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Liraglutide produced cardiometabolic benefits in patients with schizophrenia
SAN DIEGO – The glucagon-like peptide-1 (GLP-1) receptor agonist liraglutide significantly lessened glucose tolerance, glycemic control, and other cardiometabolic risk factors in overweight or obese prediabetic patients receiving clozapine or olanzapine for schizophrenia, according to the findings of a randomized, double-blind, placebo-controlled trial.
Liraglutide was generally well tolerated and conferred cardiometabolic benefits similar to those in past studies of patients who were not on antipsychotic therapy, said Louise Vedtofte, PhD, of the University of Copenhagen. After 16 weeks of treatment, a 75-gram oral glucose tolerance test showed that 2-hour plasma glucose levels were 23% lower with liraglutide compared with placebo (P less than .001), she said at the annual scientific sessions of the American Diabetes Association.
Liraglutide patients also lost an average of 5.2 kg more body weight, cut 4.1 cm more from their waist circumference, and were significantly more likely to normalize their fasting plasma glucose and hemoglobin A1c levels compared with the placebo group (P less than .001 for each comparison), she said. The report by Dr. Vedtofte and her associates was published in JAMA Psychiatry simultaneously with the presentation at the meeting (2017 June 10. doi: 10.1001/jamapsychiatry.2017.1220).
Antipsychotics are core therapies in schizophrenia spectrum disorders but also cause increased appetite, weight gain, and cardiometabolic disturbances, noted Dr. Vedtofte. About a third of patients with schizophrenia who receive antipsychotics develop metabolic syndrome, and some 15% go on to develop diabetes. Clozapine and olanzapine cause more weight gain than do other antipsychotics, but swapping either medication for a more weight-neutral alternative can threaten the well-being of patients with schizophrenia, she emphasized. “Olanzapine and clozapine are good for the patients’ mental health, but are detrimental for their somatic health.”
As a GLP-1 receptor agonist, liraglutide inhibits appetite and food intake, and the Food and Drug Administration has approved treatment at doses of 1.8 mg for type 2 diabetes and 3 mg once daily for obesity. To explore how liraglutide affects patients on antipsychotics, Dr. Vedtofte and her associates randomly assigned 103 adults with schizophrenia spectrum disorders from two clinical sites in Denmark to receive placebo or 0.6 mg liraglutide subcutaneously once daily, up-titrated by 0.6 mg weekly to a maximum dose of 1.8 mg. At baseline, all patients were receiving stable treatment with clozapine, olanzapine, or both; had a body mass index of at least 27 kg/m2; and were prediabetic, with fasting plasma glucose levels of 110 to 125 mg/dL, HbA1c levels of 6.1%-6.4%, or 2-hour plasma glucose levels of 140 mg/dL or higher during the 75-gram oral glucose tolerance test.[[{"fid":"198022","view_mode":"medstat_image_flush_right","attributes":{"alt":"Louise Vedtofte, PhD, of the University of Copenhagen","height":"220","width":"147","class":"media-element file-medstat-image-flush-right","data-delta":"1"},"fields":{"format":"medstat_image_flush_right","field_file_image_caption[und][0][value]":"Dr. Louise Vedtofte","field_file_image_credit[und][0][value]":"","field_file_image_caption[und][0][format]":"plain_text","field_file_image_credit[und][0][format]":"plain_text"},"type":"media","field_deltas":{"1":{"format":"medstat_image_flush_right","field_file_image_caption[und][0][value]":"Dr. Louise Vedtofte","field_file_image_credit[und][0][value]":""}},"link_text":false}]]
Fully 93% of patients completed the study. At week 16, glucose tolerance improved significantly in the liraglutide group (P less than .001) but not in the placebo group (P less than .001 for difference between groups) after the researchers controlled for age, sex, illness duration, BMI, Clinical Global Impressions Scale severity score, and antipsychotic treatment. Glucose tolerance normalized in 30 patients who received liraglutide (64%) compared with 8 in the placebo group (16%; P less than .001), Dr. Vedtofte said.
Besides its benefits to waist circumference and weight loss, liraglutide was associated with reductions in systolic blood pressure (average, 5 mm Hg; visceral fat, 0.25 kg; and low-density lipoprotein levels, 15 mg/dL). These changes occurred even though liraglutide did not significantly alter C-peptide or glucagon secretion in the multivariate analysis of glucose tolerance test results, Dr. Vedtofte said. “The rate of nausea was 62% in liraglutide patients and 32% with placebo, but nausea was transient and did not explain the weight loss in subgroup analyses,” she added.
Liraglutide did not alter clinical liver function, but treated patients experienced a small (1.3 U/L), statistically significant rise in amylase levels. Rates of other adverse events were similar between groups except that patients were more likely to experience orthostatic hypotension on liraglutide (8.2%) than on placebo (0%; P = .04). Treatment with liraglutide did not significantly increase the likelihood of serious somatic or psychiatric adverse events, but one patient died while on therapy. “This patient was a man in his 60s with longstanding schizophrenia who was admitted to the hospital with vomiting and diarrhea, and died 3 days later,” Dr. Vedtofte said. Autopsy did not reveal the cause of death, but the patients showed no change in mental status or other signs of adverse therapeutic effects, she added.
Novo Nordisk funded the study and provided liraglutide and placebo injections. Additional support came from Capital Region Psychiatry Research Group, the foundation of King Christian X of Denmark, and the Lundbeck Foundation. Dr. Vedtofte had no disclosures.
SAN DIEGO – The glucagon-like peptide-1 (GLP-1) receptor agonist liraglutide significantly lessened glucose tolerance, glycemic control, and other cardiometabolic risk factors in overweight or obese prediabetic patients receiving clozapine or olanzapine for schizophrenia, according to the findings of a randomized, double-blind, placebo-controlled trial.
Liraglutide was generally well tolerated and conferred cardiometabolic benefits similar to those in past studies of patients who were not on antipsychotic therapy, said Louise Vedtofte, PhD, of the University of Copenhagen. After 16 weeks of treatment, a 75-gram oral glucose tolerance test showed that 2-hour plasma glucose levels were 23% lower with liraglutide compared with placebo (P less than .001), she said at the annual scientific sessions of the American Diabetes Association.
Liraglutide patients also lost an average of 5.2 kg more body weight, cut 4.1 cm more from their waist circumference, and were significantly more likely to normalize their fasting plasma glucose and hemoglobin A1c levels compared with the placebo group (P less than .001 for each comparison), she said. The report by Dr. Vedtofte and her associates was published in JAMA Psychiatry simultaneously with the presentation at the meeting (2017 June 10. doi: 10.1001/jamapsychiatry.2017.1220).
Antipsychotics are core therapies in schizophrenia spectrum disorders but also cause increased appetite, weight gain, and cardiometabolic disturbances, noted Dr. Vedtofte. About a third of patients with schizophrenia who receive antipsychotics develop metabolic syndrome, and some 15% go on to develop diabetes. Clozapine and olanzapine cause more weight gain than do other antipsychotics, but swapping either medication for a more weight-neutral alternative can threaten the well-being of patients with schizophrenia, she emphasized. “Olanzapine and clozapine are good for the patients’ mental health, but are detrimental for their somatic health.”
As a GLP-1 receptor agonist, liraglutide inhibits appetite and food intake, and the Food and Drug Administration has approved treatment at doses of 1.8 mg for type 2 diabetes and 3 mg once daily for obesity. To explore how liraglutide affects patients on antipsychotics, Dr. Vedtofte and her associates randomly assigned 103 adults with schizophrenia spectrum disorders from two clinical sites in Denmark to receive placebo or 0.6 mg liraglutide subcutaneously once daily, up-titrated by 0.6 mg weekly to a maximum dose of 1.8 mg. At baseline, all patients were receiving stable treatment with clozapine, olanzapine, or both; had a body mass index of at least 27 kg/m2; and were prediabetic, with fasting plasma glucose levels of 110 to 125 mg/dL, HbA1c levels of 6.1%-6.4%, or 2-hour plasma glucose levels of 140 mg/dL or higher during the 75-gram oral glucose tolerance test.[[{"fid":"198022","view_mode":"medstat_image_flush_right","attributes":{"alt":"Louise Vedtofte, PhD, of the University of Copenhagen","height":"220","width":"147","class":"media-element file-medstat-image-flush-right","data-delta":"1"},"fields":{"format":"medstat_image_flush_right","field_file_image_caption[und][0][value]":"Dr. Louise Vedtofte","field_file_image_credit[und][0][value]":"","field_file_image_caption[und][0][format]":"plain_text","field_file_image_credit[und][0][format]":"plain_text"},"type":"media","field_deltas":{"1":{"format":"medstat_image_flush_right","field_file_image_caption[und][0][value]":"Dr. Louise Vedtofte","field_file_image_credit[und][0][value]":""}},"link_text":false}]]
Fully 93% of patients completed the study. At week 16, glucose tolerance improved significantly in the liraglutide group (P less than .001) but not in the placebo group (P less than .001 for difference between groups) after the researchers controlled for age, sex, illness duration, BMI, Clinical Global Impressions Scale severity score, and antipsychotic treatment. Glucose tolerance normalized in 30 patients who received liraglutide (64%) compared with 8 in the placebo group (16%; P less than .001), Dr. Vedtofte said.
Besides its benefits to waist circumference and weight loss, liraglutide was associated with reductions in systolic blood pressure (average, 5 mm Hg; visceral fat, 0.25 kg; and low-density lipoprotein levels, 15 mg/dL). These changes occurred even though liraglutide did not significantly alter C-peptide or glucagon secretion in the multivariate analysis of glucose tolerance test results, Dr. Vedtofte said. “The rate of nausea was 62% in liraglutide patients and 32% with placebo, but nausea was transient and did not explain the weight loss in subgroup analyses,” she added.
Liraglutide did not alter clinical liver function, but treated patients experienced a small (1.3 U/L), statistically significant rise in amylase levels. Rates of other adverse events were similar between groups except that patients were more likely to experience orthostatic hypotension on liraglutide (8.2%) than on placebo (0%; P = .04). Treatment with liraglutide did not significantly increase the likelihood of serious somatic or psychiatric adverse events, but one patient died while on therapy. “This patient was a man in his 60s with longstanding schizophrenia who was admitted to the hospital with vomiting and diarrhea, and died 3 days later,” Dr. Vedtofte said. Autopsy did not reveal the cause of death, but the patients showed no change in mental status or other signs of adverse therapeutic effects, she added.
Novo Nordisk funded the study and provided liraglutide and placebo injections. Additional support came from Capital Region Psychiatry Research Group, the foundation of King Christian X of Denmark, and the Lundbeck Foundation. Dr. Vedtofte had no disclosures.
SAN DIEGO – The glucagon-like peptide-1 (GLP-1) receptor agonist liraglutide significantly lessened glucose tolerance, glycemic control, and other cardiometabolic risk factors in overweight or obese prediabetic patients receiving clozapine or olanzapine for schizophrenia, according to the findings of a randomized, double-blind, placebo-controlled trial.
Liraglutide was generally well tolerated and conferred cardiometabolic benefits similar to those in past studies of patients who were not on antipsychotic therapy, said Louise Vedtofte, PhD, of the University of Copenhagen. After 16 weeks of treatment, a 75-gram oral glucose tolerance test showed that 2-hour plasma glucose levels were 23% lower with liraglutide compared with placebo (P less than .001), she said at the annual scientific sessions of the American Diabetes Association.
Liraglutide patients also lost an average of 5.2 kg more body weight, cut 4.1 cm more from their waist circumference, and were significantly more likely to normalize their fasting plasma glucose and hemoglobin A1c levels compared with the placebo group (P less than .001 for each comparison), she said. The report by Dr. Vedtofte and her associates was published in JAMA Psychiatry simultaneously with the presentation at the meeting (2017 June 10. doi: 10.1001/jamapsychiatry.2017.1220).
Antipsychotics are core therapies in schizophrenia spectrum disorders but also cause increased appetite, weight gain, and cardiometabolic disturbances, noted Dr. Vedtofte. About a third of patients with schizophrenia who receive antipsychotics develop metabolic syndrome, and some 15% go on to develop diabetes. Clozapine and olanzapine cause more weight gain than do other antipsychotics, but swapping either medication for a more weight-neutral alternative can threaten the well-being of patients with schizophrenia, she emphasized. “Olanzapine and clozapine are good for the patients’ mental health, but are detrimental for their somatic health.”
As a GLP-1 receptor agonist, liraglutide inhibits appetite and food intake, and the Food and Drug Administration has approved treatment at doses of 1.8 mg for type 2 diabetes and 3 mg once daily for obesity. To explore how liraglutide affects patients on antipsychotics, Dr. Vedtofte and her associates randomly assigned 103 adults with schizophrenia spectrum disorders from two clinical sites in Denmark to receive placebo or 0.6 mg liraglutide subcutaneously once daily, up-titrated by 0.6 mg weekly to a maximum dose of 1.8 mg. At baseline, all patients were receiving stable treatment with clozapine, olanzapine, or both; had a body mass index of at least 27 kg/m2; and were prediabetic, with fasting plasma glucose levels of 110 to 125 mg/dL, HbA1c levels of 6.1%-6.4%, or 2-hour plasma glucose levels of 140 mg/dL or higher during the 75-gram oral glucose tolerance test.[[{"fid":"198022","view_mode":"medstat_image_flush_right","attributes":{"alt":"Louise Vedtofte, PhD, of the University of Copenhagen","height":"220","width":"147","class":"media-element file-medstat-image-flush-right","data-delta":"1"},"fields":{"format":"medstat_image_flush_right","field_file_image_caption[und][0][value]":"Dr. Louise Vedtofte","field_file_image_credit[und][0][value]":"","field_file_image_caption[und][0][format]":"plain_text","field_file_image_credit[und][0][format]":"plain_text"},"type":"media","field_deltas":{"1":{"format":"medstat_image_flush_right","field_file_image_caption[und][0][value]":"Dr. Louise Vedtofte","field_file_image_credit[und][0][value]":""}},"link_text":false}]]
Fully 93% of patients completed the study. At week 16, glucose tolerance improved significantly in the liraglutide group (P less than .001) but not in the placebo group (P less than .001 for difference between groups) after the researchers controlled for age, sex, illness duration, BMI, Clinical Global Impressions Scale severity score, and antipsychotic treatment. Glucose tolerance normalized in 30 patients who received liraglutide (64%) compared with 8 in the placebo group (16%; P less than .001), Dr. Vedtofte said.
