Sleep specialists might want to take a closer look at the connections between obstructive sleep apnea, chronic pain, and reported pain intensity in younger patients. Young adults with a diagnosis of obstructive sleep apnea (OSA) are more likely to report moderate to severe pain intensity, compared with their peers who do not have the diagnosis, results from a large cross-sectional analysis of veterans showed.

“Because of the high burden of chronic pain conditions in younger adults, this study highlights the need to understand the impact of OSA diagnosis and treatment on pain intensity,” researchers led by Wardah Athar, a graduate student at Yale University, New Haven, Conn., and Lori A. Bastian, MD, MPH, a professor of internal medicine at Yale, wrote in an article published in the Annals of the American Thoracic Society. “This understanding would then help inform the development of interventions to promote screening for OSA among young adults with chronic pain and pain management among those with diagnosed OSA.”

In an effort to assess whether young adults with diagnosed OSA are more likely to report higher pain intensity, compared with those without OSA, the researchers drew from a sample of 858,226 veterans from Operation Enduring Freedom, Operation Iraqi Freedom, and Operation New Dawn who had at least one visit to a VA clinic between 2001 and 2014. They used ICD-9 codes to identify OSA and assessed self-reported responses to pain measures on a 0-10 numeric scale which were recorded in each veteran’s EMR. Next, they averaged pain intensity responses over a 12-month period and categorized them as none (0), mild (1-3), and moderate/severe (4–10). Covariates included age, sex, education, race, mental health diagnoses, headache diagnoses, pain diagnoses, hypertension, diabetes, body mass index, and smoking status. The researchers used multivariate logistic regression models and multiple imputation to generate values for missing variables.

The mean age of the patients was 30 years, 64% were White, 17% were Black, 12% were Hispanic, and remainder were other/unknown race/ethnicity. Ninety percent were male, and 20% had greater than a high school education. Of the 858,226 patients, 91,244 (11%) had a diagnosis of OSA. Compared with patients who had no diagnosis of OSA, the unadjusted odds of reporting moderate/severe pain was 48% higher among those with OSA (odds ratio 1.48; P < .0001). After the researchers adjusted for all covariates in the model, the association between OSA and moderate/severe pain remained significant though attenuated, with an adjusted odds ratio of 1.09 (P < .0001).

Several characteristics were different between those who had a diagnosis of OSA and those who did not, including age (a mean of 36 vs. 26 years, respectively) and having the following diagnoses: pain (36% vs. 16%), headache (28% vs. 14%), diabetes (12% vs. 2%), hypertension (40% vs. 12%), and a body mass index of 30 kg/m² or greater (69% vs. 35%). Certain psychiatric disorders were also common among patients with OSA, including major depressive disorder (20% vs. 10%), posttraumatic stress disorder (50% vs. 30%), and substance use disorder (26% vs. 17%). Patients with OSA were also more likely to have been prescribed benzodiazepines or opioids within 90 days of their OSA diagnosis. Although men were more likely to have a diagnosis of OSA, no differences related to sex in the association of OSA and pain were observed in sex-based stratified analyses.

“Based on these results, we suggest more thorough and more frequent pain intensity screening in patients with OSA, particularly in those patients who are younger than 60 years old without significant comorbid illness,” the researchers concluded. “Furthermore, we also recommend increased OSA screening for patients with moderate/severe pain intensity and pain diagnoses.” One tool they recommend is the STOP-Bang (Snoring, Tiredness, Observed Apnea, Blood Pressure, Body Mass Index, Age, Neck Circumference, and Gender) questionnaire, which has been validated in multiple settings.

Commenting on the findings of this study, Krishna M. Sundar, MD, FCCP, medical director of the Sleep-Wake Center at the University of Utah, Salt Lake City, commended the study design. “One of the problems with sleep apnea studies is that there are always confounding effects, especially from BMI. This is a population that has a significant medical burden of disease, but I think this is a well-done study to look at the relationship between pain and OSA in a younger population. The authors tried to adjust for all these confounders and they still found a significant association. This indicates that sleep affects one’s pain threshold. And sleep apnea, by mechanisms still yet to be defined, also alters that pain threshold. It may also affect the expression of pain or management of pain, making treatment more problematic in this population,” he said in an interview.

A key limitation of the study, he continued, was the fact it evaluated only one aspect of sleep: OSA. “They didn’t look at duration of sleep, comorbid insomnia, or fragmentation of sleep from apnea or from other causes,” Dr. Sundar said. “We have multiple ways of treating sleep apnea. Clearly, we need studies of treating sleep apnea with [continuous positive airway pressure] and how that affects the occurrence of pain. The relevant practical aspect of this is that there are pain clinics all over the country that should screen for sleep apnea. Along the same lines, sleep practitioners should be aware that pain has an important association with sleep apnea.”

The study was supported by the Health Services Research & Development in the Department of Veterans Affairs of the Veterans Health Administration, the Yale School of Medicine Medical Student Fellowship, and the U.S. National Institutes of Health.

[email protected]

SOURCE: Athar W et al. Ann Am Thorac Soc. 2020;17(10):1273-48.

Correction, 10/28/20: An earlier version of this article misstated Wardah Athar's name in the photo caption.

Sleep specialists might want to take a closer look at the connections between obstructive sleep apnea, chronic pain, and reported pain intensity in younger patients. Young adults with a diagnosis of obstructive sleep apnea (OSA) are more likely to report moderate to severe pain intensity, compared with their peers who do not have the diagnosis, results from a large cross-sectional analysis of veterans showed.

“Because of the high burden of chronic pain conditions in younger adults, this study highlights the need to understand the impact of OSA diagnosis and treatment on pain intensity,” researchers led by Wardah Athar, a graduate student at Yale University, New Haven, Conn., and Lori A. Bastian, MD, MPH, a professor of internal medicine at Yale, wrote in an article published in the Annals of the American Thoracic Society. “This understanding would then help inform the development of interventions to promote screening for OSA among young adults with chronic pain and pain management among those with diagnosed OSA.”

In an effort to assess whether young adults with diagnosed OSA are more likely to report higher pain intensity, compared with those without OSA, the researchers drew from a sample of 858,226 veterans from Operation Enduring Freedom, Operation Iraqi Freedom, and Operation New Dawn who had at least one visit to a VA clinic between 2001 and 2014. They used ICD-9 codes to identify OSA and assessed self-reported responses to pain measures on a 0-10 numeric scale which were recorded in each veteran’s EMR. Next, they averaged pain intensity responses over a 12-month period and categorized them as none (0), mild (1-3), and moderate/severe (4–10). Covariates included age, sex, education, race, mental health diagnoses, headache diagnoses, pain diagnoses, hypertension, diabetes, body mass index, and smoking status. The researchers used multivariate logistic regression models and multiple imputation to generate values for missing variables.

The mean age of the patients was 30 years, 64% were White, 17% were Black, 12% were Hispanic, and remainder were other/unknown race/ethnicity. Ninety percent were male, and 20% had greater than a high school education. Of the 858,226 patients, 91,244 (11%) had a diagnosis of OSA. Compared with patients who had no diagnosis of OSA, the unadjusted odds of reporting moderate/severe pain was 48% higher among those with OSA (odds ratio 1.48; P < .0001). After the researchers adjusted for all covariates in the model, the association between OSA and moderate/severe pain remained significant though attenuated, with an adjusted odds ratio of 1.09 (P < .0001).

Several characteristics were different between those who had a diagnosis of OSA and those who did not, including age (a mean of 36 vs. 26 years, respectively) and having the following diagnoses: pain (36% vs. 16%), headache (28% vs. 14%), diabetes (12% vs. 2%), hypertension (40% vs. 12%), and a body mass index of 30 kg/m² or greater (69% vs. 35%). Certain psychiatric disorders were also common among patients with OSA, including major depressive disorder (20% vs. 10%), posttraumatic stress disorder (50% vs. 30%), and substance use disorder (26% vs. 17%). Patients with OSA were also more likely to have been prescribed benzodiazepines or opioids within 90 days of their OSA diagnosis. Although men were more likely to have a diagnosis of OSA, no differences related to sex in the association of OSA and pain were observed in sex-based stratified analyses.

“Based on these results, we suggest more thorough and more frequent pain intensity screening in patients with OSA, particularly in those patients who are younger than 60 years old without significant comorbid illness,” the researchers concluded. “Furthermore, we also recommend increased OSA screening for patients with moderate/severe pain intensity and pain diagnoses.” One tool they recommend is the STOP-Bang (Snoring, Tiredness, Observed Apnea, Blood Pressure, Body Mass Index, Age, Neck Circumference, and Gender) questionnaire, which has been validated in multiple settings.

Commenting on the findings of this study, Krishna M. Sundar, MD, FCCP, medical director of the Sleep-Wake Center at the University of Utah, Salt Lake City, commended the study design. “One of the problems with sleep apnea studies is that there are always confounding effects, especially from BMI. This is a population that has a significant medical burden of disease, but I think this is a well-done study to look at the relationship between pain and OSA in a younger population. The authors tried to adjust for all these confounders and they still found a significant association. This indicates that sleep affects one’s pain threshold. And sleep apnea, by mechanisms still yet to be defined, also alters that pain threshold. It may also affect the expression of pain or management of pain, making treatment more problematic in this population,” he said in an interview.

A key limitation of the study, he continued, was the fact it evaluated only one aspect of sleep: OSA. “They didn’t look at duration of sleep, comorbid insomnia, or fragmentation of sleep from apnea or from other causes,” Dr. Sundar said. “We have multiple ways of treating sleep apnea. Clearly, we need studies of treating sleep apnea with [continuous positive airway pressure] and how that affects the occurrence of pain. The relevant practical aspect of this is that there are pain clinics all over the country that should screen for sleep apnea. Along the same lines, sleep practitioners should be aware that pain has an important association with sleep apnea.”

The study was supported by the Health Services Research & Development in the Department of Veterans Affairs of the Veterans Health Administration, the Yale School of Medicine Medical Student Fellowship, and the U.S. National Institutes of Health.

[email protected]

SOURCE: Athar W et al. Ann Am Thorac Soc. 2020;17(10):1273-48.

Correction, 10/28/20: An earlier version of this article misstated Wardah Athar's name in the photo caption.

Sleep specialists might want to take a closer look at the connections between obstructive sleep apnea, chronic pain, and reported pain intensity in younger patients. Young adults with a diagnosis of obstructive sleep apnea (OSA) are more likely to report moderate to severe pain intensity, compared with their peers who do not have the diagnosis, results from a large cross-sectional analysis of veterans showed.

“Because of the high burden of chronic pain conditions in younger adults, this study highlights the need to understand the impact of OSA diagnosis and treatment on pain intensity,” researchers led by Wardah Athar, a graduate student at Yale University, New Haven, Conn., and Lori A. Bastian, MD, MPH, a professor of internal medicine at Yale, wrote in an article published in the Annals of the American Thoracic Society. “This understanding would then help inform the development of interventions to promote screening for OSA among young adults with chronic pain and pain management among those with diagnosed OSA.”

In an effort to assess whether young adults with diagnosed OSA are more likely to report higher pain intensity, compared with those without OSA, the researchers drew from a sample of 858,226 veterans from Operation Enduring Freedom, Operation Iraqi Freedom, and Operation New Dawn who had at least one visit to a VA clinic between 2001 and 2014. They used ICD-9 codes to identify OSA and assessed self-reported responses to pain measures on a 0-10 numeric scale which were recorded in each veteran’s EMR. Next, they averaged pain intensity responses over a 12-month period and categorized them as none (0), mild (1-3), and moderate/severe (4–10). Covariates included age, sex, education, race, mental health diagnoses, headache diagnoses, pain diagnoses, hypertension, diabetes, body mass index, and smoking status. The researchers used multivariate logistic regression models and multiple imputation to generate values for missing variables.

The mean age of the patients was 30 years, 64% were White, 17% were Black, 12% were Hispanic, and remainder were other/unknown race/ethnicity. Ninety percent were male, and 20% had greater than a high school education. Of the 858,226 patients, 91,244 (11%) had a diagnosis of OSA. Compared with patients who had no diagnosis of OSA, the unadjusted odds of reporting moderate/severe pain was 48% higher among those with OSA (odds ratio 1.48; P < .0001). After the researchers adjusted for all covariates in the model, the association between OSA and moderate/severe pain remained significant though attenuated, with an adjusted odds ratio of 1.09 (P < .0001).

Several characteristics were different between those who had a diagnosis of OSA and those who did not, including age (a mean of 36 vs. 26 years, respectively) and having the following diagnoses: pain (36% vs. 16%), headache (28% vs. 14%), diabetes (12% vs. 2%), hypertension (40% vs. 12%), and a body mass index of 30 kg/m² or greater (69% vs. 35%). Certain psychiatric disorders were also common among patients with OSA, including major depressive disorder (20% vs. 10%), posttraumatic stress disorder (50% vs. 30%), and substance use disorder (26% vs. 17%). Patients with OSA were also more likely to have been prescribed benzodiazepines or opioids within 90 days of their OSA diagnosis. Although men were more likely to have a diagnosis of OSA, no differences related to sex in the association of OSA and pain were observed in sex-based stratified analyses.

“Based on these results, we suggest more thorough and more frequent pain intensity screening in patients with OSA, particularly in those patients who are younger than 60 years old without significant comorbid illness,” the researchers concluded. “Furthermore, we also recommend increased OSA screening for patients with moderate/severe pain intensity and pain diagnoses.” One tool they recommend is the STOP-Bang (Snoring, Tiredness, Observed Apnea, Blood Pressure, Body Mass Index, Age, Neck Circumference, and Gender) questionnaire, which has been validated in multiple settings.

