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Breast surgery may be a gateway to addictive medication use
After their surgery, 13.1% of opioid-naive patients become new persistent opioid users, and 6.6% of sedative-hypnotic–naive patients become new persistent users of sedative-hypnotics. Risk factors for persistent substance use included younger age, a breast cancer diagnosis, and chemotherapy.
“As the opioid epidemic in the United States continues, the rate of opioid dependence in the cancer population continues to increase as well,” study investigator Jacob Cogan, MD, of NewYork-Presbyterian/Columbia University Irving Medical Center in New York, said during a press conference.
“The perioperative period is one of high risk for cancer patients, with up to 10% becoming new persistent opioid users after cancer-related surgery. The rates surrounding mastectomy and reconstruction, however, are unknown. Another class of controlled substances worth our attention are the sedative-hypnotics. Despite the high rates of psychiatric disorders in the cancer population, there is little research into the rates of persistent sedative-hypnotic use in these patients.”
With this in mind, Dr. Cogan and colleagues analyzed MarketScan health care claims data for patients who underwent mastectomy and reconstruction (whether therapeutic or prophylactic) between 2008 and 2017.
The researchers then identified prescription claims for opioids and sedative-hypnotics during three periods:
- Preoperative period – 365 days to 31 days before surgery.
- Perioperative period – 31 days before to 90 days after surgery.
- Postoperative period – 90 days to 365 days after surgery.
‘Striking’ results
Analyses were based on 25,270 women who were not prior users of opioids and 27,651 women who were not prior users of sedative-hypnotics.
Women were considered new persistent substance users if they had no use in the preoperative period but filled at least one prescription in the perioperative period and at least two in the postoperative period.
Overall, 13.1% of opioid-naive patients became persistent opioid users, and 6.6% of sedative-hypnotic-naive patients became persistent sedative-hypnotic users after their mastectomy and reconstruction.
Proportions of substance use were even higher, 17.5% for opioids and 17.0% for sedative-hypnotics, after excluding women who did not receive or fill a perioperative prescription.
In multivariate analysis, patients were significantly more likely to become new persistent opioid users if they had Medicaid insurance (odds ratio, 2.31), had a breast cancer diagnosis vs a prophylactic indication (OR, 1.44), received chemotherapy (OR, 1.33), and were 50-64 years of age (OR, 1.29) or 49 years or younger (OR, 1.27), compared with 65 years or older.
Similarly, patients were significantly more likely to become new persistent sedative-hypnotic users if they received chemotherapy (OR, 2.24), had Medicaid insurance (OR, 1.85), had a breast cancer diagnosis (OR, 1.79), and were 50 to 64 years (OR, 1.65) or 49 years or younger (OR, 1.79).
Finally, patients’ likelihood of new persistent use increased with their number of risk factors. For persistent opioid use, the odds ratio rose from 2.27 in patients with two risk factors to 6.34 in those with five risk factors. For persistent sedative-hypnotic use, the odds ratio rose from 2.55 to 7.71, respectively.
The observed incidences of new persistent substance use in this patient population are “striking,” according to Dr. Cogan. Although the identified risk factors can help providers spot patients who should be monitored more closely, a proactive, systematic approach to postoperative follow-up for all patients is likely needed.
“When you are seeing patients in follow-up, this is something that you might want to explicitly ask about, for example, and not just assume that the postoperative opioids were taken and then disposed of,” Dr. Cogan recommended. “Ask them, ‘Are you still taking opioids, are you still taking your Ambien or whatever medication you were prescribed?’ That’s something to diligently follow up on and make sure the drug is disposed of, or if it somebody is still taking it, refer them for the appropriate services.”
In addition, patients should be encouraged to use over-the-counter medications as much as possible, he advised.
Prescribing: It’s complicated
“I wonder if perhaps we should not be giving opioids at all to certain patients. For example, a mastectomy and implant reconstruction, oftentimes, surprisingly, that’s not a terribly painful procedure. But a TRAM [transverse rectus abdominis] flap or abdominal flap, that really is,” commented press conference comoderator C. Kent Osborne, MD, of Baylor College of Medicine in Houston.
“I’ve been surprised that a lot of my patients get the prescription, but they don’t even use the pills, and I wonder if the prescription is given just so that we’re not bothered at nighttime by somebody calling with pain,” Dr. Osbourne added.
Prescribing opioids for postoperative pain is complicated, Dr. Cogan said, noting that the study did not assess the specific type of reconstruction patients had.
“You don’t want people in pain. Even if they need just one or two pills, it’s still reasonable for them to have it, and we certainly don’t want to imply from our study that people shouldn’t be getting these prescriptions if they need them,” Dr. Cogan elaborated. “But once patients have them, don’t just leave them there in their home because other studies have shown that that’s when people really get addicted to these medications, when they use them later on for other reasons, or they keep using them just because they have them around.”
The risk for persistent use of controlled substances “is something that all physicians need to be aware of for their patients. This is something that we are missing,” maintained press conference comoderator Virginia Kaklamani, MD, DSc, of UT Health San Antonio.
“It’s easy to just give a prescription instead of arguing with a patient about why you are not going to give them a prescription,” Dr. Kaklamani said. “And ultimately ... pain is subjective. If a patient tells you they are in pain, you are, quote-endquote, a bad physician if you tell them they should not be in pain.”
“We need to focus on other ways to deal with the pain, like physical therapy, sending patients to physical medicine and rehab physicians who are trained to help with symptoms from the surgery, with range of motion and all that; that can help with pain,” she recommended. “It’s much harder to do that, right, than to send a prescription in for a narcotic? But that easy answer is always the worst answer.”
This study was funded by the Breast Cancer Research Foundation and the National Institutes of Health. Dr. Cogan declared no conflicts of interest. Dr. Osborne disclosed relationships with Wolters Kluwer, Lilly, Tolmar, and GeneTex. Dr. Kaklamani disclosed relationships with Amgen, AstraZeneca, Athenex, Celgene, Celldex, Daiichi, Eisai, Genentech, Genomic Health, Immunomedics, Novartis, Pfizer, Puma, and Seattle Genetics.
SOURCE: Cogan JC et al. SABCS 2020, Abstract GS3-08.
After their surgery, 13.1% of opioid-naive patients become new persistent opioid users, and 6.6% of sedative-hypnotic–naive patients become new persistent users of sedative-hypnotics. Risk factors for persistent substance use included younger age, a breast cancer diagnosis, and chemotherapy.
“As the opioid epidemic in the United States continues, the rate of opioid dependence in the cancer population continues to increase as well,” study investigator Jacob Cogan, MD, of NewYork-Presbyterian/Columbia University Irving Medical Center in New York, said during a press conference.
“The perioperative period is one of high risk for cancer patients, with up to 10% becoming new persistent opioid users after cancer-related surgery. The rates surrounding mastectomy and reconstruction, however, are unknown. Another class of controlled substances worth our attention are the sedative-hypnotics. Despite the high rates of psychiatric disorders in the cancer population, there is little research into the rates of persistent sedative-hypnotic use in these patients.”
With this in mind, Dr. Cogan and colleagues analyzed MarketScan health care claims data for patients who underwent mastectomy and reconstruction (whether therapeutic or prophylactic) between 2008 and 2017.
The researchers then identified prescription claims for opioids and sedative-hypnotics during three periods:
- Preoperative period – 365 days to 31 days before surgery.
- Perioperative period – 31 days before to 90 days after surgery.
- Postoperative period – 90 days to 365 days after surgery.
‘Striking’ results
Analyses were based on 25,270 women who were not prior users of opioids and 27,651 women who were not prior users of sedative-hypnotics.
Women were considered new persistent substance users if they had no use in the preoperative period but filled at least one prescription in the perioperative period and at least two in the postoperative period.
Overall, 13.1% of opioid-naive patients became persistent opioid users, and 6.6% of sedative-hypnotic-naive patients became persistent sedative-hypnotic users after their mastectomy and reconstruction.
Proportions of substance use were even higher, 17.5% for opioids and 17.0% for sedative-hypnotics, after excluding women who did not receive or fill a perioperative prescription.
In multivariate analysis, patients were significantly more likely to become new persistent opioid users if they had Medicaid insurance (odds ratio, 2.31), had a breast cancer diagnosis vs a prophylactic indication (OR, 1.44), received chemotherapy (OR, 1.33), and were 50-64 years of age (OR, 1.29) or 49 years or younger (OR, 1.27), compared with 65 years or older.
Similarly, patients were significantly more likely to become new persistent sedative-hypnotic users if they received chemotherapy (OR, 2.24), had Medicaid insurance (OR, 1.85), had a breast cancer diagnosis (OR, 1.79), and were 50 to 64 years (OR, 1.65) or 49 years or younger (OR, 1.79).
Finally, patients’ likelihood of new persistent use increased with their number of risk factors. For persistent opioid use, the odds ratio rose from 2.27 in patients with two risk factors to 6.34 in those with five risk factors. For persistent sedative-hypnotic use, the odds ratio rose from 2.55 to 7.71, respectively.
The observed incidences of new persistent substance use in this patient population are “striking,” according to Dr. Cogan. Although the identified risk factors can help providers spot patients who should be monitored more closely, a proactive, systematic approach to postoperative follow-up for all patients is likely needed.
“When you are seeing patients in follow-up, this is something that you might want to explicitly ask about, for example, and not just assume that the postoperative opioids were taken and then disposed of,” Dr. Cogan recommended. “Ask them, ‘Are you still taking opioids, are you still taking your Ambien or whatever medication you were prescribed?’ That’s something to diligently follow up on and make sure the drug is disposed of, or if it somebody is still taking it, refer them for the appropriate services.”
In addition, patients should be encouraged to use over-the-counter medications as much as possible, he advised.
Prescribing: It’s complicated
“I wonder if perhaps we should not be giving opioids at all to certain patients. For example, a mastectomy and implant reconstruction, oftentimes, surprisingly, that’s not a terribly painful procedure. But a TRAM [transverse rectus abdominis] flap or abdominal flap, that really is,” commented press conference comoderator C. Kent Osborne, MD, of Baylor College of Medicine in Houston.
“I’ve been surprised that a lot of my patients get the prescription, but they don’t even use the pills, and I wonder if the prescription is given just so that we’re not bothered at nighttime by somebody calling with pain,” Dr. Osbourne added.
Prescribing opioids for postoperative pain is complicated, Dr. Cogan said, noting that the study did not assess the specific type of reconstruction patients had.
“You don’t want people in pain. Even if they need just one or two pills, it’s still reasonable for them to have it, and we certainly don’t want to imply from our study that people shouldn’t be getting these prescriptions if they need them,” Dr. Cogan elaborated. “But once patients have them, don’t just leave them there in their home because other studies have shown that that’s when people really get addicted to these medications, when they use them later on for other reasons, or they keep using them just because they have them around.”
The risk for persistent use of controlled substances “is something that all physicians need to be aware of for their patients. This is something that we are missing,” maintained press conference comoderator Virginia Kaklamani, MD, DSc, of UT Health San Antonio.
“It’s easy to just give a prescription instead of arguing with a patient about why you are not going to give them a prescription,” Dr. Kaklamani said. “And ultimately ... pain is subjective. If a patient tells you they are in pain, you are, quote-endquote, a bad physician if you tell them they should not be in pain.”
“We need to focus on other ways to deal with the pain, like physical therapy, sending patients to physical medicine and rehab physicians who are trained to help with symptoms from the surgery, with range of motion and all that; that can help with pain,” she recommended. “It’s much harder to do that, right, than to send a prescription in for a narcotic? But that easy answer is always the worst answer.”
This study was funded by the Breast Cancer Research Foundation and the National Institutes of Health. Dr. Cogan declared no conflicts of interest. Dr. Osborne disclosed relationships with Wolters Kluwer, Lilly, Tolmar, and GeneTex. Dr. Kaklamani disclosed relationships with Amgen, AstraZeneca, Athenex, Celgene, Celldex, Daiichi, Eisai, Genentech, Genomic Health, Immunomedics, Novartis, Pfizer, Puma, and Seattle Genetics.
SOURCE: Cogan JC et al. SABCS 2020, Abstract GS3-08.
After their surgery, 13.1% of opioid-naive patients become new persistent opioid users, and 6.6% of sedative-hypnotic–naive patients become new persistent users of sedative-hypnotics. Risk factors for persistent substance use included younger age, a breast cancer diagnosis, and chemotherapy.
“As the opioid epidemic in the United States continues, the rate of opioid dependence in the cancer population continues to increase as well,” study investigator Jacob Cogan, MD, of NewYork-Presbyterian/Columbia University Irving Medical Center in New York, said during a press conference.
“The perioperative period is one of high risk for cancer patients, with up to 10% becoming new persistent opioid users after cancer-related surgery. The rates surrounding mastectomy and reconstruction, however, are unknown. Another class of controlled substances worth our attention are the sedative-hypnotics. Despite the high rates of psychiatric disorders in the cancer population, there is little research into the rates of persistent sedative-hypnotic use in these patients.”
With this in mind, Dr. Cogan and colleagues analyzed MarketScan health care claims data for patients who underwent mastectomy and reconstruction (whether therapeutic or prophylactic) between 2008 and 2017.
The researchers then identified prescription claims for opioids and sedative-hypnotics during three periods:
- Preoperative period – 365 days to 31 days before surgery.
- Perioperative period – 31 days before to 90 days after surgery.
- Postoperative period – 90 days to 365 days after surgery.
‘Striking’ results
Analyses were based on 25,270 women who were not prior users of opioids and 27,651 women who were not prior users of sedative-hypnotics.
Women were considered new persistent substance users if they had no use in the preoperative period but filled at least one prescription in the perioperative period and at least two in the postoperative period.
Overall, 13.1% of opioid-naive patients became persistent opioid users, and 6.6% of sedative-hypnotic-naive patients became persistent sedative-hypnotic users after their mastectomy and reconstruction.
Proportions of substance use were even higher, 17.5% for opioids and 17.0% for sedative-hypnotics, after excluding women who did not receive or fill a perioperative prescription.
In multivariate analysis, patients were significantly more likely to become new persistent opioid users if they had Medicaid insurance (odds ratio, 2.31), had a breast cancer diagnosis vs a prophylactic indication (OR, 1.44), received chemotherapy (OR, 1.33), and were 50-64 years of age (OR, 1.29) or 49 years or younger (OR, 1.27), compared with 65 years or older.
Similarly, patients were significantly more likely to become new persistent sedative-hypnotic users if they received chemotherapy (OR, 2.24), had Medicaid insurance (OR, 1.85), had a breast cancer diagnosis (OR, 1.79), and were 50 to 64 years (OR, 1.65) or 49 years or younger (OR, 1.79).
Finally, patients’ likelihood of new persistent use increased with their number of risk factors. For persistent opioid use, the odds ratio rose from 2.27 in patients with two risk factors to 6.34 in those with five risk factors. For persistent sedative-hypnotic use, the odds ratio rose from 2.55 to 7.71, respectively.