Besides its benefits to waist circumference and weight loss, liraglutide was associated with reductions in systolic blood pressure (average, 5 mm Hg; visceral fat, 0.25 kg; and low-density lipoprotein levels, 15 mg/dL). These changes occurred even though liraglutide did not significantly alter C-peptide or glucagon secretion in the multivariate analysis of glucose tolerance test results, Dr. Vedtofte said. “The rate of nausea was 62% in liraglutide patients and 32% with placebo, but nausea was transient and did not explain the weight loss in subgroup analyses,” she added.
Liraglutide did not alter clinical liver function, but treated patients experienced a small (1.3 U/L), statistically significant rise in amylase levels. Rates of other adverse events were similar between groups except that patients were more likely to experience orthostatic hypotension on liraglutide (8.2%) than on placebo (0%; P = .04). Treatment with liraglutide did not significantly increase the likelihood of serious somatic or psychiatric adverse events, but one patient died while on therapy. “This patient was a man in his 60s with longstanding schizophrenia who was admitted to the hospital with vomiting and diarrhea, and died 3 days later,” Dr. Vedtofte said. Autopsy did not reveal the cause of death, but the patients showed no change in mental status or other signs of adverse therapeutic effects, she added.
Novo Nordisk funded the study and provided liraglutide and placebo injections. Additional support came from Capital Region Psychiatry Research Group, the foundation of King Christian X of Denmark, and the Lundbeck Foundation. Dr. Vedtofte had no disclosures.
AT THE ADA ANNUAL SCIENTIFIC SESSIONS
Key clinical point:
Major finding: Glucose tolerance improved significantly from baseline in the liraglutide group (P less than .001) but not in the placebo group (P less than .001 for difference between groups) after 16 weeks.
Data source: A randomized double-blinded trial of 103 overweight or obese adults with prediabetes and schizophrenia spectrum disorders on stable antipsychotic therapy with clozapine, olanzapine, or both.
Disclosures: Novo Nordisk funded the study and provided the liraglutide and placebo injections. Capital Region Psychiatry Research Group, the foundation of King Christian X of Denmark, and the Lundbeck Foundation provided additional support. Dr. Vedtofte had no disclosures. .
Telemedicine visits after NICU discharge improved care, processes
SAN FRANCISCO – Using telemedicine for a follow-up appointment 1 week after discharge of medically complex infants reduced extra visits or calls to a clinic or emergency department, a recent study found.
The telemedicine visits also helped providers identify ways to improve the neonatal ICU (NICU) discharge process while assessing infants’ home care and answering parents’ questions.
The researchers assessed whether telemedicine visits could ease the transition from neonatal intensive care to home care, respond adequately to caregivers’ needs during that transition, reduce emergency department visits and readmissions, and detect and address any potential problems. The visits also provided an opportunity for feedback on caregivers’ experiences during discharge.
The 92 patients all were medically complex infants who went home with respiratory or feeding equipment, surgical sites and/or complex medication administration. For example, 28 infants had been sent home with a nasogastric tube, 13 had a gastrostomy tube, and 13 had an apnea monitor. Overall, participants had been discharged with an average 2.3 medications and 4.8 scheduled subspecialty follow-up appointments.
The most common conditions among the participants were gastrointestinal disease, neurologic disease, and congenital diaphragmatic hernia or lung lesions. Other conditions included omphalocele, genetic disorders, tracheoesophageal fistula or esophageal atresia and chronic lung disease, or another respiratory disease, Dr. Brant reported at the Pediatric Academic Societies meeting.
Families could enroll in the study only if they had a smart device (such as a tablet) and wireless Internet access at home. One week after the infant’s discharge from the NICU, the caregivers received one telemedicine visit with a team that included neonatologists, neonatal fellows, nurse practitioners, and a telemedicine coordinator or support staffer. During the visit, the providers observed the infant and the home environment, and evaluated care practices, including tube feedings, respiratory support, management of surgical wound sites, and administration of medications.
The providers also reviewed how to use the medical equipment, gathered follow-up information about the child’s health, and answered caregivers’ questions. The providers did not bill for telemedicine visits since it was part of a pilot study, but the participants did need to reside in Pennsylvania or New Jersey to meet provider licensing regulations.
Among the 93 telemedicine visits, half (50%) prevented the family from calling or visiting a provider, and 12% of them led to an earlier follow-up appointment for the child. During the video observations, providers addressed 14 issues related to the child’s sleep environment, respiratory status, surgical sites, or dermatological issues. Among 78 total concerns identified in the visits, 35% related to the surgical site, 33% related to feeding, 19% related to respiratory concerns, and 13% related to medication administration.
The provider team also asked families during the visit about their experiences during discharge. A quarter of the families (26%) said they needed more parental education during discharge. In addition, 14% mentioned problems with scheduling follow-up appointments, and 12% had problems related to case management and insurance. Other issues raised by parents related to home equipment, early intervention, home feeding or medications, and diagnostic logistics.
In subsequent satisfaction surveys filled out by caregivers about the telemedicine visit itself, the median rating was 94.5 on a scale of 0 (not at all satisfied) to 100 (extremely satisfied). The overall intervention was 92% successful in its completion. The only follow-up telemedicine visits that did not occur resulted from malfunctioning wireless connection or a mobile app problem. On a scale of 1 to 100 (best), caregivers rated the video quality as an average 78, the Internet reliability as 79, and the ease of using the camera as 91. One of the biggest benefits of the intervention, Dr. Brant pointed out, is that using telemedicine bypasses some of the geographic and time-related obstacles that can occur with follow-ups.
Dr. Brant had no relevant financial disclosures and did not report using any external funding.
SAN FRANCISCO – Using telemedicine for a follow-up appointment 1 week after discharge of medically complex infants reduced extra visits or calls to a clinic or emergency department, a recent study found.
The telemedicine visits also helped providers identify ways to improve the neonatal ICU (NICU) discharge process while assessing infants’ home care and answering parents’ questions.
The researchers assessed whether telemedicine visits could ease the transition from neonatal intensive care to home care, respond adequately to caregivers’ needs during that transition, reduce emergency department visits and readmissions, and detect and address any potential problems. The visits also provided an opportunity for feedback on caregivers’ experiences during discharge.
The 92 patients all were medically complex infants who went home with respiratory or feeding equipment, surgical sites and/or complex medication administration. For example, 28 infants had been sent home with a nasogastric tube, 13 had a gastrostomy tube, and 13 had an apnea monitor. Overall, participants had been discharged with an average 2.3 medications and 4.8 scheduled subspecialty follow-up appointments.
The most common conditions among the participants were gastrointestinal disease, neurologic disease, and congenital diaphragmatic hernia or lung lesions. Other conditions included omphalocele, genetic disorders, tracheoesophageal fistula or esophageal atresia and chronic lung disease, or another respiratory disease, Dr. Brant reported at the Pediatric Academic Societies meeting.
Families could enroll in the study only if they had a smart device (such as a tablet) and wireless Internet access at home. One week after the infant’s discharge from the NICU, the caregivers received one telemedicine visit with a team that included neonatologists, neonatal fellows, nurse practitioners, and a telemedicine coordinator or support staffer. During the visit, the providers observed the infant and the home environment, and evaluated care practices, including tube feedings, respiratory support, management of surgical wound sites, and administration of medications.
The providers also reviewed how to use the medical equipment, gathered follow-up information about the child’s health, and answered caregivers’ questions. The providers did not bill for telemedicine visits since it was part of a pilot study, but the participants did need to reside in Pennsylvania or New Jersey to meet provider licensing regulations.
Among the 93 telemedicine visits, half (50%) prevented the family from calling or visiting a provider, and 12% of them led to an earlier follow-up appointment for the child. During the video observations, providers addressed 14 issues related to the child’s sleep environment, respiratory status, surgical sites, or dermatological issues. Among 78 total concerns identified in the visits, 35% related to the surgical site, 33% related to feeding, 19% related to respiratory concerns, and 13% related to medication administration.
The provider team also asked families during the visit about their experiences during discharge. A quarter of the families (26%) said they needed more parental education during discharge. In addition, 14% mentioned problems with scheduling follow-up appointments, and 12% had problems related to case management and insurance. Other issues raised by parents related to home equipment, early intervention, home feeding or medications, and diagnostic logistics.
In subsequent satisfaction surveys filled out by caregivers about the telemedicine visit itself, the median rating was 94.5 on a scale of 0 (not at all satisfied) to 100 (extremely satisfied). The overall intervention was 92% successful in its completion. The only follow-up telemedicine visits that did not occur resulted from malfunctioning wireless connection or a mobile app problem. On a scale of 1 to 100 (best), caregivers rated the video quality as an average 78, the Internet reliability as 79, and the ease of using the camera as 91. One of the biggest benefits of the intervention, Dr. Brant pointed out, is that using telemedicine bypasses some of the geographic and time-related obstacles that can occur with follow-ups.
Dr. Brant had no relevant financial disclosures and did not report using any external funding.
SAN FRANCISCO – Using telemedicine for a follow-up appointment 1 week after discharge of medically complex infants reduced extra visits or calls to a clinic or emergency department, a recent study found.
The telemedicine visits also helped providers identify ways to improve the neonatal ICU (NICU) discharge process while assessing infants’ home care and answering parents’ questions.
The researchers assessed whether telemedicine visits could ease the transition from neonatal intensive care to home care, respond adequately to caregivers’ needs during that transition, reduce emergency department visits and readmissions, and detect and address any potential problems. The visits also provided an opportunity for feedback on caregivers’ experiences during discharge.
The 92 patients all were medically complex infants who went home with respiratory or feeding equipment, surgical sites and/or complex medication administration. For example, 28 infants had been sent home with a nasogastric tube, 13 had a gastrostomy tube, and 13 had an apnea monitor. Overall, participants had been discharged with an average 2.3 medications and 4.8 scheduled subspecialty follow-up appointments.
The most common conditions among the participants were gastrointestinal disease, neurologic disease, and congenital diaphragmatic hernia or lung lesions. Other conditions included omphalocele, genetic disorders, tracheoesophageal fistula or esophageal atresia and chronic lung disease, or another respiratory disease, Dr. Brant reported at the Pediatric Academic Societies meeting.
Families could enroll in the study only if they had a smart device (such as a tablet) and wireless Internet access at home. One week after the infant’s discharge from the NICU, the caregivers received one telemedicine visit with a team that included neonatologists, neonatal fellows, nurse practitioners, and a telemedicine coordinator or support staffer. During the visit, the providers observed the infant and the home environment, and evaluated care practices, including tube feedings, respiratory support, management of surgical wound sites, and administration of medications.
The providers also reviewed how to use the medical equipment, gathered follow-up information about the child’s health, and answered caregivers’ questions. The providers did not bill for telemedicine visits since it was part of a pilot study, but the participants did need to reside in Pennsylvania or New Jersey to meet provider licensing regulations.
Among the 93 telemedicine visits, half (50%) prevented the family from calling or visiting a provider, and 12% of them led to an earlier follow-up appointment for the child. During the video observations, providers addressed 14 issues related to the child’s sleep environment, respiratory status, surgical sites, or dermatological issues. Among 78 total concerns identified in the visits, 35% related to the surgical site, 33% related to feeding, 19% related to respiratory concerns, and 13% related to medication administration.
The provider team also asked families during the visit about their experiences during discharge. A quarter of the families (26%) said they needed more parental education during discharge. In addition, 14% mentioned problems with scheduling follow-up appointments, and 12% had problems related to case management and insurance. Other issues raised by parents related to home equipment, early intervention, home feeding or medications, and diagnostic logistics.
In subsequent satisfaction surveys filled out by caregivers about the telemedicine visit itself, the median rating was 94.5 on a scale of 0 (not at all satisfied) to 100 (extremely satisfied). The overall intervention was 92% successful in its completion. The only follow-up telemedicine visits that did not occur resulted from malfunctioning wireless connection or a mobile app problem. On a scale of 1 to 100 (best), caregivers rated the video quality as an average 78, the Internet reliability as 79, and the ease of using the camera as 91. One of the biggest benefits of the intervention, Dr. Brant pointed out, is that using telemedicine bypasses some of the geographic and time-related obstacles that can occur with follow-ups.
Dr. Brant had no relevant financial disclosures and did not report using any external funding.
FROM PAS 17
Key clinical point:
Major finding: Telemedicine visits prevented 50% of participants from calling or visiting a provider and led 12% of families to bring infants in sooner than originally scheduled.
Data source: The findings are based on a pilot project at the Children’s Hospital of Philadelphia involving 93 medically complex infants discharged from the NICU with medical equipment, surgical sites, and/or complex medication administration.
Disclosures: Dr. Brant had no relevant financial disclosures and did not report external funding.
Deep molecular responses achievable in AML pts treated with gilteritinib
CHICAGO—Next generation sequencing (NGS) has shown that the FLT3 inhibitor gilteritinib can produce deep molecular responses in a subset of patients with acute myeloid leukemia (AML), according to new research.
Gilteritinib is a highly selective FLT3/AXL inhibitor that is active against FLT3-ITD and FLT3-D835 mutations, but minimal residual disease (MRD) had not systematically been assessed previously in AML patients treated with potent FLT3 inhibitors.
Investigators believed that MRD evaluation in these patients could serve as a useful marker of FLT3 inhibitor efficacy. They therefore conducted an exploratory analysis of a subset of AML patients treated with gilteritinib on the Chrysalis study.
Jessica K. Altman, MD, of the Robert H. Lurie Cancer Center of Northwestern University in Chicago, Illinois, presented the findings at the ASCO 2017 Annual Meeting (abstract 7003).
Chrysalis study: Efficacy and survival
The phase 1/2 Chrysalis study examined the tolerability and antileukemic activity of once daily gilteritinib in a FLT3-ITD-enriched relapsed/refractory AML population of approximately 250 patients.
Overall, gilteritinib was well tolerated and had consistency and potent FLT3 inhibition at doses of >80 mg/day.
The maximum tolerated dose was 300 mg/day. Dose-limiting toxicities were diarrhea and liver function abnormalities.
The greatest overall response rate was 52% and the longest median overall survival (OS) duration was 31 weeks, observed in patients at doses >80 mg/day.
The composite complete remission (CR) rate, comprised of CR, CR with incomplete count recovery (Cri), and CR with incomplete platelet recovery (CRp), was 41%.
The median OS was 31 weeks, and median duration of response 20 weeks.
