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Dr. Douglas Paauw: Consider rechallenging patients with penicillin allergy
PHILADELPHIA – As fluoroquinolone warnings stack up, internists seeking treatment alternatives should consider rechallenging patients with penicillin allergy or referring those patients for testing, said Douglas S. Paauw, MD, during a presentation.
This was one of the pieces of advice provided by Dr. Paauw, professor of medicine in the division of general internal medicine at the University of Washington, Seattle, at the annual meeting of the American College of Physicians.
“The FDA [Food and Drug Administration] has been just killing trees, sending us letters over the last 5-10 years, with fluoroquinolone warnings,” said Dr. Paauw, referencing previous warnings describing risks of tendon rupture, peripheral neuropathy, hypoglycemia, mental health side effects, and more.
“I think the buzz in 2019 is that we should not overreact to a history of penicillin allergy,” he said.
As many as 98% of patients who have reported penicillin allergy don’t have true allergy and can safely receive penicillin, he explained.
“If they don’t have an allergy, make sure you get it out of the electronic record,” Dr. Paauw also advised.
The latest warning on fluoroquinolones from the FDA, issued in Dec. 20, 2018, said that clinicians should avoid prescribing these antibiotics in patients who have, or are at risk of, aortic aneurysm. This comprises a very large proportion of patients in an internist’s practice, Dr. Paauw noted. The warning specifically singled out elderly patients as being in the at-risk population, along with patients who have peripheral atherosclerotic vascular diseases, hypertension, or genetic conditions such as Marfan syndrome or Ehlers-Danlos syndrome, he added.
Dr. Paauw further supported his suggestions by describing two relevant studies.
In one of those studies, which was published this year in an allergy and asthma journal, 20 subjects with a history of penicillin allergy agreed to direct oral amoxicillin rechallenge by an allergist, he said. None of those 20 patients were observed to have developed immediate or delayed hypersensitivity reactions, investigators reported. That study included a total of 50 adults with a penicillin allergy label, of whom 24 (48%) had the label removed from their medical records.
In another recent and reassuring study, penicillin allergy testing was conducted in 100 children with parent-reported penicillin allergy that was considered low risk based on reported symptoms, Dr. Paauw said. Of that group, all 100 children were found to be negative for true penicillin allergy.
Dr. Paauw had no relevant disclosures.
SOURCE: Paauw DS. Annual Meeting of the American College of Physicians, Presentation MTP 013.
PHILADELPHIA – As fluoroquinolone warnings stack up, internists seeking treatment alternatives should consider rechallenging patients with penicillin allergy or referring those patients for testing, said Douglas S. Paauw, MD, during a presentation.
This was one of the pieces of advice provided by Dr. Paauw, professor of medicine in the division of general internal medicine at the University of Washington, Seattle, at the annual meeting of the American College of Physicians.
“The FDA [Food and Drug Administration] has been just killing trees, sending us letters over the last 5-10 years, with fluoroquinolone warnings,” said Dr. Paauw, referencing previous warnings describing risks of tendon rupture, peripheral neuropathy, hypoglycemia, mental health side effects, and more.
“I think the buzz in 2019 is that we should not overreact to a history of penicillin allergy,” he said.
As many as 98% of patients who have reported penicillin allergy don’t have true allergy and can safely receive penicillin, he explained.
“If they don’t have an allergy, make sure you get it out of the electronic record,” Dr. Paauw also advised.
The latest warning on fluoroquinolones from the FDA, issued in Dec. 20, 2018, said that clinicians should avoid prescribing these antibiotics in patients who have, or are at risk of, aortic aneurysm. This comprises a very large proportion of patients in an internist’s practice, Dr. Paauw noted. The warning specifically singled out elderly patients as being in the at-risk population, along with patients who have peripheral atherosclerotic vascular diseases, hypertension, or genetic conditions such as Marfan syndrome or Ehlers-Danlos syndrome, he added.
Dr. Paauw further supported his suggestions by describing two relevant studies.
In one of those studies, which was published this year in an allergy and asthma journal, 20 subjects with a history of penicillin allergy agreed to direct oral amoxicillin rechallenge by an allergist, he said. None of those 20 patients were observed to have developed immediate or delayed hypersensitivity reactions, investigators reported. That study included a total of 50 adults with a penicillin allergy label, of whom 24 (48%) had the label removed from their medical records.
In another recent and reassuring study, penicillin allergy testing was conducted in 100 children with parent-reported penicillin allergy that was considered low risk based on reported symptoms, Dr. Paauw said. Of that group, all 100 children were found to be negative for true penicillin allergy.
Dr. Paauw had no relevant disclosures.
SOURCE: Paauw DS. Annual Meeting of the American College of Physicians, Presentation MTP 013.
PHILADELPHIA – As fluoroquinolone warnings stack up, internists seeking treatment alternatives should consider rechallenging patients with penicillin allergy or referring those patients for testing, said Douglas S. Paauw, MD, during a presentation.
This was one of the pieces of advice provided by Dr. Paauw, professor of medicine in the division of general internal medicine at the University of Washington, Seattle, at the annual meeting of the American College of Physicians.
“The FDA [Food and Drug Administration] has been just killing trees, sending us letters over the last 5-10 years, with fluoroquinolone warnings,” said Dr. Paauw, referencing previous warnings describing risks of tendon rupture, peripheral neuropathy, hypoglycemia, mental health side effects, and more.
“I think the buzz in 2019 is that we should not overreact to a history of penicillin allergy,” he said.
As many as 98% of patients who have reported penicillin allergy don’t have true allergy and can safely receive penicillin, he explained.
“If they don’t have an allergy, make sure you get it out of the electronic record,” Dr. Paauw also advised.
The latest warning on fluoroquinolones from the FDA, issued in Dec. 20, 2018, said that clinicians should avoid prescribing these antibiotics in patients who have, or are at risk of, aortic aneurysm. This comprises a very large proportion of patients in an internist’s practice, Dr. Paauw noted. The warning specifically singled out elderly patients as being in the at-risk population, along with patients who have peripheral atherosclerotic vascular diseases, hypertension, or genetic conditions such as Marfan syndrome or Ehlers-Danlos syndrome, he added.
Dr. Paauw further supported his suggestions by describing two relevant studies.
In one of those studies, which was published this year in an allergy and asthma journal, 20 subjects with a history of penicillin allergy agreed to direct oral amoxicillin rechallenge by an allergist, he said. None of those 20 patients were observed to have developed immediate or delayed hypersensitivity reactions, investigators reported. That study included a total of 50 adults with a penicillin allergy label, of whom 24 (48%) had the label removed from their medical records.
In another recent and reassuring study, penicillin allergy testing was conducted in 100 children with parent-reported penicillin allergy that was considered low risk based on reported symptoms, Dr. Paauw said. Of that group, all 100 children were found to be negative for true penicillin allergy.
Dr. Paauw had no relevant disclosures.
SOURCE: Paauw DS. Annual Meeting of the American College of Physicians, Presentation MTP 013.
REPORTING FROM INTERNAL MEDICINE 2019
Long-term CPAP use not linked to weight gain
Continuous positive airway pressure (CPAP) over several years did not lead to clinically concerning levels of weight gain among patients with obstructive sleep apnea and comorbid cardiovascular disease enrolled in a large international trial, findings from a large, multicenter trial show.
No differences in weight, body mass index (BMI), or other body measurements were found when comparing CPAP and control groups in a post hoc analysis of the Sleep Apnea Cardiovascular Endpoints (SAVE) trial, which included 2,483 adults enrolled at 89 centers in seven countries.
In a subanalysis, there was a small but statistically significant weight gain of less than 400 g in men who used CPAP at least 4 hours per night as compared to matched controls. However, there were no differences in BMI or neck and waist circumferences for these men, and no such changes were observed in women, according to the investigators, led by Qiong Ou, MD, of Guangdong (China) General Hospital and R. Doug McEvoy, MD, of the Adelaide Institute for Sleep Health at Flinders University, Adelaide, Australia.
“Such a small change in weight, even with good adherence over several years, is highly unlikely to have any serious clinical ramifications,” wrote the investigators of the study published in Chest.
“Taken together, these results indicate that long-term CPAP treatment is unlikely to exacerbate the problems of overweight and obesity that are common among patients with OSA,” they added.
In a previous meta-analysis of randomized trials, investigators concluded that CPAP promoted significant increases in BMI and weight. However, the median study duration was only 3 months.
In contrast, the analysis of the SAVE trial included adults who had regular body measurements over a mean follow-up of nearly 4 years.
That long-term follow-up provided an “ideal opportunity” to assess whether CPAP treatment promotes weight gain in OSA patients over the course of several years, the authors of the SAVE trial analysis wrote.
For men in the SAVE trial, the difference in weight change for the CPAP group vs. the control group was just 0.07 kg (95% confidence interval, –0.40 to 0.54; P = .773) while in women, the difference for CPAP vs. controls was –0.14 kg (95% CI, –0.37 to 0.09; P = .233), the investigators reported.
Weight gain was significantly higher among men with good CPAP adherence, defined as use for at least 4 hours per night, investigators said, noting a mean difference of 0.38 kg (95% CI, 0.04-0.73; P = .031), though no other differences were found in body measurements for men, and no such associations were found in women with good CPAP adherence.
It’s not exactly clear why this SAVE analysis would find no evidence of CPAP promoting weight gain over the long term, in contrast to the earlier meta-analysis of short-term studies finding a significant risk of weight gain.
However, it is possible that differences in study populations such as ethnicity, age, or comorbidities contributed to the differences, said investigators.
For example, results of regression analysis in the present study showed that, compared with recruitment in Australia, recruitment in China and India was significantly linked to weight loss, while recruitment in New Zealand was linked to weight gain.
Dr. Ou had no disclosures related to the study, while Dr. McEvoy reported disclosures related to Philips Respironics, ResMed, Fisher & Paykel, Air Liquide, and the National Health and Medical Research Council of Australia.
chestphysiciannews@chestnet.org
SOURCE: Ou Q et al. Chest. 2019 Apr;155(4):720-9.
This analysis of the Sleep Apnea Cardiovascular Endpoints (SAVE) trial had several strengths and a reassuring conclusion regarding lack of weight gain with long-term use of CPAP in patients with obstructive sleep apnea (OSA) and comorbid cardiovascular disease. However, the findings may be difficult to extrapolate to Western countries, according to authors of an editorial.
“It is conceivable that the results of the study would have been different if the predominant race of the participants had been Caucasian and had a higher BMI,” said Rohit Budhiraja, MBBS, and Stuart F. Quan, MD, in the editorial. Two-thirds of the patients in the were enrolled in China, the authors said, noting that it is “well established” that Asians with OSA are less often obese compared with Caucasians with OSA in Western countries.
For clinicians, the most important message of this analysis of the SAVE trial should be that weight loss did not occur, according to Dr. Budhiraja and Dr. Quan.
“A comprehensive approach to weight loss should be used, instead of the optimistic view that improved sleep quality and daytime symptoms will automatically translate into increase physical activity, better nutrition and weight loss,” they concluded in their editorial.
Dr. Budhiraja is affiliated with the Brigham and Women’s Hospital, and Harvard Medical School, both in Boston; Dr. Quan is affiliated with Harvard Medical School, Boston, and the University of Arizona Tucson. Their editorial appears in Chest ( 2019 Apr;155[4] 657-8 ). Dr. Budhiraja reported no conflicts of interest. Dr. Quan reported serving as a consultant for Jazz Pharmaceuticals and Best Doctors, along with grant funding from the National Institutes of Health.
This analysis of the Sleep Apnea Cardiovascular Endpoints (SAVE) trial had several strengths and a reassuring conclusion regarding lack of weight gain with long-term use of CPAP in patients with obstructive sleep apnea (OSA) and comorbid cardiovascular disease. However, the findings may be difficult to extrapolate to Western countries, according to authors of an editorial.
“It is conceivable that the results of the study would have been different if the predominant race of the participants had been Caucasian and had a higher BMI,” said Rohit Budhiraja, MBBS, and Stuart F. Quan, MD, in the editorial. Two-thirds of the patients in the were enrolled in China, the authors said, noting that it is “well established” that Asians with OSA are less often obese compared with Caucasians with OSA in Western countries.
For clinicians, the most important message of this analysis of the SAVE trial should be that weight loss did not occur, according to Dr. Budhiraja and Dr. Quan.