Commenting on the findings of this study, Krishna M. Sundar, MD, FCCP, medical director of the Sleep-Wake Center at the University of Utah, Salt Lake City, commended the study design. “One of the problems with sleep apnea studies is that there are always confounding effects, especially from BMI. This is a population that has a significant medical burden of disease, but I think this is a well-done study to look at the relationship between pain and OSA in a younger population. The authors tried to adjust for all these confounders and they still found a significant association. This indicates that sleep affects one’s pain threshold. And sleep apnea, by mechanisms still yet to be defined, also alters that pain threshold. It may also affect the expression of pain or management of pain, making treatment more problematic in this population,” he said in an interview.

A key limitation of the study, he continued, was the fact it evaluated only one aspect of sleep: OSA. “They didn’t look at duration of sleep, comorbid insomnia, or fragmentation of sleep from apnea or from other causes,” Dr. Sundar said. “We have multiple ways of treating sleep apnea. Clearly, we need studies of treating sleep apnea with [continuous positive airway pressure] and how that affects the occurrence of pain. The relevant practical aspect of this is that there are pain clinics all over the country that should screen for sleep apnea. Along the same lines, sleep practitioners should be aware that pain has an important association with sleep apnea.”

The study was supported by the Health Services Research & Development in the Department of Veterans Affairs of the Veterans Health Administration, the Yale School of Medicine Medical Student Fellowship, and the U.S. National Institutes of Health.

[email protected]

SOURCE: Athar W et al. Ann Am Thorac Soc. 2020;17(10):1273-48.

Correction, 10/28/20: An earlier version of this article misstated Wardah Athar's name in the photo caption.

New guidelines recommend against retreatment with poly (ADP-ribose) polymerase (PARP) inhibitors in women with epithelial ovarian, tubal, or primary peritoneal cancer (EOC). However, trials investigating retreatment are underway, so this recommendation may change.

The guidelines, from the American Society of Clinical Oncology (ASCO), do not recommend PARP inhibitors for the initial treatment of stage I-II EOC.

However, PARP inhibitor maintenance should be offered to women with newly diagnosed stage III-IV EOC who achieved a complete or partial response with first-line platinum-based chemotherapy, according to the guidelines. Niraparib can be offered to all women meeting those criteria, while olaparib can be considered for patients with mutations in BRCA1/2.

The guidelines, published in the Journal of Clinical Oncology, are based on a systematic review of recent randomized PARP inhibitor trials, including PRIMA and SOLO1, among others.

What’s not available now is overall survival results from key clinical trials, the guideline authors noted. They added that further research is needed to address the issue of conserving platinum sensitivity in patients with disease progression on or after PARP inhibitor maintenance.

“Given the expectation that early treatment may confer the best outcome, maintenance therapy with PARP inhibitors should be offered, with these caveats,” the authors wrote.

Olaparib can also be added to bevacizumab maintenance therapy following response to first-line chemotherapy plus bevacizumab, according to the guidelines, which also address PARP inhibitor use for women with recurrent EOC, as well as management of adverse events.

The guidelines recommend against pairing PARP inhibitors with chemotherapy, targeted therapy, or immunotherapy outside a clinical trial.
 

Which drug, which setting, which dose?

This new ASCO guidelines may help cut through the complexity of treatment decision-making for women with EOC, according to Roisin E. O’Cearbhaill, MD, of Memorial Sloan Kettering Cancer Center in New York.

“Today as clinicians, we have a whole range of opportunities to give our patients PARP inhibitors in the upfront and recurrent setting,” Dr. O’Cearbhaill said in an interview. “It is quite complicated to know which PARP inhibitor should be used in which setting and which patients.”

“We want to make sure that patients who would derive the most benefit from PARP inhibitors are offered these agents but also that we’re careful not to use PARP inhibitors in settings where there is little or no data,” added Dr. O’Cearbhaill, who was not involved in the drafting of the guidelines.

The ASCO guidelines provide a detailed review of 17 clinical trials to address key issues, including the histologic types of EOC and biomarker subsets for which PARP inhibitors are recommended in the newly diagnosed setting, as well as the settings, dose, and duration of treatment that are recommended for patients with recurrent EOC who have not yet received a PARP inhibitor.

While PARP inhibitors are generally well tolerated, some characteristic toxicities – such as anemia, neutropenia, thrombocytopenia, persistent cytopenias, and nausea – may warrant dose reductions, the guidelines state.

Special attention must be paid to low-grade adverse events since PARP inhibitors are administered continuously on a daily basis, according to the guidelines. If a dose is held because of a grade 2 adverse event, the subsequent dose should be reduced to avoid a second dose hold.

“Reescalation or resumption of the initial dose is never recommended,” the guidelines state.
 

Retreatment

Dr. O’Cearbhaill said she is eager to see future guidelines addressing PARP inhibitor retreatment following disease progression, especially since more and more patients will receive these agents in the upfront setting.

Right now, there is little data available to address PARP inhibitor retreatment. However, the ASCO guidelines do mention the ongoing OReO/ENGOT OV-38 phase 3 trial of maintenance retreatment with olaparib in women with EOC.

This study, which includes patients who previously received a PARP inhibitor and who are responding to additional platinum-based chemotherapy, has an estimated completion date in May 2021, according to details on ClinicalTrials.gov.

That’s one of several trials designed to determine how best to incorporate PARP inhibitor retreatment into the treatment paradigm, according to Dr. O’Cearbhaill.

“Even if a high proportion of patients aren’t ultimately cured by this approach, if we can delay progression of disease by the order of months or even years, whilst proactively managing side effects, it would make such a big difference for patients,” she said. “It allows them to have a better quality of life and go about their daily activities without symptomatic ovarian cancer.”

Cochairs of the ASCO expert panel for the guidelines were William P. Tew, MD, of Memorial Sloan Kettering Cancer Center in New York, and Elise C. Kohn, MD, of the National Cancer Institute in Bethesda, Md. Dr. Tew and Dr. Kohn provided no disclosures, while their coauthors reported disclosures related to Roche, AstraZeneca, Tesaro, Clovis Oncology, Merck, Seattle Genetics, and other companies. Dr. O’Cearbhaill disclosed that she is a coauthor on the PRIMA/ENGOT-OV26/GOG-3012 phase 3 clinical trial (NCT02655016) and serves on the steering committee for DUO-O (NCT0373643). She reported personal fees from Clovis, Tesaro, Regeneron, and GlaxoSmithKline.

SOURCE: Tew WP et al. J Clin Oncol. 2020 Aug 13. doi: 10.1200/JCO.20.01924.

New guidelines recommend against retreatment with poly (ADP-ribose) polymerase (PARP) inhibitors in women with epithelial ovarian, tubal, or primary peritoneal cancer (EOC). However, trials investigating retreatment are underway, so this recommendation may change.

The guidelines, from the American Society of Clinical Oncology (ASCO), do not recommend PARP inhibitors for the initial treatment of stage I-II EOC.

However, PARP inhibitor maintenance should be offered to women with newly diagnosed stage III-IV EOC who achieved a complete or partial response with first-line platinum-based chemotherapy, according to the guidelines. Niraparib can be offered to all women meeting those criteria, while olaparib can be considered for patients with mutations in BRCA1/2.

The guidelines, published in the Journal of Clinical Oncology, are based on a systematic review of recent randomized PARP inhibitor trials, including PRIMA and SOLO1, among others.

What’s not available now is overall survival results from key clinical trials, the guideline authors noted. They added that further research is needed to address the issue of conserving platinum sensitivity in patients with disease progression on or after PARP inhibitor maintenance.

“Given the expectation that early treatment may confer the best outcome, maintenance therapy with PARP inhibitors should be offered, with these caveats,” the authors wrote.

Olaparib can also be added to bevacizumab maintenance therapy following response to first-line chemotherapy plus bevacizumab, according to the guidelines, which also address PARP inhibitor use for women with recurrent EOC, as well as management of adverse events.

The guidelines recommend against pairing PARP inhibitors with chemotherapy, targeted therapy, or immunotherapy outside a clinical trial.
 

Which drug, which setting, which dose?

This new ASCO guidelines may help cut through the complexity of treatment decision-making for women with EOC, according to Roisin E. O’Cearbhaill, MD, of Memorial Sloan Kettering Cancer Center in New York.

“Today as clinicians, we have a whole range of opportunities to give our patients PARP inhibitors in the upfront and recurrent setting,” Dr. O’Cearbhaill said in an interview. “It is quite complicated to know which PARP inhibitor should be used in which setting and which patients.”

“We want to make sure that patients who would derive the most benefit from PARP inhibitors are offered these agents but also that we’re careful not to use PARP inhibitors in settings where there is little or no data,” added Dr. O’Cearbhaill, who was not involved in the drafting of the guidelines.

The ASCO guidelines provide a detailed review of 17 clinical trials to address key issues, including the histologic types of EOC and biomarker subsets for which PARP inhibitors are recommended in the newly diagnosed setting, as well as the settings, dose, and duration of treatment that are recommended for patients with recurrent EOC who have not yet received a PARP inhibitor.

While PARP inhibitors are generally well tolerated, some characteristic toxicities – such as anemia, neutropenia, thrombocytopenia, persistent cytopenias, and nausea – may warrant dose reductions, the guidelines state.

Special attention must be paid to low-grade adverse events since PARP inhibitors are administered continuously on a daily basis, according to the guidelines. If a dose is held because of a grade 2 adverse event, the subsequent dose should be reduced to avoid a second dose hold.

“Reescalation or resumption of the initial dose is never recommended,” the guidelines state.
 

Retreatment

Dr. O’Cearbhaill said she is eager to see future guidelines addressing PARP inhibitor retreatment following disease progression, especially since more and more patients will receive these agents in the upfront setting.

Right now, there is little data available to address PARP inhibitor retreatment. However, the ASCO guidelines do mention the ongoing OReO/ENGOT OV-38 phase 3 trial of maintenance retreatment with olaparib in women with EOC.

This study, which includes patients who previously received a PARP inhibitor and who are responding to additional platinum-based chemotherapy, has an estimated completion date in May 2021, according to details on ClinicalTrials.gov.

That’s one of several trials designed to determine how best to incorporate PARP inhibitor retreatment into the treatment paradigm, according to Dr. O’Cearbhaill.

“Even if a high proportion of patients aren’t ultimately cured by this approach, if we can delay progression of disease by the order of months or even years, whilst proactively managing side effects, it would make such a big difference for patients,” she said. “It allows them to have a better quality of life and go about their daily activities without symptomatic ovarian cancer.”

Cochairs of the ASCO expert panel for the guidelines were William P. Tew, MD, of Memorial Sloan Kettering Cancer Center in New York, and Elise C. Kohn, MD, of the National Cancer Institute in Bethesda, Md. Dr. Tew and Dr. Kohn provided no disclosures, while their coauthors reported disclosures related to Roche, AstraZeneca, Tesaro, Clovis Oncology, Merck, Seattle Genetics, and other companies. Dr. O’Cearbhaill disclosed that she is a coauthor on the PRIMA/ENGOT-OV26/GOG-3012 phase 3 clinical trial (NCT02655016) and serves on the steering committee for DUO-O (NCT0373643). She reported personal fees from Clovis, Tesaro, Regeneron, and GlaxoSmithKline.

SOURCE: Tew WP et al. J Clin Oncol. 2020 Aug 13. doi: 10.1200/JCO.20.01924.

New guidelines recommend against retreatment with poly (ADP-ribose) polymerase (PARP) inhibitors in women with epithelial ovarian, tubal, or primary peritoneal cancer (EOC). However, trials investigating retreatment are underway, so this recommendation may change.

The guidelines, from the American Society of Clinical Oncology (ASCO), do not recommend PARP inhibitors for the initial treatment of stage I-II EOC.

However, PARP inhibitor maintenance should be offered to women with newly diagnosed stage III-IV EOC who achieved a complete or partial response with first-line platinum-based chemotherapy, according to the guidelines. Niraparib can be offered to all women meeting those criteria, while olaparib can be considered for patients with mutations in BRCA1/2.

The guidelines, published in the Journal of Clinical Oncology, are based on a systematic review of recent randomized PARP inhibitor trials, including PRIMA and SOLO1, among others.

What’s not available now is overall survival results from key clinical trials, the guideline authors noted. They added that further research is needed to address the issue of conserving platinum sensitivity in patients with disease progression on or after PARP inhibitor maintenance.

“Given the expectation that early treatment may confer the best outcome, maintenance therapy with PARP inhibitors should be offered, with these caveats,” the authors wrote.

Olaparib can also be added to bevacizumab maintenance therapy following response to first-line chemotherapy plus bevacizumab, according to the guidelines, which also address PARP inhibitor use for women with recurrent EOC, as well as management of adverse events.

The guidelines recommend against pairing PARP inhibitors with chemotherapy, targeted therapy, or immunotherapy outside a clinical trial.
 

Which drug, which setting, which dose?

This new ASCO guidelines may help cut through the complexity of treatment decision-making for women with EOC, according to Roisin E. O’Cearbhaill, MD, of Memorial Sloan Kettering Cancer Center in New York.

“Today as clinicians, we have a whole range of opportunities to give our patients PARP inhibitors in the upfront and recurrent setting,” Dr. O’Cearbhaill said in an interview. “It is quite complicated to know which PARP inhibitor should be used in which setting and which patients.”

“We want to make sure that patients who would derive the most benefit from PARP inhibitors are offered these agents but also that we’re careful not to use PARP inhibitors in settings where there is little or no data,” added Dr. O’Cearbhaill, who was not involved in the drafting of the guidelines.

The ASCO guidelines provide a detailed review of 17 clinical trials to address key issues, including the histologic types of EOC and biomarker subsets for which PARP inhibitors are recommended in the newly diagnosed setting, as well as the settings, dose, and duration of treatment that are recommended for patients with recurrent EOC who have not yet received a PARP inhibitor.

While PARP inhibitors are generally well tolerated, some characteristic toxicities – such as anemia, neutropenia, thrombocytopenia, persistent cytopenias, and nausea – may warrant dose reductions, the guidelines state.