The observed incidences of new persistent substance use in this patient population are “striking,” according to Dr. Cogan. Although the identified risk factors can help providers spot patients who should be monitored more closely, a proactive, systematic approach to postoperative follow-up for all patients is likely needed.
“When you are seeing patients in follow-up, this is something that you might want to explicitly ask about, for example, and not just assume that the postoperative opioids were taken and then disposed of,” Dr. Cogan recommended. “Ask them, ‘Are you still taking opioids, are you still taking your Ambien or whatever medication you were prescribed?’ That’s something to diligently follow up on and make sure the drug is disposed of, or if it somebody is still taking it, refer them for the appropriate services.”
In addition, patients should be encouraged to use over-the-counter medications as much as possible, he advised.
Prescribing: It’s complicated
“I wonder if perhaps we should not be giving opioids at all to certain patients. For example, a mastectomy and implant reconstruction, oftentimes, surprisingly, that’s not a terribly painful procedure. But a TRAM [transverse rectus abdominis] flap or abdominal flap, that really is,” commented press conference comoderator C. Kent Osborne, MD, of Baylor College of Medicine in Houston.
“I’ve been surprised that a lot of my patients get the prescription, but they don’t even use the pills, and I wonder if the prescription is given just so that we’re not bothered at nighttime by somebody calling with pain,” Dr. Osbourne added.
Prescribing opioids for postoperative pain is complicated, Dr. Cogan said, noting that the study did not assess the specific type of reconstruction patients had.
“You don’t want people in pain. Even if they need just one or two pills, it’s still reasonable for them to have it, and we certainly don’t want to imply from our study that people shouldn’t be getting these prescriptions if they need them,” Dr. Cogan elaborated. “But once patients have them, don’t just leave them there in their home because other studies have shown that that’s when people really get addicted to these medications, when they use them later on for other reasons, or they keep using them just because they have them around.”
The risk for persistent use of controlled substances “is something that all physicians need to be aware of for their patients. This is something that we are missing,” maintained press conference comoderator Virginia Kaklamani, MD, DSc, of UT Health San Antonio.
“It’s easy to just give a prescription instead of arguing with a patient about why you are not going to give them a prescription,” Dr. Kaklamani said. “And ultimately ... pain is subjective. If a patient tells you they are in pain, you are, quote-endquote, a bad physician if you tell them they should not be in pain.”
“We need to focus on other ways to deal with the pain, like physical therapy, sending patients to physical medicine and rehab physicians who are trained to help with symptoms from the surgery, with range of motion and all that; that can help with pain,” she recommended. “It’s much harder to do that, right, than to send a prescription in for a narcotic? But that easy answer is always the worst answer.”
This study was funded by the Breast Cancer Research Foundation and the National Institutes of Health. Dr. Cogan declared no conflicts of interest. Dr. Osborne disclosed relationships with Wolters Kluwer, Lilly, Tolmar, and GeneTex. Dr. Kaklamani disclosed relationships with Amgen, AstraZeneca, Athenex, Celgene, Celldex, Daiichi, Eisai, Genentech, Genomic Health, Immunomedics, Novartis, Pfizer, Puma, and Seattle Genetics.
SOURCE: Cogan JC et al. SABCS 2020, Abstract GS3-08.
FROM SABCS 2020
CTCs predict overall survival in metastatic breast cancer
The CTC results are available about 4 weeks after start of therapy. Conventional imaging is carried out after about 3 months.
But an expert is not convinced that this approach is currently ready for clinical use and suggests that, for now, it should remain a tool for use in research.
The new meta-analysis, which involved data on more than 4000 patients, showed that the presence or the absence of CTCs “strongly” predicts overall survival (OS).
Median OS was greatest (47 months) for patients who had no CTCs at baseline and at follow-up. In contrast, the median OS was shortest (17.8 months) for patients who had CTCs at both time points.
The risk for death was more than 200% greater for patients in the latter group than in the former group.
The results “suggest the potential for clinical utility” of CTC monitoring as an early response marker in metastatic breast cancer, said lead author Wolfgang Janni, MD, PhD, of the Ulm University Hospital, Ulm, Germany. He was speaking at an online press conference for the virtual San Antonio Breast Cancer Symposium (SABCS) 2020, where the new study will be presented this week.
The investigators say the findings from this meta-analysis add to literature in which “several studies suggest clinical utility” of measuring CTC levels as a means of assessing response status for patients with metastatic breast cancer.
Unfortunately, the new study does not show that assessing CTCs over time improves clinical outcomes, which is an ongoing problem in the literature, said Virginia Kaklamani, MD, University of Texas Health Sciences Center, San Antonio, Texas, who is also a meeting co-director.
“Previous randomized clinical trial data have shown that assessing CTCs does not benefit patients (vs not assessing),” Kaklamani told Medscape Medical News.
Kaklamani explained how CTC assessments have worked in practice. “You do these circulating tumor cell tests and you find, for example, that the number increases. The assumption is the treatment’s not working. So you switch treatments around,” she explained. That pattern can be repeated every 3 to 4 weeks, resulting in more toxicity, which, in turn, may nullify any treatment benefit.
However, she noted that, so far, key data have come from the era of chemotherapy and do not reflect targeted therapies, which may make a difference. In addition, the more recent ability to assess and identify circulating tumor DNA may allow clinicians to match drugs to mutations, which may have greater impact on cancer outcomes.
Currently, CTCs are best used by researchers, Kaklamani said during the press conference, because they have not been definitively proven to improve patient results.
Investigator Janni did not object to that description.
But in a press statement, he suggested that CTCs can be used currently by clinicians.
“These data indicate that CTC dynamics can predict the trajectory of the disease a little more than four weeks after initiating treatment,” Janni said in the press statement. “This provides an advantage over conventional imaging methods and can help physicians determine very early on whether a treatment should be continued.”
But, to Kaklamani’s point, an article published in November in JAMA Oncology showed that use of CTCs did not yield significant clinical benefit in comparison with use of other clinical factors in determining whether to choose endocrine therapy or chemotherapy. In that randomized trial, which was conducted in Europe and included women with HR-positive, HER2-negative breast cancer, progression-free survival was similar in both arms, as reported by Medscape Medical News. However, use of chemotherapy (and attendant toxicity) was greater among women in the CTC arm, which was considered an undesirable outcome by experts not involved with the trial.
Details of the study results
For their study, Janni and colleagues conducted a comprehensive pooled analysis of globally available data. They identified 4079 metastatic breast cancer patients who had undergone baseline and follow-up CTC measurements (at least one, at a median of 29 days later) in previous clinical trials.
The investigators analyzed changes in CTC levels between baseline and follow-up to determine whether they were associated with OS.
Of the 2961 patients who were CTC-positive at baseline, 1855 remained CTC-positive after treatment was initiated (positive/positive), and 1106 patients had converted to CTC-negative status (positive/negative).
Of the 1118 patients who were CTC-negative at baseline, 813 remained CTC-negative (negative/negative), and 305 had become CTC-positive (negative/positive).
As noted above, median OS was greatest for patients who were negative/negative (47 months), followed by patients who were positive/negative (32.2 months), negative/positive (29.6 months), and positive/positive (17.8 months).
Hazard ratios in which the reference group was negative/negative were 1.52 for the positive/negative group, 1.74 for the negative/positive group, and 3.15 for the positive/positive group (P < .0001 for all groups).
These CTC dynamics were found across all breast cancer subtypes, said Janni.
“These data indicate that CTC dynamics can predict the trajectory of the disease a little more than four weeks after initiating treatment,” said Janni in the press statement. “This provides an advantage over conventional imaging methods and can help physicians determine very early on whether a treatment should be continued. It is also very reassuring that CTC dynamics predicted outcomes for all breast cancer subtypes.”
The study was supported by Menarini Silicon Biosystems, the makers of CellSearch, the CTC test used for all of the patients and studies in the meta-analysis. Janni received a research grant from Menarini Silicon Biosystems. Other study authors have financial ties to healthcare industries. Kaklamani has received consulting fees from Amgen, Eisai, Puma, Celldex, AstraZeneca, and Athenex; fees for non-CME services received directly from commercial interest or their agents from Pfizer, Celgene, Genentech, Genomic Health, Puma, Eisai, and Novartis; and has contracted research with Eisai.
This article first appeared on Medscape.com.
The CTC results are available about 4 weeks after start of therapy. Conventional imaging is carried out after about 3 months.
But an expert is not convinced that this approach is currently ready for clinical use and suggests that, for now, it should remain a tool for use in research.
The new meta-analysis, which involved data on more than 4000 patients, showed that the presence or the absence of CTCs “strongly” predicts overall survival (OS).
Median OS was greatest (47 months) for patients who had no CTCs at baseline and at follow-up. In contrast, the median OS was shortest (17.8 months) for patients who had CTCs at both time points.
The risk for death was more than 200% greater for patients in the latter group than in the former group.
The results “suggest the potential for clinical utility” of CTC monitoring as an early response marker in metastatic breast cancer, said lead author Wolfgang Janni, MD, PhD, of the Ulm University Hospital, Ulm, Germany. He was speaking at an online press conference for the virtual San Antonio Breast Cancer Symposium (SABCS) 2020, where the new study will be presented this week.
The investigators say the findings from this meta-analysis add to literature in which “several studies suggest clinical utility” of measuring CTC levels as a means of assessing response status for patients with metastatic breast cancer.
Unfortunately, the new study does not show that assessing CTCs over time improves clinical outcomes, which is an ongoing problem in the literature, said Virginia Kaklamani, MD, University of Texas Health Sciences Center, San Antonio, Texas, who is also a meeting co-director.
“Previous randomized clinical trial data have shown that assessing CTCs does not benefit patients (vs not assessing),” Kaklamani told Medscape Medical News.
Kaklamani explained how CTC assessments have worked in practice. “You do these circulating tumor cell tests and you find, for example, that the number increases. The assumption is the treatment’s not working. So you switch treatments around,” she explained. That pattern can be repeated every 3 to 4 weeks, resulting in more toxicity, which, in turn, may nullify any treatment benefit.
However, she noted that, so far, key data have come from the era of chemotherapy and do not reflect targeted therapies, which may make a difference. In addition, the more recent ability to assess and identify circulating tumor DNA may allow clinicians to match drugs to mutations, which may have greater impact on cancer outcomes.
Currently, CTCs are best used by researchers, Kaklamani said during the press conference, because they have not been definitively proven to improve patient results.
Investigator Janni did not object to that description.
But in a press statement, he suggested that CTCs can be used currently by clinicians.
“These data indicate that CTC dynamics can predict the trajectory of the disease a little more than four weeks after initiating treatment,” Janni said in the press statement. “This provides an advantage over conventional imaging methods and can help physicians determine very early on whether a treatment should be continued.”
But, to Kaklamani’s point, an article published in November in JAMA Oncology showed that use of CTCs did not yield significant clinical benefit in comparison with use of other clinical factors in determining whether to choose endocrine therapy or chemotherapy. In that randomized trial, which was conducted in Europe and included women with HR-positive, HER2-negative breast cancer, progression-free survival was similar in both arms, as reported by Medscape Medical News. However, use of chemotherapy (and attendant toxicity) was greater among women in the CTC arm, which was considered an undesirable outcome by experts not involved with the trial.
Details of the study results
For their study, Janni and colleagues conducted a comprehensive pooled analysis of globally available data. They identified 4079 metastatic breast cancer patients who had undergone baseline and follow-up CTC measurements (at least one, at a median of 29 days later) in previous clinical trials.
The investigators analyzed changes in CTC levels between baseline and follow-up to determine whether they were associated with OS.
Of the 2961 patients who were CTC-positive at baseline, 1855 remained CTC-positive after treatment was initiated (positive/positive), and 1106 patients had converted to CTC-negative status (positive/negative).
Of the 1118 patients who were CTC-negative at baseline, 813 remained CTC-negative (negative/negative), and 305 had become CTC-positive (negative/positive).
As noted above, median OS was greatest for patients who were negative/negative (47 months), followed by patients who were positive/negative (32.2 months), negative/positive (29.6 months), and positive/positive (17.8 months).
Hazard ratios in which the reference group was negative/negative were 1.52 for the positive/negative group, 1.74 for the negative/positive group, and 3.15 for the positive/positive group (P < .0001 for all groups).
These CTC dynamics were found across all breast cancer subtypes, said Janni.
“These data indicate that CTC dynamics can predict the trajectory of the disease a little more than four weeks after initiating treatment,” said Janni in the press statement. “This provides an advantage over conventional imaging methods and can help physicians determine very early on whether a treatment should be continued. It is also very reassuring that CTC dynamics predicted outcomes for all breast cancer subtypes.”
The study was supported by Menarini Silicon Biosystems, the makers of CellSearch, the CTC test used for all of the patients and studies in the meta-analysis. Janni received a research grant from Menarini Silicon Biosystems. Other study authors have financial ties to healthcare industries. Kaklamani has received consulting fees from Amgen, Eisai, Puma, Celldex, AstraZeneca, and Athenex; fees for non-CME services received directly from commercial interest or their agents from Pfizer, Celgene, Genentech, Genomic Health, Puma, Eisai, and Novartis; and has contracted research with Eisai.
This article first appeared on Medscape.com.
The CTC results are available about 4 weeks after start of therapy. Conventional imaging is carried out after about 3 months.
But an expert is not convinced that this approach is currently ready for clinical use and suggests that, for now, it should remain a tool for use in research.
The new meta-analysis, which involved data on more than 4000 patients, showed that the presence or the absence of CTCs “strongly” predicts overall survival (OS).
Median OS was greatest (47 months) for patients who had no CTCs at baseline and at follow-up. In contrast, the median OS was shortest (17.8 months) for patients who had CTCs at both time points.
The risk for death was more than 200% greater for patients in the latter group than in the former group.
The results “suggest the potential for clinical utility” of CTC monitoring as an early response marker in metastatic breast cancer, said lead author Wolfgang Janni, MD, PhD, of the Ulm University Hospital, Ulm, Germany. He was speaking at an online press conference for the virtual San Antonio Breast Cancer Symposium (SABCS) 2020, where the new study will be presented this week.
The investigators say the findings from this meta-analysis add to literature in which “several studies suggest clinical utility” of measuring CTC levels as a means of assessing response status for patients with metastatic breast cancer.
Unfortunately, the new study does not show that assessing CTCs over time improves clinical outcomes, which is an ongoing problem in the literature, said Virginia Kaklamani, MD, University of Texas Health Sciences Center, San Antonio, Texas, who is also a meeting co-director.
“Previous randomized clinical trial data have shown that assessing CTCs does not benefit patients (vs not assessing),” Kaklamani told Medscape Medical News.
Kaklamani explained how CTC assessments have worked in practice. “You do these circulating tumor cell tests and you find, for example, that the number increases. The assumption is the treatment’s not working. So you switch treatments around,” she explained. That pattern can be repeated every 3 to 4 weeks, resulting in more toxicity, which, in turn, may nullify any treatment benefit.