“A comprehensive approach to weight loss should be used, instead of the optimistic view that improved sleep quality and daytime symptoms will automatically translate into increase physical activity, better nutrition and weight loss,” they concluded in their editorial.
Dr. Budhiraja is affiliated with the Brigham and Women’s Hospital, and Harvard Medical School, both in Boston; Dr. Quan is affiliated with Harvard Medical School, Boston, and the University of Arizona Tucson. Their editorial appears in Chest ( 2019 Apr;155[4] 657-8 ). Dr. Budhiraja reported no conflicts of interest. Dr. Quan reported serving as a consultant for Jazz Pharmaceuticals and Best Doctors, along with grant funding from the National Institutes of Health.
This analysis of the Sleep Apnea Cardiovascular Endpoints (SAVE) trial had several strengths and a reassuring conclusion regarding lack of weight gain with long-term use of CPAP in patients with obstructive sleep apnea (OSA) and comorbid cardiovascular disease. However, the findings may be difficult to extrapolate to Western countries, according to authors of an editorial.
“It is conceivable that the results of the study would have been different if the predominant race of the participants had been Caucasian and had a higher BMI,” said Rohit Budhiraja, MBBS, and Stuart F. Quan, MD, in the editorial. Two-thirds of the patients in the were enrolled in China, the authors said, noting that it is “well established” that Asians with OSA are less often obese compared with Caucasians with OSA in Western countries.
For clinicians, the most important message of this analysis of the SAVE trial should be that weight loss did not occur, according to Dr. Budhiraja and Dr. Quan.
“A comprehensive approach to weight loss should be used, instead of the optimistic view that improved sleep quality and daytime symptoms will automatically translate into increase physical activity, better nutrition and weight loss,” they concluded in their editorial.
Dr. Budhiraja is affiliated with the Brigham and Women’s Hospital, and Harvard Medical School, both in Boston; Dr. Quan is affiliated with Harvard Medical School, Boston, and the University of Arizona Tucson. Their editorial appears in Chest ( 2019 Apr;155[4] 657-8 ). Dr. Budhiraja reported no conflicts of interest. Dr. Quan reported serving as a consultant for Jazz Pharmaceuticals and Best Doctors, along with grant funding from the National Institutes of Health.
Continuous positive airway pressure (CPAP) over several years did not lead to clinically concerning levels of weight gain among patients with obstructive sleep apnea and comorbid cardiovascular disease enrolled in a large international trial, findings from a large, multicenter trial show.
No differences in weight, body mass index (BMI), or other body measurements were found when comparing CPAP and control groups in a post hoc analysis of the Sleep Apnea Cardiovascular Endpoints (SAVE) trial, which included 2,483 adults enrolled at 89 centers in seven countries.
In a subanalysis, there was a small but statistically significant weight gain of less than 400 g in men who used CPAP at least 4 hours per night as compared to matched controls. However, there were no differences in BMI or neck and waist circumferences for these men, and no such changes were observed in women, according to the investigators, led by Qiong Ou, MD, of Guangdong (China) General Hospital and R. Doug McEvoy, MD, of the Adelaide Institute for Sleep Health at Flinders University, Adelaide, Australia.
“Such a small change in weight, even with good adherence over several years, is highly unlikely to have any serious clinical ramifications,” wrote the investigators of the study published in Chest.
“Taken together, these results indicate that long-term CPAP treatment is unlikely to exacerbate the problems of overweight and obesity that are common among patients with OSA,” they added.
In a previous meta-analysis of randomized trials, investigators concluded that CPAP promoted significant increases in BMI and weight. However, the median study duration was only 3 months.
In contrast, the analysis of the SAVE trial included adults who had regular body measurements over a mean follow-up of nearly 4 years.
That long-term follow-up provided an “ideal opportunity” to assess whether CPAP treatment promotes weight gain in OSA patients over the course of several years, the authors of the SAVE trial analysis wrote.
For men in the SAVE trial, the difference in weight change for the CPAP group vs. the control group was just 0.07 kg (95% confidence interval, –0.40 to 0.54; P = .773) while in women, the difference for CPAP vs. controls was –0.14 kg (95% CI, –0.37 to 0.09; P = .233), the investigators reported.
Weight gain was significantly higher among men with good CPAP adherence, defined as use for at least 4 hours per night, investigators said, noting a mean difference of 0.38 kg (95% CI, 0.04-0.73; P = .031), though no other differences were found in body measurements for men, and no such associations were found in women with good CPAP adherence.
It’s not exactly clear why this SAVE analysis would find no evidence of CPAP promoting weight gain over the long term, in contrast to the earlier meta-analysis of short-term studies finding a significant risk of weight gain.
However, it is possible that differences in study populations such as ethnicity, age, or comorbidities contributed to the differences, said investigators.
For example, results of regression analysis in the present study showed that, compared with recruitment in Australia, recruitment in China and India was significantly linked to weight loss, while recruitment in New Zealand was linked to weight gain.
Dr. Ou had no disclosures related to the study, while Dr. McEvoy reported disclosures related to Philips Respironics, ResMed, Fisher & Paykel, Air Liquide, and the National Health and Medical Research Council of Australia.
chestphysiciannews@chestnet.org
SOURCE: Ou Q et al. Chest. 2019 Apr;155(4):720-9.
Continuous positive airway pressure (CPAP) over several years did not lead to clinically concerning levels of weight gain among patients with obstructive sleep apnea and comorbid cardiovascular disease enrolled in a large international trial, findings from a large, multicenter trial show.
No differences in weight, body mass index (BMI), or other body measurements were found when comparing CPAP and control groups in a post hoc analysis of the Sleep Apnea Cardiovascular Endpoints (SAVE) trial, which included 2,483 adults enrolled at 89 centers in seven countries.
In a subanalysis, there was a small but statistically significant weight gain of less than 400 g in men who used CPAP at least 4 hours per night as compared to matched controls. However, there were no differences in BMI or neck and waist circumferences for these men, and no such changes were observed in women, according to the investigators, led by Qiong Ou, MD, of Guangdong (China) General Hospital and R. Doug McEvoy, MD, of the Adelaide Institute for Sleep Health at Flinders University, Adelaide, Australia.
“Such a small change in weight, even with good adherence over several years, is highly unlikely to have any serious clinical ramifications,” wrote the investigators of the study published in Chest.
“Taken together, these results indicate that long-term CPAP treatment is unlikely to exacerbate the problems of overweight and obesity that are common among patients with OSA,” they added.
In a previous meta-analysis of randomized trials, investigators concluded that CPAP promoted significant increases in BMI and weight. However, the median study duration was only 3 months.
In contrast, the analysis of the SAVE trial included adults who had regular body measurements over a mean follow-up of nearly 4 years.
That long-term follow-up provided an “ideal opportunity” to assess whether CPAP treatment promotes weight gain in OSA patients over the course of several years, the authors of the SAVE trial analysis wrote.
For men in the SAVE trial, the difference in weight change for the CPAP group vs. the control group was just 0.07 kg (95% confidence interval, –0.40 to 0.54; P = .773) while in women, the difference for CPAP vs. controls was –0.14 kg (95% CI, –0.37 to 0.09; P = .233), the investigators reported.
Weight gain was significantly higher among men with good CPAP adherence, defined as use for at least 4 hours per night, investigators said, noting a mean difference of 0.38 kg (95% CI, 0.04-0.73; P = .031), though no other differences were found in body measurements for men, and no such associations were found in women with good CPAP adherence.
It’s not exactly clear why this SAVE analysis would find no evidence of CPAP promoting weight gain over the long term, in contrast to the earlier meta-analysis of short-term studies finding a significant risk of weight gain.
However, it is possible that differences in study populations such as ethnicity, age, or comorbidities contributed to the differences, said investigators.
For example, results of regression analysis in the present study showed that, compared with recruitment in Australia, recruitment in China and India was significantly linked to weight loss, while recruitment in New Zealand was linked to weight gain.
Dr. Ou had no disclosures related to the study, while Dr. McEvoy reported disclosures related to Philips Respironics, ResMed, Fisher & Paykel, Air Liquide, and the National Health and Medical Research Council of Australia.
chestphysiciannews@chestnet.org
SOURCE: Ou Q et al. Chest. 2019 Apr;155(4):720-9.
FROM CHEST
CT scan honeycombing key to hypersensitivity pneumonitis prognosis
In patients with hypersensitivity pneumonitis, presence of radiologic honeycombing suggests a poor prognosis in line with what might be expected with idiopathic pulmonary fibrosis, results of a recent study suggest.
When radiologic honeycombing was present, event-free survival was uniformly poor, regardless of whether the patient had hypersensitivity pneumonitis (HP) or idiopathic pulmonary fibrosis (IPF). By contrast, HP patients with nonhoneycomb fibrosis had longer event-free survival than IPF patients with honeycomb features on CT, wrote researchers led by Margaret L. Salisbury, MD, of the division of pulmonary and critical care medicine at the University of Michigan, Ann Arbor.
“Given the uniformly poor outcome among subjects with radiologic honeycombing, pursuit of invasive diagnostic tests directed at differentiating IPF from HP may be of limited value,” Dr. Salisbury and her coinvestigators wrote in Chest.
In the study, 117 patients with HP and 161 with IPF underwent high-resolution CT, results of which were evaluated by three thoracic radiologists. Patients with HP who had no fibrosis on CT had the best event-free median survival, or time to transplant or death, at greater than 14.73 years. For HP patients with nonhoneycomb fibrosis, that median survival was greater than 7.95 years, compared with just 5.20 years in IPF patients without honeycomb features.
Looking specifically at patients with honeycomb features, median event-free survival was poor for both HP and IPF patients, at 2.76 and 2.81 years, respectively.
The HP patients with no fibrosis had a significant improvement in percent predicted forced vital capacity over time, while fibrotic patients experienced significant declines, the investigators wrote. Thus, HP patients with nonhoneycomb fibrosis had forced vital capacity declines despite longer transplant-free survival.
“These results highlight the importance of making a correct diagnosis of HP versus IPF in patients with nonhoneycomb fibrosis, as well as the limited utility in differentiating HP from IPF among patients with radiologic honeycombing,” Dr. Salisbury and her coinvestigators concluded.
Dr. Salisbury reported grants from the National Institutes of Health during the study. Her coauthors reported disclosures related to the NIH, Bayer, Centocor, Gilead, Promedior, Ikaria, Genentech, Nycomed/Takeda, Pfizer, and others.
SOURCE: Salisbury ML et al. Chest. 2019 Apr;155(4):699-711.
This study provides “clearly defined” phenotypes that are practical and potentially important for stratification and prognosis in patients with hypersensitivity pneumonitis (HP), according to David A. Lynch, MB.
“They should be widely adopted,” Dr. Lynch wrote of the three HP CT phenotypes in an editorial.
The study adds further evidence on the significance of honeycombing in the clinical course of fibrotic HP versus that of idiopathic pulmonary fibrosis, he added. Symptom duration in the HP patients was similar regardless of nonfibrotic, fibrotic, or honeycomb patterns, and was not linked to survival time. With that in mind, classifying HP based on fibrosis and its pattern may be more useful in determining prognosis than traditional acute, subacute, or chronic classification
That said, the present study does not provide much information on what demographic or exposure factors were associated with three phenotypes.
“Further study of this question will be important,” Dr. Lynch wrote. “Additionally, it will be important to understand the histologic correlates of the CT phenotypes.”
Dr. Lynch is with the department of radiology at National Jewish Health in Denver. His remarks are taken from his editorial that appeared in Chest (2019;155[4]:655-6). Dr. Lynch reported disclosures related to Genentech, Boehringer Ingelheim, Veracyte, Boehringer Ingelheim, and the France Foundation.
This study provides “clearly defined” phenotypes that are practical and potentially important for stratification and prognosis in patients with hypersensitivity pneumonitis (HP), according to David A. Lynch, MB.
“They should be widely adopted,” Dr. Lynch wrote of the three HP CT phenotypes in an editorial.
The study adds further evidence on the significance of honeycombing in the clinical course of fibrotic HP versus that of idiopathic pulmonary fibrosis, he added. Symptom duration in the HP patients was similar regardless of nonfibrotic, fibrotic, or honeycomb patterns, and was not linked to survival time. With that in mind, classifying HP based on fibrosis and its pattern may be more useful in determining prognosis than traditional acute, subacute, or chronic classification
That said, the present study does not provide much information on what demographic or exposure factors were associated with three phenotypes.