Special attention must be paid to low-grade adverse events since PARP inhibitors are administered continuously on a daily basis, according to the guidelines. If a dose is held because of a grade 2 adverse event, the subsequent dose should be reduced to avoid a second dose hold.

“Reescalation or resumption of the initial dose is never recommended,” the guidelines state.
 

Retreatment

Dr. O’Cearbhaill said she is eager to see future guidelines addressing PARP inhibitor retreatment following disease progression, especially since more and more patients will receive these agents in the upfront setting.

Right now, there is little data available to address PARP inhibitor retreatment. However, the ASCO guidelines do mention the ongoing OReO/ENGOT OV-38 phase 3 trial of maintenance retreatment with olaparib in women with EOC.

This study, which includes patients who previously received a PARP inhibitor and who are responding to additional platinum-based chemotherapy, has an estimated completion date in May 2021, according to details on ClinicalTrials.gov.

That’s one of several trials designed to determine how best to incorporate PARP inhibitor retreatment into the treatment paradigm, according to Dr. O’Cearbhaill.

“Even if a high proportion of patients aren’t ultimately cured by this approach, if we can delay progression of disease by the order of months or even years, whilst proactively managing side effects, it would make such a big difference for patients,” she said. “It allows them to have a better quality of life and go about their daily activities without symptomatic ovarian cancer.”

Cochairs of the ASCO expert panel for the guidelines were William P. Tew, MD, of Memorial Sloan Kettering Cancer Center in New York, and Elise C. Kohn, MD, of the National Cancer Institute in Bethesda, Md. Dr. Tew and Dr. Kohn provided no disclosures, while their coauthors reported disclosures related to Roche, AstraZeneca, Tesaro, Clovis Oncology, Merck, Seattle Genetics, and other companies. Dr. O’Cearbhaill disclosed that she is a coauthor on the PRIMA/ENGOT-OV26/GOG-3012 phase 3 clinical trial (NCT02655016) and serves on the steering committee for DUO-O (NCT0373643). She reported personal fees from Clovis, Tesaro, Regeneron, and GlaxoSmithKline.

SOURCE: Tew WP et al. J Clin Oncol. 2020 Aug 13. doi: 10.1200/JCO.20.01924.

Novel therapies are poised to dramatically change frontline therapy for acute myeloid leukemia (AML), and they have the potential to replace chemotherapy, a hematologist/oncologist told colleagues at the virtual Acute Leukemia Forum of Hemedicus.

But more work needs to be done, noted Alexander Perl, MD, MS, associate professor at the University of Pennsylvania, Philadelphia. While advances have transformed AML treatment in the relapsed/refractory setting, “we’re just not seeing that substantive improvement” for newly diagnosed patients, he said. “We need to find the disease-modifying drugs that work in the relapsed/refractory setting and move those frontline. That’s where we’re going to see the transformations.”

Research suggests that low-intensity therapy holds tremendous promise, he said, “with the idea that we could make therapy much more tolerable for the vast majority of patients affected by AML, who, as we know, are older patients.”

Dr. Perl highlighted the 2020 VIALE-A study – venetoclax/azacitidine versus azacitidine/placebo – which reported that “in previously untreated patients who were ineligible for intensive chemotherapy, overall survival was longer and the incidence of remission was higher among patients who received azacitidine plus venetoclax than among those who received azacitidine alone.”

Venetoclax promotes apoptosis in leukemia cells, Dr. Perl said. “To a certain extent, you can think of it as putting the rubber to the road in terms of what actually chemotherapy is designed to do, which is to make leukemic blasts apoptose. It does so without DNA damage and with much less toxicity to the patient. Therefore it can be added to any number of regimens – granted, with mild suppression, but with relatively little extramedullary toxicity.”

Dr. Perl noted that the venetoclax arm “showed a higher response rate than azacitidine in pretty much every subgroup that was looked at, whether patients had de novo leukemia, secondary leukemia, multiple mutational complements, various different karyotypes. The response rates on this study are as high as what we often will see with intensive chemotherapy.” He added that “the winning arm on this trial seems to hold up against any low-intensity therapy, and I would argue against many high-intensity therapies in older patients.”

As for other targeted agents, isocitrate dehydrogenase (IDH) inhibitors “are very promising drugs in the relapsed/refractory setting, which is primarily where these drugs are given. In regard to frontline treatment, “data are coming from a very small study, but they’re very encouraging. It’s hard to entirely say that we’re ready to change practice based on this. But it’s very encouraging – the idea that earlier use of a drug-targeting IDH mutation might lead to substantially better outcomes.”

Moving forward, he said, “we could put all of our eggs in one basket and use many active drugs [at] front line. Or we can perhaps be smart about sequencing these drugs one after another, or using more intensive approaches followed by maintenance approaches followed by more intensive approaches.”

This approach is similar to strategies in myeloma patients “who less and less are relying on an autologous transplant for durable control of their disease, and more and more are using low-intensity biologically targeted drugs,” he said.

The Acute Leukemia Forum is held by Hemedicus, which is owned by the same company as this news organization.

Dr. Perl reported numerous disclosures, including relationships with Daiichi Sankyo, Abbvie, and Astellas.

Novel therapies are poised to dramatically change frontline therapy for acute myeloid leukemia (AML), and they have the potential to replace chemotherapy, a hematologist/oncologist told colleagues at the virtual Acute Leukemia Forum of Hemedicus.

But more work needs to be done, noted Alexander Perl, MD, MS, associate professor at the University of Pennsylvania, Philadelphia. While advances have transformed AML treatment in the relapsed/refractory setting, “we’re just not seeing that substantive improvement” for newly diagnosed patients, he said. “We need to find the disease-modifying drugs that work in the relapsed/refractory setting and move those frontline. That’s where we’re going to see the transformations.”

Research suggests that low-intensity therapy holds tremendous promise, he said, “with the idea that we could make therapy much more tolerable for the vast majority of patients affected by AML, who, as we know, are older patients.”

Dr. Perl highlighted the 2020 VIALE-A study – venetoclax/azacitidine versus azacitidine/placebo – which reported that “in previously untreated patients who were ineligible for intensive chemotherapy, overall survival was longer and the incidence of remission was higher among patients who received azacitidine plus venetoclax than among those who received azacitidine alone.”

Venetoclax promotes apoptosis in leukemia cells, Dr. Perl said. “To a certain extent, you can think of it as putting the rubber to the road in terms of what actually chemotherapy is designed to do, which is to make leukemic blasts apoptose. It does so without DNA damage and with much less toxicity to the patient. Therefore it can be added to any number of regimens – granted, with mild suppression, but with relatively little extramedullary toxicity.”

Dr. Perl noted that the venetoclax arm “showed a higher response rate than azacitidine in pretty much every subgroup that was looked at, whether patients had de novo leukemia, secondary leukemia, multiple mutational complements, various different karyotypes. The response rates on this study are as high as what we often will see with intensive chemotherapy.” He added that “the winning arm on this trial seems to hold up against any low-intensity therapy, and I would argue against many high-intensity therapies in older patients.”

As for other targeted agents, isocitrate dehydrogenase (IDH) inhibitors “are very promising drugs in the relapsed/refractory setting, which is primarily where these drugs are given. In regard to frontline treatment, “data are coming from a very small study, but they’re very encouraging. It’s hard to entirely say that we’re ready to change practice based on this. But it’s very encouraging – the idea that earlier use of a drug-targeting IDH mutation might lead to substantially better outcomes.”

Moving forward, he said, “we could put all of our eggs in one basket and use many active drugs [at] front line. Or we can perhaps be smart about sequencing these drugs one after another, or using more intensive approaches followed by maintenance approaches followed by more intensive approaches.”

This approach is similar to strategies in myeloma patients “who less and less are relying on an autologous transplant for durable control of their disease, and more and more are using low-intensity biologically targeted drugs,” he said.

The Acute Leukemia Forum is held by Hemedicus, which is owned by the same company as this news organization.

Dr. Perl reported numerous disclosures, including relationships with Daiichi Sankyo, Abbvie, and Astellas.

Novel therapies are poised to dramatically change frontline therapy for acute myeloid leukemia (AML), and they have the potential to replace chemotherapy, a hematologist/oncologist told colleagues at the virtual Acute Leukemia Forum of Hemedicus.

But more work needs to be done, noted Alexander Perl, MD, MS, associate professor at the University of Pennsylvania, Philadelphia. While advances have transformed AML treatment in the relapsed/refractory setting, “we’re just not seeing that substantive improvement” for newly diagnosed patients, he said. “We need to find the disease-modifying drugs that work in the relapsed/refractory setting and move those frontline. That’s where we’re going to see the transformations.”

Research suggests that low-intensity therapy holds tremendous promise, he said, “with the idea that we could make therapy much more tolerable for the vast majority of patients affected by AML, who, as we know, are older patients.”

Dr. Perl highlighted the 2020 VIALE-A study – venetoclax/azacitidine versus azacitidine/placebo – which reported that “in previously untreated patients who were ineligible for intensive chemotherapy, overall survival was longer and the incidence of remission was higher among patients who received azacitidine plus venetoclax than among those who received azacitidine alone.”

Venetoclax promotes apoptosis in leukemia cells, Dr. Perl said. “To a certain extent, you can think of it as putting the rubber to the road in terms of what actually chemotherapy is designed to do, which is to make leukemic blasts apoptose. It does so without DNA damage and with much less toxicity to the patient. Therefore it can be added to any number of regimens – granted, with mild suppression, but with relatively little extramedullary toxicity.”

Dr. Perl noted that the venetoclax arm “showed a higher response rate than azacitidine in pretty much every subgroup that was looked at, whether patients had de novo leukemia, secondary leukemia, multiple mutational complements, various different karyotypes. The response rates on this study are as high as what we often will see with intensive chemotherapy.” He added that “the winning arm on this trial seems to hold up against any low-intensity therapy, and I would argue against many high-intensity therapies in older patients.”

As for other targeted agents, isocitrate dehydrogenase (IDH) inhibitors “are very promising drugs in the relapsed/refractory setting, which is primarily where these drugs are given. In regard to frontline treatment, “data are coming from a very small study, but they’re very encouraging. It’s hard to entirely say that we’re ready to change practice based on this. But it’s very encouraging – the idea that earlier use of a drug-targeting IDH mutation might lead to substantially better outcomes.”

Moving forward, he said, “we could put all of our eggs in one basket and use many active drugs [at] front line. Or we can perhaps be smart about sequencing these drugs one after another, or using more intensive approaches followed by maintenance approaches followed by more intensive approaches.”

This approach is similar to strategies in myeloma patients “who less and less are relying on an autologous transplant for durable control of their disease, and more and more are using low-intensity biologically targeted drugs,” he said.

The Acute Leukemia Forum is held by Hemedicus, which is owned by the same company as this news organization.

Dr. Perl reported numerous disclosures, including relationships with Daiichi Sankyo, Abbvie, and Astellas.

Vertebral fractures appear to be common in people with severe COVID-19, and also raise the mortality risk, findings from a retrospective cohort suggest.

Among 114 patients with COVID-19 who underwent lateral chest x-rays at the San Raffaele Hospital ED in Milan, more than a third were found to have thoracic vertebral fractures. And, those individuals were more than twice as likely to die as were those without vertebral fractures.

“Morphometric vertebral fractures are one of the most common comorbidities among adults hospitalized with COVID-19, and the presence of such fractures may predict the severity of disease outcomes,” lead investigator Andrea Giustina, MD, said in an interview.

This is the first study to examine vertebral fracture prevalence in any coronavirus disease, but such fractures have been linked to an increased risk of pneumonia and impaired respiratory function, including restrictive pulmonary dysfunction. One possible mechanism may be that they cause anatomical changes, such as kyphosis, which negatively impact respiratory function by decreasing vital capacity, forced expiratory volume in 1 second, and inspiratory time, explained Dr. Giustina, professor of endocrinology, San Raffaele Vita Salute University, Milan, and president of the European Society of Endocrinology. The results were published in the Journal of Clinical Endocrinology and Metabolism.

Clinically, the findings suggest that all patients with COVID-19 who are undergoing chest x-rays should have morphometric vertebral x-ray evaluation, said Dr. Giustina.

“One interesting aspect of the study is that without morphometry, approximatively two thirds of vertebral fractures [would have been] missed. Therefore, they are largely underestimated in clinical practice,” he noted.
 

Thoracic vertebral fractures assessed via lateral chest x-rays

The 114 study subjects included were those whose lateral chest x-rays allowed for a high-quality assessment and in which all the thoracic tract of T4-T12 were viewable and assessable. None had been using glucocorticoids and only 3% had a prior diagnosis of osteoporosis.

The majority (75%) were male, and median age was 57 years. Most (79%) were hospitalized after evaluation in the ED. Of those, 12% (13) were admitted to the ICU and 15% (16) died.

Thoracic vertebral fractures were detected on the lateral chest x-rays in 36% (41) of the patients. In contrast, in studies of women aged 50 years and older from the general European population, morphometric vertebral fracture prevalence ranged from 18% to 26%, the investigators noted.

Of the total 65 vertebral fractures detected, 60% were classified as mild (height ratio decrease <25%), 33.3% as moderate (25%-40% decrease) and 7.7% as severe (>40%). Patients with more than one vertebral fracture were classified by their most severe one.

Those with versus without vertebral fractures didn’t differ by sex, body mass index, or clinical or biological parameters evaluated in the ED. But, compared with those without vertebral fractures, those with them were significantly older (68 vs. 54 years) and were more likely to have arterial hypertension (56% vs. 30%) and coronary artery disease (22% vs. 7%).

In multivariate analysis, age was the only statistically significant predictor of vertebral fractures (odds ratio, 1.04; P < .001).

Mortality doubled, though not significantly

Those with vertebral fractures were more likely to be hospitalized, although not significantly (88% vs. 74%). There was no significant difference in ICU admission (11% vs. 12.5%).

