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MDedge conference coverage features onsite reporting of the latest study results and expert perspectives from leading researchers.
Newer DMTs are more effective than injectable DMTs in pediatric MS
Nevertheless, all DMTs reduce children’s annualized relapse rate (ARR), according to results presented at the 2020 CNS-ICNA Conjoint Meeting, held virtually this year.
“Our study adds weight to the argument for an imminent shift in clinical practice toward the use of newer, more efficacious DMTs in the first instance,” said Omar Abdel-Mannan, MD, of Great Ormond Street Hospital in London. MRI activity continues among patients treated with DMTs, and the number of relapses is highest in the period following diagnosis. But because the effect of treatment on brain atrophy is greatest in the initial period of disease, “this time period may represent a critical therapeutic window for the use of highly effective therapies,” said Dr. Abdel-Mannan.
An examination of medical records
MS is much less prevalent among children than among adults. Compared with adults with MS, children with MS have a higher relapse rate and slower accumulation of disability. The individual response to DMTs is variable, said Dr. Abdel-Mannan. Furthermore, current standards of care for pediatric MS vary by center and are based on adult protocols.
Dr. Abdel-Mannan and colleagues conducted a retrospective study to evaluate the real-world effectiveness of the newer oral and infusion DMTs, compared with the older injectable DMTs, in children with relapsing-remitting MS. They examined data from seven tertiary pediatric neurology centers in the United Kingdom and identified patients under age 18 years with relapsing-remitting MS who were treated with DMTs between 2012 and 2018. The investigators reviewed clinical and paraclinical data retrospectively using electronic medical records. They compared patients’ ARR, new radiological activity, and Expanded Disability Status Scale score pretreatment and on treatment.
The researchers included 103 patients in their analysis. The population’s median age was 14 years. The ratio of girls to boys was approximately 3:1. Whites and other races/ethnicities accounted for approximately equal groups of patients. About one-third of patients presented with a clinically isolated syndrome (CIS) in the form of transverse myelitis or optic neuritis. Two-thirds presented with other CIS phenotypes. Almost all children had an abnormal MRI at onset.
Most patients initiated injectable DMTs
Of the 103 patients, 89 started treatment with an injectable (e.g., glatiramer or interferon) or an older DMT. Fourteen patients began treatment with a newer DMT (e.g., dimethyl fumarate, fingolimod, natalizumab, and alemtuzumab). Three of the 89 patients on an injectable DMT switched to another injectable DMT, and two of these patients later escalated to a newer DMT. Thirty-five of the 89 patients who initiated an injectable DMT were escalated immediately to a newer DMT. One of these patients later switched to another newer DMT. Two of the 14 patients who started on a newer DMT as their first drug switched to another newer DMT.
The investigators observed a reduction in ARR for all DMTs used during the study period. Nevertheless, a significant number of patients receiving injectable DMTs continued to relapse on treatment. Almost all patients receiving newer DMTs, however, had a reduction in relapses. When Dr. Abdel-Mannan and colleagues performed Kaplan–Meier survival analysis, they found that patients receiving newer DMTs had a longer time to first relapse and a longer time to switch treatment over 2 years, compared with patients receiving injectable DMTs. In addition, patients receiving newer DMTs had a longer time to develop new radiological activity, compared with patients receiving injectables. The analysis also indicated that the proportion of patients with new radiological activity was higher than the proportion who had clinical relapses and an Expanded Disability Status Scale score increase of more than 1 point over 2 years.
In all, 55 of the children receiving injectable DMTs and 18 of the patients receiving newer DMTs had side effects. The most commonly reported side effects were flulike symptoms and injection-site reactions. Five patients discontinued or switched their DMTs because of side effects. “Reassuringly, no pediatric-specific side effects were reported,” said Dr. Abdel-Mannan. The newer DMTs had similar short-term safety, tolerability, and side-effect profiles in these children as in adult patients.
The study was conducted on behalf of the UK Childhood Inflammatory Demyelination Network. Dr. Abdel-Mannan had no relevant disclosures.