“Further study of this question will be important,” Dr. Lynch wrote. “Additionally, it will be important to understand the histologic correlates of the CT phenotypes.”
Dr. Lynch is with the department of radiology at National Jewish Health in Denver. His remarks are taken from his editorial that appeared in Chest (2019;155[4]:655-6). Dr. Lynch reported disclosures related to Genentech, Boehringer Ingelheim, Veracyte, Boehringer Ingelheim, and the France Foundation.
This study provides “clearly defined” phenotypes that are practical and potentially important for stratification and prognosis in patients with hypersensitivity pneumonitis (HP), according to David A. Lynch, MB.
“They should be widely adopted,” Dr. Lynch wrote of the three HP CT phenotypes in an editorial.
The study adds further evidence on the significance of honeycombing in the clinical course of fibrotic HP versus that of idiopathic pulmonary fibrosis, he added. Symptom duration in the HP patients was similar regardless of nonfibrotic, fibrotic, or honeycomb patterns, and was not linked to survival time. With that in mind, classifying HP based on fibrosis and its pattern may be more useful in determining prognosis than traditional acute, subacute, or chronic classification
That said, the present study does not provide much information on what demographic or exposure factors were associated with three phenotypes.
“Further study of this question will be important,” Dr. Lynch wrote. “Additionally, it will be important to understand the histologic correlates of the CT phenotypes.”
Dr. Lynch is with the department of radiology at National Jewish Health in Denver. His remarks are taken from his editorial that appeared in Chest (2019;155[4]:655-6). Dr. Lynch reported disclosures related to Genentech, Boehringer Ingelheim, Veracyte, Boehringer Ingelheim, and the France Foundation.
In patients with hypersensitivity pneumonitis, presence of radiologic honeycombing suggests a poor prognosis in line with what might be expected with idiopathic pulmonary fibrosis, results of a recent study suggest.
When radiologic honeycombing was present, event-free survival was uniformly poor, regardless of whether the patient had hypersensitivity pneumonitis (HP) or idiopathic pulmonary fibrosis (IPF). By contrast, HP patients with nonhoneycomb fibrosis had longer event-free survival than IPF patients with honeycomb features on CT, wrote researchers led by Margaret L. Salisbury, MD, of the division of pulmonary and critical care medicine at the University of Michigan, Ann Arbor.
“Given the uniformly poor outcome among subjects with radiologic honeycombing, pursuit of invasive diagnostic tests directed at differentiating IPF from HP may be of limited value,” Dr. Salisbury and her coinvestigators wrote in Chest.
In the study, 117 patients with HP and 161 with IPF underwent high-resolution CT, results of which were evaluated by three thoracic radiologists. Patients with HP who had no fibrosis on CT had the best event-free median survival, or time to transplant or death, at greater than 14.73 years. For HP patients with nonhoneycomb fibrosis, that median survival was greater than 7.95 years, compared with just 5.20 years in IPF patients without honeycomb features.
Looking specifically at patients with honeycomb features, median event-free survival was poor for both HP and IPF patients, at 2.76 and 2.81 years, respectively.
The HP patients with no fibrosis had a significant improvement in percent predicted forced vital capacity over time, while fibrotic patients experienced significant declines, the investigators wrote. Thus, HP patients with nonhoneycomb fibrosis had forced vital capacity declines despite longer transplant-free survival.
“These results highlight the importance of making a correct diagnosis of HP versus IPF in patients with nonhoneycomb fibrosis, as well as the limited utility in differentiating HP from IPF among patients with radiologic honeycombing,” Dr. Salisbury and her coinvestigators concluded.
Dr. Salisbury reported grants from the National Institutes of Health during the study. Her coauthors reported disclosures related to the NIH, Bayer, Centocor, Gilead, Promedior, Ikaria, Genentech, Nycomed/Takeda, Pfizer, and others.
SOURCE: Salisbury ML et al. Chest. 2019 Apr;155(4):699-711.
In patients with hypersensitivity pneumonitis, presence of radiologic honeycombing suggests a poor prognosis in line with what might be expected with idiopathic pulmonary fibrosis, results of a recent study suggest.
When radiologic honeycombing was present, event-free survival was uniformly poor, regardless of whether the patient had hypersensitivity pneumonitis (HP) or idiopathic pulmonary fibrosis (IPF). By contrast, HP patients with nonhoneycomb fibrosis had longer event-free survival than IPF patients with honeycomb features on CT, wrote researchers led by Margaret L. Salisbury, MD, of the division of pulmonary and critical care medicine at the University of Michigan, Ann Arbor.
“Given the uniformly poor outcome among subjects with radiologic honeycombing, pursuit of invasive diagnostic tests directed at differentiating IPF from HP may be of limited value,” Dr. Salisbury and her coinvestigators wrote in Chest.
In the study, 117 patients with HP and 161 with IPF underwent high-resolution CT, results of which were evaluated by three thoracic radiologists. Patients with HP who had no fibrosis on CT had the best event-free median survival, or time to transplant or death, at greater than 14.73 years. For HP patients with nonhoneycomb fibrosis, that median survival was greater than 7.95 years, compared with just 5.20 years in IPF patients without honeycomb features.
Looking specifically at patients with honeycomb features, median event-free survival was poor for both HP and IPF patients, at 2.76 and 2.81 years, respectively.
The HP patients with no fibrosis had a significant improvement in percent predicted forced vital capacity over time, while fibrotic patients experienced significant declines, the investigators wrote. Thus, HP patients with nonhoneycomb fibrosis had forced vital capacity declines despite longer transplant-free survival.
“These results highlight the importance of making a correct diagnosis of HP versus IPF in patients with nonhoneycomb fibrosis, as well as the limited utility in differentiating HP from IPF among patients with radiologic honeycombing,” Dr. Salisbury and her coinvestigators concluded.
Dr. Salisbury reported grants from the National Institutes of Health during the study. Her coauthors reported disclosures related to the NIH, Bayer, Centocor, Gilead, Promedior, Ikaria, Genentech, Nycomed/Takeda, Pfizer, and others.
SOURCE: Salisbury ML et al. Chest. 2019 Apr;155(4):699-711.
FROM CHEST®
AFib, CVD risks similar after ustekinumab and TNF inhibitors in psoriatic patients
Patients with psoriasis or psoriatic arthritis who started ustekinumab (Stelara) versus a tumor necrosis factor inhibitor had no differences in the overall risks of incident atrial fibrillation (AFib) or major adverse cardiovascular events (MACE), according to authors of a retrospective cohort study of two commercial insurance databases.
Subgroup analyses in the study also revealed “no statistically significant heterogeneity” in risk of AFib or MACE by age, sex, or presence of diabetes, Moa P. Lee, PharmD, of Brigham and Women’s Hospital and Harvard Medical School, Boston, and her coauthors reported in JAMA Dermatology.
These findings provide additional evidence on cardiovascular risks with ustekinumab versus other treatments.
The findings are consistent with previous observations of a small but nonsignificant increase in cardiovascular disease among patients with psoriatic disease and provide new insight into the risk of AFib with psoriatic treatments with the two therapies, Dr. Lee and her colleagues wrote.
The retrospective study of two U.S. commercial health care claims databases included 60,028 adult patients with psoriasis or psoriatic arthritis who initiated therapy with ustekinumab (n = 9,071) or a tumor necrosis factor (TNF) inhibitor (n = 50,957), including adalimumab, certolizumab pegol, golimumab, etanercept, or infliximab. The investigators excluded any patient with an AFib diagnosis at baseline and those receiving any antiarrhythmic or anticoagulant treatment.
The incidence of AFib was 5.0 and 4.1 per 1,000 person-years in the ustekinumab and TNF inhibitor groups, respectively, with an adjusted hazard ratio of 1.08 (95% CI, 0.76-1.54). The incidence of MACE (a composite endpoint of MI, stroke, and coronary revascularization) was 6.2 and 6.1 per 1,000 person-years in the ustekinumab and TNF inhibitor groups, with an adjusted hazard ratio of 1.10 (95% CI, 0.80-1.52).
In subgroup analyses, the adjusted HR for AFib with ustekinumab versus TNF inhibitor was 1.46 (95% CI, 0.98-2.18) for patients aged 60 years and older and 1.47 (95% CI, 0.93-2.31) in patients with diabetes, the investigators wrote.
The adjusted HR for AFib with ustekinumab versus TNF inhibitors was 1.21 in men (95% CI, 0.87-1.69) and 0.82 in women (95% CI, 0.49-1.39), while for MACE, the HRs were 1.31 in men (95% CI, 0.97-1.76) and 0.91 in women (95% CI, 0.56-1.47).
“Although the risk of these cardiovascular outcomes appeared to be similar across the subpopulations included in our study, further investigations on potentially modifying treatment effects stratified by important risk factors may be warranted,” Dr. Lee and her coauthors wrote.
The study was supported by the division of pharmacoepidemiology and pharmacoeconomics at Brigham and Women’s Hospital. Several authors reported financial relationships with pharmaceutical companies marketing biologics for psoriasis and psoriatic arthritis.
SOURCE: Lee MP et al. JAMA Dermatol. 2019 Mar 27. doi: 10.1001/jamadermatol.2019.0001.
Patients with psoriasis or psoriatic arthritis who started ustekinumab (Stelara) versus a tumor necrosis factor inhibitor had no differences in the overall risks of incident atrial fibrillation (AFib) or major adverse cardiovascular events (MACE), according to authors of a retrospective cohort study of two commercial insurance databases.
Subgroup analyses in the study also revealed “no statistically significant heterogeneity” in risk of AFib or MACE by age, sex, or presence of diabetes, Moa P. Lee, PharmD, of Brigham and Women’s Hospital and Harvard Medical School, Boston, and her coauthors reported in JAMA Dermatology.
These findings provide additional evidence on cardiovascular risks with ustekinumab versus other treatments.
The findings are consistent with previous observations of a small but nonsignificant increase in cardiovascular disease among patients with psoriatic disease and provide new insight into the risk of AFib with psoriatic treatments with the two therapies, Dr. Lee and her colleagues wrote.
The retrospective study of two U.S. commercial health care claims databases included 60,028 adult patients with psoriasis or psoriatic arthritis who initiated therapy with ustekinumab (n = 9,071) or a tumor necrosis factor (TNF) inhibitor (n = 50,957), including adalimumab, certolizumab pegol, golimumab, etanercept, or infliximab. The investigators excluded any patient with an AFib diagnosis at baseline and those receiving any antiarrhythmic or anticoagulant treatment.
The incidence of AFib was 5.0 and 4.1 per 1,000 person-years in the ustekinumab and TNF inhibitor groups, respectively, with an adjusted hazard ratio of 1.08 (95% CI, 0.76-1.54). The incidence of MACE (a composite endpoint of MI, stroke, and coronary revascularization) was 6.2 and 6.1 per 1,000 person-years in the ustekinumab and TNF inhibitor groups, with an adjusted hazard ratio of 1.10 (95% CI, 0.80-1.52).
In subgroup analyses, the adjusted HR for AFib with ustekinumab versus TNF inhibitor was 1.46 (95% CI, 0.98-2.18) for patients aged 60 years and older and 1.47 (95% CI, 0.93-2.31) in patients with diabetes, the investigators wrote.
The adjusted HR for AFib with ustekinumab versus TNF inhibitors was 1.21 in men (95% CI, 0.87-1.69) and 0.82 in women (95% CI, 0.49-1.39), while for MACE, the HRs were 1.31 in men (95% CI, 0.97-1.76) and 0.91 in women (95% CI, 0.56-1.47).
“Although the risk of these cardiovascular outcomes appeared to be similar across the subpopulations included in our study, further investigations on potentially modifying treatment effects stratified by important risk factors may be warranted,” Dr. Lee and her coauthors wrote.
The study was supported by the division of pharmacoepidemiology and pharmacoeconomics at Brigham and Women’s Hospital. Several authors reported financial relationships with pharmaceutical companies marketing biologics for psoriasis and psoriatic arthritis.
SOURCE: Lee MP et al. JAMA Dermatol. 2019 Mar 27. doi: 10.1001/jamadermatol.2019.0001.
Patients with psoriasis or psoriatic arthritis who started ustekinumab (Stelara) versus a tumor necrosis factor inhibitor had no differences in the overall risks of incident atrial fibrillation (AFib) or major adverse cardiovascular events (MACE), according to authors of a retrospective cohort study of two commercial insurance databases.