“Survival probabilities demonstrated that the overall survival for patients who received 80 mg of gilteritinib was higher than those who received less than 80 mg,” Dr Altman said.
Molecular response assessment
Dr Altman then presented the molecular response assessment.
The investigators included all FLT3-ITD mutated patients enrolled in the gilteritinib 120 and 200 mg/day dose cohorts and had bone marrow aspirates available at baseline and at 1 or more additional time points.
“The group I’m reporting on,” Dr Altman explained, “comprises 51% of all FLT3-ITD mutated patients treated at these 2 dose levels.”
FLT3-ITD and total FLT3 alleles were quantified by a novel NGS assay using an Illumina® sequencing platform. Read depth of at least 100,000 reads per sample were implemented.
“Evaluation of MRD was exploratory and it was not prespecified in the study,” Dr Altman noted.
Hence, the investigators defined a molecular response as an ITD signal ratio—FLT3-ITD : FLT3 total—of <10-2.
They defined major molecular response (MMR) as an ITD signal ratio of <10-3, and negative MRD status as <10-4.
Patient characteristics
Baseline characteristics of the 80 patients in the MRD analysis group were similar to those of the entire Chrysalis study population.
Median age was 61 years (range, 23 – 86) and the patients were heavily pretreated: 35% had 3 or more prior lines of AML therapy, and 28% had received a prior FLT3 inhibitor. About a third had prior allogeneic hematopoietic stem cell transplant.
Molecular response
Median OS in this cohort was 32.6 weeks, very similar to the entire study population.
Twenty patients (25%) achieved a molecular response, 18 (23%) an MMR, and 13 (16%) were MRD negative.
The median time to achieve a minimum ITD signal ratio was 8.2 weeks (range, 3.7 – 64).
And molecular response correlated with improved OS.
“The 20 patients who achieved a molecular response had a median overall survival of 59.6 weeks,” Dr Altman said, “which is statistically significantly different and I think clinically different than those who did not attain a molecular response.”
Patients who did not achieve a molecular response had a median overall survival of 28.4 weeks.
“As you could predict,” she added, “the molecular response was greater in those who attained a complete remission than those who had a CRp or Cri.”
Investigators observed similar results in patients who achieved an MMR, using the the cutoff point of 10-3.
“When we stratified by MRD negative status,” she said, “which was an ITD signal ratio of 10-4 or better, there’s clear separation of the Kaplan Meier curves for OS in this cohort again.”
Dr Altman pointed out that this was the first clinical trial to demonstrate that patients with AML treated with a FLT3 inhibitor can attain a molecular response.
“Also, and importantly, there is now a sensitive and specific assay for the detection of minimal residual disease in FLT3-ITD mutated patients and it has the potential to be widely adopted across trials and in clinical practice.”
MRD is prospectively being evaluated in 2 gilteritinib phase 3 maintenance studies.
The trial was sponsored by Astellas Pharma Global Development, Inc. 
CHICAGO—Next generation sequencing (NGS) has shown that the FLT3 inhibitor gilteritinib can produce deep molecular responses in a subset of patients with acute myeloid leukemia (AML), according to new research.
Gilteritinib is a highly selective FLT3/AXL inhibitor that is active against FLT3-ITD and FLT3-D835 mutations, but minimal residual disease (MRD) had not systematically been assessed previously in AML patients treated with potent FLT3 inhibitors.
Investigators believed that MRD evaluation in these patients could serve as a useful marker of FLT3 inhibitor efficacy. They therefore conducted an exploratory analysis of a subset of AML patients treated with gilteritinib on the Chrysalis study.
Jessica K. Altman, MD, of the Robert H. Lurie Cancer Center of Northwestern University in Chicago, Illinois, presented the findings at the ASCO 2017 Annual Meeting (abstract 7003).
Chrysalis study: Efficacy and survival
The phase 1/2 Chrysalis study examined the tolerability and antileukemic activity of once daily gilteritinib in a FLT3-ITD-enriched relapsed/refractory AML population of approximately 250 patients.
Overall, gilteritinib was well tolerated and had consistency and potent FLT3 inhibition at doses of >80 mg/day.
The maximum tolerated dose was 300 mg/day. Dose-limiting toxicities were diarrhea and liver function abnormalities.
The greatest overall response rate was 52% and the longest median overall survival (OS) duration was 31 weeks, observed in patients at doses >80 mg/day.
The composite complete remission (CR) rate, comprised of CR, CR with incomplete count recovery (Cri), and CR with incomplete platelet recovery (CRp), was 41%.
The median OS was 31 weeks, and median duration of response 20 weeks.
“Survival probabilities demonstrated that the overall survival for patients who received 80 mg of gilteritinib was higher than those who received less than 80 mg,” Dr Altman said.
Molecular response assessment
Dr Altman then presented the molecular response assessment.
The investigators included all FLT3-ITD mutated patients enrolled in the gilteritinib 120 and 200 mg/day dose cohorts and had bone marrow aspirates available at baseline and at 1 or more additional time points.
“The group I’m reporting on,” Dr Altman explained, “comprises 51% of all FLT3-ITD mutated patients treated at these 2 dose levels.”
FLT3-ITD and total FLT3 alleles were quantified by a novel NGS assay using an Illumina® sequencing platform. Read depth of at least 100,000 reads per sample were implemented.
“Evaluation of MRD was exploratory and it was not prespecified in the study,” Dr Altman noted.
Hence, the investigators defined a molecular response as an ITD signal ratio—FLT3-ITD : FLT3 total—of <10-2.
They defined major molecular response (MMR) as an ITD signal ratio of <10-3, and negative MRD status as <10-4.
Patient characteristics
Baseline characteristics of the 80 patients in the MRD analysis group were similar to those of the entire Chrysalis study population.
Median age was 61 years (range, 23 – 86) and the patients were heavily pretreated: 35% had 3 or more prior lines of AML therapy, and 28% had received a prior FLT3 inhibitor. About a third had prior allogeneic hematopoietic stem cell transplant.
Molecular response
Median OS in this cohort was 32.6 weeks, very similar to the entire study population.
Twenty patients (25%) achieved a molecular response, 18 (23%) an MMR, and 13 (16%) were MRD negative.
The median time to achieve a minimum ITD signal ratio was 8.2 weeks (range, 3.7 – 64).
And molecular response correlated with improved OS.
“The 20 patients who achieved a molecular response had a median overall survival of 59.6 weeks,” Dr Altman said, “which is statistically significantly different and I think clinically different than those who did not attain a molecular response.”
Patients who did not achieve a molecular response had a median overall survival of 28.4 weeks.
“As you could predict,” she added, “the molecular response was greater in those who attained a complete remission than those who had a CRp or Cri.”
Investigators observed similar results in patients who achieved an MMR, using the the cutoff point of 10-3.
“When we stratified by MRD negative status,” she said, “which was an ITD signal ratio of 10-4 or better, there’s clear separation of the Kaplan Meier curves for OS in this cohort again.”
Dr Altman pointed out that this was the first clinical trial to demonstrate that patients with AML treated with a FLT3 inhibitor can attain a molecular response.
“Also, and importantly, there is now a sensitive and specific assay for the detection of minimal residual disease in FLT3-ITD mutated patients and it has the potential to be widely adopted across trials and in clinical practice.”
MRD is prospectively being evaluated in 2 gilteritinib phase 3 maintenance studies.
The trial was sponsored by Astellas Pharma Global Development, Inc.
CHICAGO—Next generation sequencing (NGS) has shown that the FLT3 inhibitor gilteritinib can produce deep molecular responses in a subset of patients with acute myeloid leukemia (AML), according to new research.
Gilteritinib is a highly selective FLT3/AXL inhibitor that is active against FLT3-ITD and FLT3-D835 mutations, but minimal residual disease (MRD) had not systematically been assessed previously in AML patients treated with potent FLT3 inhibitors.
Investigators believed that MRD evaluation in these patients could serve as a useful marker of FLT3 inhibitor efficacy. They therefore conducted an exploratory analysis of a subset of AML patients treated with gilteritinib on the Chrysalis study.
Jessica K. Altman, MD, of the Robert H. Lurie Cancer Center of Northwestern University in Chicago, Illinois, presented the findings at the ASCO 2017 Annual Meeting (abstract 7003).
Chrysalis study: Efficacy and survival
The phase 1/2 Chrysalis study examined the tolerability and antileukemic activity of once daily gilteritinib in a FLT3-ITD-enriched relapsed/refractory AML population of approximately 250 patients.
Overall, gilteritinib was well tolerated and had consistency and potent FLT3 inhibition at doses of >80 mg/day.
The maximum tolerated dose was 300 mg/day. Dose-limiting toxicities were diarrhea and liver function abnormalities.
The greatest overall response rate was 52% and the longest median overall survival (OS) duration was 31 weeks, observed in patients at doses >80 mg/day.
The composite complete remission (CR) rate, comprised of CR, CR with incomplete count recovery (Cri), and CR with incomplete platelet recovery (CRp), was 41%.
The median OS was 31 weeks, and median duration of response 20 weeks.
“Survival probabilities demonstrated that the overall survival for patients who received 80 mg of gilteritinib was higher than those who received less than 80 mg,” Dr Altman said.
Molecular response assessment
Dr Altman then presented the molecular response assessment.
The investigators included all FLT3-ITD mutated patients enrolled in the gilteritinib 120 and 200 mg/day dose cohorts and had bone marrow aspirates available at baseline and at 1 or more additional time points.
“The group I’m reporting on,” Dr Altman explained, “comprises 51% of all FLT3-ITD mutated patients treated at these 2 dose levels.”
FLT3-ITD and total FLT3 alleles were quantified by a novel NGS assay using an Illumina® sequencing platform. Read depth of at least 100,000 reads per sample were implemented.
“Evaluation of MRD was exploratory and it was not prespecified in the study,” Dr Altman noted.
Hence, the investigators defined a molecular response as an ITD signal ratio—FLT3-ITD : FLT3 total—of <10-2.
They defined major molecular response (MMR) as an ITD signal ratio of <10-3, and negative MRD status as <10-4.
Patient characteristics
Baseline characteristics of the 80 patients in the MRD analysis group were similar to those of the entire Chrysalis study population.
Median age was 61 years (range, 23 – 86) and the patients were heavily pretreated: 35% had 3 or more prior lines of AML therapy, and 28% had received a prior FLT3 inhibitor. About a third had prior allogeneic hematopoietic stem cell transplant.
Molecular response
Median OS in this cohort was 32.6 weeks, very similar to the entire study population.
Twenty patients (25%) achieved a molecular response, 18 (23%) an MMR, and 13 (16%) were MRD negative.
The median time to achieve a minimum ITD signal ratio was 8.2 weeks (range, 3.7 – 64).
And molecular response correlated with improved OS.
“The 20 patients who achieved a molecular response had a median overall survival of 59.6 weeks,” Dr Altman said, “which is statistically significantly different and I think clinically different than those who did not attain a molecular response.”
Patients who did not achieve a molecular response had a median overall survival of 28.4 weeks.
“As you could predict,” she added, “the molecular response was greater in those who attained a complete remission than those who had a CRp or Cri.”
Investigators observed similar results in patients who achieved an MMR, using the the cutoff point of 10-3.
“When we stratified by MRD negative status,” she said, “which was an ITD signal ratio of 10-4 or better, there’s clear separation of the Kaplan Meier curves for OS in this cohort again.”
Dr Altman pointed out that this was the first clinical trial to demonstrate that patients with AML treated with a FLT3 inhibitor can attain a molecular response.
“Also, and importantly, there is now a sensitive and specific assay for the detection of minimal residual disease in FLT3-ITD mutated patients and it has the potential to be widely adopted across trials and in clinical practice.”
MRD is prospectively being evaluated in 2 gilteritinib phase 3 maintenance studies.
The trial was sponsored by Astellas Pharma Global Development, Inc.
Application of the MASCC and CISNE risk-stratification scores to identify low-risk febrile neutropenic patients in the emergency department
Clinical Question: Does the Multinational Association for Supportive Care in Cancer (MASCC) or Clinical Index of Stable Febrile Neutropenia (CISNE) risk-stratification score better predict patient outcomes in patients presenting to emergency departments with febrile neutropenia?
Background: Risk-stratification metrics like the MASCC and CISNE identify subsets of relatively low-risk patients with febrile neutropenia after chemotherapy for treatment at home with empiric oral antibiotic therapy and close follow-up while awaiting results of infectious work-up. Prior studies have validated these tools for admitted, but not for ED, patients.
Setting: Two academic ED at National Institutes of Health–designated cancer centers.
Synopsis: Included patients (n = 230) were at least 16 years old with a documented fever of 38° C or greater related to chemotherapy and an absolute neutrophil count less than 1,000 cells/μL. MASCC and CISNE risk stratification scores were calculated based on the documentation from the ED and recent oncology clinic visits. Outcome measures included length of stay, upgrade in level of care, positive blood cultures, clinical deterioration, and death and were assessed for up to 30 days following discharge. Low-risk patients were defined as those who experienced no negative endpoints. The CISNE score was more specific than the MASCC in identifying low-risk patients (98.1% vs. 54.2%), suggesting that the CISNE may be useful for hospitalists in identifying patients who may be safely discharged with oral antibiotics and close follow-up.
Limitations include possible misclassification bias from indirect assessment of symptom severity, lack of recent ECOG scores for six patients in the CISNE arm, and possible undocumented symptoms during ED evaluation required for subsequent score calculation. Additionally, most patients in this study reported mild symptoms which weighted their MASCC classification toward low-risk.
Bottom Line: The CISNE score may aid in risk-stratification of patients with chemotherapy-related febrile neutropenia presenting to the ED.
Reference: Coyne CJ, Le V, Brennan JJ, et al. Application of the MASCC and CISNE risk-stratification scores to identify low-risk febrile neutropenic patients in the emergency department. Ann Emerg Med. Published online 29 Dec 2016. doi: 10.1016/j.annemergmed.2016.11.007.
Dr. Frederick is assistant clinical professor in the division of hospital Medicine, department of medicine, University of California, San Diego.
Clinical Question: Does the Multinational Association for Supportive Care in Cancer (MASCC) or Clinical Index of Stable Febrile Neutropenia (CISNE) risk-stratification score better predict patient outcomes in patients presenting to emergency departments with febrile neutropenia?
Background: Risk-stratification metrics like the MASCC and CISNE identify subsets of relatively low-risk patients with febrile neutropenia after chemotherapy for treatment at home with empiric oral antibiotic therapy and close follow-up while awaiting results of infectious work-up. Prior studies have validated these tools for admitted, but not for ED, patients.