However, those with vertebral fractures required noninvasive mechanical ventilation significantly more often (48.8% vs. 27.4%; P = .02), and were more than twice as likely to die (22% vs. 10%; P = .07). While the difference in overall mortality wasn’t quite statistically significant, those with severe vertebral fractures were significantly more likely to die, compared with those with mild or moderate fractures (60%, 7%, 24%, respectively, for severe, moderate, and mild; P = .04), despite no significant differences in clinical or laboratory parameters.

“Our data from the field reinforce the need of implementing previously published recommendations concerning the importance of bone fragility care during the COVID pandemic with at least those patients already treated with antiosteoporotic drugs maintaining their adherence to treatments including vitamin D, which have also been suggested very recently to have no relevant predisposing effect on COVID-19,” Dr. Giustina and colleagues wrote.

Moreover, they added, “continuity of care should also include bone density monitoring despite very restricted access to clinical facilities, during the COVID-19 pandemic. Finally, all patients with fractures should start antiresorptive treatment right away, even during hospital stay.”

The authors reported having no disclosures.

SOURCE: Giustina A et al. J Clin Endocrinol Metab. 2020 Oct 21. doi: 10.1210/clinem/dgaa738.

Vertebral fractures appear to be common in people with severe COVID-19, and also raise the mortality risk, findings from a retrospective cohort suggest.

Among 114 patients with COVID-19 who underwent lateral chest x-rays at the San Raffaele Hospital ED in Milan, more than a third were found to have thoracic vertebral fractures. And, those individuals were more than twice as likely to die as were those without vertebral fractures.

“Morphometric vertebral fractures are one of the most common comorbidities among adults hospitalized with COVID-19, and the presence of such fractures may predict the severity of disease outcomes,” lead investigator Andrea Giustina, MD, said in an interview.

This is the first study to examine vertebral fracture prevalence in any coronavirus disease, but such fractures have been linked to an increased risk of pneumonia and impaired respiratory function, including restrictive pulmonary dysfunction. One possible mechanism may be that they cause anatomical changes, such as kyphosis, which negatively impact respiratory function by decreasing vital capacity, forced expiratory volume in 1 second, and inspiratory time, explained Dr. Giustina, professor of endocrinology, San Raffaele Vita Salute University, Milan, and president of the European Society of Endocrinology. The results were published in the Journal of Clinical Endocrinology and Metabolism.

Clinically, the findings suggest that all patients with COVID-19 who are undergoing chest x-rays should have morphometric vertebral x-ray evaluation, said Dr. Giustina.

“One interesting aspect of the study is that without morphometry, approximatively two thirds of vertebral fractures [would have been] missed. Therefore, they are largely underestimated in clinical practice,” he noted.
 

Thoracic vertebral fractures assessed via lateral chest x-rays

The 114 study subjects included were those whose lateral chest x-rays allowed for a high-quality assessment and in which all the thoracic tract of T4-T12 were viewable and assessable. None had been using glucocorticoids and only 3% had a prior diagnosis of osteoporosis.

The majority (75%) were male, and median age was 57 years. Most (79%) were hospitalized after evaluation in the ED. Of those, 12% (13) were admitted to the ICU and 15% (16) died.

Thoracic vertebral fractures were detected on the lateral chest x-rays in 36% (41) of the patients. In contrast, in studies of women aged 50 years and older from the general European population, morphometric vertebral fracture prevalence ranged from 18% to 26%, the investigators noted.

Of the total 65 vertebral fractures detected, 60% were classified as mild (height ratio decrease <25%), 33.3% as moderate (25%-40% decrease) and 7.7% as severe (>40%). Patients with more than one vertebral fracture were classified by their most severe one.

Those with versus without vertebral fractures didn’t differ by sex, body mass index, or clinical or biological parameters evaluated in the ED. But, compared with those without vertebral fractures, those with them were significantly older (68 vs. 54 years) and were more likely to have arterial hypertension (56% vs. 30%) and coronary artery disease (22% vs. 7%).

In multivariate analysis, age was the only statistically significant predictor of vertebral fractures (odds ratio, 1.04; P < .001).

Mortality doubled, though not significantly

Those with vertebral fractures were more likely to be hospitalized, although not significantly (88% vs. 74%). There was no significant difference in ICU admission (11% vs. 12.5%).

However, those with vertebral fractures required noninvasive mechanical ventilation significantly more often (48.8% vs. 27.4%; P = .02), and were more than twice as likely to die (22% vs. 10%; P = .07). While the difference in overall mortality wasn’t quite statistically significant, those with severe vertebral fractures were significantly more likely to die, compared with those with mild or moderate fractures (60%, 7%, 24%, respectively, for severe, moderate, and mild; P = .04), despite no significant differences in clinical or laboratory parameters.

“Our data from the field reinforce the need of implementing previously published recommendations concerning the importance of bone fragility care during the COVID pandemic with at least those patients already treated with antiosteoporotic drugs maintaining their adherence to treatments including vitamin D, which have also been suggested very recently to have no relevant predisposing effect on COVID-19,” Dr. Giustina and colleagues wrote.

Moreover, they added, “continuity of care should also include bone density monitoring despite very restricted access to clinical facilities, during the COVID-19 pandemic. Finally, all patients with fractures should start antiresorptive treatment right away, even during hospital stay.”

The authors reported having no disclosures.

SOURCE: Giustina A et al. J Clin Endocrinol Metab. 2020 Oct 21. doi: 10.1210/clinem/dgaa738.

Vertebral fractures appear to be common in people with severe COVID-19, and also raise the mortality risk, findings from a retrospective cohort suggest.

Among 114 patients with COVID-19 who underwent lateral chest x-rays at the San Raffaele Hospital ED in Milan, more than a third were found to have thoracic vertebral fractures. And, those individuals were more than twice as likely to die as were those without vertebral fractures.

“Morphometric vertebral fractures are one of the most common comorbidities among adults hospitalized with COVID-19, and the presence of such fractures may predict the severity of disease outcomes,” lead investigator Andrea Giustina, MD, said in an interview.

This is the first study to examine vertebral fracture prevalence in any coronavirus disease, but such fractures have been linked to an increased risk of pneumonia and impaired respiratory function, including restrictive pulmonary dysfunction. One possible mechanism may be that they cause anatomical changes, such as kyphosis, which negatively impact respiratory function by decreasing vital capacity, forced expiratory volume in 1 second, and inspiratory time, explained Dr. Giustina, professor of endocrinology, San Raffaele Vita Salute University, Milan, and president of the European Society of Endocrinology. The results were published in the Journal of Clinical Endocrinology and Metabolism.

Clinically, the findings suggest that all patients with COVID-19 who are undergoing chest x-rays should have morphometric vertebral x-ray evaluation, said Dr. Giustina.

“One interesting aspect of the study is that without morphometry, approximatively two thirds of vertebral fractures [would have been] missed. Therefore, they are largely underestimated in clinical practice,” he noted.
 

Thoracic vertebral fractures assessed via lateral chest x-rays

The 114 study subjects included were those whose lateral chest x-rays allowed for a high-quality assessment and in which all the thoracic tract of T4-T12 were viewable and assessable. None had been using glucocorticoids and only 3% had a prior diagnosis of osteoporosis.

The majority (75%) were male, and median age was 57 years. Most (79%) were hospitalized after evaluation in the ED. Of those, 12% (13) were admitted to the ICU and 15% (16) died.

Thoracic vertebral fractures were detected on the lateral chest x-rays in 36% (41) of the patients. In contrast, in studies of women aged 50 years and older from the general European population, morphometric vertebral fracture prevalence ranged from 18% to 26%, the investigators noted.

Of the total 65 vertebral fractures detected, 60% were classified as mild (height ratio decrease <25%), 33.3% as moderate (25%-40% decrease) and 7.7% as severe (>40%). Patients with more than one vertebral fracture were classified by their most severe one.

Those with versus without vertebral fractures didn’t differ by sex, body mass index, or clinical or biological parameters evaluated in the ED. But, compared with those without vertebral fractures, those with them were significantly older (68 vs. 54 years) and were more likely to have arterial hypertension (56% vs. 30%) and coronary artery disease (22% vs. 7%).

In multivariate analysis, age was the only statistically significant predictor of vertebral fractures (odds ratio, 1.04; P < .001).

Mortality doubled, though not significantly

Those with vertebral fractures were more likely to be hospitalized, although not significantly (88% vs. 74%). There was no significant difference in ICU admission (11% vs. 12.5%).

However, those with vertebral fractures required noninvasive mechanical ventilation significantly more often (48.8% vs. 27.4%; P = .02), and were more than twice as likely to die (22% vs. 10%; P = .07). While the difference in overall mortality wasn’t quite statistically significant, those with severe vertebral fractures were significantly more likely to die, compared with those with mild or moderate fractures (60%, 7%, 24%, respectively, for severe, moderate, and mild; P = .04), despite no significant differences in clinical or laboratory parameters.

“Our data from the field reinforce the need of implementing previously published recommendations concerning the importance of bone fragility care during the COVID pandemic with at least those patients already treated with antiosteoporotic drugs maintaining their adherence to treatments including vitamin D, which have also been suggested very recently to have no relevant predisposing effect on COVID-19,” Dr. Giustina and colleagues wrote.

Moreover, they added, “continuity of care should also include bone density monitoring despite very restricted access to clinical facilities, during the COVID-19 pandemic. Finally, all patients with fractures should start antiresorptive treatment right away, even during hospital stay.”

The authors reported having no disclosures.

SOURCE: Giustina A et al. J Clin Endocrinol Metab. 2020 Oct 21. doi: 10.1210/clinem/dgaa738.

Updated assessment and treatment options provide more tools to help clinicians manage osteoporosis and reduce fracture risk, according to Rick Pope, MPAS, PA-C.

iStock/Thinkstock

Criteria from the National Osteoporosis Foundation for the diagnosis of osteoporosis expanded in 2020 to include a T score measure of –2.5 or less at the wrist in postmenopausal women or in men aged 50 years and older (in addition to existing criteria of –2.5 or lower T scores at the lumbar spine, femoral neck, or total hip), he said in a presentation at the virtual annual Metabolic and Endocrine Disease Summit by Global Academy for Medical Education.

Other updated diagnostic criteria for osteoporosis include a low-trauma hip fracture regardless of bone mineral density, and a history of fracture of the pelvis or wrist in the context of osteopenia (in addition to the existing criteria of fracture of the vertebrae or proximal humerus).

When a diagnosis of osteoporosis is established, the Fracture Risk Assessment Tool calculator continues to serve as useful tool that allows clinicians to easily input patient data and obtain a projection of fracture risk, Mr. Pope said.

During a clinical visit, be sure to measure patients’ height, and look for kyphosis to help evaluate fall risk. Progressive kyphosis is important because the head weight can increase to 40 pounds if the kyphosis progresses to 30 degrees, and puts further stress on the vertebrae, he emphasized. In addition, looking at gait is important, especially for older patients, said Mr. Pope. “I want to get an assessment of how steady they are on their feet.”

Vertebral fracture assessment (VFA) is a useful strategy to evaluate the spine for silent compression fractures, especially in someone who has lost 1.5 inches in height or is on chronic steroids, Mr. Pope said. VFA has several advantages, including lower cost and lower radiation exposure than plain radiographs of the spine.

In addition, trabecular bone score (TBS) allows clinicians to evaluate bone microarchitecture, and this score can serve as an important indicator of fracture risk, Mr. Pope said.

As for treatment options, managing skeletal health in osteoporosis patients includes advising patients on healthy lifestyle practices that include not only adequate calcium and vitamin D, but also smoking cessation and a combination of weight-bearing, dynamic balance, and resistive exercises, he noted.

When considering medications, patient factors determine the most appropriate drug to use, Mr. Pope emphasized.

Bisphosphonates remain an option for treatment and have shown effectiveness at reducing fracture risk in postmenopausal women with osteoporosis, but concerns persist about side effects such as osteonecrosis of the jaw and atypical femoral fractures (AFF), he noted.

Reassure patients that AFF is more of an issue with long-term bisphosphonate use, Mr. Pope said, citing a 2012 study in which the risk of atypical femoral fracture was 1.78 per 100,000 person-years among individuals with 0.1-1.9 years of bisphosphonate exposure, but this jumped to 113 per 100,000 person-years among those with 8-9.9 years of bisphosphonate exposure.

“Eight years seems to be the sweet spot,” before a significant increase, he said. In his clinic, clinicians stop patients at about 8 years of bisphosphonate treatment, and then consider restarting.

However, nonbisphosphonate treatments are also available, including the monoclonal antibody denosumab. “It is different than bisphosphonates, and the effect wears off rapidly,” said Mr. Pope. Also, creatinine clearance is not an issue with denosumab. However, when patients have gone past the 10-year mark, should be switched to an alternative treatment because of an increased fracture risk at that point.

One relatively new treatment, abaloparatide, is currently indicated only for postmenopausal women with osteoporosis. Data have shown an 86% reduction in vertebral fracture risk, but the drug carries a black-box warning for osteosarcoma, said Mr. Pope.

Romosozumab, another newcomer drug, is indicated only for postmenopausal osteoporotic women at high risk for fracture with multiple risk factors who have failed other therapies. Romosozumab carries a black-box warning for cardiovascular risk for those with a history of MI or stroke. “This is a completely different mechanism of action” from other drugs, Mr. Pope said. The drug is given twice a month for a total of 12 months, and must be administered by a health professional in an office setting.

Mr. Pope had no financial conflicts to disclose. Global Academy for Medical Education and this news organization are owned by the same parent company.

Updated assessment and treatment options provide more tools to help clinicians manage osteoporosis and reduce fracture risk, according to Rick Pope, MPAS, PA-C.

iStock/Thinkstock

Criteria from the National Osteoporosis Foundation for the diagnosis of osteoporosis expanded in 2020 to include a T score measure of –2.5 or less at the wrist in postmenopausal women or in men aged 50 years and older (in addition to existing criteria of –2.5 or lower T scores at the lumbar spine, femoral neck, or total hip), he said in a presentation at the virtual annual Metabolic and Endocrine Disease Summit by Global Academy for Medical Education.