Subgroup analyses in the study also revealed “no statistically significant heterogeneity” in risk of AFib or MACE by age, sex, or presence of diabetes, Moa P. Lee, PharmD, of Brigham and Women’s Hospital and Harvard Medical School, Boston, and her coauthors reported in JAMA Dermatology.
These findings provide additional evidence on cardiovascular risks with ustekinumab versus other treatments.
The findings are consistent with previous observations of a small but nonsignificant increase in cardiovascular disease among patients with psoriatic disease and provide new insight into the risk of AFib with psoriatic treatments with the two therapies, Dr. Lee and her colleagues wrote.
The retrospective study of two U.S. commercial health care claims databases included 60,028 adult patients with psoriasis or psoriatic arthritis who initiated therapy with ustekinumab (n = 9,071) or a tumor necrosis factor (TNF) inhibitor (n = 50,957), including adalimumab, certolizumab pegol, golimumab, etanercept, or infliximab. The investigators excluded any patient with an AFib diagnosis at baseline and those receiving any antiarrhythmic or anticoagulant treatment.
The incidence of AFib was 5.0 and 4.1 per 1,000 person-years in the ustekinumab and TNF inhibitor groups, respectively, with an adjusted hazard ratio of 1.08 (95% CI, 0.76-1.54). The incidence of MACE (a composite endpoint of MI, stroke, and coronary revascularization) was 6.2 and 6.1 per 1,000 person-years in the ustekinumab and TNF inhibitor groups, with an adjusted hazard ratio of 1.10 (95% CI, 0.80-1.52).
In subgroup analyses, the adjusted HR for AFib with ustekinumab versus TNF inhibitor was 1.46 (95% CI, 0.98-2.18) for patients aged 60 years and older and 1.47 (95% CI, 0.93-2.31) in patients with diabetes, the investigators wrote.
The adjusted HR for AFib with ustekinumab versus TNF inhibitors was 1.21 in men (95% CI, 0.87-1.69) and 0.82 in women (95% CI, 0.49-1.39), while for MACE, the HRs were 1.31 in men (95% CI, 0.97-1.76) and 0.91 in women (95% CI, 0.56-1.47).
“Although the risk of these cardiovascular outcomes appeared to be similar across the subpopulations included in our study, further investigations on potentially modifying treatment effects stratified by important risk factors may be warranted,” Dr. Lee and her coauthors wrote.
The study was supported by the division of pharmacoepidemiology and pharmacoeconomics at Brigham and Women’s Hospital. Several authors reported financial relationships with pharmaceutical companies marketing biologics for psoriasis and psoriatic arthritis.
SOURCE: Lee MP et al. JAMA Dermatol. 2019 Mar 27. doi: 10.1001/jamadermatol.2019.0001.
FROM JAMA DERMATOLOGY
Five-fraction SRBT schedule well tolerated with high tumor-control rate in central lung cancers
For patients with centrally located lung cancers in a multicenter phase 1/2 trial, a specific five-fraction radiotherapy schedule was well tolerated and linked to fairly low rates of treatment-related toxicity, investigators say.
The 12-Gy/fraction schedule of stereotactic body radiotherapy (SBRT) had a 7.2% rate of dose-limiting toxicities and a high tumor-control rate in the NRG Oncology/RTOG 0813 trial, which enrolled 120 patients with medically inoperable stage T1/2 N0M0 non–small cell lung cancers at 43 centers in the United States and Canada.
This is an important study that has implications for clinical practice, according to the investigators, led by Andrea Bezjak, MD, of Princess Margaret Cancer Centre in Toronto.
“The ability to treat patients with centrally located node-negative tumors in multiple institutions across the United States and Canada while maintaining plan qualities and achieving good patient outcomes and relatively modest rates of toxicity is an important achievement,” Dr. Bezjak and coinvestigators said in the Journal of Clinical Oncology.
These patients are frequently at increased risk from surgery, because of advanced age and the comorbidities that come with it, they added.
The 12-Gy/fraction dose level was the highest of nine dose levels included in the study protocol. Doses were delivered in five fractions over the course of 1.5-2 weeks. Investigators sought to determine the maximum tolerated dose of SRBT, defined as the level at which the probability of dose-limiting toxicities (grade 3 or greater) within the first year was as close to 20% as possible, without going over.
Thus, the 7.2% rate of dose-limiting toxicities at this highest-allowed dose level was “well below” that protocol-specified threshold, investigators said, commenting on results of the study.
The rate of local control at 2 years was 89.4% for the 12-Gy/fraction dose level. The 2-year overall survival was 70%, which compared favorably to what has been seen previously with use of SBRT in similar patients with peripheral tumors, according to Dr. Bezjak and colleagues.
Most deaths in the study were attributable to causes other than lung cancer, according to investigators, who noted that all accrued patients were deemed medically inoperable by an experienced thoracic surgeon.
“Thus, this study provides robust data about the safety and efficacy of a five-fraction SBRT schedule that is well tolerated and associated with relatively low rates of serious treatment-related toxicity,” they concluded.
Dr. Bezjak reported disclosures related to AstraZeneca and Abbvie. Coauthors provided disclosures related to Varian Medical Systems, Elekta, Accuray, Seattle Genetics, Celgene, Exelixis, Gilead Sciences, Illumina, Ions Pharmaceuticals, and EMD Serono, among others.
SOURCE: Bezjak A et al. J Clin Oncol. 2019 Apr 3. doi: 10.1200/JCO.18.00622.
For patients with centrally located lung cancers in a multicenter phase 1/2 trial, a specific five-fraction radiotherapy schedule was well tolerated and linked to fairly low rates of treatment-related toxicity, investigators say.
The 12-Gy/fraction schedule of stereotactic body radiotherapy (SBRT) had a 7.2% rate of dose-limiting toxicities and a high tumor-control rate in the NRG Oncology/RTOG 0813 trial, which enrolled 120 patients with medically inoperable stage T1/2 N0M0 non–small cell lung cancers at 43 centers in the United States and Canada.
This is an important study that has implications for clinical practice, according to the investigators, led by Andrea Bezjak, MD, of Princess Margaret Cancer Centre in Toronto.
“The ability to treat patients with centrally located node-negative tumors in multiple institutions across the United States and Canada while maintaining plan qualities and achieving good patient outcomes and relatively modest rates of toxicity is an important achievement,” Dr. Bezjak and coinvestigators said in the Journal of Clinical Oncology.
These patients are frequently at increased risk from surgery, because of advanced age and the comorbidities that come with it, they added.
The 12-Gy/fraction dose level was the highest of nine dose levels included in the study protocol. Doses were delivered in five fractions over the course of 1.5-2 weeks. Investigators sought to determine the maximum tolerated dose of SRBT, defined as the level at which the probability of dose-limiting toxicities (grade 3 or greater) within the first year was as close to 20% as possible, without going over.
Thus, the 7.2% rate of dose-limiting toxicities at this highest-allowed dose level was “well below” that protocol-specified threshold, investigators said, commenting on results of the study.
The rate of local control at 2 years was 89.4% for the 12-Gy/fraction dose level. The 2-year overall survival was 70%, which compared favorably to what has been seen previously with use of SBRT in similar patients with peripheral tumors, according to Dr. Bezjak and colleagues.
Most deaths in the study were attributable to causes other than lung cancer, according to investigators, who noted that all accrued patients were deemed medically inoperable by an experienced thoracic surgeon.
“Thus, this study provides robust data about the safety and efficacy of a five-fraction SBRT schedule that is well tolerated and associated with relatively low rates of serious treatment-related toxicity,” they concluded.
Dr. Bezjak reported disclosures related to AstraZeneca and Abbvie. Coauthors provided disclosures related to Varian Medical Systems, Elekta, Accuray, Seattle Genetics, Celgene, Exelixis, Gilead Sciences, Illumina, Ions Pharmaceuticals, and EMD Serono, among others.
SOURCE: Bezjak A et al. J Clin Oncol. 2019 Apr 3. doi: 10.1200/JCO.18.00622.
For patients with centrally located lung cancers in a multicenter phase 1/2 trial, a specific five-fraction radiotherapy schedule was well tolerated and linked to fairly low rates of treatment-related toxicity, investigators say.
The 12-Gy/fraction schedule of stereotactic body radiotherapy (SBRT) had a 7.2% rate of dose-limiting toxicities and a high tumor-control rate in the NRG Oncology/RTOG 0813 trial, which enrolled 120 patients with medically inoperable stage T1/2 N0M0 non–small cell lung cancers at 43 centers in the United States and Canada.
This is an important study that has implications for clinical practice, according to the investigators, led by Andrea Bezjak, MD, of Princess Margaret Cancer Centre in Toronto.
“The ability to treat patients with centrally located node-negative tumors in multiple institutions across the United States and Canada while maintaining plan qualities and achieving good patient outcomes and relatively modest rates of toxicity is an important achievement,” Dr. Bezjak and coinvestigators said in the Journal of Clinical Oncology.
These patients are frequently at increased risk from surgery, because of advanced age and the comorbidities that come with it, they added.
The 12-Gy/fraction dose level was the highest of nine dose levels included in the study protocol. Doses were delivered in five fractions over the course of 1.5-2 weeks. Investigators sought to determine the maximum tolerated dose of SRBT, defined as the level at which the probability of dose-limiting toxicities (grade 3 or greater) within the first year was as close to 20% as possible, without going over.
Thus, the 7.2% rate of dose-limiting toxicities at this highest-allowed dose level was “well below” that protocol-specified threshold, investigators said, commenting on results of the study.
The rate of local control at 2 years was 89.4% for the 12-Gy/fraction dose level. The 2-year overall survival was 70%, which compared favorably to what has been seen previously with use of SBRT in similar patients with peripheral tumors, according to Dr. Bezjak and colleagues.
Most deaths in the study were attributable to causes other than lung cancer, according to investigators, who noted that all accrued patients were deemed medically inoperable by an experienced thoracic surgeon.
“Thus, this study provides robust data about the safety and efficacy of a five-fraction SBRT schedule that is well tolerated and associated with relatively low rates of serious treatment-related toxicity,” they concluded.
Dr. Bezjak reported disclosures related to AstraZeneca and Abbvie. Coauthors provided disclosures related to Varian Medical Systems, Elekta, Accuray, Seattle Genetics, Celgene, Exelixis, Gilead Sciences, Illumina, Ions Pharmaceuticals, and EMD Serono, among others.
SOURCE: Bezjak A et al. J Clin Oncol. 2019 Apr 3. doi: 10.1200/JCO.18.00622.
FROM THE JOURNAL OF CLINICAL ONCOLOGY
ASCO, CCO issue multiple myeloma treatment guidelines
New clinical practice guidelines, jointly released by two leading cancer organizations, provide nearly 50 specific recommendations for the management of newly diagnosed and relapsed multiple myeloma patients.
The guidelines from the American Society of Clinical Oncology (ASCO) and Cancer Care Ontario (CCO) were authored by a panel of 21 experts in medical oncology, surgery, radiation oncology, and advocacy who reviewed 124 relevant studies published between 2005 and 2018.
“The treatment of multiple myeloma has changed significantly in the last 5 years. Since 2015, four new drugs have been approved, thus providing more options and adding to the complexity of treatment options,” the expert panel wrote in the Journal of Clinical Oncology.
The recommendations are intended to put in context recent randomized trials and drug advances, according to the experts, led by cochairs Joseph Mikhael, MD, of City of Hope Cancer Center, Phoenix, and the International Myeloma Foundation, North Hollywood, Calif., and Tom Martin, MD, of the University of California, San Francisco.
Specifically, the recently approved agents include the proteasome inhibitor ixazomib, the histone deacetylase inhibitor panobinostat, and the monoclonal antibodies daratumumab and elotuzumab, directed at CD38 and SLAMF7, respectively.
There are 20 specific recommendations for newly diagnosed, transplant-eligible patients with multiple myeloma; 10 recommendations for newly diagnosed, transplant-ineligible patients; and 16 recommendations related to relapsed disease in the ASCO/CCO guidelines.
All transplant-eligible patients should be offered up-front autologous stem cell transplant (ASCT), according to the guidelines. By contrast, allogeneic transplant is not routinely recommended but “may be considered” in select high-risk patients, and tandem transplant “should not be routinely recommended,” the expert panelists said in their report.
Lenalidomide maintenance therapy should be routinely offered to standard-risk, transplant-eligible patients, according to the panel, whereas bortezomib maintenance could be considered in those who are intolerant of lenalidomide or can’t receive that immunomodulatory drug.