SOURCE: Abdel-Mannan O et al. CNS-ICNA 2020, Abstract PL10.
Nevertheless, all DMTs reduce children’s annualized relapse rate (ARR), according to results presented at the 2020 CNS-ICNA Conjoint Meeting, held virtually this year.
“Our study adds weight to the argument for an imminent shift in clinical practice toward the use of newer, more efficacious DMTs in the first instance,” said Omar Abdel-Mannan, MD, of Great Ormond Street Hospital in London. MRI activity continues among patients treated with DMTs, and the number of relapses is highest in the period following diagnosis. But because the effect of treatment on brain atrophy is greatest in the initial period of disease, “this time period may represent a critical therapeutic window for the use of highly effective therapies,” said Dr. Abdel-Mannan.
An examination of medical records
MS is much less prevalent among children than among adults. Compared with adults with MS, children with MS have a higher relapse rate and slower accumulation of disability. The individual response to DMTs is variable, said Dr. Abdel-Mannan. Furthermore, current standards of care for pediatric MS vary by center and are based on adult protocols.
Dr. Abdel-Mannan and colleagues conducted a retrospective study to evaluate the real-world effectiveness of the newer oral and infusion DMTs, compared with the older injectable DMTs, in children with relapsing-remitting MS. They examined data from seven tertiary pediatric neurology centers in the United Kingdom and identified patients under age 18 years with relapsing-remitting MS who were treated with DMTs between 2012 and 2018. The investigators reviewed clinical and paraclinical data retrospectively using electronic medical records. They compared patients’ ARR, new radiological activity, and Expanded Disability Status Scale score pretreatment and on treatment.
The researchers included 103 patients in their analysis. The population’s median age was 14 years. The ratio of girls to boys was approximately 3:1. Whites and other races/ethnicities accounted for approximately equal groups of patients. About one-third of patients presented with a clinically isolated syndrome (CIS) in the form of transverse myelitis or optic neuritis. Two-thirds presented with other CIS phenotypes. Almost all children had an abnormal MRI at onset.
Most patients initiated injectable DMTs
Of the 103 patients, 89 started treatment with an injectable (e.g., glatiramer or interferon) or an older DMT. Fourteen patients began treatment with a newer DMT (e.g., dimethyl fumarate, fingolimod, natalizumab, and alemtuzumab). Three of the 89 patients on an injectable DMT switched to another injectable DMT, and two of these patients later escalated to a newer DMT. Thirty-five of the 89 patients who initiated an injectable DMT were escalated immediately to a newer DMT. One of these patients later switched to another newer DMT. Two of the 14 patients who started on a newer DMT as their first drug switched to another newer DMT.
The investigators observed a reduction in ARR for all DMTs used during the study period. Nevertheless, a significant number of patients receiving injectable DMTs continued to relapse on treatment. Almost all patients receiving newer DMTs, however, had a reduction in relapses. When Dr. Abdel-Mannan and colleagues performed Kaplan–Meier survival analysis, they found that patients receiving newer DMTs had a longer time to first relapse and a longer time to switch treatment over 2 years, compared with patients receiving injectable DMTs. In addition, patients receiving newer DMTs had a longer time to develop new radiological activity, compared with patients receiving injectables. The analysis also indicated that the proportion of patients with new radiological activity was higher than the proportion who had clinical relapses and an Expanded Disability Status Scale score increase of more than 1 point over 2 years.
In all, 55 of the children receiving injectable DMTs and 18 of the patients receiving newer DMTs had side effects. The most commonly reported side effects were flulike symptoms and injection-site reactions. Five patients discontinued or switched their DMTs because of side effects. “Reassuringly, no pediatric-specific side effects were reported,” said Dr. Abdel-Mannan. The newer DMTs had similar short-term safety, tolerability, and side-effect profiles in these children as in adult patients.
The study was conducted on behalf of the UK Childhood Inflammatory Demyelination Network. Dr. Abdel-Mannan had no relevant disclosures.