Setting: Two academic ED at National Institutes of Health–designated cancer centers.
Synopsis: Included patients (n = 230) were at least 16 years old with a documented fever of 38° C or greater related to chemotherapy and an absolute neutrophil count less than 1,000 cells/μL. MASCC and CISNE risk stratification scores were calculated based on the documentation from the ED and recent oncology clinic visits. Outcome measures included length of stay, upgrade in level of care, positive blood cultures, clinical deterioration, and death and were assessed for up to 30 days following discharge. Low-risk patients were defined as those who experienced no negative endpoints. The CISNE score was more specific than the MASCC in identifying low-risk patients (98.1% vs. 54.2%), suggesting that the CISNE may be useful for hospitalists in identifying patients who may be safely discharged with oral antibiotics and close follow-up.
Limitations include possible misclassification bias from indirect assessment of symptom severity, lack of recent ECOG scores for six patients in the CISNE arm, and possible undocumented symptoms during ED evaluation required for subsequent score calculation. Additionally, most patients in this study reported mild symptoms which weighted their MASCC classification toward low-risk.
Bottom Line: The CISNE score may aid in risk-stratification of patients with chemotherapy-related febrile neutropenia presenting to the ED.
Reference: Coyne CJ, Le V, Brennan JJ, et al. Application of the MASCC and CISNE risk-stratification scores to identify low-risk febrile neutropenic patients in the emergency department. Ann Emerg Med. Published online 29 Dec 2016. doi: 10.1016/j.annemergmed.2016.11.007.
Dr. Frederick is assistant clinical professor in the division of hospital Medicine, department of medicine, University of California, San Diego.
Clinical Question: Does the Multinational Association for Supportive Care in Cancer (MASCC) or Clinical Index of Stable Febrile Neutropenia (CISNE) risk-stratification score better predict patient outcomes in patients presenting to emergency departments with febrile neutropenia?
Background: Risk-stratification metrics like the MASCC and CISNE identify subsets of relatively low-risk patients with febrile neutropenia after chemotherapy for treatment at home with empiric oral antibiotic therapy and close follow-up while awaiting results of infectious work-up. Prior studies have validated these tools for admitted, but not for ED, patients.
Setting: Two academic ED at National Institutes of Health–designated cancer centers.
Synopsis: Included patients (n = 230) were at least 16 years old with a documented fever of 38° C or greater related to chemotherapy and an absolute neutrophil count less than 1,000 cells/μL. MASCC and CISNE risk stratification scores were calculated based on the documentation from the ED and recent oncology clinic visits. Outcome measures included length of stay, upgrade in level of care, positive blood cultures, clinical deterioration, and death and were assessed for up to 30 days following discharge. Low-risk patients were defined as those who experienced no negative endpoints. The CISNE score was more specific than the MASCC in identifying low-risk patients (98.1% vs. 54.2%), suggesting that the CISNE may be useful for hospitalists in identifying patients who may be safely discharged with oral antibiotics and close follow-up.
Limitations include possible misclassification bias from indirect assessment of symptom severity, lack of recent ECOG scores for six patients in the CISNE arm, and possible undocumented symptoms during ED evaluation required for subsequent score calculation. Additionally, most patients in this study reported mild symptoms which weighted their MASCC classification toward low-risk.
Bottom Line: The CISNE score may aid in risk-stratification of patients with chemotherapy-related febrile neutropenia presenting to the ED.
Reference: Coyne CJ, Le V, Brennan JJ, et al. Application of the MASCC and CISNE risk-stratification scores to identify low-risk febrile neutropenic patients in the emergency department. Ann Emerg Med. Published online 29 Dec 2016. doi: 10.1016/j.annemergmed.2016.11.007.
Dr. Frederick is assistant clinical professor in the division of hospital Medicine, department of medicine, University of California, San Diego.
To Vaccinate, or Not, in Patients With MS
Q) Are vaccines safe for patients with multiple sclerosis?
Vaccines are an important component of general disease prevention and are especially useful for patients with chronic illnesses, such as MS, who may be at elevated risk due to disability or medications that alter the immune system. Currently, there are many disease-modifying therapies that attempt to reduce relapses and impact the immune system, MRI activity, and disability. But is it safe for patients with MS to receive vaccines, given the multitude of studies suggesting that infections may increase relapse rate?
In 2002, the American Academy of Neurology published a summary of evidence and recommendations to provide guidance for practitioners.1 The data showed an increased risk for MS relapse during the weeks following infection.2,3 Therefore, preventing infections is beneficial for patients with MS. An analysis of studies in patients with MS who were vaccinated with inactivated vaccines (influenza, hepatitis B, tetanus) found sufficient evidence to support this practice. Studies of patients with MS who were given attenuated vaccines did not find enough evidence to support or reject these vaccines, except in the case of varicella. A study with sufficient follow-up concluded that varicella vaccination was safe for patients with MS who were not immunosuppressed. As a result of this effort, the MS Council for Clinical Practice Guidelines recommends that patients and health care providers follow the CDC’s indications for immunizations (www.cdc.gov/vaccines/schedules/hcp/adult.html).1
On the other hand, administration of the live-virus yellow fever vaccine in patients with clinically relapsing MS was correlated with an increased risk for disease progression in one study.4 The researchers followed disease progression, measured by relapses and MRI activity, in patients taking glatiramer acetate and interferon ß. Relapse rates reached 8.57 within three months after vaccination, compared to a rate of 0.67 the year prior to vaccine administration. Additionally, significant changes were seen on MRI; new or enlarging T2-weighted lesions and gadolinium-enhancing lesions were observed at three months, compared to 12 months prior and nine months after.4 Therefore, the researchers concluded that patients with MS traveling to endemic yellow fever areas should be cautioned regarding the risk for disease progression with vaccination, versus the risk for exposure to yellow fever.
Over the past decade, as newer therapies with different mechanisms of action have become available, concern has risen that patients may not respond to immunizations or may have a higher risk for infection after vaccination. For that reason, several studies have evaluated the ability of patients with MS to mount a normal antibody and cellular immune response after vaccine administration. In 2016, a study by Lin et al determined that patients who received daclizumab were able to mount a normal response after influenza vaccination.5
By contrast, Kappos et al, in a 2015 study, found that patients receiving fingolimod had lower response rates to influenza and tetanus booster vaccines than patients who took a placebo.6 Similarly, in a 2014 study, Olberg et al examined patients receiving interferon ß, glatiramer acetate, natalizumab, and mitoxantrone after receiving influenza and H1N1 vaccinations. The researchers found that those treated with any therapy other than interferon ß had a reduced rate of response and should therefore be considered for vaccine response analysis.7 Bar-Or et al also published data on response rates of patients treated with teriflunomide (7 mg or 14 mg) or interferon ß; rates were reduced with 14-mg teriflunomide compared to the other treatments—but most patients exhibited seroprotection regardless.8 Studying vaccine efficacy in 2013, McCarthy et al evaluated serum antibodies against common viruses before and after treatment with alemtuzumab and found that antibodies remained detectable six months post-alemtuzumab.9
In summary, most specialists agree that vaccines are helpful for patients with MS. However, due to the varied response rates among disease-modifying therapies and the correlation between infection and increased relapse rates, special care should be taken when treating this population. Generally, inactivated vaccines are safe, but seroprotection should be established to determine if a booster is necessary. Attenuated vaccines are generally safe for patients who are not immunosuppressed and can reduce the risk for infection if given prior to immunosuppression. After immunosuppression, attenuated vaccines should not be given until immune recovery has been established. —PP
Patricia Pagnotta, ARNP, MSN, CNRN, MSCN
Neurology Associates, PA
MS Center of Greater Orlando
1. Rutschmann OT, McCrory DC, Matchar DB. Immunization and MS: a summary of published evidence and recommendations. Neurology. 2002;59(12):1837-1843.
2. Anderson O, Lygner PE, Bergstrom T, et al. Viral infections trigger multiple sclerosis relapses: a prospective seroepidemiological study. J Neurol. 1993;240(7):417-422.
3. Panitch HS, Bever CT, Katz E, Johnson KP. Upper respiratory tract infections trigger attacks of multiple sclerosis in patients treated with interferon. J Neuroimmunol. 1991; 36:125.
4. Farez MF, Correale J. Yellow fever vaccination and increased relapse rate in travelers with multiple sclerosis. Arch Neurol. 2011;68(10):1267-1271.
5. Lin YC, Winokur P, Blake A, et al. Patients with MS under daclizumab therapy mount normal immune responses to influenza vaccine. Neurol Neuroimmunol Neuroinflamm. 2016;3(1):1-10.
6. Kappos L, Mehling M, Arroyo R, et al. Randomized trial of vaccination in fingolimod-treated patients with multiple sclerosis. Neurology. 2015;84(9):872-879.
7. Olberg HK, Cox RJ, Nostbakken JK, et al. Immunotherapies influence the influenza vaccination response in multiple sclerosis patients: an explorative study. Mult Scler. 2014;20(8):1074-1080.
8. Bar-Or A, Freedman MS, Kremenchutzky M, et al. Teriflunomide effect on immune response to influenza vaccine in patients with multiple sclerosis. Neurology. 2013;81(6):552-558.
9. McCarthy CL, Tuohy O, Compston DA, et al. Immune competence after alemtuzumab treatment of multiple sclerosis. Neurology. 2013;81(10):872-876.
Clinician Reviews in partnership with
MS Consult is edited by Colleen J. Harris, MN, NP, MSCN, Nurse Practitioner/Manager of the Multiple Sclerosis Clinic at Foothills Medical Centre in Calgary, Alberta, Canada, and Bryan Walker, MHS, PA-C, who is in the Department of Neurology, Division of MS and Neuroimmunology, at Duke University Medical Center in Durham, North Carolina. This month's responses were authored by Stephanie Agrella, MSN, RN, APRN, ANP-BC, MSCN, Director of Clinical Services at the Multiple Sclerosis Clinic of Central Texas, Round Rock, and Patricia Pagnotta, ARNP, MSN, CNRN, MSCN, who is with Neurology Associates, PA, and the MS Center of Greater Orlando.
Clinician Reviews in partnership with
MS Consult is edited by Colleen J. Harris, MN, NP, MSCN, Nurse Practitioner/Manager of the Multiple Sclerosis Clinic at Foothills Medical Centre in Calgary, Alberta, Canada, and Bryan Walker, MHS, PA-C, who is in the Department of Neurology, Division of MS and Neuroimmunology, at Duke University Medical Center in Durham, North Carolina. This month's responses were authored by Stephanie Agrella, MSN, RN, APRN, ANP-BC, MSCN, Director of Clinical Services at the Multiple Sclerosis Clinic of Central Texas, Round Rock, and Patricia Pagnotta, ARNP, MSN, CNRN, MSCN, who is with Neurology Associates, PA, and the MS Center of Greater Orlando.
Clinician Reviews in partnership with
MS Consult is edited by Colleen J. Harris, MN, NP, MSCN, Nurse Practitioner/Manager of the Multiple Sclerosis Clinic at Foothills Medical Centre in Calgary, Alberta, Canada, and Bryan Walker, MHS, PA-C, who is in the Department of Neurology, Division of MS and Neuroimmunology, at Duke University Medical Center in Durham, North Carolina. This month's responses were authored by Stephanie Agrella, MSN, RN, APRN, ANP-BC, MSCN, Director of Clinical Services at the Multiple Sclerosis Clinic of Central Texas, Round Rock, and Patricia Pagnotta, ARNP, MSN, CNRN, MSCN, who is with Neurology Associates, PA, and the MS Center of Greater Orlando.
Q) Are vaccines safe for patients with multiple sclerosis?
Vaccines are an important component of general disease prevention and are especially useful for patients with chronic illnesses, such as MS, who may be at elevated risk due to disability or medications that alter the immune system. Currently, there are many disease-modifying therapies that attempt to reduce relapses and impact the immune system, MRI activity, and disability. But is it safe for patients with MS to receive vaccines, given the multitude of studies suggesting that infections may increase relapse rate?
In 2002, the American Academy of Neurology published a summary of evidence and recommendations to provide guidance for practitioners.1 The data showed an increased risk for MS relapse during the weeks following infection.2,3 Therefore, preventing infections is beneficial for patients with MS. An analysis of studies in patients with MS who were vaccinated with inactivated vaccines (influenza, hepatitis B, tetanus) found sufficient evidence to support this practice. Studies of patients with MS who were given attenuated vaccines did not find enough evidence to support or reject these vaccines, except in the case of varicella. A study with sufficient follow-up concluded that varicella vaccination was safe for patients with MS who were not immunosuppressed. As a result of this effort, the MS Council for Clinical Practice Guidelines recommends that patients and health care providers follow the CDC’s indications for immunizations (www.cdc.gov/vaccines/schedules/hcp/adult.html).1
On the other hand, administration of the live-virus yellow fever vaccine in patients with clinically relapsing MS was correlated with an increased risk for disease progression in one study.4 The researchers followed disease progression, measured by relapses and MRI activity, in patients taking glatiramer acetate and interferon ß. Relapse rates reached 8.57 within three months after vaccination, compared to a rate of 0.67 the year prior to vaccine administration. Additionally, significant changes were seen on MRI; new or enlarging T2-weighted lesions and gadolinium-enhancing lesions were observed at three months, compared to 12 months prior and nine months after.4 Therefore, the researchers concluded that patients with MS traveling to endemic yellow fever areas should be cautioned regarding the risk for disease progression with vaccination, versus the risk for exposure to yellow fever.