“Evidence is emerging for the use of ixazomib as maintenance therapy and may also be considered,” the panel members said, citing the TOURMALINE-MM3 study results presented at the 2018 annual meeting of the American Society of Hematology and recently published in the Lancet.
Although minimal residual disease (MRD)–negative status is linked to improved outcomes, there is insufficient evidence that MRD can be used today to modify maintenance therapy based on depth of response in transplant-eligible patients, according to the guidelines. Likewise, in transplant-ineligible patients, MRD shouldn’t be used to guide treatment goals in clinical practice, the authors said.
Triplet therapies such as bortezomib, lenalidomide, and dexamethasone (VRd) can be considered for transplant ineligible patients, as can the combination of daratumumab and bortezomib plus melphalan and prednisone that was approved by the Food and Drug Administration in May 2018.
For patients with biochemically relapsed myeloma and high-risk disease – defined as early relapse and presence of high-risk cytogenetics – treatment should begin immediately, whereas close observation may be appropriate for patients with asymptomatic, slowly progressive relapse.
Triplets containing two novel therapies should be administered on first relapse, and should continue until disease progression, the expert panel advised.
If it was not already done after primary induction, ASCT should be offered to relapsed, transplant-eligible myeloma patients.
The expert panel reported numerous financial relationships with industry, including Celgene, Sanofi, AbbVie, TeneoBio, Roche, June Therapeutics, and others.
SOURCE: Mikhael J et al. J Clin Oncol. 2019 Apr 1. doi: 10.1200/JCO.18.02096.
New clinical practice guidelines, jointly released by two leading cancer organizations, provide nearly 50 specific recommendations for the management of newly diagnosed and relapsed multiple myeloma patients.
The guidelines from the American Society of Clinical Oncology (ASCO) and Cancer Care Ontario (CCO) were authored by a panel of 21 experts in medical oncology, surgery, radiation oncology, and advocacy who reviewed 124 relevant studies published between 2005 and 2018.
“The treatment of multiple myeloma has changed significantly in the last 5 years. Since 2015, four new drugs have been approved, thus providing more options and adding to the complexity of treatment options,” the expert panel wrote in the Journal of Clinical Oncology.
The recommendations are intended to put in context recent randomized trials and drug advances, according to the experts, led by cochairs Joseph Mikhael, MD, of City of Hope Cancer Center, Phoenix, and the International Myeloma Foundation, North Hollywood, Calif., and Tom Martin, MD, of the University of California, San Francisco.
Specifically, the recently approved agents include the proteasome inhibitor ixazomib, the histone deacetylase inhibitor panobinostat, and the monoclonal antibodies daratumumab and elotuzumab, directed at CD38 and SLAMF7, respectively.
There are 20 specific recommendations for newly diagnosed, transplant-eligible patients with multiple myeloma; 10 recommendations for newly diagnosed, transplant-ineligible patients; and 16 recommendations related to relapsed disease in the ASCO/CCO guidelines.
All transplant-eligible patients should be offered up-front autologous stem cell transplant (ASCT), according to the guidelines. By contrast, allogeneic transplant is not routinely recommended but “may be considered” in select high-risk patients, and tandem transplant “should not be routinely recommended,” the expert panelists said in their report.
Lenalidomide maintenance therapy should be routinely offered to standard-risk, transplant-eligible patients, according to the panel, whereas bortezomib maintenance could be considered in those who are intolerant of lenalidomide or can’t receive that immunomodulatory drug.
“Evidence is emerging for the use of ixazomib as maintenance therapy and may also be considered,” the panel members said, citing the TOURMALINE-MM3 study results presented at the 2018 annual meeting of the American Society of Hematology and recently published in the Lancet.
Although minimal residual disease (MRD)–negative status is linked to improved outcomes, there is insufficient evidence that MRD can be used today to modify maintenance therapy based on depth of response in transplant-eligible patients, according to the guidelines. Likewise, in transplant-ineligible patients, MRD shouldn’t be used to guide treatment goals in clinical practice, the authors said.
Triplet therapies such as bortezomib, lenalidomide, and dexamethasone (VRd) can be considered for transplant ineligible patients, as can the combination of daratumumab and bortezomib plus melphalan and prednisone that was approved by the Food and Drug Administration in May 2018.
For patients with biochemically relapsed myeloma and high-risk disease – defined as early relapse and presence of high-risk cytogenetics – treatment should begin immediately, whereas close observation may be appropriate for patients with asymptomatic, slowly progressive relapse.
Triplets containing two novel therapies should be administered on first relapse, and should continue until disease progression, the expert panel advised.
If it was not already done after primary induction, ASCT should be offered to relapsed, transplant-eligible myeloma patients.
The expert panel reported numerous financial relationships with industry, including Celgene, Sanofi, AbbVie, TeneoBio, Roche, June Therapeutics, and others.
SOURCE: Mikhael J et al. J Clin Oncol. 2019 Apr 1. doi: 10.1200/JCO.18.02096.
New clinical practice guidelines, jointly released by two leading cancer organizations, provide nearly 50 specific recommendations for the management of newly diagnosed and relapsed multiple myeloma patients.
The guidelines from the American Society of Clinical Oncology (ASCO) and Cancer Care Ontario (CCO) were authored by a panel of 21 experts in medical oncology, surgery, radiation oncology, and advocacy who reviewed 124 relevant studies published between 2005 and 2018.
“The treatment of multiple myeloma has changed significantly in the last 5 years. Since 2015, four new drugs have been approved, thus providing more options and adding to the complexity of treatment options,” the expert panel wrote in the Journal of Clinical Oncology.
The recommendations are intended to put in context recent randomized trials and drug advances, according to the experts, led by cochairs Joseph Mikhael, MD, of City of Hope Cancer Center, Phoenix, and the International Myeloma Foundation, North Hollywood, Calif., and Tom Martin, MD, of the University of California, San Francisco.
Specifically, the recently approved agents include the proteasome inhibitor ixazomib, the histone deacetylase inhibitor panobinostat, and the monoclonal antibodies daratumumab and elotuzumab, directed at CD38 and SLAMF7, respectively.
There are 20 specific recommendations for newly diagnosed, transplant-eligible patients with multiple myeloma; 10 recommendations for newly diagnosed, transplant-ineligible patients; and 16 recommendations related to relapsed disease in the ASCO/CCO guidelines.
All transplant-eligible patients should be offered up-front autologous stem cell transplant (ASCT), according to the guidelines. By contrast, allogeneic transplant is not routinely recommended but “may be considered” in select high-risk patients, and tandem transplant “should not be routinely recommended,” the expert panelists said in their report.
Lenalidomide maintenance therapy should be routinely offered to standard-risk, transplant-eligible patients, according to the panel, whereas bortezomib maintenance could be considered in those who are intolerant of lenalidomide or can’t receive that immunomodulatory drug.
“Evidence is emerging for the use of ixazomib as maintenance therapy and may also be considered,” the panel members said, citing the TOURMALINE-MM3 study results presented at the 2018 annual meeting of the American Society of Hematology and recently published in the Lancet.
Although minimal residual disease (MRD)–negative status is linked to improved outcomes, there is insufficient evidence that MRD can be used today to modify maintenance therapy based on depth of response in transplant-eligible patients, according to the guidelines. Likewise, in transplant-ineligible patients, MRD shouldn’t be used to guide treatment goals in clinical practice, the authors said.
Triplet therapies such as bortezomib, lenalidomide, and dexamethasone (VRd) can be considered for transplant ineligible patients, as can the combination of daratumumab and bortezomib plus melphalan and prednisone that was approved by the Food and Drug Administration in May 2018.
For patients with biochemically relapsed myeloma and high-risk disease – defined as early relapse and presence of high-risk cytogenetics – treatment should begin immediately, whereas close observation may be appropriate for patients with asymptomatic, slowly progressive relapse.
Triplets containing two novel therapies should be administered on first relapse, and should continue until disease progression, the expert panel advised.
If it was not already done after primary induction, ASCT should be offered to relapsed, transplant-eligible myeloma patients.
The expert panel reported numerous financial relationships with industry, including Celgene, Sanofi, AbbVie, TeneoBio, Roche, June Therapeutics, and others.
SOURCE: Mikhael J et al. J Clin Oncol. 2019 Apr 1. doi: 10.1200/JCO.18.02096.
FROM THE JOURNAL OF CLINICAL ONCOLOGY
Guidelines demur, but probiotics, curcumin may help in some UC patients
PHILADELPHIA – Although the new ulcerative colitis guidelines make no current recommendations on probiotics and curcumin because of gaps in knowledge, both may be beneficial today in selected patients, an expert said at the meeting jointly provided by Rutgers and Global Academy for Medical Education.
“Probiotics can be added, in my opinion, to patients on mesalamine with mild to moderate ulcerative colitis in order to help induce remission without having to go to immunosuppressive medication,” said Steven R. Brant, MD, chief of the division of gastroenterology and hepatology at Robert Wood Johnson Medical School, New Brunswick, N.J.
Likewise, curcumin has shown “minimal harm” in mild ulcerative colitis and may help nudge patients toward disease control without having to resort to corticosteroids or other immunosuppressive therapy, Dr. Brant said.
The new American Gastroenterological Association guidelines for treatment of mild to moderate ulcerative colitis, published in February in the journal Gastroenterology, declined to make recommendations on either probiotics or curcumin, citing “knowledge gaps and areas for future research.”
“Although these modalities appear to be safe, their use risks delaying proven effective therapy with the potential for worsening symptoms or complications,” Cynthia W. Ko, MD, and guideline coauthors said in the recommendations.
From the patient perspective, probiotics are “popular,” Dr. Brant said in his presentation, noting that some patients will request probiotics as a first-line therapy or even ask to be taken off mesalamine and put on probiotics.
Meta-analyses have provided differing conclusions on the benefits of probiotics. One recently published analysis of probiotics versus mesalamine showed a slight trend to favor mesalamine, but when looking at good-quality studies only, the meta-analysis showed a nonsignificant trend in favor of probiotics, Dr. Brant said.
By contrast, in a Cochrane meta-analysis of mesalamine at standard doses versus placebo, there was consistent evidence for a benefit of mesalamine: “so the main problem with giving probiotics as a choice is that you’re going to put the patient at risk for progressive symptoms and complications,” said Dr. Brant.
However, looking specifically at the probiotic VSL#3, the Toronto Ulcerative Colitis Consensus Group said that it was linked to significantly improved remission (44% vs. 25%; odds ratio, 2.4; P = .0007). Coverage issues could be a snag, since the amount of the probiotic associated with improved remission was equivalent to four double-strength packets. “Try getting that approved,” Dr. Brant told attendees. “You’ll have some challenges.”
Curcumin was evaluated in a multicenter trial showing that, when added to maximal mesalamine, it may be helpful in avoiding an advance in therapy, with 54% achieving clinical remission at week 4 versus 0% of placebo-treated patients.
That was a “reasonable study” but more research needs to be done, Dr. Brant said.
“I think that given the minimal harm, it may be worth a trial, though not in patients that are really having systemic symptoms, severe bleeding, and are getting worse,” he said. “It’s patients that have some response on mesalamine where it may be valuable, if you have time to spare to give them curcumin.”
Dr. Brant indicated that he had no relevant financial relationships to disclose.
Global Academy and this news organization are owned by the same parent company.
PHILADELPHIA – Although the new ulcerative colitis guidelines make no current recommendations on probiotics and curcumin because of gaps in knowledge, both may be beneficial today in selected patients, an expert said at the meeting jointly provided by Rutgers and Global Academy for Medical Education.
“Probiotics can be added, in my opinion, to patients on mesalamine with mild to moderate ulcerative colitis in order to help induce remission without having to go to immunosuppressive medication,” said Steven R. Brant, MD, chief of the division of gastroenterology and hepatology at Robert Wood Johnson Medical School, New Brunswick, N.J.
Likewise, curcumin has shown “minimal harm” in mild ulcerative colitis and may help nudge patients toward disease control without having to resort to corticosteroids or other immunosuppressive therapy, Dr. Brant said.
The new American Gastroenterological Association guidelines for treatment of mild to moderate ulcerative colitis, published in February in the journal Gastroenterology, declined to make recommendations on either probiotics or curcumin, citing “knowledge gaps and areas for future research.”
“Although these modalities appear to be safe, their use risks delaying proven effective therapy with the potential for worsening symptoms or complications,” Cynthia W. Ko, MD, and guideline coauthors said in the recommendations.