However, she noted that, so far, key data have come from the era of chemotherapy and do not reflect targeted therapies, which may make a difference. In addition, the more recent ability to assess and identify circulating tumor DNA may allow clinicians to match drugs to mutations, which may have greater impact on cancer outcomes.
Currently, CTCs are best used by researchers, Kaklamani said during the press conference, because they have not been definitively proven to improve patient results.
Investigator Janni did not object to that description.
But in a press statement, he suggested that CTCs can be used currently by clinicians.
“These data indicate that CTC dynamics can predict the trajectory of the disease a little more than four weeks after initiating treatment,” Janni said in the press statement. “This provides an advantage over conventional imaging methods and can help physicians determine very early on whether a treatment should be continued.”
But, to Kaklamani’s point, an article published in November in JAMA Oncology showed that use of CTCs did not yield significant clinical benefit in comparison with use of other clinical factors in determining whether to choose endocrine therapy or chemotherapy. In that randomized trial, which was conducted in Europe and included women with HR-positive, HER2-negative breast cancer, progression-free survival was similar in both arms, as reported by Medscape Medical News. However, use of chemotherapy (and attendant toxicity) was greater among women in the CTC arm, which was considered an undesirable outcome by experts not involved with the trial.
Details of the study results
For their study, Janni and colleagues conducted a comprehensive pooled analysis of globally available data. They identified 4079 metastatic breast cancer patients who had undergone baseline and follow-up CTC measurements (at least one, at a median of 29 days later) in previous clinical trials.
The investigators analyzed changes in CTC levels between baseline and follow-up to determine whether they were associated with OS.
Of the 2961 patients who were CTC-positive at baseline, 1855 remained CTC-positive after treatment was initiated (positive/positive), and 1106 patients had converted to CTC-negative status (positive/negative).
Of the 1118 patients who were CTC-negative at baseline, 813 remained CTC-negative (negative/negative), and 305 had become CTC-positive (negative/positive).
As noted above, median OS was greatest for patients who were negative/negative (47 months), followed by patients who were positive/negative (32.2 months), negative/positive (29.6 months), and positive/positive (17.8 months).
Hazard ratios in which the reference group was negative/negative were 1.52 for the positive/negative group, 1.74 for the negative/positive group, and 3.15 for the positive/positive group (P < .0001 for all groups).
These CTC dynamics were found across all breast cancer subtypes, said Janni.
“These data indicate that CTC dynamics can predict the trajectory of the disease a little more than four weeks after initiating treatment,” said Janni in the press statement. “This provides an advantage over conventional imaging methods and can help physicians determine very early on whether a treatment should be continued. It is also very reassuring that CTC dynamics predicted outcomes for all breast cancer subtypes.”
The study was supported by Menarini Silicon Biosystems, the makers of CellSearch, the CTC test used for all of the patients and studies in the meta-analysis. Janni received a research grant from Menarini Silicon Biosystems. Other study authors have financial ties to healthcare industries. Kaklamani has received consulting fees from Amgen, Eisai, Puma, Celldex, AstraZeneca, and Athenex; fees for non-CME services received directly from commercial interest or their agents from Pfizer, Celgene, Genentech, Genomic Health, Puma, Eisai, and Novartis; and has contracted research with Eisai.
This article first appeared on Medscape.com.
FROM SABCS 2020
Getting closer to an accurate early Alzheimer’s test
Researchers have created the most sensitive test yet
Scientists at Washington University in St. Louis have developed the most sensitive blood test yet for Alzheimer’s. In studies, the test identified patients with amyloid deposits, using mass spectrometry, before brain scans did.
Of course, amyloid is a normal brain protein; most people with amyloid deposits will not develop dementia, but it’s a significant risk factor. When blood amyloid levels are low, it may indicate it is clumping in the brain.
Researchers used mass spectrometry to test volunteers’ stored blood for beta amyloid, then checked if the levels predicted the results of PET scans. Mass spectrometry identified asymptomatic people accumulating beta amyloid in their brains when PET scans were still negative. The scans only showed beta amyloid in the brain years later. The blood test predicted the presence of plaque even in mostly asymptomatic people with 94% accuracy.
The test will not be available for clinical use for years, but prior to that it will be helpful to scientists conducting trials of drugs to prevent Alzheimer’s, seeking participants in the earliest stages of the disease.
Reference
1. Kolata G. A Blood Test for Alzheimer’s? It’s Coming, Scientists Report. New York Times. Aug. 1, 2019. https://www.nytimes.com/2019/08/01/health/alzheimers-blood-test.html.
Researchers have created the most sensitive test yet
Researchers have created the most sensitive test yet
Scientists at Washington University in St. Louis have developed the most sensitive blood test yet for Alzheimer’s. In studies, the test identified patients with amyloid deposits, using mass spectrometry, before brain scans did.
Of course, amyloid is a normal brain protein; most people with amyloid deposits will not develop dementia, but it’s a significant risk factor. When blood amyloid levels are low, it may indicate it is clumping in the brain.
Researchers used mass spectrometry to test volunteers’ stored blood for beta amyloid, then checked if the levels predicted the results of PET scans. Mass spectrometry identified asymptomatic people accumulating beta amyloid in their brains when PET scans were still negative. The scans only showed beta amyloid in the brain years later. The blood test predicted the presence of plaque even in mostly asymptomatic people with 94% accuracy.
The test will not be available for clinical use for years, but prior to that it will be helpful to scientists conducting trials of drugs to prevent Alzheimer’s, seeking participants in the earliest stages of the disease.
Reference
1. Kolata G. A Blood Test for Alzheimer’s? It’s Coming, Scientists Report. New York Times. Aug. 1, 2019. https://www.nytimes.com/2019/08/01/health/alzheimers-blood-test.html.
Scientists at Washington University in St. Louis have developed the most sensitive blood test yet for Alzheimer’s. In studies, the test identified patients with amyloid deposits, using mass spectrometry, before brain scans did.
Of course, amyloid is a normal brain protein; most people with amyloid deposits will not develop dementia, but it’s a significant risk factor. When blood amyloid levels are low, it may indicate it is clumping in the brain.
Researchers used mass spectrometry to test volunteers’ stored blood for beta amyloid, then checked if the levels predicted the results of PET scans. Mass spectrometry identified asymptomatic people accumulating beta amyloid in their brains when PET scans were still negative. The scans only showed beta amyloid in the brain years later. The blood test predicted the presence of plaque even in mostly asymptomatic people with 94% accuracy.
The test will not be available for clinical use for years, but prior to that it will be helpful to scientists conducting trials of drugs to prevent Alzheimer’s, seeking participants in the earliest stages of the disease.
Reference
1. Kolata G. A Blood Test for Alzheimer’s? It’s Coming, Scientists Report. New York Times. Aug. 1, 2019. https://www.nytimes.com/2019/08/01/health/alzheimers-blood-test.html.
Endoscopic intragastric balloon improved NASH parameters
Endoscopically placed intragastric balloons were safe and effective for managing nonalcoholic fatty liver disease (NAFLD), according to the findings of an open-label, prospective study of 21 patients.
Six months after balloon placement, nonalcoholic fatty liver disease activity scores (NAS) had improved in 18 of 20 biopsied patients (90%), with a median decrease of 3 points (range, 1-4 points). Magnetic resonance elastography showed that fibrosis had improved by 1.5 stages in half of patients (10 of 20). “Other than postprocedural pain (in 5% of patients), no serious adverse events were reported,” Fateh Bazerbachi, MD, of Massachusetts General Hospital in Boston, and associates wrote in Clinical Gastroenterology and Hepatology.
Nonalcoholic fatty liver disease affects approximately 70% of obese adults and half of obese children, meaning that tens of millions of individuals are affected in the United States alone. Lifestyle changes rarely induce more than 10% body weight loss, the threshold for “meaningful improvement in NASH,” and bariatric surgery is not recommended for managing mild or moderate obesity and often is not desired by patients who do qualify, the researchers noted. “Endoscopic bariatric therapies are garnering more attention as potential strategies to address these shortcomings in obesity care and its comorbidities [, but] their influences on the driving and prognostic parameters of NAFLD remain unclear.”
In all, 81% of the study participants were women, with a mean age of 54 years and an average body mass index (BMI) of 44 kg/m2. At baseline, more than half had NAS scores of 4 or 5 and histologic fibrosis scores of 2 or 3. Baseline hemoglobin A1c levels averaged 7.4% (range, 5.1%-11.1%) and 29% of patients had impaired glucose tolerance. After receiving endoscopic ultrasound (EUS)–guided core liver biopsies, patients received an endoscopically placed fluid-filled intragastric balloon (Orbera, Apollo Endosurgery, Austin, Tex.). The balloon was removed 6 months later and magnetic resonance elastography and a second core biopsy were performed. One patient did not receive an exit biopsy (because of starting antithrombotic therapy) and thus was excluded from the final analysis.
Of 20 patients, 16 (80%) had at least a two-point improvement in NAS at 6 months, and half had NAS scores of less than 2, indicating remission of NASH. Three of 20 patients (15%) showed improvements in mild fibrosis, 12 showed no change, and 5 showed worsening. Patients lost an average of 11.7% of body weight (standard deviation, 7.7%; P = .01), BMI dropped by a mean of 5.2 (SD, 0.75; P = .01) and A1c fell by an average of 1.3% (SD, 0.5%; P = .02). Waist circumference also decreased significantly (mean, –14.4 cm; SD, –2.2 cm; P = .001), as did hip circumference, fasting glucose, AST, ALT, and AST-to-platelet ratio index. “Percent total body weight loss did not correlate with reductions in NAS or fibrosis,” the researchers noted.
Together, these findings suggest that intragastric balloon placement “may allow a reversal in the natural history of NAFLD and NASH, despite the short duration of the intervention,” they concluded. “The logistics of IGB [intragastric balloon] placement will enable accurate risk stratification of these patients in a safe and reproducible manner, obviating the need for additional investigations, and clarifying the real risk of patients afflicted with NAFLD.”
Apollo Endosurgery provided intragastric balloons, and Medtronic provided SharkCore needles. The senior author and two coinvestigators disclosed ties to Apollo Endosurgery, Medtronic, Metamodix, Boston Scientific, Cairn Diagnostics, Aspire Bariatrics, Johnson and Johnson, AstraZeneca, Genfit, Gila Therapeutics, and several other companies. The other investigators reported having no conflicts of interest.
SOURCE: Bazerbachi F et al. Clin Gastroenterol Hepatol. 2020 Apr 30. doi: 10.1016/j.cgh.2020.04.068.
Obesity a well-known risk factor for the development of nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis, the latter of which is expected to become the leading indication for liver transplantation. As such addressing the steatosis in these patients is critical. A drop of even 5%-10% of total body weight with diet and exercise can result in significant improvement in liver disease.
In this article, Dr. Bazerbachi and colleagues work to advance the case for intragastric balloons as a successful treatment option for NAFLD. They performed a prospective, open-label study on 21 patients treated with an intragastric balloon for 6 months. Using gold-standard histology and noninvasive magnetic resonance elastography before and after therapy, they show significant improvement in NAFLD activity score (median change, 3 points; range, 1-4) over a short duration of treatment. Interestingly, the collection of the liver biopsy sample is done via endoscopic ultrasound, which can be easily performed during placement and removal of this intragastric balloon. While promising, follow-up studies are needed to show sustained improvement in NAFLD after the balloon is removed.
Wasif M. Abidi, MD, PhD, is assistant professor of medicine, gastroenterology, Baylor College of Medicine, Houston.
Obesity a well-known risk factor for the development of nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis, the latter of which is expected to become the leading indication for liver transplantation. As such addressing the steatosis in these patients is critical. A drop of even 5%-10% of total body weight with diet and exercise can result in significant improvement in liver disease.
In this article, Dr. Bazerbachi and colleagues work to advance the case for intragastric balloons as a successful treatment option for NAFLD. They performed a prospective, open-label study on 21 patients treated with an intragastric balloon for 6 months. Using gold-standard histology and noninvasive magnetic resonance elastography before and after therapy, they show significant improvement in NAFLD activity score (median change, 3 points; range, 1-4) over a short duration of treatment. Interestingly, the collection of the liver biopsy sample is done via endoscopic ultrasound, which can be easily performed during placement and removal of this intragastric balloon. While promising, follow-up studies are needed to show sustained improvement in NAFLD after the balloon is removed.
Wasif M. Abidi, MD, PhD, is assistant professor of medicine, gastroenterology, Baylor College of Medicine, Houston.
Obesity a well-known risk factor for the development of nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis, the latter of which is expected to become the leading indication for liver transplantation. As such addressing the steatosis in these patients is critical. A drop of even 5%-10% of total body weight with diet and exercise can result in significant improvement in liver disease.
In this article, Dr. Bazerbachi and colleagues work to advance the case for intragastric balloons as a successful treatment option for NAFLD. They performed a prospective, open-label study on 21 patients treated with an intragastric balloon for 6 months. Using gold-standard histology and noninvasive magnetic resonance elastography before and after therapy, they show significant improvement in NAFLD activity score (median change, 3 points; range, 1-4) over a short duration of treatment. Interestingly, the collection of the liver biopsy sample is done via endoscopic ultrasound, which can be easily performed during placement and removal of this intragastric balloon. While promising, follow-up studies are needed to show sustained improvement in NAFLD after the balloon is removed.
Wasif M. Abidi, MD, PhD, is assistant professor of medicine, gastroenterology, Baylor College of Medicine, Houston.
Endoscopically placed intragastric balloons were safe and effective for managing nonalcoholic fatty liver disease (NAFLD), according to the findings of an open-label, prospective study of 21 patients.
Six months after balloon placement, nonalcoholic fatty liver disease activity scores (NAS) had improved in 18 of 20 biopsied patients (90%), with a median decrease of 3 points (range, 1-4 points). Magnetic resonance elastography showed that fibrosis had improved by 1.5 stages in half of patients (10 of 20). “Other than postprocedural pain (in 5% of patients), no serious adverse events were reported,” Fateh Bazerbachi, MD, of Massachusetts General Hospital in Boston, and associates wrote in Clinical Gastroenterology and Hepatology.
Nonalcoholic fatty liver disease affects approximately 70% of obese adults and half of obese children, meaning that tens of millions of individuals are affected in the United States alone. Lifestyle changes rarely induce more than 10% body weight loss, the threshold for “meaningful improvement in NASH,” and bariatric surgery is not recommended for managing mild or moderate obesity and often is not desired by patients who do qualify, the researchers noted. “Endoscopic bariatric therapies are garnering more attention as potential strategies to address these shortcomings in obesity care and its comorbidities [, but] their influences on the driving and prognostic parameters of NAFLD remain unclear.”