Over the past decade, as newer therapies with different mechanisms of action have become available, concern has risen that patients may not respond to immunizations or may have a higher risk for infection after vaccination. For that reason, several studies have evaluated the ability of patients with MS to mount a normal antibody and cellular immune response after vaccine administration. In 2016, a study by Lin et al determined that patients who received daclizumab were able to mount a normal response after influenza vaccination.5
By contrast, Kappos et al, in a 2015 study, found that patients receiving fingolimod had lower response rates to influenza and tetanus booster vaccines than patients who took a placebo.6 Similarly, in a 2014 study, Olberg et al examined patients receiving interferon ß, glatiramer acetate, natalizumab, and mitoxantrone after receiving influenza and H1N1 vaccinations. The researchers found that those treated with any therapy other than interferon ß had a reduced rate of response and should therefore be considered for vaccine response analysis.7 Bar-Or et al also published data on response rates of patients treated with teriflunomide (7 mg or 14 mg) or interferon ß; rates were reduced with 14-mg teriflunomide compared to the other treatments—but most patients exhibited seroprotection regardless.8 Studying vaccine efficacy in 2013, McCarthy et al evaluated serum antibodies against common viruses before and after treatment with alemtuzumab and found that antibodies remained detectable six months post-alemtuzumab.9
In summary, most specialists agree that vaccines are helpful for patients with MS. However, due to the varied response rates among disease-modifying therapies and the correlation between infection and increased relapse rates, special care should be taken when treating this population. Generally, inactivated vaccines are safe, but seroprotection should be established to determine if a booster is necessary. Attenuated vaccines are generally safe for patients who are not immunosuppressed and can reduce the risk for infection if given prior to immunosuppression. After immunosuppression, attenuated vaccines should not be given until immune recovery has been established. —PP
Patricia Pagnotta, ARNP, MSN, CNRN, MSCN
Neurology Associates, PA
MS Center of Greater Orlando
Q) Are vaccines safe for patients with multiple sclerosis?
Vaccines are an important component of general disease prevention and are especially useful for patients with chronic illnesses, such as MS, who may be at elevated risk due to disability or medications that alter the immune system. Currently, there are many disease-modifying therapies that attempt to reduce relapses and impact the immune system, MRI activity, and disability. But is it safe for patients with MS to receive vaccines, given the multitude of studies suggesting that infections may increase relapse rate?
In 2002, the American Academy of Neurology published a summary of evidence and recommendations to provide guidance for practitioners.1 The data showed an increased risk for MS relapse during the weeks following infection.2,3 Therefore, preventing infections is beneficial for patients with MS. An analysis of studies in patients with MS who were vaccinated with inactivated vaccines (influenza, hepatitis B, tetanus) found sufficient evidence to support this practice. Studies of patients with MS who were given attenuated vaccines did not find enough evidence to support or reject these vaccines, except in the case of varicella. A study with sufficient follow-up concluded that varicella vaccination was safe for patients with MS who were not immunosuppressed. As a result of this effort, the MS Council for Clinical Practice Guidelines recommends that patients and health care providers follow the CDC’s indications for immunizations (www.cdc.gov/vaccines/schedules/hcp/adult.html).1
On the other hand, administration of the live-virus yellow fever vaccine in patients with clinically relapsing MS was correlated with an increased risk for disease progression in one study.4 The researchers followed disease progression, measured by relapses and MRI activity, in patients taking glatiramer acetate and interferon ß. Relapse rates reached 8.57 within three months after vaccination, compared to a rate of 0.67 the year prior to vaccine administration. Additionally, significant changes were seen on MRI; new or enlarging T2-weighted lesions and gadolinium-enhancing lesions were observed at three months, compared to 12 months prior and nine months after.4 Therefore, the researchers concluded that patients with MS traveling to endemic yellow fever areas should be cautioned regarding the risk for disease progression with vaccination, versus the risk for exposure to yellow fever.
Over the past decade, as newer therapies with different mechanisms of action have become available, concern has risen that patients may not respond to immunizations or may have a higher risk for infection after vaccination. For that reason, several studies have evaluated the ability of patients with MS to mount a normal antibody and cellular immune response after vaccine administration. In 2016, a study by Lin et al determined that patients who received daclizumab were able to mount a normal response after influenza vaccination.5
By contrast, Kappos et al, in a 2015 study, found that patients receiving fingolimod had lower response rates to influenza and tetanus booster vaccines than patients who took a placebo.6 Similarly, in a 2014 study, Olberg et al examined patients receiving interferon ß, glatiramer acetate, natalizumab, and mitoxantrone after receiving influenza and H1N1 vaccinations. The researchers found that those treated with any therapy other than interferon ß had a reduced rate of response and should therefore be considered for vaccine response analysis.7 Bar-Or et al also published data on response rates of patients treated with teriflunomide (7 mg or 14 mg) or interferon ß; rates were reduced with 14-mg teriflunomide compared to the other treatments—but most patients exhibited seroprotection regardless.8 Studying vaccine efficacy in 2013, McCarthy et al evaluated serum antibodies against common viruses before and after treatment with alemtuzumab and found that antibodies remained detectable six months post-alemtuzumab.9
In summary, most specialists agree that vaccines are helpful for patients with MS. However, due to the varied response rates among disease-modifying therapies and the correlation between infection and increased relapse rates, special care should be taken when treating this population. Generally, inactivated vaccines are safe, but seroprotection should be established to determine if a booster is necessary. Attenuated vaccines are generally safe for patients who are not immunosuppressed and can reduce the risk for infection if given prior to immunosuppression. After immunosuppression, attenuated vaccines should not be given until immune recovery has been established. —PP
Patricia Pagnotta, ARNP, MSN, CNRN, MSCN
Neurology Associates, PA
MS Center of Greater Orlando
1. Rutschmann OT, McCrory DC, Matchar DB. Immunization and MS: a summary of published evidence and recommendations. Neurology. 2002;59(12):1837-1843.
2. Anderson O, Lygner PE, Bergstrom T, et al. Viral infections trigger multiple sclerosis relapses: a prospective seroepidemiological study. J Neurol. 1993;240(7):417-422.
3. Panitch HS, Bever CT, Katz E, Johnson KP. Upper respiratory tract infections trigger attacks of multiple sclerosis in patients treated with interferon. J Neuroimmunol. 1991; 36:125.
4. Farez MF, Correale J. Yellow fever vaccination and increased relapse rate in travelers with multiple sclerosis. Arch Neurol. 2011;68(10):1267-1271.
5. Lin YC, Winokur P, Blake A, et al. Patients with MS under daclizumab therapy mount normal immune responses to influenza vaccine. Neurol Neuroimmunol Neuroinflamm. 2016;3(1):1-10.
6. Kappos L, Mehling M, Arroyo R, et al. Randomized trial of vaccination in fingolimod-treated patients with multiple sclerosis. Neurology. 2015;84(9):872-879.
7. Olberg HK, Cox RJ, Nostbakken JK, et al. Immunotherapies influence the influenza vaccination response in multiple sclerosis patients: an explorative study. Mult Scler. 2014;20(8):1074-1080.
8. Bar-Or A, Freedman MS, Kremenchutzky M, et al. Teriflunomide effect on immune response to influenza vaccine in patients with multiple sclerosis. Neurology. 2013;81(6):552-558.
9. McCarthy CL, Tuohy O, Compston DA, et al. Immune competence after alemtuzumab treatment of multiple sclerosis. Neurology. 2013;81(10):872-876.
1. Rutschmann OT, McCrory DC, Matchar DB. Immunization and MS: a summary of published evidence and recommendations. Neurology. 2002;59(12):1837-1843.
2. Anderson O, Lygner PE, Bergstrom T, et al. Viral infections trigger multiple sclerosis relapses: a prospective seroepidemiological study. J Neurol. 1993;240(7):417-422.
3. Panitch HS, Bever CT, Katz E, Johnson KP. Upper respiratory tract infections trigger attacks of multiple sclerosis in patients treated with interferon. J Neuroimmunol. 1991; 36:125.
4. Farez MF, Correale J. Yellow fever vaccination and increased relapse rate in travelers with multiple sclerosis. Arch Neurol. 2011;68(10):1267-1271.
5. Lin YC, Winokur P, Blake A, et al. Patients with MS under daclizumab therapy mount normal immune responses to influenza vaccine. Neurol Neuroimmunol Neuroinflamm. 2016;3(1):1-10.
6. Kappos L, Mehling M, Arroyo R, et al. Randomized trial of vaccination in fingolimod-treated patients with multiple sclerosis. Neurology. 2015;84(9):872-879.
7. Olberg HK, Cox RJ, Nostbakken JK, et al. Immunotherapies influence the influenza vaccination response in multiple sclerosis patients: an explorative study. Mult Scler. 2014;20(8):1074-1080.
8. Bar-Or A, Freedman MS, Kremenchutzky M, et al. Teriflunomide effect on immune response to influenza vaccine in patients with multiple sclerosis. Neurology. 2013;81(6):552-558.
9. McCarthy CL, Tuohy O, Compston DA, et al. Immune competence after alemtuzumab treatment of multiple sclerosis. Neurology. 2013;81(10):872-876.
Atrial fibrillation blunts beta-blockers for HFrEF
PARIS – Maximal beta-blocker treatment and lower heart rates are effective at cutting all-cause mortality in patients with heart failure with reduced ejection fraction (HFrEF) who are also in sinus rhythm, but it’s a totally different story for patients with similar heart failure plus atrial fibrillation. In the atrial fibrillation subgroup, treatment with a beta-blocker linked with no mortality benefit, and lower heart rates – below 70 beats per minute – appeared to actually link with worse patient survival, based on a meta-analysis of data from 11 beta-blocker trials with a total of more than 17,000 patients.
“Beta blockers may be doing good in heart failure patients with atrial fibrillation, but they also are doing harm that neutralizes any good they do.” In patients with HFrEF and atrial fibrillation, “I don’t like to see the heart rate below 80 beats per minute,” John G.F. Cleland, MD, said at a meeting held by the Heart Failure Association of the ESC.
“We’ve perhaps been too aggressive with heart-rate control in HFrEF patients with atrial fibrillation,” he added in an interview. In these patients “in the range of 60-100 bpm it doesn’t seem to make a lot of difference what the heart rate is, and, if it is less than 70 bpm, patients seem to do a little worse. When we treat these patients with a beta-blocker we don’t see benefit in any way that we’ve looked at the data.”
In contrast, among HFrEF patients in sinus rhythm “beta-blocker treatment is similarly effective regardless of what the baseline heart rate was. The benefit was as great when the baseline rate was 70 bpm or 90 bpm, so heart rate is not a great predictor of beta-blocker benefit in these patients. Patients who tolerated the full beta-blocker dosage had the greatest benefit, and patients who achieved the slowest heart rates also had the greatest benefit.”
In the multivariate models that Dr. Cleland and his associates tested in their meta-analysis, in HFrEF patients in sinus rhythm, the relationship between reduced heart rate and mortality benefit was stronger statistically than between beta-blocker dosage and reduced mortality, he said. “This suggests to me that, while we should use the targeted beta-blocker dosages when we can, it’s more important to achieve a target heart rate in these patients of 55-65 bpm.”
Dr. Cleland hypothesized, based on a report presented at the same meeting by a different research group, that reduced heart rate is not beneficial in HFrEF patients with atrial fibrillation because in this subgroup slower heart rates linked with an increased number of brief pauses in left ventricular pumping. These pauses may result in ventricular arrhythmias, he speculated. “It may be that beta-blockers are equally effective at slowing heart rate in patients with or without atrial fibrillation, but there is also harm from beta-blockers because they’re causing pauses in patients with atrial fibrillation,” he said.
These days, if he has a HFrEF patient with atrial fibrillation whose heart rate slows to 60 bpm, he will stop digoxin treatment if the patient is on that drug, and he will also reduce the beta-blocker dosage but not discontinue it.
The findings came from the Collaborative Systematic Overview of Randomized Controlled Trials of Beta-Blockers in the Treatment of Heart Failure (BB-META-HF), which included data from 11 large beta-blocker randomized trials in heart failure that had been published during 1993-2005. The analysis included data from 17,378 HFrEF patients, with 14,313 (82%) in sinus rhythm and 3,065 (18%) with atrial fibrillation. Follow-up data of patients on treatment was available for 15,007 of these patients.
Dr. Cleland and his associates showed in multivariate analyses that, when they controlled for several baseline demographic and clinical variables among patients in sinus rhythm who received a beta-blocker, the follow-up all-cause mortality fell by 36%, compared with placebo, in patients with a resting baseline heart rate of less than 70 bpm; by 21%, compared with placebo, in patients with a baseline heart rate of 70-90 bpm; and by 38%, compared with placebo, in patients with a baseline heart rate of more than 90 bpm. All three reductions were statistically significant. In contrast, among patients who also had atrial fibrillation beta-blocker treatment linked with no significant mortality reduction, compared with placebo, for patients with any baseline heart rate.
Concurrently with Dr. Cleland’s report at the meeting the results appeared online (J Amer Coll Cardiol. 2017 Apr 30. doi: 10.1016/j.jacc.2017.04.001).
[email protected]
On Twitter @mitchelzoler
The findings from this analysis have several implications. First, the association of reduced mortality with reduced heart rate occurred only in patients in sinus rhythm. The irregular heart rhythms in patients with atrial fibrillation may counterbalance any reverse remodeling effects that come from reducing heart rate.
Also, the beneficial effect of beta-blocker treatment was roughly similar regardless of whether baseline heart rate was high or low. This distinguishes beta-blockers from ivabradine, a drug that only reduces heart rate. The magnitude of benefit from ivabradine treatment depends on a patient’s baseline heart rate. The observation that beta-blockers do not have the same limitation suggests that the mechanism of action of beta-blockers may go beyond their heart rate effect. It may also result from the effect of beta-blockers on antagonizing toxic effects from beta-adrenergic stimulation.
The pooled analysis also showed that many patients with HFrEF in sinus rhythm continued to have a high heart rate despite beta-blocker treatment. These patients may get additional benefit from further treatment to reduce their heart rate, with an agent like ivabradine.
But we must be cautious in interpreting the findings because they represent a secondary analysis, and the endpoint studied does not take into account quality of life, exercise tolerance, heart rate control, and tachyarrhythmias. We need prospective, randomized trials of HFrEF patients in sinus rhythm and with atrial fibrillation to better understand how to optimally treat these different types of patients.
The findings highlight that beta-blockers remain a mainstay of treatment for patients with HFrEF in sinus rhythm, and that we have more limited treatment options for HFrEF patients with atrial fibrillation.
Michael Böhm, MD, is professor and director of the cardiology clinic at Saarland University Hospital in Homburg, Germany. He has received honoraria from Bayer, Medtronic, Servier, and Pfizer, and he was a coauthor on the report presented by Dr. Cleland. He made these comments as designated discussant for the study.
The findings from this analysis have several implications. First, the association of reduced mortality with reduced heart rate occurred only in patients in sinus rhythm. The irregular heart rhythms in patients with atrial fibrillation may counterbalance any reverse remodeling effects that come from reducing heart rate.