From the patient perspective, probiotics are “popular,” Dr. Brant said in his presentation, noting that some patients will request probiotics as a first-line therapy or even ask to be taken off mesalamine and put on probiotics.
Meta-analyses have provided differing conclusions on the benefits of probiotics. One recently published analysis of probiotics versus mesalamine showed a slight trend to favor mesalamine, but when looking at good-quality studies only, the meta-analysis showed a nonsignificant trend in favor of probiotics, Dr. Brant said.
By contrast, in a Cochrane meta-analysis of mesalamine at standard doses versus placebo, there was consistent evidence for a benefit of mesalamine: “so the main problem with giving probiotics as a choice is that you’re going to put the patient at risk for progressive symptoms and complications,” said Dr. Brant.
However, looking specifically at the probiotic VSL#3, the Toronto Ulcerative Colitis Consensus Group said that it was linked to significantly improved remission (44% vs. 25%; odds ratio, 2.4; P = .0007). Coverage issues could be a snag, since the amount of the probiotic associated with improved remission was equivalent to four double-strength packets. “Try getting that approved,” Dr. Brant told attendees. “You’ll have some challenges.”
Curcumin was evaluated in a multicenter trial showing that, when added to maximal mesalamine, it may be helpful in avoiding an advance in therapy, with 54% achieving clinical remission at week 4 versus 0% of placebo-treated patients.
That was a “reasonable study” but more research needs to be done, Dr. Brant said.
“I think that given the minimal harm, it may be worth a trial, though not in patients that are really having systemic symptoms, severe bleeding, and are getting worse,” he said. “It’s patients that have some response on mesalamine where it may be valuable, if you have time to spare to give them curcumin.”
Dr. Brant indicated that he had no relevant financial relationships to disclose.
Global Academy and this news organization are owned by the same parent company.
PHILADELPHIA – Although the new ulcerative colitis guidelines make no current recommendations on probiotics and curcumin because of gaps in knowledge, both may be beneficial today in selected patients, an expert said at the meeting jointly provided by Rutgers and Global Academy for Medical Education.
“Probiotics can be added, in my opinion, to patients on mesalamine with mild to moderate ulcerative colitis in order to help induce remission without having to go to immunosuppressive medication,” said Steven R. Brant, MD, chief of the division of gastroenterology and hepatology at Robert Wood Johnson Medical School, New Brunswick, N.J.
Likewise, curcumin has shown “minimal harm” in mild ulcerative colitis and may help nudge patients toward disease control without having to resort to corticosteroids or other immunosuppressive therapy, Dr. Brant said.
The new American Gastroenterological Association guidelines for treatment of mild to moderate ulcerative colitis, published in February in the journal Gastroenterology, declined to make recommendations on either probiotics or curcumin, citing “knowledge gaps and areas for future research.”
“Although these modalities appear to be safe, their use risks delaying proven effective therapy with the potential for worsening symptoms or complications,” Cynthia W. Ko, MD, and guideline coauthors said in the recommendations.
From the patient perspective, probiotics are “popular,” Dr. Brant said in his presentation, noting that some patients will request probiotics as a first-line therapy or even ask to be taken off mesalamine and put on probiotics.
Meta-analyses have provided differing conclusions on the benefits of probiotics. One recently published analysis of probiotics versus mesalamine showed a slight trend to favor mesalamine, but when looking at good-quality studies only, the meta-analysis showed a nonsignificant trend in favor of probiotics, Dr. Brant said.
By contrast, in a Cochrane meta-analysis of mesalamine at standard doses versus placebo, there was consistent evidence for a benefit of mesalamine: “so the main problem with giving probiotics as a choice is that you’re going to put the patient at risk for progressive symptoms and complications,” said Dr. Brant.
However, looking specifically at the probiotic VSL#3, the Toronto Ulcerative Colitis Consensus Group said that it was linked to significantly improved remission (44% vs. 25%; odds ratio, 2.4; P = .0007). Coverage issues could be a snag, since the amount of the probiotic associated with improved remission was equivalent to four double-strength packets. “Try getting that approved,” Dr. Brant told attendees. “You’ll have some challenges.”
Curcumin was evaluated in a multicenter trial showing that, when added to maximal mesalamine, it may be helpful in avoiding an advance in therapy, with 54% achieving clinical remission at week 4 versus 0% of placebo-treated patients.
That was a “reasonable study” but more research needs to be done, Dr. Brant said.
“I think that given the minimal harm, it may be worth a trial, though not in patients that are really having systemic symptoms, severe bleeding, and are getting worse,” he said. “It’s patients that have some response on mesalamine where it may be valuable, if you have time to spare to give them curcumin.”
Dr. Brant indicated that he had no relevant financial relationships to disclose.
Global Academy and this news organization are owned by the same parent company.
REPORTING FROM DIGESTIVE DISEASES: NEW ADVANCES
Future of NASH care means multiple targets, multiple providers, expert says
PHILADELPHIA – While current treatment options are limited for patients with nonalcoholic steatohepatitis (NASH), a number of potential agents in clinical trials, Zobair M. Younossi, MD, MPH, said here at the 6th annual Digestive Diseases: New Advances conference.
With agents currently available and those to come, the future will be focused on long-term management of NASH as a chronic disease in specialized centers, according to Dr. Younossi, chairman in the department of medicine at Inova Fairfax Hospital and vice president for research at Inova Health System, both in Falls Church, Va.
“We are not going to be able to cure NASH – we need to manage it,” Dr. Younossi said in a podium presentation. “NASH will be managed like type 2 diabetes. It’s not going to be treated like hepatitis C.”
Current treatment options are limited, with no Food and Drug Administration–approved options, and just two agents, vitamin E and pioglitazone, supported by guidance from the American Association for the Study of Liver Diseases (AASLD), Dr. Younossi said.
Public health interventions are needed to address the obesity and type 2 diabetes that are “the root of this disease,” Dr. Younossi said at the meeting, which was jointly provided by Rutgers and Global Academy for Medical Education.
Current AASLD guidance is based on studies suggesting that weight loss in the 3%-5% range may improve steatosis, and a 7%-10% weight loss can improve most histologic features of NASH, including fibrosis.
“The problem is that this is very hard to achieve,” Dr. Younossi said, adding that it is also hard to maintain. In a 2011 meta-analysis of clinical trials for reduction in nonalcoholic fatty liver disease, only a small minority of patients were able to maintain weight loss.
Bariatric surgery may be “very effective” for weight loss in the right patients, with some trials showing a proportion of patients maintaining improvement at 5-year follow-up, he said.
Exercise alone might prevent or reduce steatosis, but its effects on other aspects of liver histology, such as fibrosis, remain unknown, Dr. Younossi said.
Pioglitazone improves liver histology in patients with biopsy-proven NASH, although the benefits and risks, including potential adverse effects such as bone loss, diastolic dysfunction, or weight gain, should be discussed with each individual patient, he said.
Dr. Younossi highlighted randomized phase 3 trials for several agents that could figure into the treatment paradigm of NASH in the future by targeting different promoters of NASH and fibrosis progression. One of those was elafibranor, which targets the PPAR alpha/gamma pathways and is being evaluated versus placebo in NASH patients in the phase 3 RESOLVE-IT study. In a post hoc analysis of a previous randomized trial, the treatment resolved NASH without fibrosis worsening.
Other agents being evaluated in phase 3 trials include the CCR2/CCR5 receptor blocker cenicriviroc, the FXR agonist obeticholic acid, and the ASK-1 inhibitor selonsertib, Dr. Younossi said.
Optimal NASH care in the future may be based on targeting multiple such pathways, with patients increasingly treated at specialized centers that incorporate not only hepatologists, but also diabetes experts, dietitians, and exercise specialists.
“My own belief is that you have to treat this in the long term and also in a multidisciplinary sort of approach,” he said.
Dr. Younossi indicated that he is a consultant for Gilead, Intercept, Bristol-Myers Squibb, Novo Nordisk, Viking, Terms, Shionogi, AbbVie, Merck, and Novartis.
Global Academy and this news organization are owned by the same parent company.
PHILADELPHIA – While current treatment options are limited for patients with nonalcoholic steatohepatitis (NASH), a number of potential agents in clinical trials, Zobair M. Younossi, MD, MPH, said here at the 6th annual Digestive Diseases: New Advances conference.
With agents currently available and those to come, the future will be focused on long-term management of NASH as a chronic disease in specialized centers, according to Dr. Younossi, chairman in the department of medicine at Inova Fairfax Hospital and vice president for research at Inova Health System, both in Falls Church, Va.
“We are not going to be able to cure NASH – we need to manage it,” Dr. Younossi said in a podium presentation. “NASH will be managed like type 2 diabetes. It’s not going to be treated like hepatitis C.”
Current treatment options are limited, with no Food and Drug Administration–approved options, and just two agents, vitamin E and pioglitazone, supported by guidance from the American Association for the Study of Liver Diseases (AASLD), Dr. Younossi said.
Public health interventions are needed to address the obesity and type 2 diabetes that are “the root of this disease,” Dr. Younossi said at the meeting, which was jointly provided by Rutgers and Global Academy for Medical Education.
Current AASLD guidance is based on studies suggesting that weight loss in the 3%-5% range may improve steatosis, and a 7%-10% weight loss can improve most histologic features of NASH, including fibrosis.
“The problem is that this is very hard to achieve,” Dr. Younossi said, adding that it is also hard to maintain. In a 2011 meta-analysis of clinical trials for reduction in nonalcoholic fatty liver disease, only a small minority of patients were able to maintain weight loss.
Bariatric surgery may be “very effective” for weight loss in the right patients, with some trials showing a proportion of patients maintaining improvement at 5-year follow-up, he said.
Exercise alone might prevent or reduce steatosis, but its effects on other aspects of liver histology, such as fibrosis, remain unknown, Dr. Younossi said.
Pioglitazone improves liver histology in patients with biopsy-proven NASH, although the benefits and risks, including potential adverse effects such as bone loss, diastolic dysfunction, or weight gain, should be discussed with each individual patient, he said.
Dr. Younossi highlighted randomized phase 3 trials for several agents that could figure into the treatment paradigm of NASH in the future by targeting different promoters of NASH and fibrosis progression. One of those was elafibranor, which targets the PPAR alpha/gamma pathways and is being evaluated versus placebo in NASH patients in the phase 3 RESOLVE-IT study. In a post hoc analysis of a previous randomized trial, the treatment resolved NASH without fibrosis worsening.
Other agents being evaluated in phase 3 trials include the CCR2/CCR5 receptor blocker cenicriviroc, the FXR agonist obeticholic acid, and the ASK-1 inhibitor selonsertib, Dr. Younossi said.
Optimal NASH care in the future may be based on targeting multiple such pathways, with patients increasingly treated at specialized centers that incorporate not only hepatologists, but also diabetes experts, dietitians, and exercise specialists.
“My own belief is that you have to treat this in the long term and also in a multidisciplinary sort of approach,” he said.
Dr. Younossi indicated that he is a consultant for Gilead, Intercept, Bristol-Myers Squibb, Novo Nordisk, Viking, Terms, Shionogi, AbbVie, Merck, and Novartis.
Global Academy and this news organization are owned by the same parent company.
PHILADELPHIA – While current treatment options are limited for patients with nonalcoholic steatohepatitis (NASH), a number of potential agents in clinical trials, Zobair M. Younossi, MD, MPH, said here at the 6th annual Digestive Diseases: New Advances conference.
With agents currently available and those to come, the future will be focused on long-term management of NASH as a chronic disease in specialized centers, according to Dr. Younossi, chairman in the department of medicine at Inova Fairfax Hospital and vice president for research at Inova Health System, both in Falls Church, Va.
“We are not going to be able to cure NASH – we need to manage it,” Dr. Younossi said in a podium presentation. “NASH will be managed like type 2 diabetes. It’s not going to be treated like hepatitis C.”
Current treatment options are limited, with no Food and Drug Administration–approved options, and just two agents, vitamin E and pioglitazone, supported by guidance from the American Association for the Study of Liver Diseases (AASLD), Dr. Younossi said.
Public health interventions are needed to address the obesity and type 2 diabetes that are “the root of this disease,” Dr. Younossi said at the meeting, which was jointly provided by Rutgers and Global Academy for Medical Education.
Current AASLD guidance is based on studies suggesting that weight loss in the 3%-5% range may improve steatosis, and a 7%-10% weight loss can improve most histologic features of NASH, including fibrosis.