In all, 81% of the study participants were women, with a mean age of 54 years and an average body mass index (BMI) of 44 kg/m2. At baseline, more than half had NAS scores of 4 or 5 and histologic fibrosis scores of 2 or 3. Baseline hemoglobin A1c levels averaged 7.4% (range, 5.1%-11.1%) and 29% of patients had impaired glucose tolerance. After receiving endoscopic ultrasound (EUS)–guided core liver biopsies, patients received an endoscopically placed fluid-filled intragastric balloon (Orbera, Apollo Endosurgery, Austin, Tex.). The balloon was removed 6 months later and magnetic resonance elastography and a second core biopsy were performed. One patient did not receive an exit biopsy (because of starting antithrombotic therapy) and thus was excluded from the final analysis.
Of 20 patients, 16 (80%) had at least a two-point improvement in NAS at 6 months, and half had NAS scores of less than 2, indicating remission of NASH. Three of 20 patients (15%) showed improvements in mild fibrosis, 12 showed no change, and 5 showed worsening. Patients lost an average of 11.7% of body weight (standard deviation, 7.7%; P = .01), BMI dropped by a mean of 5.2 (SD, 0.75; P = .01) and A1c fell by an average of 1.3% (SD, 0.5%; P = .02). Waist circumference also decreased significantly (mean, –14.4 cm; SD, –2.2 cm; P = .001), as did hip circumference, fasting glucose, AST, ALT, and AST-to-platelet ratio index. “Percent total body weight loss did not correlate with reductions in NAS or fibrosis,” the researchers noted.
Together, these findings suggest that intragastric balloon placement “may allow a reversal in the natural history of NAFLD and NASH, despite the short duration of the intervention,” they concluded. “The logistics of IGB [intragastric balloon] placement will enable accurate risk stratification of these patients in a safe and reproducible manner, obviating the need for additional investigations, and clarifying the real risk of patients afflicted with NAFLD.”
Apollo Endosurgery provided intragastric balloons, and Medtronic provided SharkCore needles. The senior author and two coinvestigators disclosed ties to Apollo Endosurgery, Medtronic, Metamodix, Boston Scientific, Cairn Diagnostics, Aspire Bariatrics, Johnson and Johnson, AstraZeneca, Genfit, Gila Therapeutics, and several other companies. The other investigators reported having no conflicts of interest.
SOURCE: Bazerbachi F et al. Clin Gastroenterol Hepatol. 2020 Apr 30. doi: 10.1016/j.cgh.2020.04.068.
Endoscopically placed intragastric balloons were safe and effective for managing nonalcoholic fatty liver disease (NAFLD), according to the findings of an open-label, prospective study of 21 patients.
Six months after balloon placement, nonalcoholic fatty liver disease activity scores (NAS) had improved in 18 of 20 biopsied patients (90%), with a median decrease of 3 points (range, 1-4 points). Magnetic resonance elastography showed that fibrosis had improved by 1.5 stages in half of patients (10 of 20). “Other than postprocedural pain (in 5% of patients), no serious adverse events were reported,” Fateh Bazerbachi, MD, of Massachusetts General Hospital in Boston, and associates wrote in Clinical Gastroenterology and Hepatology.
Nonalcoholic fatty liver disease affects approximately 70% of obese adults and half of obese children, meaning that tens of millions of individuals are affected in the United States alone. Lifestyle changes rarely induce more than 10% body weight loss, the threshold for “meaningful improvement in NASH,” and bariatric surgery is not recommended for managing mild or moderate obesity and often is not desired by patients who do qualify, the researchers noted. “Endoscopic bariatric therapies are garnering more attention as potential strategies to address these shortcomings in obesity care and its comorbidities [, but] their influences on the driving and prognostic parameters of NAFLD remain unclear.”
In all, 81% of the study participants were women, with a mean age of 54 years and an average body mass index (BMI) of 44 kg/m2. At baseline, more than half had NAS scores of 4 or 5 and histologic fibrosis scores of 2 or 3. Baseline hemoglobin A1c levels averaged 7.4% (range, 5.1%-11.1%) and 29% of patients had impaired glucose tolerance. After receiving endoscopic ultrasound (EUS)–guided core liver biopsies, patients received an endoscopically placed fluid-filled intragastric balloon (Orbera, Apollo Endosurgery, Austin, Tex.). The balloon was removed 6 months later and magnetic resonance elastography and a second core biopsy were performed. One patient did not receive an exit biopsy (because of starting antithrombotic therapy) and thus was excluded from the final analysis.
Of 20 patients, 16 (80%) had at least a two-point improvement in NAS at 6 months, and half had NAS scores of less than 2, indicating remission of NASH. Three of 20 patients (15%) showed improvements in mild fibrosis, 12 showed no change, and 5 showed worsening. Patients lost an average of 11.7% of body weight (standard deviation, 7.7%; P = .01), BMI dropped by a mean of 5.2 (SD, 0.75; P = .01) and A1c fell by an average of 1.3% (SD, 0.5%; P = .02). Waist circumference also decreased significantly (mean, –14.4 cm; SD, –2.2 cm; P = .001), as did hip circumference, fasting glucose, AST, ALT, and AST-to-platelet ratio index. “Percent total body weight loss did not correlate with reductions in NAS or fibrosis,” the researchers noted.
Together, these findings suggest that intragastric balloon placement “may allow a reversal in the natural history of NAFLD and NASH, despite the short duration of the intervention,” they concluded. “The logistics of IGB [intragastric balloon] placement will enable accurate risk stratification of these patients in a safe and reproducible manner, obviating the need for additional investigations, and clarifying the real risk of patients afflicted with NAFLD.”
Apollo Endosurgery provided intragastric balloons, and Medtronic provided SharkCore needles. The senior author and two coinvestigators disclosed ties to Apollo Endosurgery, Medtronic, Metamodix, Boston Scientific, Cairn Diagnostics, Aspire Bariatrics, Johnson and Johnson, AstraZeneca, Genfit, Gila Therapeutics, and several other companies. The other investigators reported having no conflicts of interest.
SOURCE: Bazerbachi F et al. Clin Gastroenterol Hepatol. 2020 Apr 30. doi: 10.1016/j.cgh.2020.04.068.
FROM CLINICAL GASTROENTEROLOGY AND HEPATOLOGY
Prioritize COVID-19 vaccination in both types of diabetes, say docs
The risk for increased COVID-19 severity in people with type 1 diabetes appears similar to that of type 2 diabetes, contrary to some official advice from the Centers for Disease Control and Prevention. The new finding indicates that people with both types should be priority for receiving a vaccine, investigators say.
The study is the first to prospectively evaluate both inpatients and outpatients and to examine COVID-19 severity factors in addition to death in people with type 1 and type 2 diabetes separately, and was published online Dec. 2 in Diabetes Care.
Among the patients, who were seen at Vanderbilt University Medical Center in Nashville, Tenn., between March and August of 2020, those with both type 1 and type 2 diabetes had between a three- and fourfold greater risk for COVID-19 hospitalization and greater illness severity compared with people without diabetes after adjustments for age, race, and a number of other risk factors.
This finding is important since as of Dec. 1, 2020, the CDC has classified the diabetes types differently in terms of underlying medical conditions that increase the risk for severe COVID-19.
Adults of any age with type 2 diabetes are considered “at increased risk of severe illness” from the virus that causes COVID-19 whereas the CDC says those with type 1 “might be at an increased risk.”
Lead author of the new paper Justin M. Gregory, MD, said in an interview: “I think this needs revision based on the current evidence. I think the data presented in our study and that of Barron et al. in Lancet Endocrinology 2020 indicate the need to place type 1 diabetes at parity with type 2 diabetes.
“These studies indicate both conditions carry an adjusted odds ratio of three to four when compared with people without diabetes for hospitalization, illness severity, and mortality,” he stressed.
Vaccines look promising for patients with diabetes
There were no phase 3 vaccine data available for the vaccine at the time that Dr. Gregory, of the Ian M. Burr Division of Pediatric Endocrinology and Diabetes, Vanderbilt University, Nashville, Tenn., and colleagues were writing their manuscript in late summer, so the article does not mention this.
But now, Dr. Gregory said, “Based on the initial press releases from Pfizer and Moderna, I am now optimistic that these vaccines might mitigate the excess morbidity and mortality from COVID-19 experienced by patients with diabetes.
“I am eager to see what we learn on December 10 and 17 [the scheduled dates for the meetings of the Food and Drug Administration’s Vaccines and Related Biological Products Advisory Committee to review the Pfizer and Moderna vaccines, respectively].”
But with the winter pandemic surge in the meantime, “Our investigation suggests that as COVID-19 hospitalizations rise, patients with both type 1 and 2 diabetes will comprise a disproportionately higher number of those admissions and, once hospitalized, demonstrate a greater degree of illness severity,” he and his colleagues said.
“In light of these data, we call on our colleagues to emphasize the importance of social distancing measures and hand hygiene, with particular emphasis on patients with diabetes, including those in the most vulnerable communities whom our study affirms will face the most severe impact.”
After adjustments, excess severity risk similar for both diabetes types
The new study data came from electronic health records at Vanderbilt University Medical Center, comprising 137 primary care, urgent care, and hospital facilities where patients were tested for SARS-CoV-2 regardless of the reason for their visit.
Between March 17 and August 7, 2020, 6,451 patients tested positive for COVID-19. Of those, 273 had type 2 diabetes and 40 had type 1 diabetes.
Children younger than 18 years accounted for 20% of those with type 1 diabetes and 9.4% of those without diabetes, but none of the type 2 group. The group with type 2 diabetes was considerably older than the type 1 diabetes and no-diabetes groups, 58 years versus 37 and 33 years, respectively.
Before adjustment for baseline characteristics that differed between groups, patients with type 1 diabetes appeared to have a risk for hospitalization and greater illness severity that was intermediate between the group with no diabetes and the group with type 2 diabetes, the researchers said.
But after adjustment for age, race, sex, hypertension, smoking, and body mass index, people with type 1 diabetes had odds ratios of 3.90 for hospitalization and 3.35 for greater illness severity, which was similar to risk in type 2 diabetes (3.36 and 3.42, respectively), compared to those without diabetes.
Deep dive explores COVID-19 severity risk factors in type 1 diabetes
The investigators then conducted a detailed chart review for 37 of the 40 patients with type 1 diabetes and phone surveys with 15 of them.
The majority (28) had not been hospitalized, and only one was hospitalized for diabetic ketoacidosis (DKA) within 14 days of positive SARS-CoV-2 testing.
This contrasts with a report from the T1D Exchange, in which nearly half of 33 patients with type 1 diabetes and COVID-19 had been hospitalized with DKA. The reason for the discrepancy may be that more severe patients would more likely be referred to the T1D Exchange Registry, Dr. Gregory and colleagues hypothesized.
Clinical factors associated with COVID-19 severity (P < .05) in their study included a prior hypertension diagnosis, higher hemoglobin A1c, at least one prior DKA admission in the past year, and not using a continuous glucose monitor (CGM).
Hospitalizations were twice as likely and illness severity nearly twice as great among those with type 1 diabetes who were Black versus White. Just 8% of those with private insurance were hospitalized, compared with 60% of those with public insurance and 67% with no insurance (P = .001).
“Whereas previous reports have indicated proportionally higher rates of hospitalizations from COVID-19 among Black patients and those with public insurance, this study is the first to show a similar finding in the population with type 1 diabetes,” Dr. Gregory and colleagues wrote.
Only 9% of patients using a CGM were hospitalized versus 47% who used blood glucose meters (P < .016). Similarly, hospitalizations occurred in 6% using an insulin pump versus 33% using multiple daily injections (P < .085).
“Our analysis cannot exclude the possibility that greater amounts of diabetes technology use are a surrogate for higher socioeconomic status,” they noted.
This research was supported by the National Institute of Diabetes and Digestive and Kidney Diseases, JDRF, and the Appleby Foundation. The authors have reported no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
The risk for increased COVID-19 severity in people with type 1 diabetes appears similar to that of type 2 diabetes, contrary to some official advice from the Centers for Disease Control and Prevention. The new finding indicates that people with both types should be priority for receiving a vaccine, investigators say.
The study is the first to prospectively evaluate both inpatients and outpatients and to examine COVID-19 severity factors in addition to death in people with type 1 and type 2 diabetes separately, and was published online Dec. 2 in Diabetes Care.
Among the patients, who were seen at Vanderbilt University Medical Center in Nashville, Tenn., between March and August of 2020, those with both type 1 and type 2 diabetes had between a three- and fourfold greater risk for COVID-19 hospitalization and greater illness severity compared with people without diabetes after adjustments for age, race, and a number of other risk factors.
This finding is important since as of Dec. 1, 2020, the CDC has classified the diabetes types differently in terms of underlying medical conditions that increase the risk for severe COVID-19.
Adults of any age with type 2 diabetes are considered “at increased risk of severe illness” from the virus that causes COVID-19 whereas the CDC says those with type 1 “might be at an increased risk.”
Lead author of the new paper Justin M. Gregory, MD, said in an interview: “I think this needs revision based on the current evidence. I think the data presented in our study and that of Barron et al. in Lancet Endocrinology 2020 indicate the need to place type 1 diabetes at parity with type 2 diabetes.
“These studies indicate both conditions carry an adjusted odds ratio of three to four when compared with people without diabetes for hospitalization, illness severity, and mortality,” he stressed.
Vaccines look promising for patients with diabetes
There were no phase 3 vaccine data available for the vaccine at the time that Dr. Gregory, of the Ian M. Burr Division of Pediatric Endocrinology and Diabetes, Vanderbilt University, Nashville, Tenn., and colleagues were writing their manuscript in late summer, so the article does not mention this.
But now, Dr. Gregory said, “Based on the initial press releases from Pfizer and Moderna, I am now optimistic that these vaccines might mitigate the excess morbidity and mortality from COVID-19 experienced by patients with diabetes.
“I am eager to see what we learn on December 10 and 17 [the scheduled dates for the meetings of the Food and Drug Administration’s Vaccines and Related Biological Products Advisory Committee to review the Pfizer and Moderna vaccines, respectively].”
But with the winter pandemic surge in the meantime, “Our investigation suggests that as COVID-19 hospitalizations rise, patients with both type 1 and 2 diabetes will comprise a disproportionately higher number of those admissions and, once hospitalized, demonstrate a greater degree of illness severity,” he and his colleagues said.
“In light of these data, we call on our colleagues to emphasize the importance of social distancing measures and hand hygiene, with particular emphasis on patients with diabetes, including those in the most vulnerable communities whom our study affirms will face the most severe impact.”
After adjustments, excess severity risk similar for both diabetes types
The new study data came from electronic health records at Vanderbilt University Medical Center, comprising 137 primary care, urgent care, and hospital facilities where patients were tested for SARS-CoV-2 regardless of the reason for their visit.
Between March 17 and August 7, 2020, 6,451 patients tested positive for COVID-19. Of those, 273 had type 2 diabetes and 40 had type 1 diabetes.