Other updated diagnostic criteria for osteoporosis include a low-trauma hip fracture regardless of bone mineral density, and a history of fracture of the pelvis or wrist in the context of osteopenia (in addition to the existing criteria of fracture of the vertebrae or proximal humerus).

When a diagnosis of osteoporosis is established, the Fracture Risk Assessment Tool calculator continues to serve as useful tool that allows clinicians to easily input patient data and obtain a projection of fracture risk, Mr. Pope said.

During a clinical visit, be sure to measure patients’ height, and look for kyphosis to help evaluate fall risk. Progressive kyphosis is important because the head weight can increase to 40 pounds if the kyphosis progresses to 30 degrees, and puts further stress on the vertebrae, he emphasized. In addition, looking at gait is important, especially for older patients, said Mr. Pope. “I want to get an assessment of how steady they are on their feet.”

Vertebral fracture assessment (VFA) is a useful strategy to evaluate the spine for silent compression fractures, especially in someone who has lost 1.5 inches in height or is on chronic steroids, Mr. Pope said. VFA has several advantages, including lower cost and lower radiation exposure than plain radiographs of the spine.

In addition, trabecular bone score (TBS) allows clinicians to evaluate bone microarchitecture, and this score can serve as an important indicator of fracture risk, Mr. Pope said.

As for treatment options, managing skeletal health in osteoporosis patients includes advising patients on healthy lifestyle practices that include not only adequate calcium and vitamin D, but also smoking cessation and a combination of weight-bearing, dynamic balance, and resistive exercises, he noted.

When considering medications, patient factors determine the most appropriate drug to use, Mr. Pope emphasized.

Bisphosphonates remain an option for treatment and have shown effectiveness at reducing fracture risk in postmenopausal women with osteoporosis, but concerns persist about side effects such as osteonecrosis of the jaw and atypical femoral fractures (AFF), he noted.

Reassure patients that AFF is more of an issue with long-term bisphosphonate use, Mr. Pope said, citing a 2012 study in which the risk of atypical femoral fracture was 1.78 per 100,000 person-years among individuals with 0.1-1.9 years of bisphosphonate exposure, but this jumped to 113 per 100,000 person-years among those with 8-9.9 years of bisphosphonate exposure.

“Eight years seems to be the sweet spot,” before a significant increase, he said. In his clinic, clinicians stop patients at about 8 years of bisphosphonate treatment, and then consider restarting.

However, nonbisphosphonate treatments are also available, including the monoclonal antibody denosumab. “It is different than bisphosphonates, and the effect wears off rapidly,” said Mr. Pope. Also, creatinine clearance is not an issue with denosumab. However, when patients have gone past the 10-year mark, should be switched to an alternative treatment because of an increased fracture risk at that point.

One relatively new treatment, abaloparatide, is currently indicated only for postmenopausal women with osteoporosis. Data have shown an 86% reduction in vertebral fracture risk, but the drug carries a black-box warning for osteosarcoma, said Mr. Pope.

Romosozumab, another newcomer drug, is indicated only for postmenopausal osteoporotic women at high risk for fracture with multiple risk factors who have failed other therapies. Romosozumab carries a black-box warning for cardiovascular risk for those with a history of MI or stroke. “This is a completely different mechanism of action” from other drugs, Mr. Pope said. The drug is given twice a month for a total of 12 months, and must be administered by a health professional in an office setting.

Mr. Pope had no financial conflicts to disclose. Global Academy for Medical Education and this news organization are owned by the same parent company.

Updated assessment and treatment options provide more tools to help clinicians manage osteoporosis and reduce fracture risk, according to Rick Pope, MPAS, PA-C.

iStock/Thinkstock

Criteria from the National Osteoporosis Foundation for the diagnosis of osteoporosis expanded in 2020 to include a T score measure of –2.5 or less at the wrist in postmenopausal women or in men aged 50 years and older (in addition to existing criteria of –2.5 or lower T scores at the lumbar spine, femoral neck, or total hip), he said in a presentation at the virtual annual Metabolic and Endocrine Disease Summit by Global Academy for Medical Education.

Other updated diagnostic criteria for osteoporosis include a low-trauma hip fracture regardless of bone mineral density, and a history of fracture of the pelvis or wrist in the context of osteopenia (in addition to the existing criteria of fracture of the vertebrae or proximal humerus).

When a diagnosis of osteoporosis is established, the Fracture Risk Assessment Tool calculator continues to serve as useful tool that allows clinicians to easily input patient data and obtain a projection of fracture risk, Mr. Pope said.

During a clinical visit, be sure to measure patients’ height, and look for kyphosis to help evaluate fall risk. Progressive kyphosis is important because the head weight can increase to 40 pounds if the kyphosis progresses to 30 degrees, and puts further stress on the vertebrae, he emphasized. In addition, looking at gait is important, especially for older patients, said Mr. Pope. “I want to get an assessment of how steady they are on their feet.”

Vertebral fracture assessment (VFA) is a useful strategy to evaluate the spine for silent compression fractures, especially in someone who has lost 1.5 inches in height or is on chronic steroids, Mr. Pope said. VFA has several advantages, including lower cost and lower radiation exposure than plain radiographs of the spine.

In addition, trabecular bone score (TBS) allows clinicians to evaluate bone microarchitecture, and this score can serve as an important indicator of fracture risk, Mr. Pope said.

As for treatment options, managing skeletal health in osteoporosis patients includes advising patients on healthy lifestyle practices that include not only adequate calcium and vitamin D, but also smoking cessation and a combination of weight-bearing, dynamic balance, and resistive exercises, he noted.

When considering medications, patient factors determine the most appropriate drug to use, Mr. Pope emphasized.

Bisphosphonates remain an option for treatment and have shown effectiveness at reducing fracture risk in postmenopausal women with osteoporosis, but concerns persist about side effects such as osteonecrosis of the jaw and atypical femoral fractures (AFF), he noted.

Reassure patients that AFF is more of an issue with long-term bisphosphonate use, Mr. Pope said, citing a 2012 study in which the risk of atypical femoral fracture was 1.78 per 100,000 person-years among individuals with 0.1-1.9 years of bisphosphonate exposure, but this jumped to 113 per 100,000 person-years among those with 8-9.9 years of bisphosphonate exposure.

“Eight years seems to be the sweet spot,” before a significant increase, he said. In his clinic, clinicians stop patients at about 8 years of bisphosphonate treatment, and then consider restarting.

However, nonbisphosphonate treatments are also available, including the monoclonal antibody denosumab. “It is different than bisphosphonates, and the effect wears off rapidly,” said Mr. Pope. Also, creatinine clearance is not an issue with denosumab. However, when patients have gone past the 10-year mark, should be switched to an alternative treatment because of an increased fracture risk at that point.

One relatively new treatment, abaloparatide, is currently indicated only for postmenopausal women with osteoporosis. Data have shown an 86% reduction in vertebral fracture risk, but the drug carries a black-box warning for osteosarcoma, said Mr. Pope.

Romosozumab, another newcomer drug, is indicated only for postmenopausal osteoporotic women at high risk for fracture with multiple risk factors who have failed other therapies. Romosozumab carries a black-box warning for cardiovascular risk for those with a history of MI or stroke. “This is a completely different mechanism of action” from other drugs, Mr. Pope said. The drug is given twice a month for a total of 12 months, and must be administered by a health professional in an office setting.

Mr. Pope had no financial conflicts to disclose. Global Academy for Medical Education and this news organization are owned by the same parent company.

Is it time to consider chimeric antigen receptor (CAR) T-cell therapy for all relapsed/refractory diffuse large B-cell lymphoma patients? Maybe not, according to Andrew Zelenetz, MD, PhD.

CAR T-cell therapy has demonstrated activity in relapsed/refractory non-Hodgkin lymphoma (NHL), including diffuse large B-cell lymphoma (DLBCL), transformed indolent NHL, and mantle cell lymphoma, and can provide durable complete responses in a portion of patients with chemorefractory disease, Dr. Zelenetz, chair of the National Comprehensive Cancer Network Lymphoma Guidelines Panel and a specialist in lymphoma at Memorial Sloan Kettering Cancer Center in New York, said at the NCCN Hematologic Malignancies Annual Congress.

In chemosensitive patients, however, its role requires further examination, especially given findings from a recent analysis of patients from the Center for International Blood & Marrow Transplant Research (CIBMTR) registry showing comparable outcomes with high-dose chemotherapy and autologous stem cell rescue for patients with a positron emission testing–positive partial response (PR) after second-line chemotherapy, he said.

Of 249 patients who underwent a first autologous transplant for DLBCL between 2003 and 2018, received front-line rituximab chemotherapy, and had PET– or computed tomography–positive disease prior to transplant, 182 had early chemotherapy failure (within 12 months) and 67 had late chemotherapy failure (at 12 months or later) after therapy, according to findings from the study as reported at ASCO 2020.

The adjusted nonrelapse mortality rates in the early- and late-failure patients, respectively, were not significantly different at 7% and 3% at 1 year, and at 10% and 8% at 5 years. The corresponding progression/relapse rates were 41% and 35% at 1 year and 48% and 57% at 5 years; these were also not significantly different.

The adjusted progression-free survival (PFS) and overall survival (OS) in the groups at 5 years also did not differ significantly (PFS of 41% in both the early- and late-failure groups, and OS of 51% and 63%, respectively).

These outcomes are comparable to those seen with CAR T-cell therapy in refractory DLBCL patients in trials of CAR T-cell products, including the ZUMA-1 study of axicabtagene cyloleucel (Yescarta), which, in a 2019 update, showed survival plateaus of about 40% vs. the 5%-10% expected rate based on pre-CAR-T outcomes data; the JULIET trial of tisagenlecleucel (Kymriah), which showed survival plateaus in the range of 30%-35%; and the recently published TRANSCEND study of the investigational modified CAR-T product, lisocabtagene maraleucel, which also showed survival plateaus “in the range of 40%.”

“So all three agents are showing that CAR T cells represent a new treatment for diffuse large B-cell lymphoma in the relapsed/refractory setting,” Dr. Zelenetz said. “And as a result, [CAR T-cell therapy has] been included in the NCCN guidelines for transformed follicular lymphoma, for transformed marginal zone lymphoma, and for diffuse large B-cell lymphoma, as well as for refractory large B-cell lymphoma.

“But are CAR T cells absolutely required? Generally what we consider these days is that if you’re not in a PET-negative CR prior to high-dose therapy stem cell rescue, you should go on to CAR T cells,” Dr. Zelenetz said.

The analysis based on the CIBMTR registry data, however, suggests there may be other alternatives.

“The bottom line is that nonrelapse mortality was very low. Progression occurred in about half of the patients, but if we look at the overall and progression-free survival curves, there’s a plateau at around 45%,” Dr. Zelenetz said, explaining that the results are “very similar to the results that we’re getting in third-line treatment with CAR T cells, and this is a very similar population [of] PET-positive patients after second-line chemotherapy.”

CAR T-cell therapy can provide a durable CR in a portion of chemorefractory patients, and although there is room for improvement, “this represents a major step forward for these patients,” he said.

However, it’s not clear that CAR T cells are clearly superior to high-dose therapy and stem cell rescue for chemosensitive patients, he added, noting that “additional randomized trials are needed to answer this question, and they are ongoing as we speak.”

Dr. Zelenetz reported clinical research support or data safety monitoring board activity for BeiGene, Genentech, Juno Therapeutics, and MEI Pharma, and scientific advisory board, consulting, or expert witness activity for Celgene Corporation, Curries, Genentech, Gilead Sciences, Janssen Pharmaceutical Products, and several other pharmaceutical and biotechnology companies.
 

[email protected]

Is it time to consider chimeric antigen receptor (CAR) T-cell therapy for all relapsed/refractory diffuse large B-cell lymphoma patients? Maybe not, according to Andrew Zelenetz, MD, PhD.

CAR T-cell therapy has demonstrated activity in relapsed/refractory non-Hodgkin lymphoma (NHL), including diffuse large B-cell lymphoma (DLBCL), transformed indolent NHL, and mantle cell lymphoma, and can provide durable complete responses in a portion of patients with chemorefractory disease, Dr. Zelenetz, chair of the National Comprehensive Cancer Network Lymphoma Guidelines Panel and a specialist in lymphoma at Memorial Sloan Kettering Cancer Center in New York, said at the NCCN Hematologic Malignancies Annual Congress.

In chemosensitive patients, however, its role requires further examination, especially given findings from a recent analysis of patients from the Center for International Blood & Marrow Transplant Research (CIBMTR) registry showing comparable outcomes with high-dose chemotherapy and autologous stem cell rescue for patients with a positron emission testing–positive partial response (PR) after second-line chemotherapy, he said.

Of 249 patients who underwent a first autologous transplant for DLBCL between 2003 and 2018, received front-line rituximab chemotherapy, and had PET– or computed tomography–positive disease prior to transplant, 182 had early chemotherapy failure (within 12 months) and 67 had late chemotherapy failure (at 12 months or later) after therapy, according to findings from the study as reported at ASCO 2020.

The adjusted nonrelapse mortality rates in the early- and late-failure patients, respectively, were not significantly different at 7% and 3% at 1 year, and at 10% and 8% at 5 years. The corresponding progression/relapse rates were 41% and 35% at 1 year and 48% and 57% at 5 years; these were also not significantly different.

The adjusted progression-free survival (PFS) and overall survival (OS) in the groups at 5 years also did not differ significantly (PFS of 41% in both the early- and late-failure groups, and OS of 51% and 63%, respectively).

