or directly given to infants, and the risk of developing AD up to 18 months of age. They found that overall, probiotic exposure resulted in decreased risk of developing AD. In stratified analyses, the strongest association was observed for those who received probiotics during their pregnancy, during breastfeeding, and as an infant, which conferred about a 25% reduced risk.
 

Antibiotic exposure

What about early-life exposure to antibiotics on one’s risk for developing AD? A meta-analysis of 22 studies found that children who had been exposed to antibiotics during the first 2 years of life had an increased risk of eczema (OR, 1.26), compared with children who had not been exposed during the same period of time. “Interesting hypotheses can be generated from this study,” she said. “Perhaps future steps should focus on the impact of antibiotic exposure, the gut microbiome, and maternal risk factors for AD.”

In a separate study that supported these findings, researchers evaluated the association between the use of acid-suppressive medications and antibiotics during infancy and the development of allergic disease in early childhood. They found that exposure to either of these medications during the first six months of infancy resulted in a mild increased risk of developing AD, and concluded that they should be used during infancy only in situations of clear clinical benefit. “We should be good stewards of antibiotic use, in particular due to concern for antibiotic resistance in the population overall,” Dr. Chiesa Fuxench said.
 

Prevention strategies

Several AD prevention strategies have also been described in the medical literature, including the use of daily emollients during infancy. In a multicenter trial carried out in the United Kingdom, researchers tested whether daily use of emollient in the first year of life could prevent eczema in high-risk children, which was defined as having at least one first-degree relative with parent-reported eczema, allergic rhinitis, or asthma. The primary outcome was eczema at age 2 years. The researchers found no evidence to suggest that daily emollient use during the first year of life prevents eczema.

Another study, the PreventADALL trial of 2,397 infants, consisted of four treatment arms: a control group advised to follow national guidelines on infant nutrition; a skin intervention group that was asked to use skin emollients, a food intervention group with early introduction of peanut, cow’s milk, wheat, and egg, and a combined skin and food intervention. The investigators found no difference in the risk reduction of developing AD among patients who were treated with skin emollients or early complementary feeding, and concluded that these types of interventions should not be considered as interventions to prevent AD in this cohort of patients.

However, Dr. Chiesa Fuxench emphasized that emollients and moisturizers are an important part of the treatment regimen for AD patients. A Cochrane systematic review of nearly 80 randomized, controlled trials evaluating the use of emollients in eczema found that most moisturizers showed some beneficial effects in addition to active treatment, including prolonging the time to flare, reducing the number of flares, and reducing the amount of topical corticosteroids used.

For treatment, Dr. Chiesa Fuxench recommends a proactive approach focused on short-term induction therapy with intensive topical anti-inflammatories until the affected area is almost healed, followed by maintenance therapy that involves use of a long-term, low- to mid-potency steroid or a topical calcineurin inhibitor to previously affected areas. “These interventions have been shown to decrease the risk of recurrence and can shorten the treatment duration in the event of a flare,” she said.

She also favors a time-contingent approach to treating patients with AD. “As physicians, we tend to do our visits more as symptom contingent, which means when a patient is flaring. This reinforces the view that this is a difficult disease to treat, and that there is no hope,” she pointed out. But for chronic diseases, she added, “a time-contingent approach with appointments at set intervals leads to a different perception. It can result in better compliance, because skin care might be performed more regularly. It’s analogous to when you know you’re going to see the dentist so you floss more regularly the week before your appointment. There also seems to be less pressure on physicians and patients because you are seeing each other more frequently; you can talk more openly about what’s working and what’s not.”

Dr. Chiesa Fuxench reported having no disclosures relevant to her presentation.

dbrunk@mdedge.com

Loss-of-function mutations in the FLG gene are the strongest known genetic risk factor for developing atopic dermatitis (AD), according to Zelma Chiesa Fuxench, MD.

This gene codes for profilaggrin, a protein, which is then cleaved to form filaggrin, which helps to organize the cytoskeleton of the skin and is an important structural component of the skin. The understanding is that patients who have filaggrin mutations tend to have earlier onset and more persistent disease, Dr. Chiesa Fuxench, of the department of dermatology at the University of Pennsylvania, Philadelphia, said during the Revolutionizing Atopic Dermatitis virtual symposium.

“Prior studies have shown that mutations in the FLG gene can confer a risk of developed AD that is two- to sevenfold with variants R501X and the 22804del4 frequently described. It is important to note that most of these findings have been described primarily in populations of European descent, with other variants being found in populations of African nation descent, and seem to be more prevalent in populations with early onset disease.”
 

Environmental factors

Other AD-related risk factors that have been previously described in the literature include environmental factors such as climate, diet, breastfeeding, obesity, pollution, tobacco smoke, pet ownership, and microbiome or gut microflora. “The list of culprits is ever increasing,” she said. “However, it’s important to recognize that data to support some of these associations are lacking, and oftentimes, a lot of the results are contradictory.”

As part of the International Study of Asthma and Allergies in Childhood, researchers evaluated the association between climate factors with the 12-month period prevalence rates of symptoms of atopic eczema in children. They found that patients who lived at higher latitudes and those who lived in areas where there were lower mean outdoor temperatures tended to have a higher prevalence of eczema symptoms. Worldwide, they found that symptoms of eczema were also prevalent in areas where there was lower indoor humidity.