Children younger than 18 years accounted for 20% of those with type 1 diabetes and 9.4% of those without diabetes, but none of the type 2 group. The group with type 2 diabetes was considerably older than the type 1 diabetes and no-diabetes groups, 58 years versus 37 and 33 years, respectively.
Before adjustment for baseline characteristics that differed between groups, patients with type 1 diabetes appeared to have a risk for hospitalization and greater illness severity that was intermediate between the group with no diabetes and the group with type 2 diabetes, the researchers said.
But after adjustment for age, race, sex, hypertension, smoking, and body mass index, people with type 1 diabetes had odds ratios of 3.90 for hospitalization and 3.35 for greater illness severity, which was similar to risk in type 2 diabetes (3.36 and 3.42, respectively), compared to those without diabetes.
Deep dive explores COVID-19 severity risk factors in type 1 diabetes
The investigators then conducted a detailed chart review for 37 of the 40 patients with type 1 diabetes and phone surveys with 15 of them.
The majority (28) had not been hospitalized, and only one was hospitalized for diabetic ketoacidosis (DKA) within 14 days of positive SARS-CoV-2 testing.
This contrasts with a report from the T1D Exchange, in which nearly half of 33 patients with type 1 diabetes and COVID-19 had been hospitalized with DKA. The reason for the discrepancy may be that more severe patients would more likely be referred to the T1D Exchange Registry, Dr. Gregory and colleagues hypothesized.
Clinical factors associated with COVID-19 severity (P < .05) in their study included a prior hypertension diagnosis, higher hemoglobin A1c, at least one prior DKA admission in the past year, and not using a continuous glucose monitor (CGM).
Hospitalizations were twice as likely and illness severity nearly twice as great among those with type 1 diabetes who were Black versus White. Just 8% of those with private insurance were hospitalized, compared with 60% of those with public insurance and 67% with no insurance (P = .001).
“Whereas previous reports have indicated proportionally higher rates of hospitalizations from COVID-19 among Black patients and those with public insurance, this study is the first to show a similar finding in the population with type 1 diabetes,” Dr. Gregory and colleagues wrote.
Only 9% of patients using a CGM were hospitalized versus 47% who used blood glucose meters (P < .016). Similarly, hospitalizations occurred in 6% using an insulin pump versus 33% using multiple daily injections (P < .085).
“Our analysis cannot exclude the possibility that greater amounts of diabetes technology use are a surrogate for higher socioeconomic status,” they noted.
This research was supported by the National Institute of Diabetes and Digestive and Kidney Diseases, JDRF, and the Appleby Foundation. The authors have reported no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
The risk for increased COVID-19 severity in people with type 1 diabetes appears similar to that of type 2 diabetes, contrary to some official advice from the Centers for Disease Control and Prevention. The new finding indicates that people with both types should be priority for receiving a vaccine, investigators say.
The study is the first to prospectively evaluate both inpatients and outpatients and to examine COVID-19 severity factors in addition to death in people with type 1 and type 2 diabetes separately, and was published online Dec. 2 in Diabetes Care.
Among the patients, who were seen at Vanderbilt University Medical Center in Nashville, Tenn., between March and August of 2020, those with both type 1 and type 2 diabetes had between a three- and fourfold greater risk for COVID-19 hospitalization and greater illness severity compared with people without diabetes after adjustments for age, race, and a number of other risk factors.
This finding is important since as of Dec. 1, 2020, the CDC has classified the diabetes types differently in terms of underlying medical conditions that increase the risk for severe COVID-19.
Adults of any age with type 2 diabetes are considered “at increased risk of severe illness” from the virus that causes COVID-19 whereas the CDC says those with type 1 “might be at an increased risk.”
Lead author of the new paper Justin M. Gregory, MD, said in an interview: “I think this needs revision based on the current evidence. I think the data presented in our study and that of Barron et al. in Lancet Endocrinology 2020 indicate the need to place type 1 diabetes at parity with type 2 diabetes.
“These studies indicate both conditions carry an adjusted odds ratio of three to four when compared with people without diabetes for hospitalization, illness severity, and mortality,” he stressed.
Vaccines look promising for patients with diabetes
There were no phase 3 vaccine data available for the vaccine at the time that Dr. Gregory, of the Ian M. Burr Division of Pediatric Endocrinology and Diabetes, Vanderbilt University, Nashville, Tenn., and colleagues were writing their manuscript in late summer, so the article does not mention this.
But now, Dr. Gregory said, “Based on the initial press releases from Pfizer and Moderna, I am now optimistic that these vaccines might mitigate the excess morbidity and mortality from COVID-19 experienced by patients with diabetes.
“I am eager to see what we learn on December 10 and 17 [the scheduled dates for the meetings of the Food and Drug Administration’s Vaccines and Related Biological Products Advisory Committee to review the Pfizer and Moderna vaccines, respectively].”
But with the winter pandemic surge in the meantime, “Our investigation suggests that as COVID-19 hospitalizations rise, patients with both type 1 and 2 diabetes will comprise a disproportionately higher number of those admissions and, once hospitalized, demonstrate a greater degree of illness severity,” he and his colleagues said.
“In light of these data, we call on our colleagues to emphasize the importance of social distancing measures and hand hygiene, with particular emphasis on patients with diabetes, including those in the most vulnerable communities whom our study affirms will face the most severe impact.”
After adjustments, excess severity risk similar for both diabetes types
The new study data came from electronic health records at Vanderbilt University Medical Center, comprising 137 primary care, urgent care, and hospital facilities where patients were tested for SARS-CoV-2 regardless of the reason for their visit.
Between March 17 and August 7, 2020, 6,451 patients tested positive for COVID-19. Of those, 273 had type 2 diabetes and 40 had type 1 diabetes.
Children younger than 18 years accounted for 20% of those with type 1 diabetes and 9.4% of those without diabetes, but none of the type 2 group. The group with type 2 diabetes was considerably older than the type 1 diabetes and no-diabetes groups, 58 years versus 37 and 33 years, respectively.
Before adjustment for baseline characteristics that differed between groups, patients with type 1 diabetes appeared to have a risk for hospitalization and greater illness severity that was intermediate between the group with no diabetes and the group with type 2 diabetes, the researchers said.
But after adjustment for age, race, sex, hypertension, smoking, and body mass index, people with type 1 diabetes had odds ratios of 3.90 for hospitalization and 3.35 for greater illness severity, which was similar to risk in type 2 diabetes (3.36 and 3.42, respectively), compared to those without diabetes.
Deep dive explores COVID-19 severity risk factors in type 1 diabetes
The investigators then conducted a detailed chart review for 37 of the 40 patients with type 1 diabetes and phone surveys with 15 of them.
The majority (28) had not been hospitalized, and only one was hospitalized for diabetic ketoacidosis (DKA) within 14 days of positive SARS-CoV-2 testing.
This contrasts with a report from the T1D Exchange, in which nearly half of 33 patients with type 1 diabetes and COVID-19 had been hospitalized with DKA. The reason for the discrepancy may be that more severe patients would more likely be referred to the T1D Exchange Registry, Dr. Gregory and colleagues hypothesized.
Clinical factors associated with COVID-19 severity (P < .05) in their study included a prior hypertension diagnosis, higher hemoglobin A1c, at least one prior DKA admission in the past year, and not using a continuous glucose monitor (CGM).
Hospitalizations were twice as likely and illness severity nearly twice as great among those with type 1 diabetes who were Black versus White. Just 8% of those with private insurance were hospitalized, compared with 60% of those with public insurance and 67% with no insurance (P = .001).
“Whereas previous reports have indicated proportionally higher rates of hospitalizations from COVID-19 among Black patients and those with public insurance, this study is the first to show a similar finding in the population with type 1 diabetes,” Dr. Gregory and colleagues wrote.
Only 9% of patients using a CGM were hospitalized versus 47% who used blood glucose meters (P < .016). Similarly, hospitalizations occurred in 6% using an insulin pump versus 33% using multiple daily injections (P < .085).
“Our analysis cannot exclude the possibility that greater amounts of diabetes technology use are a surrogate for higher socioeconomic status,” they noted.
This research was supported by the National Institute of Diabetes and Digestive and Kidney Diseases, JDRF, and the Appleby Foundation. The authors have reported no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
A multicenter trial of vena cava filters in severely injured patients
Background: Venous thromboembolism and pulmonary embolism are common after major trauma. Anticoagulant prophylaxis usually is not considered because of the increased risk of bleeding. Despite the limited data, many trauma centers use inferior vena cava (IVC) filters as a primary means to prevent pulmonary embolism.
Study design: Randomized, controlled, and multicenter trial.
Setting: Four tertiary hospitals in Australia.
Synopsis: 240 major trauma patients were randomly assigned to receive either IVC filter or no IVC filter within 72 hours after admission. The primary endpoint was a composite of 90-day mortality or symptomatic pulmonary embolism confirmed on imaging. There was no difference in the rate of composite outcome in those with IVC filter, compared with those with no IVC filter.
Bottom line: After major trauma, early prophylactic placement of IVC filter did not reduce the 90-day mortality or incidence of symptomatic pulmonary embolism.
Citation: Ho KM et al. A multicenter trial of vena cava filters in severely injured patients. N Engl J Med. 2019 Jul 25;381:328-37.
Dr. Hoque Sharmy is a hospitalist and assistant professor of medicine in the division of hospital medicine at St. Louis University School of Medicine.
Background: Venous thromboembolism and pulmonary embolism are common after major trauma. Anticoagulant prophylaxis usually is not considered because of the increased risk of bleeding. Despite the limited data, many trauma centers use inferior vena cava (IVC) filters as a primary means to prevent pulmonary embolism.
Study design: Randomized, controlled, and multicenter trial.
Setting: Four tertiary hospitals in Australia.
Synopsis: 240 major trauma patients were randomly assigned to receive either IVC filter or no IVC filter within 72 hours after admission. The primary endpoint was a composite of 90-day mortality or symptomatic pulmonary embolism confirmed on imaging. There was no difference in the rate of composite outcome in those with IVC filter, compared with those with no IVC filter.
Bottom line: After major trauma, early prophylactic placement of IVC filter did not reduce the 90-day mortality or incidence of symptomatic pulmonary embolism.
Citation: Ho KM et al. A multicenter trial of vena cava filters in severely injured patients. N Engl J Med. 2019 Jul 25;381:328-37.
Dr. Hoque Sharmy is a hospitalist and assistant professor of medicine in the division of hospital medicine at St. Louis University School of Medicine.
Background: Venous thromboembolism and pulmonary embolism are common after major trauma. Anticoagulant prophylaxis usually is not considered because of the increased risk of bleeding. Despite the limited data, many trauma centers use inferior vena cava (IVC) filters as a primary means to prevent pulmonary embolism.
Study design: Randomized, controlled, and multicenter trial.
Setting: Four tertiary hospitals in Australia.
Synopsis: 240 major trauma patients were randomly assigned to receive either IVC filter or no IVC filter within 72 hours after admission. The primary endpoint was a composite of 90-day mortality or symptomatic pulmonary embolism confirmed on imaging. There was no difference in the rate of composite outcome in those with IVC filter, compared with those with no IVC filter.
Bottom line: After major trauma, early prophylactic placement of IVC filter did not reduce the 90-day mortality or incidence of symptomatic pulmonary embolism.
Citation: Ho KM et al. A multicenter trial of vena cava filters in severely injured patients. N Engl J Med. 2019 Jul 25;381:328-37.
Dr. Hoque Sharmy is a hospitalist and assistant professor of medicine in the division of hospital medicine at St. Louis University School of Medicine.
Five-minute SC injection of daratumumab in RRMM
Data from the Apollo study provide proof for the subcutaneous administration (SC) of daratumumab (Darzalex Faspro) in combination with pomalidomide (Pomalyst) and dexamethasone (Pd) for patients with relapsed or refractory multiple myeloma (RRMM).
The SC formulation of daratumumab (with hyaluronidase) was approved in the United States in May, and is administered by injection into the abdomen over 3-5 minutes. Previously the drug was available only as an intravenous infusion.
“The appeal of subcutaneous daratumumab is the 5 minutes it needs for administering, cutting down considerable on ‘chair/clinic’ time. Intravenous daratumumab is given over several hours,” said Joseph Mikhael, MD, MEd, chief medical officer of the International Myeloma Foundation. He also highlighted the low rates of infusion reactions seen with the subcutaneous daratumumab triplet.
“In the COVID era the subcutaneous route may be the way to go,” he said in an interview.
“This is an effective combination with a predictable safety profile that allows for the use of SC daratumumab along with oral pomalidomide and dexamethasone for patients who have received at least one prior line of therapy that included lenalidomide [Revlimid] and a proteasome inhibitor,” commented lead author Meletios A. Dimopoulos, MD, of the National and Kapodistrian University of Athens.
The triplet combination was associated with a 37% reduced risk for progression or death, compared with the two-drug combination of pomalidomide and dexamethasone.
He presented the results from the Apollo trial at the annual meeting of the American Society of Hematology.
Treatment landscape of RRMM
Dr. Mikhael, who is also professor in the applied cancer research and drug discovery division at the Translational Genomics Research Institute, Phoenix, provided his insights into Apollo as well as how this triplet fits into the treatment landscape of RRMM.
Daratumumab is approved for use in both RRMM and newly diagnosed MM, either alone or in combination with standard-of-care regimens. The drug already has eight specific indications for the intravenous formulation, and five indications for the SC formulation of daratumumab, Dr. Mikhael noted. The Apollo study “will likely provide the subcutaneous approval for the daratumumab triplet in MM.”
According to Dr. Mikhael, the triplet of daratumumab with pomalidomide and dexamethasone is the most commonly used combination at first relapse, and this phase 3 study provides confirmatory evidence for its initial approval. The initial approval for intravenous daratumumab and Pd was based on a phase 1b study, he noted.
“The Apollo study is the first randomized trial comparing the triplet of D-Pd to Pd,” Noopur Raje, MD, of the Massachusetts General Hospital, Boston, said in an interview. She explained that the majority of patients included in Apollo were refractory to lenalidomide, which is the patient population typically seen at the time of first relapse. “This regimen will be adopted at either first or second relapse in the majority of patients,” Dr. Raje said.
“In keeping with strategy in MM, we use the best triplet first and do not save the best for last,” Dr. Mikhael said. The triplet of the proteasome inhibitor bortezomib (Velcade), lenalidomide, and dexamethasone is used in first-line MM. “Most patients meet the criteria for using D-Pd at first relapse,” he added, noting that all patients in the study have received a proteasome inhibitor and lenalidomide as first-line therapy and had relapsed with or were refractory to these agents.
“The short administration time and significantly low rates of infusion-site reactions are two important considerations for using this triplet with the subcutaneous formulation of daratumumab [at first relapse],” he said.
In the treatment landscape of MM, the triplet of isatuximab (Sarclisa), pomalidomide, and dexamethasone has recently been approved for RRMM based on data from the ICARIA study. Isatuximab and daratumumab are both CD38-directed antibodies. Dr. Mikhael pointed out that the datasets from ICARIA and Apollo with respect to progression-free survival (PFS) and hazard ratios overlapped and were remarkably similar. However, daratumumab now has an advantage in being available as an SC formulation.