These outcomes are comparable to those seen with CAR T-cell therapy in refractory DLBCL patients in trials of CAR T-cell products, including the ZUMA-1 study of axicabtagene cyloleucel (Yescarta), which, in a 2019 update, showed survival plateaus of about 40% vs. the 5%-10% expected rate based on pre-CAR-T outcomes data; the JULIET trial of tisagenlecleucel (Kymriah), which showed survival plateaus in the range of 30%-35%; and the recently published TRANSCEND study of the investigational modified CAR-T product, lisocabtagene maraleucel, which also showed survival plateaus “in the range of 40%.”

“So all three agents are showing that CAR T cells represent a new treatment for diffuse large B-cell lymphoma in the relapsed/refractory setting,” Dr. Zelenetz said. “And as a result, [CAR T-cell therapy has] been included in the NCCN guidelines for transformed follicular lymphoma, for transformed marginal zone lymphoma, and for diffuse large B-cell lymphoma, as well as for refractory large B-cell lymphoma.

“But are CAR T cells absolutely required? Generally what we consider these days is that if you’re not in a PET-negative CR prior to high-dose therapy stem cell rescue, you should go on to CAR T cells,” Dr. Zelenetz said.

The analysis based on the CIBMTR registry data, however, suggests there may be other alternatives.

“The bottom line is that nonrelapse mortality was very low. Progression occurred in about half of the patients, but if we look at the overall and progression-free survival curves, there’s a plateau at around 45%,” Dr. Zelenetz said, explaining that the results are “very similar to the results that we’re getting in third-line treatment with CAR T cells, and this is a very similar population [of] PET-positive patients after second-line chemotherapy.”

CAR T-cell therapy can provide a durable CR in a portion of chemorefractory patients, and although there is room for improvement, “this represents a major step forward for these patients,” he said.

However, it’s not clear that CAR T cells are clearly superior to high-dose therapy and stem cell rescue for chemosensitive patients, he added, noting that “additional randomized trials are needed to answer this question, and they are ongoing as we speak.”

Dr. Zelenetz reported clinical research support or data safety monitoring board activity for BeiGene, Genentech, Juno Therapeutics, and MEI Pharma, and scientific advisory board, consulting, or expert witness activity for Celgene Corporation, Curries, Genentech, Gilead Sciences, Janssen Pharmaceutical Products, and several other pharmaceutical and biotechnology companies.
 

[email protected]

Is it time to consider chimeric antigen receptor (CAR) T-cell therapy for all relapsed/refractory diffuse large B-cell lymphoma patients? Maybe not, according to Andrew Zelenetz, MD, PhD.

CAR T-cell therapy has demonstrated activity in relapsed/refractory non-Hodgkin lymphoma (NHL), including diffuse large B-cell lymphoma (DLBCL), transformed indolent NHL, and mantle cell lymphoma, and can provide durable complete responses in a portion of patients with chemorefractory disease, Dr. Zelenetz, chair of the National Comprehensive Cancer Network Lymphoma Guidelines Panel and a specialist in lymphoma at Memorial Sloan Kettering Cancer Center in New York, said at the NCCN Hematologic Malignancies Annual Congress.

In chemosensitive patients, however, its role requires further examination, especially given findings from a recent analysis of patients from the Center for International Blood & Marrow Transplant Research (CIBMTR) registry showing comparable outcomes with high-dose chemotherapy and autologous stem cell rescue for patients with a positron emission testing–positive partial response (PR) after second-line chemotherapy, he said.

Of 249 patients who underwent a first autologous transplant for DLBCL between 2003 and 2018, received front-line rituximab chemotherapy, and had PET– or computed tomography–positive disease prior to transplant, 182 had early chemotherapy failure (within 12 months) and 67 had late chemotherapy failure (at 12 months or later) after therapy, according to findings from the study as reported at ASCO 2020.

The adjusted nonrelapse mortality rates in the early- and late-failure patients, respectively, were not significantly different at 7% and 3% at 1 year, and at 10% and 8% at 5 years. The corresponding progression/relapse rates were 41% and 35% at 1 year and 48% and 57% at 5 years; these were also not significantly different.

The adjusted progression-free survival (PFS) and overall survival (OS) in the groups at 5 years also did not differ significantly (PFS of 41% in both the early- and late-failure groups, and OS of 51% and 63%, respectively).

These outcomes are comparable to those seen with CAR T-cell therapy in refractory DLBCL patients in trials of CAR T-cell products, including the ZUMA-1 study of axicabtagene cyloleucel (Yescarta), which, in a 2019 update, showed survival plateaus of about 40% vs. the 5%-10% expected rate based on pre-CAR-T outcomes data; the JULIET trial of tisagenlecleucel (Kymriah), which showed survival plateaus in the range of 30%-35%; and the recently published TRANSCEND study of the investigational modified CAR-T product, lisocabtagene maraleucel, which also showed survival plateaus “in the range of 40%.”

“So all three agents are showing that CAR T cells represent a new treatment for diffuse large B-cell lymphoma in the relapsed/refractory setting,” Dr. Zelenetz said. “And as a result, [CAR T-cell therapy has] been included in the NCCN guidelines for transformed follicular lymphoma, for transformed marginal zone lymphoma, and for diffuse large B-cell lymphoma, as well as for refractory large B-cell lymphoma.

“But are CAR T cells absolutely required? Generally what we consider these days is that if you’re not in a PET-negative CR prior to high-dose therapy stem cell rescue, you should go on to CAR T cells,” Dr. Zelenetz said.

The analysis based on the CIBMTR registry data, however, suggests there may be other alternatives.

“The bottom line is that nonrelapse mortality was very low. Progression occurred in about half of the patients, but if we look at the overall and progression-free survival curves, there’s a plateau at around 45%,” Dr. Zelenetz said, explaining that the results are “very similar to the results that we’re getting in third-line treatment with CAR T cells, and this is a very similar population [of] PET-positive patients after second-line chemotherapy.”

CAR T-cell therapy can provide a durable CR in a portion of chemorefractory patients, and although there is room for improvement, “this represents a major step forward for these patients,” he said.

However, it’s not clear that CAR T cells are clearly superior to high-dose therapy and stem cell rescue for chemosensitive patients, he added, noting that “additional randomized trials are needed to answer this question, and they are ongoing as we speak.”

Dr. Zelenetz reported clinical research support or data safety monitoring board activity for BeiGene, Genentech, Juno Therapeutics, and MEI Pharma, and scientific advisory board, consulting, or expert witness activity for Celgene Corporation, Curries, Genentech, Gilead Sciences, Janssen Pharmaceutical Products, and several other pharmaceutical and biotechnology companies.
 

[email protected]

The differences between politically left- and right-leaning individuals may have neural underpinnings, results from a new brain imaging study suggest.

Jochen Sand/Thinkstock

Investigators found that despite watching the same videos related to immigration policy, neural responses differed between liberals and conservatives.

“This divergence was strongest when the videos used language that highlighted threat, morality, and emotions, suggesting that certain words are more likely to drive polarized response,” lead researcher Yuan Chang Leong, PhD, a postdoctoral scholar in cognitive neuroscience at the University of California, Berkeley, told Medscape Medical News.

“The results suggest a neural basis for partisan biases in interpreting political messages, the effects these biases have on attitude change, and the type of language most likely to drive biased interpretations,” Leong added.

The study was published online Oct. 20 in Proceedings of the National Academy of Sciences.
 

Hardwired to disagree?

The researchers combined fMRI with semantic content analysis to investigate neural mechanisms that underlie the biased processing of political content.

They scanned 38 middle-aged men and women with liberal- or conservative-leaning immigration attitudes while the participants watched short news clips, campaign ads, and public speeches related to various immigration policies.

These policies included those that led to the United States–Mexico border wall, Deferred Action for Childhood Arrivals (DACA) protections for undocumented immigrants, the ban on refugees from majority-Muslim countries coming to the United States, and the cutting of federal funding to sanctuary cities.

After each video, participants rated on a scale of 1 to 5 how much they agreed with the general message of the video, the credibility of the information presented, and the extent to which the video made them likely to change their position and to support the policy in question.

The study revealed evidence of “neural polarization” – activity in the brain that diverges between people who hold liberal vs. conservative political views, the researchers reported.

Neural polarization was observed in the dorsomedial prefrontal cortex (DMPFC), a brain region associated with the interpretation of narrative content.

Neural polarization in this region intensified during moments in the videos that included risk-related and moral-emotional language, highlighting content features most likely to drive divergent interpretations between conservatives and liberals, they noted.

For a given individual, the closer that brain activity resembled that of the “average conservative” or “average liberal,” the more likely the person was to adopt that group’s position after watching the videos.

“We know that partisans respond differently to the same information. So in that sense, it’s not surprising to find that their brains respond differently as well,” Leong told Medscape Medical News.

“What we weren’t sure about was where in the brain we would find these differences, how neural differences were related to attitude change, and what type of content would be most likely to be associated with these differences,” he said.

Importantly, said Leong, these differences do not imply that people are hardwired to disagree. Rather, individual experiences and the media that is consumed likely contribute to neural polarization.

“If our goal is to reduce polarization and change minds, we need to think carefully about how we frame and structure political information – for example, by framing messages to appeal to the core values of the respective voter,” he said.
 

Brain stimulation to alter political perception?

Reached for comment, Shaheen Lakhan, MD, PhD, neurologist in Newton, Mass., and executive director, Global Neuroscience Initiative Foundation, said the research “puts us one step closer to identifying how our brains interpret political information.”

The study, Lakhan noted, implicates a specific brain structure, the DMPFC, which is the “lens” in which information that gets into our brain is “viewed and acted on.”

“I trust that there will be plenty more work using a similar fMRI approach to tease out scenarios outside of immigration policy, as used in this study. Down the line, brain signatures through fMRI may be able to tell an individual’s political bent, and perhaps technologies like transcranial magnetic stimulation may be able to modulate our perceptions of political content, Shaheen said.

The research was supported by a grant from the Army Research Office. Leong and Lakhan have disclosed no relevant financial relationships.
 

This article first appeared on Medscape.com.

The differences between politically left- and right-leaning individuals may have neural underpinnings, results from a new brain imaging study suggest.

Jochen Sand/Thinkstock

Investigators found that despite watching the same videos related to immigration policy, neural responses differed between liberals and conservatives.

“This divergence was strongest when the videos used language that highlighted threat, morality, and emotions, suggesting that certain words are more likely to drive polarized response,” lead researcher Yuan Chang Leong, PhD, a postdoctoral scholar in cognitive neuroscience at the University of California, Berkeley, told Medscape Medical News.

“The results suggest a neural basis for partisan biases in interpreting political messages, the effects these biases have on attitude change, and the type of language most likely to drive biased interpretations,” Leong added.

The study was published online Oct. 20 in Proceedings of the National Academy of Sciences.
 

Hardwired to disagree?

The researchers combined fMRI with semantic content analysis to investigate neural mechanisms that underlie the biased processing of political content.

They scanned 38 middle-aged men and women with liberal- or conservative-leaning immigration attitudes while the participants watched short news clips, campaign ads, and public speeches related to various immigration policies.

These policies included those that led to the United States–Mexico border wall, Deferred Action for Childhood Arrivals (DACA) protections for undocumented immigrants, the ban on refugees from majority-Muslim countries coming to the United States, and the cutting of federal funding to sanctuary cities.

After each video, participants rated on a scale of 1 to 5 how much they agreed with the general message of the video, the credibility of the information presented, and the extent to which the video made them likely to change their position and to support the policy in question.

The study revealed evidence of “neural polarization” – activity in the brain that diverges between people who hold liberal vs. conservative political views, the researchers reported.

Neural polarization was observed in the dorsomedial prefrontal cortex (DMPFC), a brain region associated with the interpretation of narrative content.

Neural polarization in this region intensified during moments in the videos that included risk-related and moral-emotional language, highlighting content features most likely to drive divergent interpretations between conservatives and liberals, they noted.

For a given individual, the closer that brain activity resembled that of the “average conservative” or “average liberal,” the more likely the person was to adopt that group’s position after watching the videos.

“We know that partisans respond differently to the same information. So in that sense, it’s not surprising to find that their brains respond differently as well,” Leong told Medscape Medical News.

“What we weren’t sure about was where in the brain we would find these differences, how neural differences were related to attitude change, and what type of content would be most likely to be associated with these differences,” he said.

Importantly, said Leong, these differences do not imply that people are hardwired to disagree. Rather, individual experiences and the media that is consumed likely contribute to neural polarization.

“If our goal is to reduce polarization and change minds, we need to think carefully about how we frame and structure political information – for example, by framing messages to appeal to the core values of the respective voter,” he said.
 

Brain stimulation to alter political perception?

Reached for comment, Shaheen Lakhan, MD, PhD, neurologist in Newton, Mass., and executive director, Global Neuroscience Initiative Foundation, said the research “puts us one step closer to identifying how our brains interpret political information.”

The study, Lakhan noted, implicates a specific brain structure, the DMPFC, which is the “lens” in which information that gets into our brain is “viewed and acted on.”

“I trust that there will be plenty more work using a similar fMRI approach to tease out scenarios outside of immigration policy, as used in this study. Down the line, brain signatures through fMRI may be able to tell an individual’s political bent, and perhaps technologies like transcranial magnetic stimulation may be able to modulate our perceptions of political content, Shaheen said.

The research was supported by a grant from the Army Research Office. Leong and Lakhan have disclosed no relevant financial relationships.
 

This article first appeared on Medscape.com.

The differences between politically left- and right-leaning individuals may have neural underpinnings, results from a new brain imaging study suggest.

Jochen Sand/Thinkstock

Investigators found that despite watching the same videos related to immigration policy, neural responses differed between liberals and conservatives.

“This divergence was strongest when the videos used language that highlighted threat, morality, and emotions, suggesting that certain words are more likely to drive polarized response,” lead researcher Yuan Chang Leong, PhD, a postdoctoral scholar in cognitive neuroscience at the University of California, Berkeley, told Medscape Medical News.