Also, the beneficial effect of beta-blocker treatment was roughly similar regardless of whether baseline heart rate was high or low. This distinguishes beta-blockers from ivabradine, a drug that only reduces heart rate. The magnitude of benefit from ivabradine treatment depends on a patient’s baseline heart rate. The observation that beta-blockers do not have the same limitation suggests that the mechanism of action of beta-blockers may go beyond their heart rate effect. It may also result from the effect of beta-blockers on antagonizing toxic effects from beta-adrenergic stimulation.
The pooled analysis also showed that many patients with HFrEF in sinus rhythm continued to have a high heart rate despite beta-blocker treatment. These patients may get additional benefit from further treatment to reduce their heart rate, with an agent like ivabradine.
But we must be cautious in interpreting the findings because they represent a secondary analysis, and the endpoint studied does not take into account quality of life, exercise tolerance, heart rate control, and tachyarrhythmias. We need prospective, randomized trials of HFrEF patients in sinus rhythm and with atrial fibrillation to better understand how to optimally treat these different types of patients.
The findings highlight that beta-blockers remain a mainstay of treatment for patients with HFrEF in sinus rhythm, and that we have more limited treatment options for HFrEF patients with atrial fibrillation.
Michael Böhm, MD, is professor and director of the cardiology clinic at Saarland University Hospital in Homburg, Germany. He has received honoraria from Bayer, Medtronic, Servier, and Pfizer, and he was a coauthor on the report presented by Dr. Cleland. He made these comments as designated discussant for the study.
The findings from this analysis have several implications. First, the association of reduced mortality with reduced heart rate occurred only in patients in sinus rhythm. The irregular heart rhythms in patients with atrial fibrillation may counterbalance any reverse remodeling effects that come from reducing heart rate.
Also, the beneficial effect of beta-blocker treatment was roughly similar regardless of whether baseline heart rate was high or low. This distinguishes beta-blockers from ivabradine, a drug that only reduces heart rate. The magnitude of benefit from ivabradine treatment depends on a patient’s baseline heart rate. The observation that beta-blockers do not have the same limitation suggests that the mechanism of action of beta-blockers may go beyond their heart rate effect. It may also result from the effect of beta-blockers on antagonizing toxic effects from beta-adrenergic stimulation.
The pooled analysis also showed that many patients with HFrEF in sinus rhythm continued to have a high heart rate despite beta-blocker treatment. These patients may get additional benefit from further treatment to reduce their heart rate, with an agent like ivabradine.
But we must be cautious in interpreting the findings because they represent a secondary analysis, and the endpoint studied does not take into account quality of life, exercise tolerance, heart rate control, and tachyarrhythmias. We need prospective, randomized trials of HFrEF patients in sinus rhythm and with atrial fibrillation to better understand how to optimally treat these different types of patients.
The findings highlight that beta-blockers remain a mainstay of treatment for patients with HFrEF in sinus rhythm, and that we have more limited treatment options for HFrEF patients with atrial fibrillation.
Michael Böhm, MD, is professor and director of the cardiology clinic at Saarland University Hospital in Homburg, Germany. He has received honoraria from Bayer, Medtronic, Servier, and Pfizer, and he was a coauthor on the report presented by Dr. Cleland. He made these comments as designated discussant for the study.
PARIS – Maximal beta-blocker treatment and lower heart rates are effective at cutting all-cause mortality in patients with heart failure with reduced ejection fraction (HFrEF) who are also in sinus rhythm, but it’s a totally different story for patients with similar heart failure plus atrial fibrillation. In the atrial fibrillation subgroup, treatment with a beta-blocker linked with no mortality benefit, and lower heart rates – below 70 beats per minute – appeared to actually link with worse patient survival, based on a meta-analysis of data from 11 beta-blocker trials with a total of more than 17,000 patients.
“Beta blockers may be doing good in heart failure patients with atrial fibrillation, but they also are doing harm that neutralizes any good they do.” In patients with HFrEF and atrial fibrillation, “I don’t like to see the heart rate below 80 beats per minute,” John G.F. Cleland, MD, said at a meeting held by the Heart Failure Association of the ESC.
“We’ve perhaps been too aggressive with heart-rate control in HFrEF patients with atrial fibrillation,” he added in an interview. In these patients “in the range of 60-100 bpm it doesn’t seem to make a lot of difference what the heart rate is, and, if it is less than 70 bpm, patients seem to do a little worse. When we treat these patients with a beta-blocker we don’t see benefit in any way that we’ve looked at the data.”
In contrast, among HFrEF patients in sinus rhythm “beta-blocker treatment is similarly effective regardless of what the baseline heart rate was. The benefit was as great when the baseline rate was 70 bpm or 90 bpm, so heart rate is not a great predictor of beta-blocker benefit in these patients. Patients who tolerated the full beta-blocker dosage had the greatest benefit, and patients who achieved the slowest heart rates also had the greatest benefit.”
In the multivariate models that Dr. Cleland and his associates tested in their meta-analysis, in HFrEF patients in sinus rhythm, the relationship between reduced heart rate and mortality benefit was stronger statistically than between beta-blocker dosage and reduced mortality, he said. “This suggests to me that, while we should use the targeted beta-blocker dosages when we can, it’s more important to achieve a target heart rate in these patients of 55-65 bpm.”
Dr. Cleland hypothesized, based on a report presented at the same meeting by a different research group, that reduced heart rate is not beneficial in HFrEF patients with atrial fibrillation because in this subgroup slower heart rates linked with an increased number of brief pauses in left ventricular pumping. These pauses may result in ventricular arrhythmias, he speculated. “It may be that beta-blockers are equally effective at slowing heart rate in patients with or without atrial fibrillation, but there is also harm from beta-blockers because they’re causing pauses in patients with atrial fibrillation,” he said.
These days, if he has a HFrEF patient with atrial fibrillation whose heart rate slows to 60 bpm, he will stop digoxin treatment if the patient is on that drug, and he will also reduce the beta-blocker dosage but not discontinue it.
The findings came from the Collaborative Systematic Overview of Randomized Controlled Trials of Beta-Blockers in the Treatment of Heart Failure (BB-META-HF), which included data from 11 large beta-blocker randomized trials in heart failure that had been published during 1993-2005. The analysis included data from 17,378 HFrEF patients, with 14,313 (82%) in sinus rhythm and 3,065 (18%) with atrial fibrillation. Follow-up data of patients on treatment was available for 15,007 of these patients.
Dr. Cleland and his associates showed in multivariate analyses that, when they controlled for several baseline demographic and clinical variables among patients in sinus rhythm who received a beta-blocker, the follow-up all-cause mortality fell by 36%, compared with placebo, in patients with a resting baseline heart rate of less than 70 bpm; by 21%, compared with placebo, in patients with a baseline heart rate of 70-90 bpm; and by 38%, compared with placebo, in patients with a baseline heart rate of more than 90 bpm. All three reductions were statistically significant. In contrast, among patients who also had atrial fibrillation beta-blocker treatment linked with no significant mortality reduction, compared with placebo, for patients with any baseline heart rate.
Concurrently with Dr. Cleland’s report at the meeting the results appeared online (J Amer Coll Cardiol. 2017 Apr 30. doi: 10.1016/j.jacc.2017.04.001).
[email protected]
On Twitter @mitchelzoler
PARIS – Maximal beta-blocker treatment and lower heart rates are effective at cutting all-cause mortality in patients with heart failure with reduced ejection fraction (HFrEF) who are also in sinus rhythm, but it’s a totally different story for patients with similar heart failure plus atrial fibrillation. In the atrial fibrillation subgroup, treatment with a beta-blocker linked with no mortality benefit, and lower heart rates – below 70 beats per minute – appeared to actually link with worse patient survival, based on a meta-analysis of data from 11 beta-blocker trials with a total of more than 17,000 patients.
“Beta blockers may be doing good in heart failure patients with atrial fibrillation, but they also are doing harm that neutralizes any good they do.” In patients with HFrEF and atrial fibrillation, “I don’t like to see the heart rate below 80 beats per minute,” John G.F. Cleland, MD, said at a meeting held by the Heart Failure Association of the ESC.
“We’ve perhaps been too aggressive with heart-rate control in HFrEF patients with atrial fibrillation,” he added in an interview. In these patients “in the range of 60-100 bpm it doesn’t seem to make a lot of difference what the heart rate is, and, if it is less than 70 bpm, patients seem to do a little worse. When we treat these patients with a beta-blocker we don’t see benefit in any way that we’ve looked at the data.”
In contrast, among HFrEF patients in sinus rhythm “beta-blocker treatment is similarly effective regardless of what the baseline heart rate was. The benefit was as great when the baseline rate was 70 bpm or 90 bpm, so heart rate is not a great predictor of beta-blocker benefit in these patients. Patients who tolerated the full beta-blocker dosage had the greatest benefit, and patients who achieved the slowest heart rates also had the greatest benefit.”
In the multivariate models that Dr. Cleland and his associates tested in their meta-analysis, in HFrEF patients in sinus rhythm, the relationship between reduced heart rate and mortality benefit was stronger statistically than between beta-blocker dosage and reduced mortality, he said. “This suggests to me that, while we should use the targeted beta-blocker dosages when we can, it’s more important to achieve a target heart rate in these patients of 55-65 bpm.”
Dr. Cleland hypothesized, based on a report presented at the same meeting by a different research group, that reduced heart rate is not beneficial in HFrEF patients with atrial fibrillation because in this subgroup slower heart rates linked with an increased number of brief pauses in left ventricular pumping. These pauses may result in ventricular arrhythmias, he speculated. “It may be that beta-blockers are equally effective at slowing heart rate in patients with or without atrial fibrillation, but there is also harm from beta-blockers because they’re causing pauses in patients with atrial fibrillation,” he said.
These days, if he has a HFrEF patient with atrial fibrillation whose heart rate slows to 60 bpm, he will stop digoxin treatment if the patient is on that drug, and he will also reduce the beta-blocker dosage but not discontinue it.
The findings came from the Collaborative Systematic Overview of Randomized Controlled Trials of Beta-Blockers in the Treatment of Heart Failure (BB-META-HF), which included data from 11 large beta-blocker randomized trials in heart failure that had been published during 1993-2005. The analysis included data from 17,378 HFrEF patients, with 14,313 (82%) in sinus rhythm and 3,065 (18%) with atrial fibrillation. Follow-up data of patients on treatment was available for 15,007 of these patients.
Dr. Cleland and his associates showed in multivariate analyses that, when they controlled for several baseline demographic and clinical variables among patients in sinus rhythm who received a beta-blocker, the follow-up all-cause mortality fell by 36%, compared with placebo, in patients with a resting baseline heart rate of less than 70 bpm; by 21%, compared with placebo, in patients with a baseline heart rate of 70-90 bpm; and by 38%, compared with placebo, in patients with a baseline heart rate of more than 90 bpm. All three reductions were statistically significant. In contrast, among patients who also had atrial fibrillation beta-blocker treatment linked with no significant mortality reduction, compared with placebo, for patients with any baseline heart rate.
Concurrently with Dr. Cleland’s report at the meeting the results appeared online (J Amer Coll Cardiol. 2017 Apr 30. doi: 10.1016/j.jacc.2017.04.001).
[email protected]
On Twitter @mitchelzoler
AT HEART FAILURE 2017
Key clinical point:
Major finding: All-cause mortality was similar in patients with HFrEF and atrial fibrillation regardless of whether they received a beta-blocker or placebo.
Data source: BB-META-HF, a meta-analysis of 11 beta-blocker treatment trials with 17,378 HFrEF patients.
Disclosures: BB-META-HF received funding from Menarini and GlaxoSmithKline. Dr. Cleland has received research funding and honoraria from GlaxoSmithKline.
Immediate-completion lymph node dissection in metastatic melanoma
In patients who have melanoma with sentinel node metastasis, immediate-completion lymph node dissection doesn’t improve melanoma-specific survival, compared with nodal observation using ultrasound, according to a report published online June 8 in the New England Journal of Medicine.
Immediate-completion lymph node dissection – removal of the remaining regional lymph nodes after sentinel node excision – is usually recommended for patients found to have sentinel node metastasis, even though the evidence supporting this practice is inconclusive. A large prospective phase III trial was performed to compare outcomes with this approach against outcomes in patients who instead underwent observation using frequent nodal ultrasound and had lymph node dissection only if nodal recurrence developed, said Mark B. Faries, MD, of the John Wayne Cancer Institute at Saint John’s Health Center, Santa Monica, Calif., and his associates.
The second Multicenter Selective Lymphadenectomy Trial (MSLT-II) involved 1,939 adults at 63 medical centers who had clinically localized cutaneous melanoma of intermediate thickness, at least one tumor-positive sentinel node as determined by standard pathological assessment or a quantitative reverse transcriptase–polymerase chain reaction assay, and a life expectancy of 10 years or more. These participants were randomly assigned to immediate-completion node dissection (971 patients) or nodal observation (931 patients).
At 3 years of follow-up, the primary end point – the rate of melanoma-specific survival – was the same in the immediate-dissection group as in the observation group (86%). Further analyses showed that no subgroup of patients, including those defined by tumor burden, showed a significant melanoma-specific benefit from immediate completion lymph node dissection. However, the immediate-dissection group had a significant disadvantage regarding adverse events; 24.1% developed lymphedema, compared with only 6.3% of the observation group.
Secondary end points slightly favored immediate dissection. At 3 years, the rate of disease-free survival was slightly higher in that group (68%) than in the observation group (63%), and the rate of disease control in the regional nodes was higher (92% vs. 77%). However, “differences with respect to the secondary end points must be interpreted with caution,” Dr. Faries and his associates said (N Engl J Med. 2017 Jun 8. doi: 10.1056/NEJMoa1613210).
“Overall, some value may be derived from immediate-completion lymph node dissection with regard to staging and an increased rate of regional disease control. However, this value comes at the cost of increased complications,” the investigators said.
This study was supported by the National Cancer Institute, the Borstein Family Foundation, Amy’s Foundation, the Dr. Miriam and Sheldon G. Adelson Medical Research Foundation, and the John Wayne Cancer Institute Auxiliary. Dr. Faries reported serving on advisory boards for Myriad Genetic Laboratories, Amgen, and Immune Design; his associates reported ties to numerous industry sources.
The findings of Dr. Faries and his associates are definitive, unequivocal, and completely consistent with previously published results of retrospective series and one other prospective randomized trial: Immediate completion lymph node dissection doesn’t increase melanoma-specific survival, compared with active ultrasound surveillance of the nodal basin.
These findings should be construed as practice changing.
It appears that in melanoma, as in so many other cancers, the elective removal of clinically negative nodes has rarely if ever been shown to improve disease-specific survival.