The landscape of MM treatment has been changing rapidly in recent years, and more changes may be afoot. Dr. Mikhael suggested that the quartet of daratumumab, bortezomib, lenalidomide, and dexamethasone is likely to move into the first-line setting for MM based on data from the GRIFFIN study (trial update in Abstract 3243), and then the choice of drugs to use in first relapse would also change.
Apollo study details
Apollo was an open-label, phase 3 study that randomly assigned patients with RRMM to receive SC daratumumab in combination with pomalidomide and low-dose dexamethasone (D-Pd; n = 151) or the two-drug combination of Pd (n = 153).
Approximately 80% of the patients were refractory to lenalidomide and half were refractory to a proteasome inhibitor.
Median duration of SC daratumumab administration was 5 minutes. Median duration of study treatment was longer for patients on D-Pd (11.5 months vs. 6.6 months for Pd).
For the primary endpoint, at a median follow up of 16.9 months, median PFS was 12.4 months for patients receiving D-Pd and 6.9 months for those receiving Pd. One-year PFS was 52% for patients receiving the triplet combination and 35% for those receiving Pd. Treatment effect was generally consistent across subgroups examined, Dr. Dimopoulos reported.
Depth of response was significantly higher for patients on D-Pd. Stringent complete remission or CR was seen in 25% of patients on D-Pd versus 4% on Pd. Overall response rate was 69% for patients on D-Pd and 45% for patients on Pd alone (P < .0001). Minimal residual disease negativity was more than four times higher with D-Pd (9% vs. 2% for Pd; P = .0102).
The safety profile of D-Pd was consistent with the known safety profile of SC daratumumab and Pd. Infusion-site reactions were grade 1-2 and occurred in 5% of patients; in addition, only grade 1 injection-site reactions were seen and occurred in 2% of patients. The most serious treatment-emergent adverse events in patients on D-Pd were pneumonia (15% vs. 8% for Pd) and lower respiratory tract infection (12% vs. 9% for Pd). Incidence of secondary primary malignancy was 2% for each group.
Apollo results were ‘no surprise’
“These results are of no surprise and further support the current practice of using a three-drug combination in the relapsed setting,” Henry Fung, MD, chair of the department of bone marrow transplant and cellular therapies at Fox Chase Cancer Center, Philadelphia, said in an interview.
Although Dr. Fung agreed that the triplet of a proteasome inhibitor, an immunomodulating drug such as lenalidomide, and the steroid dexamethasone is becoming the standard of care for newly diagnosed MM, D-Pd should be considered an excellent option for patients who have limited choices in the relapsed/refractory setting.
However, he said that the median PFS of 12.4 months for patients receiving D-Pd after a median of two prior regimens is not satisfactory.
“The impact on the natural history of the disease will be limited and the duration of responses decline with each treatment regimen, and the true impact on the disease will be an effective frontline strategy.” Dr. Fung said. “This will not be a practice-changing trial. We need to find out which three-drug regimen works best and what biomarkers can predict the response to individual regimen.”
Dr. Dimopoulos reported receiving honoraria from Beigene, Bristol-Myers Squibb, Amgen, Takeda, Celgene, and Janssen. Dr. Mikhael reported receiving honoraria from Amgen, GlaxoSmithKline, Janssen, Karyopharm, Sanofi, Takeda; consulting with Celgene; and receiving research funding from Celgene and Sanofi. Dr. Fung is on the speakers’ bureau of Apollo and receives honoraria from Jansen Oncology and Celgene/Bristol-Myers Squibb. Dr. Raje is a consultant for Bristol-Myers Squibb and Janssen.
A version of this article originally appeared on Medscape.com.
Data from the Apollo study provide proof for the subcutaneous administration (SC) of daratumumab (Darzalex Faspro) in combination with pomalidomide (Pomalyst) and dexamethasone (Pd) for patients with relapsed or refractory multiple myeloma (RRMM).
The SC formulation of daratumumab (with hyaluronidase) was approved in the United States in May, and is administered by injection into the abdomen over 3-5 minutes. Previously the drug was available only as an intravenous infusion.
“The appeal of subcutaneous daratumumab is the 5 minutes it needs for administering, cutting down considerable on ‘chair/clinic’ time. Intravenous daratumumab is given over several hours,” said Joseph Mikhael, MD, MEd, chief medical officer of the International Myeloma Foundation. He also highlighted the low rates of infusion reactions seen with the subcutaneous daratumumab triplet.
“In the COVID era the subcutaneous route may be the way to go,” he said in an interview.
“This is an effective combination with a predictable safety profile that allows for the use of SC daratumumab along with oral pomalidomide and dexamethasone for patients who have received at least one prior line of therapy that included lenalidomide [Revlimid] and a proteasome inhibitor,” commented lead author Meletios A. Dimopoulos, MD, of the National and Kapodistrian University of Athens.
The triplet combination was associated with a 37% reduced risk for progression or death, compared with the two-drug combination of pomalidomide and dexamethasone.
He presented the results from the Apollo trial at the annual meeting of the American Society of Hematology.
Treatment landscape of RRMM
Dr. Mikhael, who is also professor in the applied cancer research and drug discovery division at the Translational Genomics Research Institute, Phoenix, provided his insights into Apollo as well as how this triplet fits into the treatment landscape of RRMM.
Daratumumab is approved for use in both RRMM and newly diagnosed MM, either alone or in combination with standard-of-care regimens. The drug already has eight specific indications for the intravenous formulation, and five indications for the SC formulation of daratumumab, Dr. Mikhael noted. The Apollo study “will likely provide the subcutaneous approval for the daratumumab triplet in MM.”
According to Dr. Mikhael, the triplet of daratumumab with pomalidomide and dexamethasone is the most commonly used combination at first relapse, and this phase 3 study provides confirmatory evidence for its initial approval. The initial approval for intravenous daratumumab and Pd was based on a phase 1b study, he noted.
“The Apollo study is the first randomized trial comparing the triplet of D-Pd to Pd,” Noopur Raje, MD, of the Massachusetts General Hospital, Boston, said in an interview. She explained that the majority of patients included in Apollo were refractory to lenalidomide, which is the patient population typically seen at the time of first relapse. “This regimen will be adopted at either first or second relapse in the majority of patients,” Dr. Raje said.
“In keeping with strategy in MM, we use the best triplet first and do not save the best for last,” Dr. Mikhael said. The triplet of the proteasome inhibitor bortezomib (Velcade), lenalidomide, and dexamethasone is used in first-line MM. “Most patients meet the criteria for using D-Pd at first relapse,” he added, noting that all patients in the study have received a proteasome inhibitor and lenalidomide as first-line therapy and had relapsed with or were refractory to these agents.
“The short administration time and significantly low rates of infusion-site reactions are two important considerations for using this triplet with the subcutaneous formulation of daratumumab [at first relapse],” he said.
In the treatment landscape of MM, the triplet of isatuximab (Sarclisa), pomalidomide, and dexamethasone has recently been approved for RRMM based on data from the ICARIA study. Isatuximab and daratumumab are both CD38-directed antibodies. Dr. Mikhael pointed out that the datasets from ICARIA and Apollo with respect to progression-free survival (PFS) and hazard ratios overlapped and were remarkably similar. However, daratumumab now has an advantage in being available as an SC formulation.
The landscape of MM treatment has been changing rapidly in recent years, and more changes may be afoot. Dr. Mikhael suggested that the quartet of daratumumab, bortezomib, lenalidomide, and dexamethasone is likely to move into the first-line setting for MM based on data from the GRIFFIN study (trial update in Abstract 3243), and then the choice of drugs to use in first relapse would also change.
Apollo study details
Apollo was an open-label, phase 3 study that randomly assigned patients with RRMM to receive SC daratumumab in combination with pomalidomide and low-dose dexamethasone (D-Pd; n = 151) or the two-drug combination of Pd (n = 153).
Approximately 80% of the patients were refractory to lenalidomide and half were refractory to a proteasome inhibitor.
Median duration of SC daratumumab administration was 5 minutes. Median duration of study treatment was longer for patients on D-Pd (11.5 months vs. 6.6 months for Pd).
For the primary endpoint, at a median follow up of 16.9 months, median PFS was 12.4 months for patients receiving D-Pd and 6.9 months for those receiving Pd. One-year PFS was 52% for patients receiving the triplet combination and 35% for those receiving Pd. Treatment effect was generally consistent across subgroups examined, Dr. Dimopoulos reported.
Depth of response was significantly higher for patients on D-Pd. Stringent complete remission or CR was seen in 25% of patients on D-Pd versus 4% on Pd. Overall response rate was 69% for patients on D-Pd and 45% for patients on Pd alone (P < .0001). Minimal residual disease negativity was more than four times higher with D-Pd (9% vs. 2% for Pd; P = .0102).
The safety profile of D-Pd was consistent with the known safety profile of SC daratumumab and Pd. Infusion-site reactions were grade 1-2 and occurred in 5% of patients; in addition, only grade 1 injection-site reactions were seen and occurred in 2% of patients. The most serious treatment-emergent adverse events in patients on D-Pd were pneumonia (15% vs. 8% for Pd) and lower respiratory tract infection (12% vs. 9% for Pd). Incidence of secondary primary malignancy was 2% for each group.
Apollo results were ‘no surprise’
“These results are of no surprise and further support the current practice of using a three-drug combination in the relapsed setting,” Henry Fung, MD, chair of the department of bone marrow transplant and cellular therapies at Fox Chase Cancer Center, Philadelphia, said in an interview.
Although Dr. Fung agreed that the triplet of a proteasome inhibitor, an immunomodulating drug such as lenalidomide, and the steroid dexamethasone is becoming the standard of care for newly diagnosed MM, D-Pd should be considered an excellent option for patients who have limited choices in the relapsed/refractory setting.
However, he said that the median PFS of 12.4 months for patients receiving D-Pd after a median of two prior regimens is not satisfactory.
“The impact on the natural history of the disease will be limited and the duration of responses decline with each treatment regimen, and the true impact on the disease will be an effective frontline strategy.” Dr. Fung said. “This will not be a practice-changing trial. We need to find out which three-drug regimen works best and what biomarkers can predict the response to individual regimen.”
Dr. Dimopoulos reported receiving honoraria from Beigene, Bristol-Myers Squibb, Amgen, Takeda, Celgene, and Janssen. Dr. Mikhael reported receiving honoraria from Amgen, GlaxoSmithKline, Janssen, Karyopharm, Sanofi, Takeda; consulting with Celgene; and receiving research funding from Celgene and Sanofi. Dr. Fung is on the speakers’ bureau of Apollo and receives honoraria from Jansen Oncology and Celgene/Bristol-Myers Squibb. Dr. Raje is a consultant for Bristol-Myers Squibb and Janssen.
A version of this article originally appeared on Medscape.com.
Data from the Apollo study provide proof for the subcutaneous administration (SC) of daratumumab (Darzalex Faspro) in combination with pomalidomide (Pomalyst) and dexamethasone (Pd) for patients with relapsed or refractory multiple myeloma (RRMM).
The SC formulation of daratumumab (with hyaluronidase) was approved in the United States in May, and is administered by injection into the abdomen over 3-5 minutes. Previously the drug was available only as an intravenous infusion.
“The appeal of subcutaneous daratumumab is the 5 minutes it needs for administering, cutting down considerable on ‘chair/clinic’ time. Intravenous daratumumab is given over several hours,” said Joseph Mikhael, MD, MEd, chief medical officer of the International Myeloma Foundation. He also highlighted the low rates of infusion reactions seen with the subcutaneous daratumumab triplet.
“In the COVID era the subcutaneous route may be the way to go,” he said in an interview.
“This is an effective combination with a predictable safety profile that allows for the use of SC daratumumab along with oral pomalidomide and dexamethasone for patients who have received at least one prior line of therapy that included lenalidomide [Revlimid] and a proteasome inhibitor,” commented lead author Meletios A. Dimopoulos, MD, of the National and Kapodistrian University of Athens.
The triplet combination was associated with a 37% reduced risk for progression or death, compared with the two-drug combination of pomalidomide and dexamethasone.
He presented the results from the Apollo trial at the annual meeting of the American Society of Hematology.
Treatment landscape of RRMM
Dr. Mikhael, who is also professor in the applied cancer research and drug discovery division at the Translational Genomics Research Institute, Phoenix, provided his insights into Apollo as well as how this triplet fits into the treatment landscape of RRMM.
Daratumumab is approved for use in both RRMM and newly diagnosed MM, either alone or in combination with standard-of-care regimens. The drug already has eight specific indications for the intravenous formulation, and five indications for the SC formulation of daratumumab, Dr. Mikhael noted. The Apollo study “will likely provide the subcutaneous approval for the daratumumab triplet in MM.”
According to Dr. Mikhael, the triplet of daratumumab with pomalidomide and dexamethasone is the most commonly used combination at first relapse, and this phase 3 study provides confirmatory evidence for its initial approval. The initial approval for intravenous daratumumab and Pd was based on a phase 1b study, he noted.
“The Apollo study is the first randomized trial comparing the triplet of D-Pd to Pd,” Noopur Raje, MD, of the Massachusetts General Hospital, Boston, said in an interview. She explained that the majority of patients included in Apollo were refractory to lenalidomide, which is the patient population typically seen at the time of first relapse. “This regimen will be adopted at either first or second relapse in the majority of patients,” Dr. Raje said.
“In keeping with strategy in MM, we use the best triplet first and do not save the best for last,” Dr. Mikhael said. The triplet of the proteasome inhibitor bortezomib (Velcade), lenalidomide, and dexamethasone is used in first-line MM. “Most patients meet the criteria for using D-Pd at first relapse,” he added, noting that all patients in the study have received a proteasome inhibitor and lenalidomide as first-line therapy and had relapsed with or were refractory to these agents.
“The short administration time and significantly low rates of infusion-site reactions are two important considerations for using this triplet with the subcutaneous formulation of daratumumab [at first relapse],” he said.
In the treatment landscape of MM, the triplet of isatuximab (Sarclisa), pomalidomide, and dexamethasone has recently been approved for RRMM based on data from the ICARIA study. Isatuximab and daratumumab are both CD38-directed antibodies. Dr. Mikhael pointed out that the datasets from ICARIA and Apollo with respect to progression-free survival (PFS) and hazard ratios overlapped and were remarkably similar. However, daratumumab now has an advantage in being available as an SC formulation.
The landscape of MM treatment has been changing rapidly in recent years, and more changes may be afoot. Dr. Mikhael suggested that the quartet of daratumumab, bortezomib, lenalidomide, and dexamethasone is likely to move into the first-line setting for MM based on data from the GRIFFIN study (trial update in Abstract 3243), and then the choice of drugs to use in first relapse would also change.