“The results suggest a neural basis for partisan biases in interpreting political messages, the effects these biases have on attitude change, and the type of language most likely to drive biased interpretations,” Leong added.

The study was published online Oct. 20 in Proceedings of the National Academy of Sciences.
 

Hardwired to disagree?

The researchers combined fMRI with semantic content analysis to investigate neural mechanisms that underlie the biased processing of political content.

They scanned 38 middle-aged men and women with liberal- or conservative-leaning immigration attitudes while the participants watched short news clips, campaign ads, and public speeches related to various immigration policies.

These policies included those that led to the United States–Mexico border wall, Deferred Action for Childhood Arrivals (DACA) protections for undocumented immigrants, the ban on refugees from majority-Muslim countries coming to the United States, and the cutting of federal funding to sanctuary cities.

After each video, participants rated on a scale of 1 to 5 how much they agreed with the general message of the video, the credibility of the information presented, and the extent to which the video made them likely to change their position and to support the policy in question.

The study revealed evidence of “neural polarization” – activity in the brain that diverges between people who hold liberal vs. conservative political views, the researchers reported.

Neural polarization was observed in the dorsomedial prefrontal cortex (DMPFC), a brain region associated with the interpretation of narrative content.

Neural polarization in this region intensified during moments in the videos that included risk-related and moral-emotional language, highlighting content features most likely to drive divergent interpretations between conservatives and liberals, they noted.

For a given individual, the closer that brain activity resembled that of the “average conservative” or “average liberal,” the more likely the person was to adopt that group’s position after watching the videos.

“We know that partisans respond differently to the same information. So in that sense, it’s not surprising to find that their brains respond differently as well,” Leong told Medscape Medical News.

“What we weren’t sure about was where in the brain we would find these differences, how neural differences were related to attitude change, and what type of content would be most likely to be associated with these differences,” he said.

Importantly, said Leong, these differences do not imply that people are hardwired to disagree. Rather, individual experiences and the media that is consumed likely contribute to neural polarization.

“If our goal is to reduce polarization and change minds, we need to think carefully about how we frame and structure political information – for example, by framing messages to appeal to the core values of the respective voter,” he said.
 

Brain stimulation to alter political perception?

Reached for comment, Shaheen Lakhan, MD, PhD, neurologist in Newton, Mass., and executive director, Global Neuroscience Initiative Foundation, said the research “puts us one step closer to identifying how our brains interpret political information.”

The study, Lakhan noted, implicates a specific brain structure, the DMPFC, which is the “lens” in which information that gets into our brain is “viewed and acted on.”

“I trust that there will be plenty more work using a similar fMRI approach to tease out scenarios outside of immigration policy, as used in this study. Down the line, brain signatures through fMRI may be able to tell an individual’s political bent, and perhaps technologies like transcranial magnetic stimulation may be able to modulate our perceptions of political content, Shaheen said.

The research was supported by a grant from the Army Research Office. Leong and Lakhan have disclosed no relevant financial relationships.
 

This article first appeared on Medscape.com.

The United States just passed a dubious COVID-19 milestone: Just over 1% of all children have been infected by the coronavirus this year, according to a report from the American Academy of Pediatrics and the Children’s Hospital Association.

There have been 1,052 cases of COVID-19 per 100,000 children as of Oct. 22, and that works out to 1.05% of all children in the country. The cumulative number of pediatric cases is 792,188, and children now represent 11% of all COVID-19 cases, the AAP and the CHA reported Oct. 26.

There were just over 50,000 new child cases reported in the week ending Oct. 22, which was 13.6% of the national total of almost 370,000. That’s up slightly from the 13.3% the previous week but still down from the spike seen in mid-September, based on the data collected from the websites of 49 state health departments (New York does not report ages), along with the District of Columbia, New York City, Puerto Rico, and Guam.

The state-level data show that California has had more COVID-19 cases in children (92,864) than any other state, although Texas has reported ages for only 7% of its confirmed cases. Illinois is next with 46,006 cases, followed by Florida at 45,575, although Florida is using an age range of 0-14 years to define a child case, the AAP and CHA noted.

Other measures largely put small states at the extremes:

• North Dakota has the highest cumulative rate: 2,954 cases per 100,000 children.
• Vermont has the lowest cumulative rate: 190.5 per 100,000.
• Wyoming has the highest proportion of cases in children: 27.7%.
• New Jersey has the lowest proportion of child cases: 4.6%.

There were no COVID-19–related deaths in children reported the week ending Oct. 22, so the total number remains at 120, which is just 0.06% of the total for all ages, based on data from 42 states and New York City. Hospitalization figures put admissions at almost 5,600 in children, or 1.7% of all hospitalizations, although those data come from just 24 states and New York City, the AAP and CHA said.

[email protected]

The United States just passed a dubious COVID-19 milestone: Just over 1% of all children have been infected by the coronavirus this year, according to a report from the American Academy of Pediatrics and the Children’s Hospital Association.

There have been 1,052 cases of COVID-19 per 100,000 children as of Oct. 22, and that works out to 1.05% of all children in the country. The cumulative number of pediatric cases is 792,188, and children now represent 11% of all COVID-19 cases, the AAP and the CHA reported Oct. 26.

There were just over 50,000 new child cases reported in the week ending Oct. 22, which was 13.6% of the national total of almost 370,000. That’s up slightly from the 13.3% the previous week but still down from the spike seen in mid-September, based on the data collected from the websites of 49 state health departments (New York does not report ages), along with the District of Columbia, New York City, Puerto Rico, and Guam.

The state-level data show that California has had more COVID-19 cases in children (92,864) than any other state, although Texas has reported ages for only 7% of its confirmed cases. Illinois is next with 46,006 cases, followed by Florida at 45,575, although Florida is using an age range of 0-14 years to define a child case, the AAP and CHA noted.

Other measures largely put small states at the extremes:

• North Dakota has the highest cumulative rate: 2,954 cases per 100,000 children.
• Vermont has the lowest cumulative rate: 190.5 per 100,000.
• Wyoming has the highest proportion of cases in children: 27.7%.
• New Jersey has the lowest proportion of child cases: 4.6%.

There were no COVID-19–related deaths in children reported the week ending Oct. 22, so the total number remains at 120, which is just 0.06% of the total for all ages, based on data from 42 states and New York City. Hospitalization figures put admissions at almost 5,600 in children, or 1.7% of all hospitalizations, although those data come from just 24 states and New York City, the AAP and CHA said.

[email protected]

The United States just passed a dubious COVID-19 milestone: Just over 1% of all children have been infected by the coronavirus this year, according to a report from the American Academy of Pediatrics and the Children’s Hospital Association.

There have been 1,052 cases of COVID-19 per 100,000 children as of Oct. 22, and that works out to 1.05% of all children in the country. The cumulative number of pediatric cases is 792,188, and children now represent 11% of all COVID-19 cases, the AAP and the CHA reported Oct. 26.

There were just over 50,000 new child cases reported in the week ending Oct. 22, which was 13.6% of the national total of almost 370,000. That’s up slightly from the 13.3% the previous week but still down from the spike seen in mid-September, based on the data collected from the websites of 49 state health departments (New York does not report ages), along with the District of Columbia, New York City, Puerto Rico, and Guam.

The state-level data show that California has had more COVID-19 cases in children (92,864) than any other state, although Texas has reported ages for only 7% of its confirmed cases. Illinois is next with 46,006 cases, followed by Florida at 45,575, although Florida is using an age range of 0-14 years to define a child case, the AAP and CHA noted.

Other measures largely put small states at the extremes:

• North Dakota has the highest cumulative rate: 2,954 cases per 100,000 children.
• Vermont has the lowest cumulative rate: 190.5 per 100,000.
• Wyoming has the highest proportion of cases in children: 27.7%.
• New Jersey has the lowest proportion of child cases: 4.6%.

There were no COVID-19–related deaths in children reported the week ending Oct. 22, so the total number remains at 120, which is just 0.06% of the total for all ages, based on data from 42 states and New York City. Hospitalization figures put admissions at almost 5,600 in children, or 1.7% of all hospitalizations, although those data come from just 24 states and New York City, the AAP and CHA said.

[email protected]

Antibody response to the SARS-CoV-2 virus wanes over time, latest research has suggested.

An ongoing study led by Imperial College London (ICL) found that the proportion of people testing positive for COVID-19 antibodies dropped by 26.5% over a 3-month period between June and September.

The findings from a non–peer reviewed preprint suggested that infection with SARS-CoV-2 confers only limited protection against reinfection.

Professor Paul Elliott, director of the REACT-2 programme at ICL, said: “Testing positive for antibodies does not mean you are immune to COVID-19.

“It remains unclear what level of immunity antibodies provide, or for how long this immunity lasts.”

Experts said that, while the findings suggested that immunity might fade over time, the severity of illness from further infections could be reduced.
 

Antibody prevalence declined in all adults

Results from cross-sectional studies over the 3-month period involved 365,104 adults who self-administered a lateral flow immunoassay test.

There were 17,576 positive tests over the three rounds.

Antibody prevalence, adjusted for test characteristics and weighted to the adult population of England, declined from 6.0% to 4.4%, a reduction of 26.5% over the 3 months.

The decline was seen in all age groups. However, the lowest prevalence of a positive test, and the largest fall, was seen in those aged 75 years and older.

No change was seen in positive antibody tests in health care workers over the 3 months.

The results suggested that people who did not show symptoms of COVID-19 were more likely to lose detectable antibodies sooner than those who did show symptoms.

Prof Helen Ward, one of the lead authors of the report said that, while it was clear that the proportion of people with antibodies was falling over time, “We don’t yet know whether this will leave these people at risk of reinfection with the virus that causes COVID-19, but it is essential that everyone continues to follow guidance to reduce the risk to themselves and others.”
 

Results ‘weaken argument for herd immunity’

Commenting on the results to the Science Media Centre, Rowland Kao, professor of veterinary epidemiology and data science at the University of Edinburgh, warned that, if the results were correct, “any strategy that relies on ‘herd immunity’ lacks credibility.”

However, he added that, “while the decline is substantial, nevertheless substantial proportions of the population do retain some immune response, over 4 months after the peak of the epidemic”.

Eleanor Riley, professor of immunology and infectious disease, also from the University of Edinburgh, said it was too early to assume that immunity to SARS-CoV-2 did not last because “the study does not look at antibody concentrations, antibody function, or other aspects of immunity such as T-cell immunity and does not look at the trajectory of antibody levels in the same individuals over time”.

However, she said the findings did not mean that a vaccine would be ineffective because vaccines contained adjuvants that could induce durable immune responses, particularly with multiple immunizations.

“What is not clear is how quickly antibody levels would rise again if a person encounters the SARS-CoV-2 virus a second time. It is possible they will still rapidly respond, and either have a milder illness, or remain protected through immune memory,” commented Dr. Alexander Edwards, associate professor in biomedical technology at the University of Reading.

Health Minister Lord Bethell said: “Regardless of the result of an antibody test, everyone must continue to comply with government guidelines including social distancing, self-isolating, and getting a test if you have symptoms, and always remember: hands, face, space.”
 

This article first appeared on Medscape.com.

Antibody response to the SARS-CoV-2 virus wanes over time, latest research has suggested.

An ongoing study led by Imperial College London (ICL) found that the proportion of people testing positive for COVID-19 antibodies dropped by 26.5% over a 3-month period between June and September.

The findings from a non–peer reviewed preprint suggested that infection with SARS-CoV-2 confers only limited protection against reinfection.

Professor Paul Elliott, director of the REACT-2 programme at ICL, said: “Testing positive for antibodies does not mean you are immune to COVID-19.

“It remains unclear what level of immunity antibodies provide, or for how long this immunity lasts.”

Experts said that, while the findings suggested that immunity might fade over time, the severity of illness from further infections could be reduced.
 

Antibody prevalence declined in all adults

Results from cross-sectional studies over the 3-month period involved 365,104 adults who self-administered a lateral flow immunoassay test.

There were 17,576 positive tests over the three rounds.

Antibody prevalence, adjusted for test characteristics and weighted to the adult population of England, declined from 6.0% to 4.4%, a reduction of 26.5% over the 3 months.

The decline was seen in all age groups. However, the lowest prevalence of a positive test, and the largest fall, was seen in those aged 75 years and older.

No change was seen in positive antibody tests in health care workers over the 3 months.

The results suggested that people who did not show symptoms of COVID-19 were more likely to lose detectable antibodies sooner than those who did show symptoms.

Prof Helen Ward, one of the lead authors of the report said that, while it was clear that the proportion of people with antibodies was falling over time, “We don’t yet know whether this will leave these people at risk of reinfection with the virus that causes COVID-19, but it is essential that everyone continues to follow guidance to reduce the risk to themselves and others.”
 

Results ‘weaken argument for herd immunity’

Commenting on the results to the Science Media Centre, Rowland Kao, professor of veterinary epidemiology and data science at the University of Edinburgh, warned that, if the results were correct, “any strategy that relies on ‘herd immunity’ lacks credibility.”

However, he added that, “while the decline is substantial, nevertheless substantial proportions of the population do retain some immune response, over 4 months after the peak of the epidemic”.

Eleanor Riley, professor of immunology and infectious disease, also from the University of Edinburgh, said it was too early to assume that immunity to SARS-CoV-2 did not last because “the study does not look at antibody concentrations, antibody function, or other aspects of immunity such as T-cell immunity and does not look at the trajectory of antibody levels in the same individuals over time”.

However, she said the findings did not mean that a vaccine would be ineffective because vaccines contained adjuvants that could induce durable immune responses, particularly with multiple immunizations.

“What is not clear is how quickly antibody levels would rise again if a person encounters the SARS-CoV-2 virus a second time. It is possible they will still rapidly respond, and either have a milder illness, or remain protected through immune memory,” commented Dr. Alexander Edwards, associate professor in biomedical technology at the University of Reading.