“The problem is that this is very hard to achieve,” Dr. Younossi said, adding that it is also hard to maintain. In a 2011 meta-analysis of clinical trials for reduction in nonalcoholic fatty liver disease, only a small minority of patients were able to maintain weight loss.
Bariatric surgery may be “very effective” for weight loss in the right patients, with some trials showing a proportion of patients maintaining improvement at 5-year follow-up, he said.
Exercise alone might prevent or reduce steatosis, but its effects on other aspects of liver histology, such as fibrosis, remain unknown, Dr. Younossi said.
Pioglitazone improves liver histology in patients with biopsy-proven NASH, although the benefits and risks, including potential adverse effects such as bone loss, diastolic dysfunction, or weight gain, should be discussed with each individual patient, he said.
Dr. Younossi highlighted randomized phase 3 trials for several agents that could figure into the treatment paradigm of NASH in the future by targeting different promoters of NASH and fibrosis progression. One of those was elafibranor, which targets the PPAR alpha/gamma pathways and is being evaluated versus placebo in NASH patients in the phase 3 RESOLVE-IT study. In a post hoc analysis of a previous randomized trial, the treatment resolved NASH without fibrosis worsening.
Other agents being evaluated in phase 3 trials include the CCR2/CCR5 receptor blocker cenicriviroc, the FXR agonist obeticholic acid, and the ASK-1 inhibitor selonsertib, Dr. Younossi said.
Optimal NASH care in the future may be based on targeting multiple such pathways, with patients increasingly treated at specialized centers that incorporate not only hepatologists, but also diabetes experts, dietitians, and exercise specialists.
“My own belief is that you have to treat this in the long term and also in a multidisciplinary sort of approach,” he said.
Dr. Younossi indicated that he is a consultant for Gilead, Intercept, Bristol-Myers Squibb, Novo Nordisk, Viking, Terms, Shionogi, AbbVie, Merck, and Novartis.
Global Academy and this news organization are owned by the same parent company.
EXPERT ANALYSIS FROM DIGESTIVE DISEASES: NEW ADVANCES
Renal denervation reduced BP in sham-controlled trials, meta-analysis shows
although previous investigations of the procedure have had conflicting results.
Renal sympathetic denervation (RSD) was associated with statistically significant reductions in blood pressure assessed by 24-hour ambulatory, daytime ambulatory, and office measurements in the analysis of six trials including a total of 977 participants.
However, the benefit was particularly pronounced in more recent randomized trials that had few patients with isolated systolic hypertension, had highly experienced operators; used more complete techniques of radiofrequency ablation, used novel approaches such as endovascular renal denervation, and used efficacy endpoints such as clinical outcomes, according to investigator Partha Sardar, MD, of Brown University, Providence, R.I., and his colleagues.
“Altogether, the present study affirms the safety and efficacy of renal denervation for blood pressure reduction, and highlights the importance of incorporating the previously described modifications in trial design,” wrote Dr. Sardar and his coauthors. The report is in the Journal of the American College of Cardiology.
While initial trials of catheter-based denervation of renal arteries were positive, three blinded randomized, controlled trials showed no difference in blood pressure between the procedure and a sham procedure, the investigators said. Those findings led to several small, sham-controlled trials that incorporated the aforementioned changes.
For the six trials combined in the meta-analysis, reductions in 24-hour ambulatory systolic blood pressure were significantly lower for RSD, with a weighted mean difference of –3.65 mm Hg (P less than .001), Dr. Sardar and his colleagues reported.
For the earlier trials, the average reductions in 24-hour ambulatory systolic and diastolic blood pressure were 2.23 and 0.66 for RSD and sham patients, respectively.
By contrast, in the second-generation trials, those blood pressure reductions were 4.85 for RSD and 2.98 mm Hg for sham, they said in the report, adding that the reduction in daytime ambulatory systolic blood pressure with RSD was significantly greater for the second-generation studies.
The second-generation studies excluded patients with isolated systolic hypertension, based in part on observations that RSD has a more pronounced impact on blood pressure with combined systolic and diastolic hypertension, according to the authors.
Moreover, the second-generation studies required that very experienced operators perform the procedures, incorporated advanced catheter and ablation techniques, less often used modified medication regimens, and set ambulatory blood pressure as the primary end point, they added.
“These results should inform the design and powering of larger, pivotal trials to evaluate the long-term efficacy and safety of RSD in patients with uncontrolled and resistant hypertension,” Dr. Sardar and his coauthors said.
Dr. Sardar reported no relevant financial disclosures, as did most of the coauthors. Three coauthors provided disclosures related to Regado Biosciences, Abbott Vascular, Amgen, Bristol-Myers Squibb, Lilly, Medtronic, and ReCor Medical, among others.
SOURCE: Sardar P et al. J Am Coll Cardiol. 2019;73(13):1633-42.
While questions remain about the future of renal sympathetic denervation for treatment of hypertension, the present meta-analysis provides “interesting” findings that confirm a benefit of the procedure, particularly in the more recent randomized trials, editorialists said.
“The evidence is now there to conclude that RSD does lower blood pressure in hypertensive patients,” Sverre E. Kjeldsen, MD, PhD, Fadl E.M. Fadl Elmula, MD, PhD, and Alexandre Persu, MD, PhD, wrote in their editorial. That conclusion makes sense in light of knowledge that sympathetic overactivity is a known contributor to hypertension pathogenesis.
Although the blood pressure benefits of RSD in the second-generation trials still seem “relatively modest” and equate roughly to the effect of one antihypertensive drug, the aggregate results mask a wide variation in individual patient response, with up to 30% of patients experiencing dramatic improvements after the procedure, they said.
Accordingly, one key research priority is to figure out what patient characteristics might be used to single out patients who are extreme responders to the therapy.
That kind of optimized patient selection, in tandem with technical improvements in the procedure, they said, may help break the “glass ceiling” in blood pressure reduction reported in randomized trials to date.
“Research on RSD still has good days to come, and patients may eventually benefit from this research effort,” Dr. Kjeldsen, Dr. Fadl Elmula, and Dr. Persu concluded.
Dr. Kjeldsen and Dr. Fadl Elmula are at Oslo University Hospital, Ullevaal, and the University of Oslo; Dr. Persu is at the Université Catholique de Louvain, Brussels. The comments summarize an editorial accompanying the article by Sardar et al. (J Am Coll Cardiol. 2019. doi: 10.1016/j.jacc.2019.02.008). Dr. Kjeldsen reported disclosures related to Merck KGaA, Merck Sharp and Dohme, Sanofi, and Takeda.
While questions remain about the future of renal sympathetic denervation for treatment of hypertension, the present meta-analysis provides “interesting” findings that confirm a benefit of the procedure, particularly in the more recent randomized trials, editorialists said.
“The evidence is now there to conclude that RSD does lower blood pressure in hypertensive patients,” Sverre E. Kjeldsen, MD, PhD, Fadl E.M. Fadl Elmula, MD, PhD, and Alexandre Persu, MD, PhD, wrote in their editorial. That conclusion makes sense in light of knowledge that sympathetic overactivity is a known contributor to hypertension pathogenesis.
Although the blood pressure benefits of RSD in the second-generation trials still seem “relatively modest” and equate roughly to the effect of one antihypertensive drug, the aggregate results mask a wide variation in individual patient response, with up to 30% of patients experiencing dramatic improvements after the procedure, they said.
Accordingly, one key research priority is to figure out what patient characteristics might be used to single out patients who are extreme responders to the therapy.
That kind of optimized patient selection, in tandem with technical improvements in the procedure, they said, may help break the “glass ceiling” in blood pressure reduction reported in randomized trials to date.
“Research on RSD still has good days to come, and patients may eventually benefit from this research effort,” Dr. Kjeldsen, Dr. Fadl Elmula, and Dr. Persu concluded.
Dr. Kjeldsen and Dr. Fadl Elmula are at Oslo University Hospital, Ullevaal, and the University of Oslo; Dr. Persu is at the Université Catholique de Louvain, Brussels. The comments summarize an editorial accompanying the article by Sardar et al. (J Am Coll Cardiol. 2019. doi: 10.1016/j.jacc.2019.02.008). Dr. Kjeldsen reported disclosures related to Merck KGaA, Merck Sharp and Dohme, Sanofi, and Takeda.
While questions remain about the future of renal sympathetic denervation for treatment of hypertension, the present meta-analysis provides “interesting” findings that confirm a benefit of the procedure, particularly in the more recent randomized trials, editorialists said.
“The evidence is now there to conclude that RSD does lower blood pressure in hypertensive patients,” Sverre E. Kjeldsen, MD, PhD, Fadl E.M. Fadl Elmula, MD, PhD, and Alexandre Persu, MD, PhD, wrote in their editorial. That conclusion makes sense in light of knowledge that sympathetic overactivity is a known contributor to hypertension pathogenesis.
Although the blood pressure benefits of RSD in the second-generation trials still seem “relatively modest” and equate roughly to the effect of one antihypertensive drug, the aggregate results mask a wide variation in individual patient response, with up to 30% of patients experiencing dramatic improvements after the procedure, they said.
Accordingly, one key research priority is to figure out what patient characteristics might be used to single out patients who are extreme responders to the therapy.
That kind of optimized patient selection, in tandem with technical improvements in the procedure, they said, may help break the “glass ceiling” in blood pressure reduction reported in randomized trials to date.
“Research on RSD still has good days to come, and patients may eventually benefit from this research effort,” Dr. Kjeldsen, Dr. Fadl Elmula, and Dr. Persu concluded.
Dr. Kjeldsen and Dr. Fadl Elmula are at Oslo University Hospital, Ullevaal, and the University of Oslo; Dr. Persu is at the Université Catholique de Louvain, Brussels. The comments summarize an editorial accompanying the article by Sardar et al. (J Am Coll Cardiol. 2019. doi: 10.1016/j.jacc.2019.02.008). Dr. Kjeldsen reported disclosures related to Merck KGaA, Merck Sharp and Dohme, Sanofi, and Takeda.
although previous investigations of the procedure have had conflicting results.
Renal sympathetic denervation (RSD) was associated with statistically significant reductions in blood pressure assessed by 24-hour ambulatory, daytime ambulatory, and office measurements in the analysis of six trials including a total of 977 participants.
However, the benefit was particularly pronounced in more recent randomized trials that had few patients with isolated systolic hypertension, had highly experienced operators; used more complete techniques of radiofrequency ablation, used novel approaches such as endovascular renal denervation, and used efficacy endpoints such as clinical outcomes, according to investigator Partha Sardar, MD, of Brown University, Providence, R.I., and his colleagues.
“Altogether, the present study affirms the safety and efficacy of renal denervation for blood pressure reduction, and highlights the importance of incorporating the previously described modifications in trial design,” wrote Dr. Sardar and his coauthors. The report is in the Journal of the American College of Cardiology.
While initial trials of catheter-based denervation of renal arteries were positive, three blinded randomized, controlled trials showed no difference in blood pressure between the procedure and a sham procedure, the investigators said. Those findings led to several small, sham-controlled trials that incorporated the aforementioned changes.
For the six trials combined in the meta-analysis, reductions in 24-hour ambulatory systolic blood pressure were significantly lower for RSD, with a weighted mean difference of –3.65 mm Hg (P less than .001), Dr. Sardar and his colleagues reported.
For the earlier trials, the average reductions in 24-hour ambulatory systolic and diastolic blood pressure were 2.23 and 0.66 for RSD and sham patients, respectively.
By contrast, in the second-generation trials, those blood pressure reductions were 4.85 for RSD and 2.98 mm Hg for sham, they said in the report, adding that the reduction in daytime ambulatory systolic blood pressure with RSD was significantly greater for the second-generation studies.
The second-generation studies excluded patients with isolated systolic hypertension, based in part on observations that RSD has a more pronounced impact on blood pressure with combined systolic and diastolic hypertension, according to the authors.
Moreover, the second-generation studies required that very experienced operators perform the procedures, incorporated advanced catheter and ablation techniques, less often used modified medication regimens, and set ambulatory blood pressure as the primary end point, they added.
“These results should inform the design and powering of larger, pivotal trials to evaluate the long-term efficacy and safety of RSD in patients with uncontrolled and resistant hypertension,” Dr. Sardar and his coauthors said.