“The authors concluded that they can’t really demonstrate a cause and effect, and that while latitude and temperature changes appear to affect the prevalence of eczema, they may do so indirectly, perhaps to changes in behavior and differences in sun exposure,” said Dr. Chiesa Fuxench, who was not involved with the study. “For example, we know that vitamin D is a protective risk factor for AD. Low vitamin D has been associated with more severe disease in some studies. We also know that UV exposure leads to the conversion of filaggrin degradation products such as trans-urocanic acid into cis-urocanic acid, which has been demonstrated to have immunosuppressive effects.”

A systematic review and meta-analysis of nine articles found small associations, which were significant, between being born in the winter (odds ratio, 1.15) and fall (OR, 1.16) and the risk of developing AD, compared with being born in the spring and summer. However, an analysis of satellite-derived data on air temperature across the United States from 1993 to 2011 found that as ambient air temperature increases, so did the risk for an ambulatory visit for AD to physicians from the National Ambulatory Medical Care Survey.

In all areas but the south, the largest number of AD visits occur in the spring. In the south, more AD visits occur in the summer. “This raises the point that we don’t really know everything when it comes to the influence of temperature and climate change on AD,” Dr. Chiesa Fuxench said.

Several maternal and neonatal risk factors for AD have been described in the literature, including the effect of prenatal exposure to antibiotics. In one large analysis, investigators assessed the association among 18-month-old children in the Danish National Birth Cohort, which included 62,560 mother-child pairs. They found that prenatal antibiotic use was associated with an increased odds of AD among children born to atopic mothers but only when used during all three trimesters (adjusted OR, 1.45). When they further stratified these analyses by type of birth (vaginal versus C-section), the association persisted in both groups, but was stronger among those delivered by C-section.

 

Probiotics

The role of probiotics to reduce the risk for AD has also been investigated. “We do know that probiotics could potentially be helpful, and it is often a readily available intervention,” Dr. Chiesa Fuxench said. “But the question still is how and when to supplement.”

In a systematic review and meta-analysis, researchers examined supplementation with probiotics given to breastfeeding mothers, pregnant mothers, or directly given to infants, and the risk of developing AD up to 18 months of age. They found that overall, probiotic exposure resulted in decreased risk of developing AD. In stratified analyses, the strongest association was observed for those who received probiotics during their pregnancy, during breastfeeding, and as an infant, which conferred about a 25% reduced risk.
 

Antibiotic exposure

What about early-life exposure to antibiotics on one’s risk for developing AD? A meta-analysis of 22 studies found that children who had been exposed to antibiotics during the first 2 years of life had an increased risk of eczema (OR, 1.26), compared with children who had not been exposed during the same period of time. “Interesting hypotheses can be generated from this study,” she said. “Perhaps future steps should focus on the impact of antibiotic exposure, the gut microbiome, and maternal risk factors for AD.”

In a separate study that supported these findings, researchers evaluated the association between the use of acid-suppressive medications and antibiotics during infancy and the development of allergic disease in early childhood. They found that exposure to either of these medications during the first six months of infancy resulted in a mild increased risk of developing AD, and concluded that they should be used during infancy only in situations of clear clinical benefit. “We should be good stewards of antibiotic use, in particular due to concern for antibiotic resistance in the population overall,” Dr. Chiesa Fuxench said.
 

Prevention strategies

Several AD prevention strategies have also been described in the medical literature, including the use of daily emollients during infancy. In a multicenter trial carried out in the United Kingdom, researchers tested whether daily use of emollient in the first year of life could prevent eczema in high-risk children, which was defined as having at least one first-degree relative with parent-reported eczema, allergic rhinitis, or asthma. The primary outcome was eczema at age 2 years. The researchers found no evidence to suggest that daily emollient use during the first year of life prevents eczema.

Another study, the PreventADALL trial of 2,397 infants, consisted of four treatment arms: a control group advised to follow national guidelines on infant nutrition; a skin intervention group that was asked to use skin emollients, a food intervention group with early introduction of peanut, cow’s milk, wheat, and egg, and a combined skin and food intervention. The investigators found no difference in the risk reduction of developing AD among patients who were treated with skin emollients or early complementary feeding, and concluded that these types of interventions should not be considered as interventions to prevent AD in this cohort of patients.

However, Dr. Chiesa Fuxench emphasized that emollients and moisturizers are an important part of the treatment regimen for AD patients. A Cochrane systematic review of nearly 80 randomized, controlled trials evaluating the use of emollients in eczema found that most moisturizers showed some beneficial effects in addition to active treatment, including prolonging the time to flare, reducing the number of flares, and reducing the amount of topical corticosteroids used.

For treatment, Dr. Chiesa Fuxench recommends a proactive approach focused on short-term induction therapy with intensive topical anti-inflammatories until the affected area is almost healed, followed by maintenance therapy that involves use of a long-term, low- to mid-potency steroid or a topical calcineurin inhibitor to previously affected areas. “These interventions have been shown to decrease the risk of recurrence and can shorten the treatment duration in the event of a flare,” she said.

She also favors a time-contingent approach to treating patients with AD. “As physicians, we tend to do our visits more as symptom contingent, which means when a patient is flaring. This reinforces the view that this is a difficult disease to treat, and that there is no hope,” she pointed out. But for chronic diseases, she added, “a time-contingent approach with appointments at set intervals leads to a different perception. It can result in better compliance, because skin care might be performed more regularly. It’s analogous to when you know you’re going to see the dentist so you floss more regularly the week before your appointment. There also seems to be less pressure on physicians and patients because you are seeing each other more frequently; you can talk more openly about what’s working and what’s not.”

Dr. Chiesa Fuxench reported having no disclosures relevant to her presentation.

dbrunk@mdedge.com