Health Minister Lord Bethell said: “Regardless of the result of an antibody test, everyone must continue to comply with government guidelines including social distancing, self-isolating, and getting a test if you have symptoms, and always remember: hands, face, space.”
 

This article first appeared on Medscape.com.

Antibody response to the SARS-CoV-2 virus wanes over time, latest research has suggested.

An ongoing study led by Imperial College London (ICL) found that the proportion of people testing positive for COVID-19 antibodies dropped by 26.5% over a 3-month period between June and September.

The findings from a non–peer reviewed preprint suggested that infection with SARS-CoV-2 confers only limited protection against reinfection.

Professor Paul Elliott, director of the REACT-2 programme at ICL, said: “Testing positive for antibodies does not mean you are immune to COVID-19.

“It remains unclear what level of immunity antibodies provide, or for how long this immunity lasts.”

Experts said that, while the findings suggested that immunity might fade over time, the severity of illness from further infections could be reduced.
 

Antibody prevalence declined in all adults

Results from cross-sectional studies over the 3-month period involved 365,104 adults who self-administered a lateral flow immunoassay test.

There were 17,576 positive tests over the three rounds.

Antibody prevalence, adjusted for test characteristics and weighted to the adult population of England, declined from 6.0% to 4.4%, a reduction of 26.5% over the 3 months.

The decline was seen in all age groups. However, the lowest prevalence of a positive test, and the largest fall, was seen in those aged 75 years and older.

No change was seen in positive antibody tests in health care workers over the 3 months.

The results suggested that people who did not show symptoms of COVID-19 were more likely to lose detectable antibodies sooner than those who did show symptoms.

Prof Helen Ward, one of the lead authors of the report said that, while it was clear that the proportion of people with antibodies was falling over time, “We don’t yet know whether this will leave these people at risk of reinfection with the virus that causes COVID-19, but it is essential that everyone continues to follow guidance to reduce the risk to themselves and others.”
 

Results ‘weaken argument for herd immunity’

Commenting on the results to the Science Media Centre, Rowland Kao, professor of veterinary epidemiology and data science at the University of Edinburgh, warned that, if the results were correct, “any strategy that relies on ‘herd immunity’ lacks credibility.”

However, he added that, “while the decline is substantial, nevertheless substantial proportions of the population do retain some immune response, over 4 months after the peak of the epidemic”.

Eleanor Riley, professor of immunology and infectious disease, also from the University of Edinburgh, said it was too early to assume that immunity to SARS-CoV-2 did not last because “the study does not look at antibody concentrations, antibody function, or other aspects of immunity such as T-cell immunity and does not look at the trajectory of antibody levels in the same individuals over time”.

However, she said the findings did not mean that a vaccine would be ineffective because vaccines contained adjuvants that could induce durable immune responses, particularly with multiple immunizations.

“What is not clear is how quickly antibody levels would rise again if a person encounters the SARS-CoV-2 virus a second time. It is possible they will still rapidly respond, and either have a milder illness, or remain protected through immune memory,” commented Dr. Alexander Edwards, associate professor in biomedical technology at the University of Reading.

Health Minister Lord Bethell said: “Regardless of the result of an antibody test, everyone must continue to comply with government guidelines including social distancing, self-isolating, and getting a test if you have symptoms, and always remember: hands, face, space.”
 

This article first appeared on Medscape.com.

Long-term treatment with ataluren delays loss of ambulation and may delay decline in pulmonary function in patients with nonsense mutation Duchenne muscular dystrophy (nmDMD), according to study results presented at the 2020 CNS-ICNA Conjoint Meeting, held virtually this year. Because so few patients in the study reached one of the negative pulmonary endpoints, longer follow-up will be needed to assess more conclusively the effect of ataluren on pulmonary function, said Francesco Bibbiani, MD, vice president of clinical development at PTC Therapeutics.

DMD is a rare and fatal neuromuscular disorder that causes progressive muscle weakness. Between 10% and 15% of patients with DMD have a nonsense mutation in the DMD gene. This mutation creates a premature stop codon that prevents the translation of a full-length dystrophin protein. Ataluren is designed to promote readthrough of this premature stop codon, thus enabling the production of a full-length dystrophin protein. An oral formulation of the drug has been approved in several European and South American countries.
 

Comparing treatment and standard of care

Study 019 was a phase 3, multicenter, open-label, long-term safety study of ataluren that enrolled international patients with nmDMD, most of whom had participated previously in a trial of ataluren. Dr. Bibbiani and colleagues conducted a post hoc analysis of Study 019 data to determine whether patients with nmDMD who received ataluren and standard of care for as long as 240 weeks had a different time to loss of ambulation and to decline of pulmonary function, compared with patients who received standard of care alone. Patients who were eligible to participate in Study 019 were male, had nmDMD, and had completed the blinded study drug treatment in a previous PTC-sponsored study. Treatment consisted of two 10-mg/kg doses and one 20-mg/kg dose of ataluren per day.

Dr. Bibbiani and colleagues used participants in the Cooperative International Neuromuscular Research Group Duchenne Natural History Study (CINRG DNHS) as a control group. CINRG DNHS was a prospective, longitudinal study of patients with DMD who received standard of care at 20 centers worldwide from 2006 to 2016. Dr. Bibbiani and colleagues used propensity-score matching to pair participants in this study with participants in Study 019. They matched patients with respect to age at onset of first symptoms, age at initiation of corticosteroid use, duration of deflazacort use, and duration of use of other corticosteroids. These factors are established predictors of disease progression in DMD.

Patients were eligible for inclusion in the post hoc analysis if they had available data for age, loss of ambulation, and the covariates selected for matching. Of 94 Study 019 participants, 60 were eligible for propensity-score matching with participants in CINRG DNHS. Forty-five nonambulatory patients were eligible for matching in the analysis of age at the decline in pulmonary function because data for age at loss of ambulation and for the three pulmonary endpoints measured were available for them. Thus, comparable population sizes were available for each analysis.
 

Treatment delayed disease milestones

Kaplan–Meier analysis indicated that the median age at various disease milestones was higher among patients who received ataluren and standard of care, compared with those who received standard of care alone. The median age at loss of ambulation was 15.5 years for Study 019 participants and 13.3 years for CINRG DNHS patients. The median age at predicted forced vital capacity (FVC) of less than 60% was 18.1 years for Study 019 participants and 15.8 years for CINRG DNHS participants. The median age at predicted FVC of less than 50% was 19.1 years for Study 019 participants and 17.9 years for CINRG DNHS participants. Finally, the median age at FVC of less than 1 L was not calculable for Study 019 participants and 23.8 years for CINRG DNHS participants.

The Study 019 and CINRG DNHS study groups are sponsored by PTC Therapeutics, which developed ataluren. Dr. Bibbiani is an employee of PTC Therapeutics.

[email protected]

SOURCE: McDonald C, et al. CNS-ICNA 2020. Abstract PL69.

Long-term treatment with ataluren delays loss of ambulation and may delay decline in pulmonary function in patients with nonsense mutation Duchenne muscular dystrophy (nmDMD), according to study results presented at the 2020 CNS-ICNA Conjoint Meeting, held virtually this year. Because so few patients in the study reached one of the negative pulmonary endpoints, longer follow-up will be needed to assess more conclusively the effect of ataluren on pulmonary function, said Francesco Bibbiani, MD, vice president of clinical development at PTC Therapeutics.

DMD is a rare and fatal neuromuscular disorder that causes progressive muscle weakness. Between 10% and 15% of patients with DMD have a nonsense mutation in the DMD gene. This mutation creates a premature stop codon that prevents the translation of a full-length dystrophin protein. Ataluren is designed to promote readthrough of this premature stop codon, thus enabling the production of a full-length dystrophin protein. An oral formulation of the drug has been approved in several European and South American countries.
 

Comparing treatment and standard of care

Study 019 was a phase 3, multicenter, open-label, long-term safety study of ataluren that enrolled international patients with nmDMD, most of whom had participated previously in a trial of ataluren. Dr. Bibbiani and colleagues conducted a post hoc analysis of Study 019 data to determine whether patients with nmDMD who received ataluren and standard of care for as long as 240 weeks had a different time to loss of ambulation and to decline of pulmonary function, compared with patients who received standard of care alone. Patients who were eligible to participate in Study 019 were male, had nmDMD, and had completed the blinded study drug treatment in a previous PTC-sponsored study. Treatment consisted of two 10-mg/kg doses and one 20-mg/kg dose of ataluren per day.

Dr. Bibbiani and colleagues used participants in the Cooperative International Neuromuscular Research Group Duchenne Natural History Study (CINRG DNHS) as a control group. CINRG DNHS was a prospective, longitudinal study of patients with DMD who received standard of care at 20 centers worldwide from 2006 to 2016. Dr. Bibbiani and colleagues used propensity-score matching to pair participants in this study with participants in Study 019. They matched patients with respect to age at onset of first symptoms, age at initiation of corticosteroid use, duration of deflazacort use, and duration of use of other corticosteroids. These factors are established predictors of disease progression in DMD.

Patients were eligible for inclusion in the post hoc analysis if they had available data for age, loss of ambulation, and the covariates selected for matching. Of 94 Study 019 participants, 60 were eligible for propensity-score matching with participants in CINRG DNHS. Forty-five nonambulatory patients were eligible for matching in the analysis of age at the decline in pulmonary function because data for age at loss of ambulation and for the three pulmonary endpoints measured were available for them. Thus, comparable population sizes were available for each analysis.
 

Treatment delayed disease milestones

Kaplan–Meier analysis indicated that the median age at various disease milestones was higher among patients who received ataluren and standard of care, compared with those who received standard of care alone. The median age at loss of ambulation was 15.5 years for Study 019 participants and 13.3 years for CINRG DNHS patients. The median age at predicted forced vital capacity (FVC) of less than 60% was 18.1 years for Study 019 participants and 15.8 years for CINRG DNHS participants. The median age at predicted FVC of less than 50% was 19.1 years for Study 019 participants and 17.9 years for CINRG DNHS participants. Finally, the median age at FVC of less than 1 L was not calculable for Study 019 participants and 23.8 years for CINRG DNHS participants.

The Study 019 and CINRG DNHS study groups are sponsored by PTC Therapeutics, which developed ataluren. Dr. Bibbiani is an employee of PTC Therapeutics.

[email protected]

SOURCE: McDonald C, et al. CNS-ICNA 2020. Abstract PL69.

Long-term treatment with ataluren delays loss of ambulation and may delay decline in pulmonary function in patients with nonsense mutation Duchenne muscular dystrophy (nmDMD), according to study results presented at the 2020 CNS-ICNA Conjoint Meeting, held virtually this year. Because so few patients in the study reached one of the negative pulmonary endpoints, longer follow-up will be needed to assess more conclusively the effect of ataluren on pulmonary function, said Francesco Bibbiani, MD, vice president of clinical development at PTC Therapeutics.

DMD is a rare and fatal neuromuscular disorder that causes progressive muscle weakness. Between 10% and 15% of patients with DMD have a nonsense mutation in the DMD gene. This mutation creates a premature stop codon that prevents the translation of a full-length dystrophin protein. Ataluren is designed to promote readthrough of this premature stop codon, thus enabling the production of a full-length dystrophin protein. An oral formulation of the drug has been approved in several European and South American countries.
 

Comparing treatment and standard of care

Study 019 was a phase 3, multicenter, open-label, long-term safety study of ataluren that enrolled international patients with nmDMD, most of whom had participated previously in a trial of ataluren. Dr. Bibbiani and colleagues conducted a post hoc analysis of Study 019 data to determine whether patients with nmDMD who received ataluren and standard of care for as long as 240 weeks had a different time to loss of ambulation and to decline of pulmonary function, compared with patients who received standard of care alone. Patients who were eligible to participate in Study 019 were male, had nmDMD, and had completed the blinded study drug treatment in a previous PTC-sponsored study. Treatment consisted of two 10-mg/kg doses and one 20-mg/kg dose of ataluren per day.

Dr. Bibbiani and colleagues used participants in the Cooperative International Neuromuscular Research Group Duchenne Natural History Study (CINRG DNHS) as a control group. CINRG DNHS was a prospective, longitudinal study of patients with DMD who received standard of care at 20 centers worldwide from 2006 to 2016. Dr. Bibbiani and colleagues used propensity-score matching to pair participants in this study with participants in Study 019. They matched patients with respect to age at onset of first symptoms, age at initiation of corticosteroid use, duration of deflazacort use, and duration of use of other corticosteroids. These factors are established predictors of disease progression in DMD.

Patients were eligible for inclusion in the post hoc analysis if they had available data for age, loss of ambulation, and the covariates selected for matching. Of 94 Study 019 participants, 60 were eligible for propensity-score matching with participants in CINRG DNHS. Forty-five nonambulatory patients were eligible for matching in the analysis of age at the decline in pulmonary function because data for age at loss of ambulation and for the three pulmonary endpoints measured were available for them. Thus, comparable population sizes were available for each analysis.
 

Treatment delayed disease milestones

Kaplan–Meier analysis indicated that the median age at various disease milestones was higher among patients who received ataluren and standard of care, compared with those who received standard of care alone. The median age at loss of ambulation was 15.5 years for Study 019 participants and 13.3 years for CINRG DNHS patients. The median age at predicted forced vital capacity (FVC) of less than 60% was 18.1 years for Study 019 participants and 15.8 years for CINRG DNHS participants. The median age at predicted FVC of less than 50% was 19.1 years for Study 019 participants and 17.9 years for CINRG DNHS participants. Finally, the median age at FVC of less than 1 L was not calculable for Study 019 participants and 23.8 years for CINRG DNHS participants.

The Study 019 and CINRG DNHS study groups are sponsored by PTC Therapeutics, which developed ataluren. Dr. Bibbiani is an employee of PTC Therapeutics.

[email protected]

SOURCE: McDonald C, et al. CNS-ICNA 2020. Abstract PL69.