Daniel Coit, MD, is at Memorial Sloan Kettering Cancer Center in New York. He reported receiving personal fees for serving as an advisory board member for the MSLT-II trial. Dr. Coit made these remarks in an editorial accompanying Dr. Faries’ report (N Engl J Med. 2017 Jun 8. doi: 10.1056/NEJMe1704290 ).
The findings of Dr. Faries and his associates are definitive, unequivocal, and completely consistent with previously published results of retrospective series and one other prospective randomized trial: Immediate completion lymph node dissection doesn’t increase melanoma-specific survival, compared with active ultrasound surveillance of the nodal basin.
These findings should be construed as practice changing.
It appears that in melanoma, as in so many other cancers, the elective removal of clinically negative nodes has rarely if ever been shown to improve disease-specific survival.
Daniel Coit, MD, is at Memorial Sloan Kettering Cancer Center in New York. He reported receiving personal fees for serving as an advisory board member for the MSLT-II trial. Dr. Coit made these remarks in an editorial accompanying Dr. Faries’ report (N Engl J Med. 2017 Jun 8. doi: 10.1056/NEJMe1704290 ).
The findings of Dr. Faries and his associates are definitive, unequivocal, and completely consistent with previously published results of retrospective series and one other prospective randomized trial: Immediate completion lymph node dissection doesn’t increase melanoma-specific survival, compared with active ultrasound surveillance of the nodal basin.
These findings should be construed as practice changing.
It appears that in melanoma, as in so many other cancers, the elective removal of clinically negative nodes has rarely if ever been shown to improve disease-specific survival.
Daniel Coit, MD, is at Memorial Sloan Kettering Cancer Center in New York. He reported receiving personal fees for serving as an advisory board member for the MSLT-II trial. Dr. Coit made these remarks in an editorial accompanying Dr. Faries’ report (N Engl J Med. 2017 Jun 8. doi: 10.1056/NEJMe1704290 ).
In patients who have melanoma with sentinel node metastasis, immediate-completion lymph node dissection doesn’t improve melanoma-specific survival, compared with nodal observation using ultrasound, according to a report published online June 8 in the New England Journal of Medicine.
Immediate-completion lymph node dissection – removal of the remaining regional lymph nodes after sentinel node excision – is usually recommended for patients found to have sentinel node metastasis, even though the evidence supporting this practice is inconclusive. A large prospective phase III trial was performed to compare outcomes with this approach against outcomes in patients who instead underwent observation using frequent nodal ultrasound and had lymph node dissection only if nodal recurrence developed, said Mark B. Faries, MD, of the John Wayne Cancer Institute at Saint John’s Health Center, Santa Monica, Calif., and his associates.
The second Multicenter Selective Lymphadenectomy Trial (MSLT-II) involved 1,939 adults at 63 medical centers who had clinically localized cutaneous melanoma of intermediate thickness, at least one tumor-positive sentinel node as determined by standard pathological assessment or a quantitative reverse transcriptase–polymerase chain reaction assay, and a life expectancy of 10 years or more. These participants were randomly assigned to immediate-completion node dissection (971 patients) or nodal observation (931 patients).
At 3 years of follow-up, the primary end point – the rate of melanoma-specific survival – was the same in the immediate-dissection group as in the observation group (86%). Further analyses showed that no subgroup of patients, including those defined by tumor burden, showed a significant melanoma-specific benefit from immediate completion lymph node dissection. However, the immediate-dissection group had a significant disadvantage regarding adverse events; 24.1% developed lymphedema, compared with only 6.3% of the observation group.
Secondary end points slightly favored immediate dissection. At 3 years, the rate of disease-free survival was slightly higher in that group (68%) than in the observation group (63%), and the rate of disease control in the regional nodes was higher (92% vs. 77%). However, “differences with respect to the secondary end points must be interpreted with caution,” Dr. Faries and his associates said (N Engl J Med. 2017 Jun 8. doi: 10.1056/NEJMoa1613210).
“Overall, some value may be derived from immediate-completion lymph node dissection with regard to staging and an increased rate of regional disease control. However, this value comes at the cost of increased complications,” the investigators said.
This study was supported by the National Cancer Institute, the Borstein Family Foundation, Amy’s Foundation, the Dr. Miriam and Sheldon G. Adelson Medical Research Foundation, and the John Wayne Cancer Institute Auxiliary. Dr. Faries reported serving on advisory boards for Myriad Genetic Laboratories, Amgen, and Immune Design; his associates reported ties to numerous industry sources.
In patients who have melanoma with sentinel node metastasis, immediate-completion lymph node dissection doesn’t improve melanoma-specific survival, compared with nodal observation using ultrasound, according to a report published online June 8 in the New England Journal of Medicine.
Immediate-completion lymph node dissection – removal of the remaining regional lymph nodes after sentinel node excision – is usually recommended for patients found to have sentinel node metastasis, even though the evidence supporting this practice is inconclusive. A large prospective phase III trial was performed to compare outcomes with this approach against outcomes in patients who instead underwent observation using frequent nodal ultrasound and had lymph node dissection only if nodal recurrence developed, said Mark B. Faries, MD, of the John Wayne Cancer Institute at Saint John’s Health Center, Santa Monica, Calif., and his associates.
The second Multicenter Selective Lymphadenectomy Trial (MSLT-II) involved 1,939 adults at 63 medical centers who had clinically localized cutaneous melanoma of intermediate thickness, at least one tumor-positive sentinel node as determined by standard pathological assessment or a quantitative reverse transcriptase–polymerase chain reaction assay, and a life expectancy of 10 years or more. These participants were randomly assigned to immediate-completion node dissection (971 patients) or nodal observation (931 patients).
At 3 years of follow-up, the primary end point – the rate of melanoma-specific survival – was the same in the immediate-dissection group as in the observation group (86%). Further analyses showed that no subgroup of patients, including those defined by tumor burden, showed a significant melanoma-specific benefit from immediate completion lymph node dissection. However, the immediate-dissection group had a significant disadvantage regarding adverse events; 24.1% developed lymphedema, compared with only 6.3% of the observation group.
Secondary end points slightly favored immediate dissection. At 3 years, the rate of disease-free survival was slightly higher in that group (68%) than in the observation group (63%), and the rate of disease control in the regional nodes was higher (92% vs. 77%). However, “differences with respect to the secondary end points must be interpreted with caution,” Dr. Faries and his associates said (N Engl J Med. 2017 Jun 8. doi: 10.1056/NEJMoa1613210).
“Overall, some value may be derived from immediate-completion lymph node dissection with regard to staging and an increased rate of regional disease control. However, this value comes at the cost of increased complications,” the investigators said.
This study was supported by the National Cancer Institute, the Borstein Family Foundation, Amy’s Foundation, the Dr. Miriam and Sheldon G. Adelson Medical Research Foundation, and the John Wayne Cancer Institute Auxiliary. Dr. Faries reported serving on advisory boards for Myriad Genetic Laboratories, Amgen, and Immune Design; his associates reported ties to numerous industry sources.
FROM THE NEW ENGLAND JOURNAL OF MEDICINE
Key clinical point:
Major finding: At 3 years of follow-up, the primary end point – the rate of melanoma-specific survival – was the same in the immediate-dissection group as in the observation group (86%).
Data source: A prospective international randomized phase-III trial involving 1,939 adults followed for a median of 43 months at 63 medical centers.
Disclosures: This study was supported by the National Cancer Institute, the Borstein Family Foundation, Amy’s Foundation, the Dr. Miriam and Sheldon G. Adelson Medical Research Foundation, and the John Wayne Cancer Institute Auxiliary. Dr. Faries reported serving on advisory boards for Myriad Genetic Laboratories, Amgen, and Immune Design; his associates reported ties to numerous industry sources.
Quality measures and diabetic foot care: What endos need to know
SAN DIEGO – As quality measures in health care continue to grow in importance, it behooves endocrinologists to pay more attention to the mental as well as physical well-being of patients with diabetic foot conditions before and after treatment.
“We’re on a path from volume-based practice to really showing that what we’re doing actually works, and diabetic foot is going to be caught up in there. It’s really important that we understand how [the diabetic foot] is affecting our patients physically and mentally. We’ll have to measure what we do and see it if improves,” said Dane K. Wukich, MD, professor and Dr. Charles F. Gregory distinguished chair of the department of orthopedic surgery at University of Texas Southwestern Medical Center, Dallas, in a presentation at the annual scientific sessions of the American Diabetes Association.
Foot amputations are becoming less common but remain a dreaded complication of diabetes. The Centers for Disease Control and Prevention has estimated that hospital discharges for lower-extremity amputation among people with diabetes declined dramatically – by as much as 50% or more depending on the type – from 2003 to 2009. Still, in 2009, the levels were 1.8 cases per 1,000 patients for toe amputation, 0.5 cases per 1,000 patients for foot amputation, and 0.9 and 0.4 cases per 1,000 for below- and above-knee amputation, respectively.
The commonly used 36-Item Short Form Quality of Life Survey (SF-36 QOL) may offer useful insight into quality of life in diabetic foot patients after treatment, but it is not precise enough to gauge patients’ mental health issues.
Patient-reported outcomes will become more important in diabetic foot treatments, Dr. Wukich said, “but sometimes a successful outcome in what we do does not always equate to an improvement in quality of life.”
For example, he said, it’s true that patients with diabetic foot disease fear losing their legs more than death. He led a study published earlier this year that found patients with diabetic foot conditions were 79% more likely to say amputation is their greatest fear, topping even death (odds ratio, 1.79; 96% confidence interval, 1.13-2.81; P = .01 [Foot Ankle Spec. 2017 Feb 1]).
But “saving a foot that’s not in a good position” can be devastating for a patient, even worse than amputation, he said.
Quality of life measurements will provide insight for doctors and insurers as they track the success of diabetic foot treatments. But Dr. Wukich said there’s a big mystery about one aspect of quality of life (QOL) measurements: Why don’t diabetic foot problems significantly disrupt the mental component of quality of life measures?
He coauthored a 2014 study – of 50 patients with diabetes and Charcot foot and 56 patients with diabetes only – that found a significant gap in physical QOL measures (P less than .001) but nearly identical measures in mental QOL (P less than .644) (Foot Ankle Int. 2014;35[3]195-200).
He asked: “How could somebody have a Charcot problem with a deformed foot, walking around in a boot for years and not have it affect their mental quality of life?”
One possibility is that neuropathy reduces the mental burden of pain because it hurts less, he suggested. But the answer could lie in the strategies used in calculating scores commonly used in the SF-36 QOL tool, he said. Recent unpublished research suggests that the orthogonal calculation may artificially increase mental QOL scores in these cases, he said. The oblique method may be more accurate, he said, but more study is needed.
In the big picture, he said, “assessing quality of life can help us establish the optimal methods of treatment, evaluate treatment outcomes, and identify patients at risk of mortality, admission, and depression. It’s going to guide us in the pay-for-performance arena.”
During the meeting, Dr. Wukich was presented with the American Diabetes Associations 2017 Roger Pecoraro Award, which recognizes a researcher “who has made significant scientific contributions and demonstrates an untiring commitment to improving the understanding of the detection, treatment, and prevention of diabetic foot complications.”
Dr. Wukich reported that he has no relevant financial disclosures.
SAN DIEGO – As quality measures in health care continue to grow in importance, it behooves endocrinologists to pay more attention to the mental as well as physical well-being of patients with diabetic foot conditions before and after treatment.
“We’re on a path from volume-based practice to really showing that what we’re doing actually works, and diabetic foot is going to be caught up in there. It’s really important that we understand how [the diabetic foot] is affecting our patients physically and mentally. We’ll have to measure what we do and see it if improves,” said Dane K. Wukich, MD, professor and Dr. Charles F. Gregory distinguished chair of the department of orthopedic surgery at University of Texas Southwestern Medical Center, Dallas, in a presentation at the annual scientific sessions of the American Diabetes Association.
Foot amputations are becoming less common but remain a dreaded complication of diabetes. The Centers for Disease Control and Prevention has estimated that hospital discharges for lower-extremity amputation among people with diabetes declined dramatically – by as much as 50% or more depending on the type – from 2003 to 2009. Still, in 2009, the levels were 1.8 cases per 1,000 patients for toe amputation, 0.5 cases per 1,000 patients for foot amputation, and 0.9 and 0.4 cases per 1,000 for below- and above-knee amputation, respectively.
The commonly used 36-Item Short Form Quality of Life Survey (SF-36 QOL) may offer useful insight into quality of life in diabetic foot patients after treatment, but it is not precise enough to gauge patients’ mental health issues.
Patient-reported outcomes will become more important in diabetic foot treatments, Dr. Wukich said, “but sometimes a successful outcome in what we do does not always equate to an improvement in quality of life.”
For example, he said, it’s true that patients with diabetic foot disease fear losing their legs more than death. He led a study published earlier this year that found patients with diabetic foot conditions were 79% more likely to say amputation is their greatest fear, topping even death (odds ratio, 1.79; 96% confidence interval, 1.13-2.81; P = .01 [Foot Ankle Spec. 2017 Feb 1]).
But “saving a foot that’s not in a good position” can be devastating for a patient, even worse than amputation, he said.
Quality of life measurements will provide insight for doctors and insurers as they track the success of diabetic foot treatments. But Dr. Wukich said there’s a big mystery about one aspect of quality of life (QOL) measurements: Why don’t diabetic foot problems significantly disrupt the mental component of quality of life measures?
He coauthored a 2014 study – of 50 patients with diabetes and Charcot foot and 56 patients with diabetes only – that found a significant gap in physical QOL measures (P less than .001) but nearly identical measures in mental QOL (P less than .644) (Foot Ankle Int. 2014;35[3]195-200).
He asked: “How could somebody have a Charcot problem with a deformed foot, walking around in a boot for years and not have it affect their mental quality of life?”
One possibility is that neuropathy reduces the mental burden of pain because it hurts less, he suggested. But the answer could lie in the strategies used in calculating scores commonly used in the SF-36 QOL tool, he said. Recent unpublished research suggests that the orthogonal calculation may artificially increase mental QOL scores in these cases, he said. The oblique method may be more accurate, he said, but more study is needed.
In the big picture, he said, “assessing quality of life can help us establish the optimal methods of treatment, evaluate treatment outcomes, and identify patients at risk of mortality, admission, and depression. It’s going to guide us in the pay-for-performance arena.”