Apollo study details
Apollo was an open-label, phase 3 study that randomly assigned patients with RRMM to receive SC daratumumab in combination with pomalidomide and low-dose dexamethasone (D-Pd; n = 151) or the two-drug combination of Pd (n = 153).
Approximately 80% of the patients were refractory to lenalidomide and half were refractory to a proteasome inhibitor.
Median duration of SC daratumumab administration was 5 minutes. Median duration of study treatment was longer for patients on D-Pd (11.5 months vs. 6.6 months for Pd).
For the primary endpoint, at a median follow up of 16.9 months, median PFS was 12.4 months for patients receiving D-Pd and 6.9 months for those receiving Pd. One-year PFS was 52% for patients receiving the triplet combination and 35% for those receiving Pd. Treatment effect was generally consistent across subgroups examined, Dr. Dimopoulos reported.
Depth of response was significantly higher for patients on D-Pd. Stringent complete remission or CR was seen in 25% of patients on D-Pd versus 4% on Pd. Overall response rate was 69% for patients on D-Pd and 45% for patients on Pd alone (P < .0001). Minimal residual disease negativity was more than four times higher with D-Pd (9% vs. 2% for Pd; P = .0102).
The safety profile of D-Pd was consistent with the known safety profile of SC daratumumab and Pd. Infusion-site reactions were grade 1-2 and occurred in 5% of patients; in addition, only grade 1 injection-site reactions were seen and occurred in 2% of patients. The most serious treatment-emergent adverse events in patients on D-Pd were pneumonia (15% vs. 8% for Pd) and lower respiratory tract infection (12% vs. 9% for Pd). Incidence of secondary primary malignancy was 2% for each group.
Apollo results were ‘no surprise’
“These results are of no surprise and further support the current practice of using a three-drug combination in the relapsed setting,” Henry Fung, MD, chair of the department of bone marrow transplant and cellular therapies at Fox Chase Cancer Center, Philadelphia, said in an interview.
Although Dr. Fung agreed that the triplet of a proteasome inhibitor, an immunomodulating drug such as lenalidomide, and the steroid dexamethasone is becoming the standard of care for newly diagnosed MM, D-Pd should be considered an excellent option for patients who have limited choices in the relapsed/refractory setting.
However, he said that the median PFS of 12.4 months for patients receiving D-Pd after a median of two prior regimens is not satisfactory.
“The impact on the natural history of the disease will be limited and the duration of responses decline with each treatment regimen, and the true impact on the disease will be an effective frontline strategy.” Dr. Fung said. “This will not be a practice-changing trial. We need to find out which three-drug regimen works best and what biomarkers can predict the response to individual regimen.”
Dr. Dimopoulos reported receiving honoraria from Beigene, Bristol-Myers Squibb, Amgen, Takeda, Celgene, and Janssen. Dr. Mikhael reported receiving honoraria from Amgen, GlaxoSmithKline, Janssen, Karyopharm, Sanofi, Takeda; consulting with Celgene; and receiving research funding from Celgene and Sanofi. Dr. Fung is on the speakers’ bureau of Apollo and receives honoraria from Jansen Oncology and Celgene/Bristol-Myers Squibb. Dr. Raje is a consultant for Bristol-Myers Squibb and Janssen.
A version of this article originally appeared on Medscape.com.
FDA safety alert: Face masks with metal can burn during MRI
After a patient’s face was burned in the outline of a mask worn during a 3-Tesla MRI neck scan, the US Food and Drug Administration (FDA) cautioned that face masks containing metal can heat to unsafe temperatures during scanning.
Clinicians have known for years to ask patients to remove all metal jewelry and other objects prior to an MRI. The widespread wearing of face masks during the COVID-19 pandemic, however, adds one more consideration to the list.
The FDA’s December 7 safety communication applies to surgical and nonsurgical face masks and respirators.
The injury risk relates to rapid heating of metal components. Many face masks contain a nose wire or metal clip that helps the product conform to the face. Some masks contain metal nanoparticles, while others feature antimicrobial coatings with silver or copper. Each of these products should be avoided during MRI scanning. Also watch out for staples on headbands, the FDA warned.
If the metal content of a face mask is unknown, the FDA suggests providing the patient with a facial covering that is known not to contain any metal.
Robert E. Watson Jr, MD, PhD, chair of the American College of Radiology (ACR) Committee on MR Safety, agreed. He recommended that facilities “provide patients with masks known to be MRI-safe and not permit patient-owned masks in the MRI.”
Watson suggested this strategy at a time when face masks are required.
“COVID-19 safety protocols require that patients wear masks when being scanned, to decrease infection risk to MRI staff, decrease risk of contaminating the MRI scanner, and to protect themselves from infection,” he told Medscape Medical News. “Any conducting metal that enters the MRI machine is at risk of heating due to the radiofrequency fields inherent to image generation.”
Adverse events related to the metal components of a face mask should be reported to the FDA using the MedWatch voluntary reporting form. In addition, healthcare providers subject to the FDA user facility reporting requirements should follow procedures at their facilities to report such events.
This article first appeared on Medscape.com.
After a patient’s face was burned in the outline of a mask worn during a 3-Tesla MRI neck scan, the US Food and Drug Administration (FDA) cautioned that face masks containing metal can heat to unsafe temperatures during scanning.
Clinicians have known for years to ask patients to remove all metal jewelry and other objects prior to an MRI. The widespread wearing of face masks during the COVID-19 pandemic, however, adds one more consideration to the list.
The FDA’s December 7 safety communication applies to surgical and nonsurgical face masks and respirators.
The injury risk relates to rapid heating of metal components. Many face masks contain a nose wire or metal clip that helps the product conform to the face. Some masks contain metal nanoparticles, while others feature antimicrobial coatings with silver or copper. Each of these products should be avoided during MRI scanning. Also watch out for staples on headbands, the FDA warned.
If the metal content of a face mask is unknown, the FDA suggests providing the patient with a facial covering that is known not to contain any metal.
Robert E. Watson Jr, MD, PhD, chair of the American College of Radiology (ACR) Committee on MR Safety, agreed. He recommended that facilities “provide patients with masks known to be MRI-safe and not permit patient-owned masks in the MRI.”
Watson suggested this strategy at a time when face masks are required.
“COVID-19 safety protocols require that patients wear masks when being scanned, to decrease infection risk to MRI staff, decrease risk of contaminating the MRI scanner, and to protect themselves from infection,” he told Medscape Medical News. “Any conducting metal that enters the MRI machine is at risk of heating due to the radiofrequency fields inherent to image generation.”
Adverse events related to the metal components of a face mask should be reported to the FDA using the MedWatch voluntary reporting form. In addition, healthcare providers subject to the FDA user facility reporting requirements should follow procedures at their facilities to report such events.
This article first appeared on Medscape.com.
After a patient’s face was burned in the outline of a mask worn during a 3-Tesla MRI neck scan, the US Food and Drug Administration (FDA) cautioned that face masks containing metal can heat to unsafe temperatures during scanning.
Clinicians have known for years to ask patients to remove all metal jewelry and other objects prior to an MRI. The widespread wearing of face masks during the COVID-19 pandemic, however, adds one more consideration to the list.
The FDA’s December 7 safety communication applies to surgical and nonsurgical face masks and respirators.
The injury risk relates to rapid heating of metal components. Many face masks contain a nose wire or metal clip that helps the product conform to the face. Some masks contain metal nanoparticles, while others feature antimicrobial coatings with silver or copper. Each of these products should be avoided during MRI scanning. Also watch out for staples on headbands, the FDA warned.
If the metal content of a face mask is unknown, the FDA suggests providing the patient with a facial covering that is known not to contain any metal.
Robert E. Watson Jr, MD, PhD, chair of the American College of Radiology (ACR) Committee on MR Safety, agreed. He recommended that facilities “provide patients with masks known to be MRI-safe and not permit patient-owned masks in the MRI.”
Watson suggested this strategy at a time when face masks are required.
“COVID-19 safety protocols require that patients wear masks when being scanned, to decrease infection risk to MRI staff, decrease risk of contaminating the MRI scanner, and to protect themselves from infection,” he told Medscape Medical News. “Any conducting metal that enters the MRI machine is at risk of heating due to the radiofrequency fields inherent to image generation.”
Adverse events related to the metal components of a face mask should be reported to the FDA using the MedWatch voluntary reporting form. In addition, healthcare providers subject to the FDA user facility reporting requirements should follow procedures at their facilities to report such events.
This article first appeared on Medscape.com.
Advent of biologics extended life expectancy but also expenses for RA patients
The widespread use of biologics extended life expectancy but also increased medical costs for adults with RA, based on insurance claims data from nearly 30,000 cases.
“With the advancement of treatment in recent decades, the mortality seems to decrease, while medical expenditures increase,” but previous studies estimating the life-years lost because of RA have shown large variations in results, wrote Ying-Ming Chiu, MD, PhD, of China Medical University, Taichung, Taiwan, and colleagues.
“Estimating long-term or lifetime costs could provide an overall figure of the future impact on the health care system after disease occurrence, and would be useful for cost-effectiveness analysis,” they added.
In a study published in Arthritis & Rheumatology, the researchers identified 29,352 new cases of RA in Taiwan between 2003 and 2016, after the introduction of biologics in Taiwan in 2003. They estimate survival using an algorithm with matched controls and used the survival rates to calculate monthly and lifetime health care expenses.
Overall, the average estimated life expectancy after a diagnosis of RA was 26.3 years, and the average lifetime cost was $72,953 (USD). The average life expectancy was 23.4 years for women and 21.6 years for men. The average lifetime cost was higher for women than for men ($73,112 vs. $63,557), but the annual costs were similar for women and men ($3,123 vs. $2,942). However, “the older the age of diagnosis of RA, the higher the average annual cost for treating RA,” regardless of gender, the researchers noted.
Despite the reduced mortality during the study period, the researchers also identified some loss of life expectancy among RA patients, compared with the general population. The average loss of life expectancy was nearly 5 years during the 14-year study period. The loss of life expectancy ranged from 2 to 13 years (average 9.7 years) for women with RA and from 2 to 8 years (average 4.1 years) for men with RA, compared with those without RA after controlling for age, gender, and year of diagnosis.
The study findings were limited by several factors including the lack of data on quality of life and functional disability, possible underestimation of life expectancy because of delayed RA diagnosis, and limited accuracy on follow-up of younger patients, the researchers noted.
However, the results support evidence from previous studies of an overall increase in life expectancy after the introduction of biologics, with increased expenses that should be monitored for cost-effectiveness, they concluded. More research is needed to determine the effect of biologics on functional disability, quality of life, and cost-effectiveness in a way that also incorporates productivity loss and the need for social services such as long-term care in order to inform decision-making for RA treatment.
The study was supported by the Ministry of Science and Technology, Taiwan, and China Medical University Hospital. The researchers had no financial conflicts to disclose.
SOURCE: Chiu Y-M et al. Arthritis Rheumatol. 2020 Dec 8. doi: 10.1002/ART.41597.
The widespread use of biologics extended life expectancy but also increased medical costs for adults with RA, based on insurance claims data from nearly 30,000 cases.
“With the advancement of treatment in recent decades, the mortality seems to decrease, while medical expenditures increase,” but previous studies estimating the life-years lost because of RA have shown large variations in results, wrote Ying-Ming Chiu, MD, PhD, of China Medical University, Taichung, Taiwan, and colleagues.
“Estimating long-term or lifetime costs could provide an overall figure of the future impact on the health care system after disease occurrence, and would be useful for cost-effectiveness analysis,” they added.
In a study published in Arthritis & Rheumatology, the researchers identified 29,352 new cases of RA in Taiwan between 2003 and 2016, after the introduction of biologics in Taiwan in 2003. They estimate survival using an algorithm with matched controls and used the survival rates to calculate monthly and lifetime health care expenses.
Overall, the average estimated life expectancy after a diagnosis of RA was 26.3 years, and the average lifetime cost was $72,953 (USD). The average life expectancy was 23.4 years for women and 21.6 years for men. The average lifetime cost was higher for women than for men ($73,112 vs. $63,557), but the annual costs were similar for women and men ($3,123 vs. $2,942). However, “the older the age of diagnosis of RA, the higher the average annual cost for treating RA,” regardless of gender, the researchers noted.
Despite the reduced mortality during the study period, the researchers also identified some loss of life expectancy among RA patients, compared with the general population. The average loss of life expectancy was nearly 5 years during the 14-year study period. The loss of life expectancy ranged from 2 to 13 years (average 9.7 years) for women with RA and from 2 to 8 years (average 4.1 years) for men with RA, compared with those without RA after controlling for age, gender, and year of diagnosis.
The study findings were limited by several factors including the lack of data on quality of life and functional disability, possible underestimation of life expectancy because of delayed RA diagnosis, and limited accuracy on follow-up of younger patients, the researchers noted.
However, the results support evidence from previous studies of an overall increase in life expectancy after the introduction of biologics, with increased expenses that should be monitored for cost-effectiveness, they concluded. More research is needed to determine the effect of biologics on functional disability, quality of life, and cost-effectiveness in a way that also incorporates productivity loss and the need for social services such as long-term care in order to inform decision-making for RA treatment.
The study was supported by the Ministry of Science and Technology, Taiwan, and China Medical University Hospital. The researchers had no financial conflicts to disclose.
SOURCE: Chiu Y-M et al. Arthritis Rheumatol. 2020 Dec 8. doi: 10.1002/ART.41597.
The widespread use of biologics extended life expectancy but also increased medical costs for adults with RA, based on insurance claims data from nearly 30,000 cases.
“With the advancement of treatment in recent decades, the mortality seems to decrease, while medical expenditures increase,” but previous studies estimating the life-years lost because of RA have shown large variations in results, wrote Ying-Ming Chiu, MD, PhD, of China Medical University, Taichung, Taiwan, and colleagues.
“Estimating long-term or lifetime costs could provide an overall figure of the future impact on the health care system after disease occurrence, and would be useful for cost-effectiveness analysis,” they added.
In a study published in Arthritis & Rheumatology, the researchers identified 29,352 new cases of RA in Taiwan between 2003 and 2016, after the introduction of biologics in Taiwan in 2003. They estimate survival using an algorithm with matched controls and used the survival rates to calculate monthly and lifetime health care expenses.
Overall, the average estimated life expectancy after a diagnosis of RA was 26.3 years, and the average lifetime cost was $72,953 (USD). The average life expectancy was 23.4 years for women and 21.6 years for men. The average lifetime cost was higher for women than for men ($73,112 vs. $63,557), but the annual costs were similar for women and men ($3,123 vs. $2,942). However, “the older the age of diagnosis of RA, the higher the average annual cost for treating RA,” regardless of gender, the researchers noted.
Despite the reduced mortality during the study period, the researchers also identified some loss of life expectancy among RA patients, compared with the general population. The average loss of life expectancy was nearly 5 years during the 14-year study period. The loss of life expectancy ranged from 2 to 13 years (average 9.7 years) for women with RA and from 2 to 8 years (average 4.1 years) for men with RA, compared with those without RA after controlling for age, gender, and year of diagnosis.