Dr. Sardar reported no relevant financial disclosures, as did most of the coauthors. Three coauthors provided disclosures related to Regado Biosciences, Abbott Vascular, Amgen, Bristol-Myers Squibb, Lilly, Medtronic, and ReCor Medical, among others.
SOURCE: Sardar P et al. J Am Coll Cardiol. 2019;73(13):1633-42.
although previous investigations of the procedure have had conflicting results.
Renal sympathetic denervation (RSD) was associated with statistically significant reductions in blood pressure assessed by 24-hour ambulatory, daytime ambulatory, and office measurements in the analysis of six trials including a total of 977 participants.
However, the benefit was particularly pronounced in more recent randomized trials that had few patients with isolated systolic hypertension, had highly experienced operators; used more complete techniques of radiofrequency ablation, used novel approaches such as endovascular renal denervation, and used efficacy endpoints such as clinical outcomes, according to investigator Partha Sardar, MD, of Brown University, Providence, R.I., and his colleagues.
“Altogether, the present study affirms the safety and efficacy of renal denervation for blood pressure reduction, and highlights the importance of incorporating the previously described modifications in trial design,” wrote Dr. Sardar and his coauthors. The report is in the Journal of the American College of Cardiology.
While initial trials of catheter-based denervation of renal arteries were positive, three blinded randomized, controlled trials showed no difference in blood pressure between the procedure and a sham procedure, the investigators said. Those findings led to several small, sham-controlled trials that incorporated the aforementioned changes.
For the six trials combined in the meta-analysis, reductions in 24-hour ambulatory systolic blood pressure were significantly lower for RSD, with a weighted mean difference of –3.65 mm Hg (P less than .001), Dr. Sardar and his colleagues reported.
For the earlier trials, the average reductions in 24-hour ambulatory systolic and diastolic blood pressure were 2.23 and 0.66 for RSD and sham patients, respectively.
By contrast, in the second-generation trials, those blood pressure reductions were 4.85 for RSD and 2.98 mm Hg for sham, they said in the report, adding that the reduction in daytime ambulatory systolic blood pressure with RSD was significantly greater for the second-generation studies.
The second-generation studies excluded patients with isolated systolic hypertension, based in part on observations that RSD has a more pronounced impact on blood pressure with combined systolic and diastolic hypertension, according to the authors.
Moreover, the second-generation studies required that very experienced operators perform the procedures, incorporated advanced catheter and ablation techniques, less often used modified medication regimens, and set ambulatory blood pressure as the primary end point, they added.
“These results should inform the design and powering of larger, pivotal trials to evaluate the long-term efficacy and safety of RSD in patients with uncontrolled and resistant hypertension,” Dr. Sardar and his coauthors said.
Dr. Sardar reported no relevant financial disclosures, as did most of the coauthors. Three coauthors provided disclosures related to Regado Biosciences, Abbott Vascular, Amgen, Bristol-Myers Squibb, Lilly, Medtronic, and ReCor Medical, among others.
SOURCE: Sardar P et al. J Am Coll Cardiol. 2019;73(13):1633-42.
FROM THE JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
Key clinical point: Renal sympathetic denervation significantly reduced blood pressure in randomized, sham-controlled trials.
Major finding: In second-generation trials of renal sympathetic denervation for hypertension therapy, 24-hour ambulatory blood pressure reductions were 4.85 for RSD and 2.98 mm Hg for sham.
Study details: Renal sympathetic denervation for treating hypertension was tested in six randomized, sham-controlled trials of 24-hour ambulatory, daytime ambulatory, and blood pressure office measurements including a total of 977 participants.
Disclosures: Dr. Sardar reported no relevant financial disclosures, as did most of the coauthors. Three coauthors provided disclosures related to Regado Biosciences, Abbott Vascular, Amgen, Bristol-Myers Squibb, Lilly, Medtronic, and ReCor Medical, among others.
Source: Sardar P et al. J Am Coll Cardiol. 2019;73(13):1633-42.
Valproate, topiramate prescribed in young women despite known teratogenicity risks
results of a retrospective analysis suggest.
Topiramate, linked to increased risk of cleft palate and smaller-than-gestational-age newborns, was among the top three antiepileptic drugs (AEDs) prescribed to women 15-44 years of age in the population-based cohort study.
Valproate, linked to increases in both anatomic and behavioral teratogenicity, was less often prescribed, but nevertheless still prescribed in a considerable proportion of patients in the study, which looked at U.S. commercial, Medicare, and Medicaid claims data from 2009 to 2013.
Presence of comorbidities could be influencing whether or not a woman of childbearing age receives one of these AEDs, the investigators said. Specifically, they found valproate more often prescribed for women with epilepsy who also had mood or anxiety and dissociative disorder, while topiramate was more often prescribed in women with headaches or migraines.
Taken together, these findings suggest a lack of awareness of the teratogenic risks of valproate and topiramate, said the investigators, led by Hyunmi Kim, MD, PhD, MPH, of the department of neurology at Stanford (Calif.) University.
“To improve current practice, knowledge of the teratogenicity of certain AEDs should be disseminated to health care professionals and patients,” they wrote. The report is in JAMA Neurology.
The findings of Dr. Kim and her colleagues were based on data for 46,767 women of childbearing age: 8,003 incident (new) cases with a mean age of 27 years, and 38,764 prevalent cases with a mean age of 30 years.
Topiramate was the second- or third-most prescribed AED in the analyses, alongside levetiracetam and lamotrigine. In particular, topiramate prescriptions were found in incident cases receiving first-line monotherapy (15%), prevalent cases receiving first-line monotherapy (13%), and prevalent cases receiving polytherapy (29%).
Valproate was the fifth-most prescribed AED for incident and prevalent cases receiving first-line monotherapy (5% and 10%, respectively), and came in fourth place among prevalent cases receiving polytherapy (22%).
The somewhat lower rate of valproate prescriptions tracks with other recent analyses showing that valproate use decreased among women of childbearing age following recommendations against its use during pregnancy, according to Dr. Kim and her coauthors.
However, topiramate is another story: “Although the magnitude of risk and range of adverse reproductive outcomes associated with topiramate use appear substantially less than those associated with valproate, some reduction in the use of topiramate in this population might be expected after evidence emerged in 2008 of its association with cleft palate,” they said in their report.
UCB Pharma sponsored this study. Study authors reported disclosures related to UCB Pharma, Biogen, Eisai, SK Life Science, Brain Sentinel, UCB Pharma, and the University of Alabama at Birmingham.
SOURCE: Kim H et al. JAMA Neurol. 2019 Apr 1. doi: 10.1001/jamaneurol.2019.0447.
results of a retrospective analysis suggest.
Topiramate, linked to increased risk of cleft palate and smaller-than-gestational-age newborns, was among the top three antiepileptic drugs (AEDs) prescribed to women 15-44 years of age in the population-based cohort study.
Valproate, linked to increases in both anatomic and behavioral teratogenicity, was less often prescribed, but nevertheless still prescribed in a considerable proportion of patients in the study, which looked at U.S. commercial, Medicare, and Medicaid claims data from 2009 to 2013.
Presence of comorbidities could be influencing whether or not a woman of childbearing age receives one of these AEDs, the investigators said. Specifically, they found valproate more often prescribed for women with epilepsy who also had mood or anxiety and dissociative disorder, while topiramate was more often prescribed in women with headaches or migraines.
Taken together, these findings suggest a lack of awareness of the teratogenic risks of valproate and topiramate, said the investigators, led by Hyunmi Kim, MD, PhD, MPH, of the department of neurology at Stanford (Calif.) University.
“To improve current practice, knowledge of the teratogenicity of certain AEDs should be disseminated to health care professionals and patients,” they wrote. The report is in JAMA Neurology.
The findings of Dr. Kim and her colleagues were based on data for 46,767 women of childbearing age: 8,003 incident (new) cases with a mean age of 27 years, and 38,764 prevalent cases with a mean age of 30 years.
Topiramate was the second- or third-most prescribed AED in the analyses, alongside levetiracetam and lamotrigine. In particular, topiramate prescriptions were found in incident cases receiving first-line monotherapy (15%), prevalent cases receiving first-line monotherapy (13%), and prevalent cases receiving polytherapy (29%).
Valproate was the fifth-most prescribed AED for incident and prevalent cases receiving first-line monotherapy (5% and 10%, respectively), and came in fourth place among prevalent cases receiving polytherapy (22%).
The somewhat lower rate of valproate prescriptions tracks with other recent analyses showing that valproate use decreased among women of childbearing age following recommendations against its use during pregnancy, according to Dr. Kim and her coauthors.
However, topiramate is another story: “Although the magnitude of risk and range of adverse reproductive outcomes associated with topiramate use appear substantially less than those associated with valproate, some reduction in the use of topiramate in this population might be expected after evidence emerged in 2008 of its association with cleft palate,” they said in their report.
UCB Pharma sponsored this study. Study authors reported disclosures related to UCB Pharma, Biogen, Eisai, SK Life Science, Brain Sentinel, UCB Pharma, and the University of Alabama at Birmingham.
SOURCE: Kim H et al. JAMA Neurol. 2019 Apr 1. doi: 10.1001/jamaneurol.2019.0447.
results of a retrospective analysis suggest.
Topiramate, linked to increased risk of cleft palate and smaller-than-gestational-age newborns, was among the top three antiepileptic drugs (AEDs) prescribed to women 15-44 years of age in the population-based cohort study.
Valproate, linked to increases in both anatomic and behavioral teratogenicity, was less often prescribed, but nevertheless still prescribed in a considerable proportion of patients in the study, which looked at U.S. commercial, Medicare, and Medicaid claims data from 2009 to 2013.
Presence of comorbidities could be influencing whether or not a woman of childbearing age receives one of these AEDs, the investigators said. Specifically, they found valproate more often prescribed for women with epilepsy who also had mood or anxiety and dissociative disorder, while topiramate was more often prescribed in women with headaches or migraines.
Taken together, these findings suggest a lack of awareness of the teratogenic risks of valproate and topiramate, said the investigators, led by Hyunmi Kim, MD, PhD, MPH, of the department of neurology at Stanford (Calif.) University.
“To improve current practice, knowledge of the teratogenicity of certain AEDs should be disseminated to health care professionals and patients,” they wrote. The report is in JAMA Neurology.
The findings of Dr. Kim and her colleagues were based on data for 46,767 women of childbearing age: 8,003 incident (new) cases with a mean age of 27 years, and 38,764 prevalent cases with a mean age of 30 years.
Topiramate was the second- or third-most prescribed AED in the analyses, alongside levetiracetam and lamotrigine. In particular, topiramate prescriptions were found in incident cases receiving first-line monotherapy (15%), prevalent cases receiving first-line monotherapy (13%), and prevalent cases receiving polytherapy (29%).
Valproate was the fifth-most prescribed AED for incident and prevalent cases receiving first-line monotherapy (5% and 10%, respectively), and came in fourth place among prevalent cases receiving polytherapy (22%).
The somewhat lower rate of valproate prescriptions tracks with other recent analyses showing that valproate use decreased among women of childbearing age following recommendations against its use during pregnancy, according to Dr. Kim and her coauthors.
However, topiramate is another story: “Although the magnitude of risk and range of adverse reproductive outcomes associated with topiramate use appear substantially less than those associated with valproate, some reduction in the use of topiramate in this population might be expected after evidence emerged in 2008 of its association with cleft palate,” they said in their report.
UCB Pharma sponsored this study. Study authors reported disclosures related to UCB Pharma, Biogen, Eisai, SK Life Science, Brain Sentinel, UCB Pharma, and the University of Alabama at Birmingham.
SOURCE: Kim H et al. JAMA Neurol. 2019 Apr 1. doi: 10.1001/jamaneurol.2019.0447.
FROM JAMA NEUROLOGY
Key clinical point: Both valproate and topiramate are prescribed relatively often in women of childbearing age despite known teratogenic risks.
Major finding: Topiramate was the second- or third-most prescribed AED in the analyses. Valproate was the fifth-most prescribed AED for incident and prevalent cases receiving first-line monotherapy.
Study details: Retrospective cohort study including nearly 47,000 women of childbearing age enrolled in claims databases between 2009 and 2013.
Disclosures: UCB Pharma sponsored the study. Study authors reported disclosures related to UCB Pharma, Biogen, Eisai, SK Life Science, Brain Sentinel, UCB Pharma, and the University of Alabama at Birmingham.
Source: Kim H et al. JAMA Neurol. 2019 Apr 1. doi: 10.1001/jamaneurol.2019.0447.