During the meeting, Dr. Wukich was presented with the American Diabetes Associations 2017 Roger Pecoraro Award, which recognizes a researcher “who has made significant scientific contributions and demonstrates an untiring commitment to improving the understanding of the detection, treatment, and prevention of diabetic foot complications.”
Dr. Wukich reported that he has no relevant financial disclosures.
SAN DIEGO – As quality measures in health care continue to grow in importance, it behooves endocrinologists to pay more attention to the mental as well as physical well-being of patients with diabetic foot conditions before and after treatment.
“We’re on a path from volume-based practice to really showing that what we’re doing actually works, and diabetic foot is going to be caught up in there. It’s really important that we understand how [the diabetic foot] is affecting our patients physically and mentally. We’ll have to measure what we do and see it if improves,” said Dane K. Wukich, MD, professor and Dr. Charles F. Gregory distinguished chair of the department of orthopedic surgery at University of Texas Southwestern Medical Center, Dallas, in a presentation at the annual scientific sessions of the American Diabetes Association.
Foot amputations are becoming less common but remain a dreaded complication of diabetes. The Centers for Disease Control and Prevention has estimated that hospital discharges for lower-extremity amputation among people with diabetes declined dramatically – by as much as 50% or more depending on the type – from 2003 to 2009. Still, in 2009, the levels were 1.8 cases per 1,000 patients for toe amputation, 0.5 cases per 1,000 patients for foot amputation, and 0.9 and 0.4 cases per 1,000 for below- and above-knee amputation, respectively.
The commonly used 36-Item Short Form Quality of Life Survey (SF-36 QOL) may offer useful insight into quality of life in diabetic foot patients after treatment, but it is not precise enough to gauge patients’ mental health issues.
Patient-reported outcomes will become more important in diabetic foot treatments, Dr. Wukich said, “but sometimes a successful outcome in what we do does not always equate to an improvement in quality of life.”
For example, he said, it’s true that patients with diabetic foot disease fear losing their legs more than death. He led a study published earlier this year that found patients with diabetic foot conditions were 79% more likely to say amputation is their greatest fear, topping even death (odds ratio, 1.79; 96% confidence interval, 1.13-2.81; P = .01 [Foot Ankle Spec. 2017 Feb 1]).
But “saving a foot that’s not in a good position” can be devastating for a patient, even worse than amputation, he said.
Quality of life measurements will provide insight for doctors and insurers as they track the success of diabetic foot treatments. But Dr. Wukich said there’s a big mystery about one aspect of quality of life (QOL) measurements: Why don’t diabetic foot problems significantly disrupt the mental component of quality of life measures?
He coauthored a 2014 study – of 50 patients with diabetes and Charcot foot and 56 patients with diabetes only – that found a significant gap in physical QOL measures (P less than .001) but nearly identical measures in mental QOL (P less than .644) (Foot Ankle Int. 2014;35[3]195-200).
He asked: “How could somebody have a Charcot problem with a deformed foot, walking around in a boot for years and not have it affect their mental quality of life?”
One possibility is that neuropathy reduces the mental burden of pain because it hurts less, he suggested. But the answer could lie in the strategies used in calculating scores commonly used in the SF-36 QOL tool, he said. Recent unpublished research suggests that the orthogonal calculation may artificially increase mental QOL scores in these cases, he said. The oblique method may be more accurate, he said, but more study is needed.
In the big picture, he said, “assessing quality of life can help us establish the optimal methods of treatment, evaluate treatment outcomes, and identify patients at risk of mortality, admission, and depression. It’s going to guide us in the pay-for-performance arena.”
During the meeting, Dr. Wukich was presented with the American Diabetes Associations 2017 Roger Pecoraro Award, which recognizes a researcher “who has made significant scientific contributions and demonstrates an untiring commitment to improving the understanding of the detection, treatment, and prevention of diabetic foot complications.”
Dr. Wukich reported that he has no relevant financial disclosures.
AT THE ADA ANNUAL SCIENTIFIC SESSIONS
IL-23 antibody risankizumab can effect, maintain remission in Crohn’s
CHICAGO – Subcutaneous risankizumab maintained clinical remission for half a year in 76% of Crohn’s disease patients who responded to it during an induction study.
The interleukin-23 antibody (ABBV-066; AbbVie) also maintained endoscopic remission in 52% of patients who entered the open-label maintenance phase of the 52-week study, Brian Feagan, MD, said at the annual Digestive Disease Week®.
The three-phase study enrolled 121 patients with moderate to severe Crohn’s disease. The first 12 weeks consisted of intravenous induction therapy; patients were randomized to monthly infusions of risankizumab 200 mg or 600 mg or placebo. The endpoint was deep clinical remission. Patients who achieved remission exited the study. Results of this study were published in April (Lancet.2017;389[10080]:1699-09).
Phase II included only the patients who did not achieve deep clinical remission. They all received open label 600 mg risankizumab infusions every 4 weeks from weeks 14-26. The endpoints were clinical and endoscopic remission.
Phase III, on which Dr. Feagan reported, included the patients who achieved remission in phase II. These patients continued with subcutaneous risankizumab 180 mg every 8 weeks, from week 26-52.
Patients were an average of about 38 years old, with mean disease duration of 16 years. Their median Crohn’s Disease Activity Index (CDAI) score was around 300; their mean Crohn’s Disease Endoscopic Index score was 12. About a quarter had already taken at least one tumor necrosis factor–alpha inhibitor; half of those had taken at least two of those drugs.
At the end of the first induction period, 25 taking the study drug and 6 taking placebo achieved clinical remission (31% vs. 15%). Those taking 600 mg did better than those taking 200 mg (37% vs. 9%).
Patients who didn’t achieve deep clinical remission (a CDAI of less than 150 plus endoscopic remission) entered into the open-label reinduction phase; all received monthly 600-mg infusions from weeks 14 to 26. Of these, 62 achieved clinical remission and entered the open-label maintenance phase.
By week 52, the majority of patients were still in clinical remission, although this varied by the original treatment group: 76% of those first randomized to 600 mg, 59% of those randomized to 200 mg, and 79% of those randomized to placebo. Endoscopic remission was maintained in 52% of the 600-mg group, 23% of the 200-mg group, and 32% of the placebo group.
Deep remission occurred in a subset of patients: 43% of the 600-mg group, 13.6% of the 200-mg group, and 31.6% of the placebo group.
Dr. Feagan also said C-reactive protein levels remained suppressed in the maintenance period. Patients who entered that period had experienced a mean drop of about 9 mg/L in CRP. By week 52, this had risen slightly, but the median decrease was still around 8 mg/L from baseline measures.
There were 11 drug-related adverse events; these were severe in five patients, causing two to withdraw. There were 22 infections during the study, one of which was serious, but no cases of tuberculosis, cancer, or fungal or opportunistic infections.
“We did not see any new or unexpected safety signals,” Dr. Feagan said. “The drug was well tolerated and appears safe.”
This study showed a superior response for the 600-mg induction dose, but Dr. Feagan said the company may explore higher doses before making a final determination. Last November, the Food and Drug Administration granted Orphan Drug Designation to risankizumab for the investigational treatment of Crohn’s disease in pediatric patients. The company is also investigating it in psoriasis; it recently outperformed ustekinumab in a small phase II study of patients with moderate to severe psoriasis.
The study was funded by Boehringer Ingelheim. Dr. Feagan reported financial relationships with AbbVie and Boehringer Ingelheim.
[email protected]
On Twitter @alz_gal
CHICAGO – Subcutaneous risankizumab maintained clinical remission for half a year in 76% of Crohn’s disease patients who responded to it during an induction study.
The interleukin-23 antibody (ABBV-066; AbbVie) also maintained endoscopic remission in 52% of patients who entered the open-label maintenance phase of the 52-week study, Brian Feagan, MD, said at the annual Digestive Disease Week®.
The three-phase study enrolled 121 patients with moderate to severe Crohn’s disease. The first 12 weeks consisted of intravenous induction therapy; patients were randomized to monthly infusions of risankizumab 200 mg or 600 mg or placebo. The endpoint was deep clinical remission. Patients who achieved remission exited the study. Results of this study were published in April (Lancet.2017;389[10080]:1699-09).
Phase II included only the patients who did not achieve deep clinical remission. They all received open label 600 mg risankizumab infusions every 4 weeks from weeks 14-26. The endpoints were clinical and endoscopic remission.
Phase III, on which Dr. Feagan reported, included the patients who achieved remission in phase II. These patients continued with subcutaneous risankizumab 180 mg every 8 weeks, from week 26-52.
Patients were an average of about 38 years old, with mean disease duration of 16 years. Their median Crohn’s Disease Activity Index (CDAI) score was around 300; their mean Crohn’s Disease Endoscopic Index score was 12. About a quarter had already taken at least one tumor necrosis factor–alpha inhibitor; half of those had taken at least two of those drugs.
At the end of the first induction period, 25 taking the study drug and 6 taking placebo achieved clinical remission (31% vs. 15%). Those taking 600 mg did better than those taking 200 mg (37% vs. 9%).
Patients who didn’t achieve deep clinical remission (a CDAI of less than 150 plus endoscopic remission) entered into the open-label reinduction phase; all received monthly 600-mg infusions from weeks 14 to 26. Of these, 62 achieved clinical remission and entered the open-label maintenance phase.
By week 52, the majority of patients were still in clinical remission, although this varied by the original treatment group: 76% of those first randomized to 600 mg, 59% of those randomized to 200 mg, and 79% of those randomized to placebo. Endoscopic remission was maintained in 52% of the 600-mg group, 23% of the 200-mg group, and 32% of the placebo group.
Deep remission occurred in a subset of patients: 43% of the 600-mg group, 13.6% of the 200-mg group, and 31.6% of the placebo group.
Dr. Feagan also said C-reactive protein levels remained suppressed in the maintenance period. Patients who entered that period had experienced a mean drop of about 9 mg/L in CRP. By week 52, this had risen slightly, but the median decrease was still around 8 mg/L from baseline measures.
There were 11 drug-related adverse events; these were severe in five patients, causing two to withdraw. There were 22 infections during the study, one of which was serious, but no cases of tuberculosis, cancer, or fungal or opportunistic infections.
“We did not see any new or unexpected safety signals,” Dr. Feagan said. “The drug was well tolerated and appears safe.”
This study showed a superior response for the 600-mg induction dose, but Dr. Feagan said the company may explore higher doses before making a final determination. Last November, the Food and Drug Administration granted Orphan Drug Designation to risankizumab for the investigational treatment of Crohn’s disease in pediatric patients. The company is also investigating it in psoriasis; it recently outperformed ustekinumab in a small phase II study of patients with moderate to severe psoriasis.
The study was funded by Boehringer Ingelheim. Dr. Feagan reported financial relationships with AbbVie and Boehringer Ingelheim.
[email protected]
On Twitter @alz_gal
CHICAGO – Subcutaneous risankizumab maintained clinical remission for half a year in 76% of Crohn’s disease patients who responded to it during an induction study.
The interleukin-23 antibody (ABBV-066; AbbVie) also maintained endoscopic remission in 52% of patients who entered the open-label maintenance phase of the 52-week study, Brian Feagan, MD, said at the annual Digestive Disease Week®.
The three-phase study enrolled 121 patients with moderate to severe Crohn’s disease. The first 12 weeks consisted of intravenous induction therapy; patients were randomized to monthly infusions of risankizumab 200 mg or 600 mg or placebo. The endpoint was deep clinical remission. Patients who achieved remission exited the study. Results of this study were published in April (Lancet.2017;389[10080]:1699-09).
Phase II included only the patients who did not achieve deep clinical remission. They all received open label 600 mg risankizumab infusions every 4 weeks from weeks 14-26. The endpoints were clinical and endoscopic remission.
Phase III, on which Dr. Feagan reported, included the patients who achieved remission in phase II. These patients continued with subcutaneous risankizumab 180 mg every 8 weeks, from week 26-52.
Patients were an average of about 38 years old, with mean disease duration of 16 years. Their median Crohn’s Disease Activity Index (CDAI) score was around 300; their mean Crohn’s Disease Endoscopic Index score was 12. About a quarter had already taken at least one tumor necrosis factor–alpha inhibitor; half of those had taken at least two of those drugs.
At the end of the first induction period, 25 taking the study drug and 6 taking placebo achieved clinical remission (31% vs. 15%). Those taking 600 mg did better than those taking 200 mg (37% vs. 9%).
Patients who didn’t achieve deep clinical remission (a CDAI of less than 150 plus endoscopic remission) entered into the open-label reinduction phase; all received monthly 600-mg infusions from weeks 14 to 26. Of these, 62 achieved clinical remission and entered the open-label maintenance phase.
By week 52, the majority of patients were still in clinical remission, although this varied by the original treatment group: 76% of those first randomized to 600 mg, 59% of those randomized to 200 mg, and 79% of those randomized to placebo. Endoscopic remission was maintained in 52% of the 600-mg group, 23% of the 200-mg group, and 32% of the placebo group.
Deep remission occurred in a subset of patients: 43% of the 600-mg group, 13.6% of the 200-mg group, and 31.6% of the placebo group.
Dr. Feagan also said C-reactive protein levels remained suppressed in the maintenance period. Patients who entered that period had experienced a mean drop of about 9 mg/L in CRP. By week 52, this had risen slightly, but the median decrease was still around 8 mg/L from baseline measures.
There were 11 drug-related adverse events; these were severe in five patients, causing two to withdraw. There were 22 infections during the study, one of which was serious, but no cases of tuberculosis, cancer, or fungal or opportunistic infections.
“We did not see any new or unexpected safety signals,” Dr. Feagan said. “The drug was well tolerated and appears safe.”
This study showed a superior response for the 600-mg induction dose, but Dr. Feagan said the company may explore higher doses before making a final determination. Last November, the Food and Drug Administration granted Orphan Drug Designation to risankizumab for the investigational treatment of Crohn’s disease in pediatric patients. The company is also investigating it in psoriasis; it recently outperformed ustekinumab in a small phase II study of patients with moderate to severe psoriasis.
The study was funded by Boehringer Ingelheim. Dr. Feagan reported financial relationships with AbbVie and Boehringer Ingelheim.
[email protected]
On Twitter @alz_gal
AT DDW
Key clinical point:
Major finding: By week 52, clinical remission was maintained in 76% of those first randomized to 600 mg, 59% of those randomized to 200 mg, and 79% of those randomized to placebo.
Disclosures: Dr. Feagan reported financial relationships with Boehringer Ingelheim and AbbVie.