The study findings were limited by several factors including the lack of data on quality of life and functional disability, possible underestimation of life expectancy because of delayed RA diagnosis, and limited accuracy on follow-up of younger patients, the researchers noted.
However, the results support evidence from previous studies of an overall increase in life expectancy after the introduction of biologics, with increased expenses that should be monitored for cost-effectiveness, they concluded. More research is needed to determine the effect of biologics on functional disability, quality of life, and cost-effectiveness in a way that also incorporates productivity loss and the need for social services such as long-term care in order to inform decision-making for RA treatment.
The study was supported by the Ministry of Science and Technology, Taiwan, and China Medical University Hospital. The researchers had no financial conflicts to disclose.
SOURCE: Chiu Y-M et al. Arthritis Rheumatol. 2020 Dec 8. doi: 10.1002/ART.41597.
FROM ARTHRITIS & RHEUMATOLOGY
Expert spotlights three emerging technologies for dermatology practice
New technologies being developed at the Wellman Center for Photomedicine, Boston, that .
During a virtual course on laser and aesthetic skin therapy, Lilit Garibyan, MD, PhD, discussed findings from a swine study published online in January 2020 that used an injectable physiologic ice slurry for the nonsurgical removal of fat, a technology that could give CoolSculpting a run for its money. “It does lead to more efficient and effective cryolipolysis,” said Dr. Garibyan, the lead study author who is an assistant professor of dermatology at Harvard University, and director of The Magic Wand Initiative at the Wellman Center for Photomedicine at Massachusetts General Hospital, Boston. “The treatment of fat tissue with ice slurry injection can be done in less than 1 minute, as opposed to an hour of cooling with CoolSculpting. In addition, because cooling is delivered directly into target tissue, it is more effective.”
For the study, she and her colleagues at the Wellman Center injected the slurry – a mix of ice, saline, and glycol – into the flanks of swine and followed them for up to 8 weeks. They used ultrasound imaging to show the location of the fat loss and to quantify it. The researchers observed about 40%-50% loss of fat in the treated area, compared with a 60% fat gain in swine who served as controls. “This is because the pig is growing and gaining weight, so the fat is increasing,” she explained.
Gross histologic images also showed fat loss in the subcutaneous fat tissue of treated swine, but not in controls. “When we quantified this loss, there was about a 60% loss of fat after a single injection of ice slurry in the subcutaneous fat,” Dr. Garibyan said during the meeting, which was sponsored by Harvard Medical School, Massachusetts General Hospital, and the Wellman Center for Photomedicine. “On histology there was loss of fat in the subcutaneous area and it was replaced by new collagen. No damage to surrounding skin or muscle tissue was seen.”
She characterized the approach as “a minimally invasive and novel method of adipose tissue removal. It’s very simple, because it’s just a simple injection, and it’s very efficient and effective in fat removal. Most importantly, it can target any anatomic site accessible with a needle.”
Human studies are currently underway.
Another emerging technology Dr. Garibyan discussed is a novel controlled skin cooling device for the treatment of benign pigmented lesions. The approach, known as Cryomodulation, was invented by R. Rox Anderson, MD, Dieter Manstein, MD, PhD, and Henry HL Chan, MD, at Massachusetts General Hospital, Boston, and is being commercialized by R2 Technologies. It delivers precise controlled and titratable freezing of benign pigmented lesions without damage to the epidermal barrier. It has been cleared by the Food and Drug Administration, and R2 Technologies plans to launch its first commercial product in the United States in December 2020.
The handpiece of the device, which is placed on top of the skin, provides localized and controlled freezing to targeted benign pigmented lesions. “The cold, or the freeze, is delivered to where the melanocytes reside,” Dr. Garibyan said. “The ice nucleation essentially pauses melanin production. As cell turnover occurs, cells that are melanin-free migrate upward and renew freshly healthy skin. So, melanocyte function is still preserved but there is no destruction to the epidermal barrier. This technology is totally color blind, and there is no persistent inflammatory response.”
After this treatment, histology reveals a reduction of epidermal melanin without destruction of melanocytes. The treatment impairs melanocyte transfer, but not the melanocytes. “Clinically, that is seen as lightening of the skin,” she said. More than 550 patients have been treated with Cryomodulation to demonstrate its safety and effectiveness, described in a study published in 2019, and an ASLMS e-poster.
The final technology Dr. Garibyan discussed is a novel device for removing dermal pigment with a highly focused laser beam. “The problem with current lasers is that the maximum absorption of energy happens at the dermal/epidermal junction,” she said. “This not only increases the risk of epidermal injury, especially in skin of color, but it also leaves very little energy to reach the pigmented target tissue or cells. In addition, there is scattering in the skin, which also reduces the amount of fluence or energy that can reach the target depth, therefore reducing the efficacy of treatment with currently available laser.”
The investigative focused laser beam with high-speed scanning creates a large differential between the fluence at the surface and the fluence at the target, which improves safety. “It’s able to deliver enhanced energy to the target,” she said. “Therefore it’s more effective than destroying the target pigmented cells. There is no injury outside of the focal point, so it offers improved safety, efficacy, and spatial selectivity. The end result on histology is a selective destruction of the pigmented cells, which are typically melanophages.”
Dr. Garibyan predicted that this device will be an ideal therapy for postinflammatory hyperpigmentation and for melasma, “as no effective therapies are available for those conditions.”
She disclosed that she has received royalties/inventorship assigned to MGH. She holds equity in, is a consultant to, and is a member of the scientific advisory board of Brixton Biosciences. She is a consultant to Vyome Therapeutics, Blossom Innovations, Aegle Therapeutics, and ClearifiRx.
New technologies being developed at the Wellman Center for Photomedicine, Boston, that .
During a virtual course on laser and aesthetic skin therapy, Lilit Garibyan, MD, PhD, discussed findings from a swine study published online in January 2020 that used an injectable physiologic ice slurry for the nonsurgical removal of fat, a technology that could give CoolSculpting a run for its money. “It does lead to more efficient and effective cryolipolysis,” said Dr. Garibyan, the lead study author who is an assistant professor of dermatology at Harvard University, and director of The Magic Wand Initiative at the Wellman Center for Photomedicine at Massachusetts General Hospital, Boston. “The treatment of fat tissue with ice slurry injection can be done in less than 1 minute, as opposed to an hour of cooling with CoolSculpting. In addition, because cooling is delivered directly into target tissue, it is more effective.”
For the study, she and her colleagues at the Wellman Center injected the slurry – a mix of ice, saline, and glycol – into the flanks of swine and followed them for up to 8 weeks. They used ultrasound imaging to show the location of the fat loss and to quantify it. The researchers observed about 40%-50% loss of fat in the treated area, compared with a 60% fat gain in swine who served as controls. “This is because the pig is growing and gaining weight, so the fat is increasing,” she explained.
Gross histologic images also showed fat loss in the subcutaneous fat tissue of treated swine, but not in controls. “When we quantified this loss, there was about a 60% loss of fat after a single injection of ice slurry in the subcutaneous fat,” Dr. Garibyan said during the meeting, which was sponsored by Harvard Medical School, Massachusetts General Hospital, and the Wellman Center for Photomedicine. “On histology there was loss of fat in the subcutaneous area and it was replaced by new collagen. No damage to surrounding skin or muscle tissue was seen.”
She characterized the approach as “a minimally invasive and novel method of adipose tissue removal. It’s very simple, because it’s just a simple injection, and it’s very efficient and effective in fat removal. Most importantly, it can target any anatomic site accessible with a needle.”
Human studies are currently underway.
Another emerging technology Dr. Garibyan discussed is a novel controlled skin cooling device for the treatment of benign pigmented lesions. The approach, known as Cryomodulation, was invented by R. Rox Anderson, MD, Dieter Manstein, MD, PhD, and Henry HL Chan, MD, at Massachusetts General Hospital, Boston, and is being commercialized by R2 Technologies. It delivers precise controlled and titratable freezing of benign pigmented lesions without damage to the epidermal barrier. It has been cleared by the Food and Drug Administration, and R2 Technologies plans to launch its first commercial product in the United States in December 2020.
The handpiece of the device, which is placed on top of the skin, provides localized and controlled freezing to targeted benign pigmented lesions. “The cold, or the freeze, is delivered to where the melanocytes reside,” Dr. Garibyan said. “The ice nucleation essentially pauses melanin production. As cell turnover occurs, cells that are melanin-free migrate upward and renew freshly healthy skin. So, melanocyte function is still preserved but there is no destruction to the epidermal barrier. This technology is totally color blind, and there is no persistent inflammatory response.”
After this treatment, histology reveals a reduction of epidermal melanin without destruction of melanocytes. The treatment impairs melanocyte transfer, but not the melanocytes. “Clinically, that is seen as lightening of the skin,” she said. More than 550 patients have been treated with Cryomodulation to demonstrate its safety and effectiveness, described in a study published in 2019, and an ASLMS e-poster.
The final technology Dr. Garibyan discussed is a novel device for removing dermal pigment with a highly focused laser beam. “The problem with current lasers is that the maximum absorption of energy happens at the dermal/epidermal junction,” she said. “This not only increases the risk of epidermal injury, especially in skin of color, but it also leaves very little energy to reach the pigmented target tissue or cells. In addition, there is scattering in the skin, which also reduces the amount of fluence or energy that can reach the target depth, therefore reducing the efficacy of treatment with currently available laser.”
The investigative focused laser beam with high-speed scanning creates a large differential between the fluence at the surface and the fluence at the target, which improves safety. “It’s able to deliver enhanced energy to the target,” she said. “Therefore it’s more effective than destroying the target pigmented cells. There is no injury outside of the focal point, so it offers improved safety, efficacy, and spatial selectivity. The end result on histology is a selective destruction of the pigmented cells, which are typically melanophages.”
Dr. Garibyan predicted that this device will be an ideal therapy for postinflammatory hyperpigmentation and for melasma, “as no effective therapies are available for those conditions.”
She disclosed that she has received royalties/inventorship assigned to MGH. She holds equity in, is a consultant to, and is a member of the scientific advisory board of Brixton Biosciences. She is a consultant to Vyome Therapeutics, Blossom Innovations, Aegle Therapeutics, and ClearifiRx.
New technologies being developed at the Wellman Center for Photomedicine, Boston, that .
During a virtual course on laser and aesthetic skin therapy, Lilit Garibyan, MD, PhD, discussed findings from a swine study published online in January 2020 that used an injectable physiologic ice slurry for the nonsurgical removal of fat, a technology that could give CoolSculpting a run for its money. “It does lead to more efficient and effective cryolipolysis,” said Dr. Garibyan, the lead study author who is an assistant professor of dermatology at Harvard University, and director of The Magic Wand Initiative at the Wellman Center for Photomedicine at Massachusetts General Hospital, Boston. “The treatment of fat tissue with ice slurry injection can be done in less than 1 minute, as opposed to an hour of cooling with CoolSculpting. In addition, because cooling is delivered directly into target tissue, it is more effective.”
For the study, she and her colleagues at the Wellman Center injected the slurry – a mix of ice, saline, and glycol – into the flanks of swine and followed them for up to 8 weeks. They used ultrasound imaging to show the location of the fat loss and to quantify it. The researchers observed about 40%-50% loss of fat in the treated area, compared with a 60% fat gain in swine who served as controls. “This is because the pig is growing and gaining weight, so the fat is increasing,” she explained.
Gross histologic images also showed fat loss in the subcutaneous fat tissue of treated swine, but not in controls. “When we quantified this loss, there was about a 60% loss of fat after a single injection of ice slurry in the subcutaneous fat,” Dr. Garibyan said during the meeting, which was sponsored by Harvard Medical School, Massachusetts General Hospital, and the Wellman Center for Photomedicine. “On histology there was loss of fat in the subcutaneous area and it was replaced by new collagen. No damage to surrounding skin or muscle tissue was seen.”
She characterized the approach as “a minimally invasive and novel method of adipose tissue removal. It’s very simple, because it’s just a simple injection, and it’s very efficient and effective in fat removal. Most importantly, it can target any anatomic site accessible with a needle.”
Human studies are currently underway.
Another emerging technology Dr. Garibyan discussed is a novel controlled skin cooling device for the treatment of benign pigmented lesions. The approach, known as Cryomodulation, was invented by R. Rox Anderson, MD, Dieter Manstein, MD, PhD, and Henry HL Chan, MD, at Massachusetts General Hospital, Boston, and is being commercialized by R2 Technologies. It delivers precise controlled and titratable freezing of benign pigmented lesions without damage to the epidermal barrier. It has been cleared by the Food and Drug Administration, and R2 Technologies plans to launch its first commercial product in the United States in December 2020.
The handpiece of the device, which is placed on top of the skin, provides localized and controlled freezing to targeted benign pigmented lesions. “The cold, or the freeze, is delivered to where the melanocytes reside,” Dr. Garibyan said. “The ice nucleation essentially pauses melanin production. As cell turnover occurs, cells that are melanin-free migrate upward and renew freshly healthy skin. So, melanocyte function is still preserved but there is no destruction to the epidermal barrier. This technology is totally color blind, and there is no persistent inflammatory response.”
After this treatment, histology reveals a reduction of epidermal melanin without destruction of melanocytes. The treatment impairs melanocyte transfer, but not the melanocytes. “Clinically, that is seen as lightening of the skin,” she said. More than 550 patients have been treated with Cryomodulation to demonstrate its safety and effectiveness, described in a study published in 2019, and an ASLMS e-poster.
The final technology Dr. Garibyan discussed is a novel device for removing dermal pigment with a highly focused laser beam. “The problem with current lasers is that the maximum absorption of energy happens at the dermal/epidermal junction,” she said. “This not only increases the risk of epidermal injury, especially in skin of color, but it also leaves very little energy to reach the pigmented target tissue or cells. In addition, there is scattering in the skin, which also reduces the amount of fluence or energy that can reach the target depth, therefore reducing the efficacy of treatment with currently available laser.”
The investigative focused laser beam with high-speed scanning creates a large differential between the fluence at the surface and the fluence at the target, which improves safety. “It’s able to deliver enhanced energy to the target,” she said. “Therefore it’s more effective than destroying the target pigmented cells. There is no injury outside of the focal point, so it offers improved safety, efficacy, and spatial selectivity. The end result on histology is a selective destruction of the pigmented cells, which are typically melanophages.”
Dr. Garibyan predicted that this device will be an ideal therapy for postinflammatory hyperpigmentation and for melasma, “as no effective therapies are available for those conditions.”
She disclosed that she has received royalties/inventorship assigned to MGH. She holds equity in, is a consultant to, and is a member of the scientific advisory board of Brixton Biosciences. She is a consultant to Vyome Therapeutics, Blossom Innovations, Aegle Therapeutics, and ClearifiRx.
EXPERT ANALYSIS FROM A LASER & AESTHETIC SKIN THERAPY COURSE