SOURCE: Abdel-Mannan O et al. CNS-ICNA 2020, Abstract PL10.
Nevertheless, all DMTs reduce children’s annualized relapse rate (ARR), according to results presented at the 2020 CNS-ICNA Conjoint Meeting, held virtually this year.
“Our study adds weight to the argument for an imminent shift in clinical practice toward the use of newer, more efficacious DMTs in the first instance,” said Omar Abdel-Mannan, MD, of Great Ormond Street Hospital in London. MRI activity continues among patients treated with DMTs, and the number of relapses is highest in the period following diagnosis. But because the effect of treatment on brain atrophy is greatest in the initial period of disease, “this time period may represent a critical therapeutic window for the use of highly effective therapies,” said Dr. Abdel-Mannan.
An examination of medical records
MS is much less prevalent among children than among adults. Compared with adults with MS, children with MS have a higher relapse rate and slower accumulation of disability. The individual response to DMTs is variable, said Dr. Abdel-Mannan. Furthermore, current standards of care for pediatric MS vary by center and are based on adult protocols.
Dr. Abdel-Mannan and colleagues conducted a retrospective study to evaluate the real-world effectiveness of the newer oral and infusion DMTs, compared with the older injectable DMTs, in children with relapsing-remitting MS. They examined data from seven tertiary pediatric neurology centers in the United Kingdom and identified patients under age 18 years with relapsing-remitting MS who were treated with DMTs between 2012 and 2018. The investigators reviewed clinical and paraclinical data retrospectively using electronic medical records. They compared patients’ ARR, new radiological activity, and Expanded Disability Status Scale score pretreatment and on treatment.
The researchers included 103 patients in their analysis. The population’s median age was 14 years. The ratio of girls to boys was approximately 3:1. Whites and other races/ethnicities accounted for approximately equal groups of patients. About one-third of patients presented with a clinically isolated syndrome (CIS) in the form of transverse myelitis or optic neuritis. Two-thirds presented with other CIS phenotypes. Almost all children had an abnormal MRI at onset.
Most patients initiated injectable DMTs
Of the 103 patients, 89 started treatment with an injectable (e.g., glatiramer or interferon) or an older DMT. Fourteen patients began treatment with a newer DMT (e.g., dimethyl fumarate, fingolimod, natalizumab, and alemtuzumab). Three of the 89 patients on an injectable DMT switched to another injectable DMT, and two of these patients later escalated to a newer DMT. Thirty-five of the 89 patients who initiated an injectable DMT were escalated immediately to a newer DMT. One of these patients later switched to another newer DMT. Two of the 14 patients who started on a newer DMT as their first drug switched to another newer DMT.
The investigators observed a reduction in ARR for all DMTs used during the study period. Nevertheless, a significant number of patients receiving injectable DMTs continued to relapse on treatment. Almost all patients receiving newer DMTs, however, had a reduction in relapses. When Dr. Abdel-Mannan and colleagues performed Kaplan–Meier survival analysis, they found that patients receiving newer DMTs had a longer time to first relapse and a longer time to switch treatment over 2 years, compared with patients receiving injectable DMTs. In addition, patients receiving newer DMTs had a longer time to develop new radiological activity, compared with patients receiving injectables. The analysis also indicated that the proportion of patients with new radiological activity was higher than the proportion who had clinical relapses and an Expanded Disability Status Scale score increase of more than 1 point over 2 years.
In all, 55 of the children receiving injectable DMTs and 18 of the patients receiving newer DMTs had side effects. The most commonly reported side effects were flulike symptoms and injection-site reactions. Five patients discontinued or switched their DMTs because of side effects. “Reassuringly, no pediatric-specific side effects were reported,” said Dr. Abdel-Mannan. The newer DMTs had similar short-term safety, tolerability, and side-effect profiles in these children as in adult patients.
The study was conducted on behalf of the UK Childhood Inflammatory Demyelination Network. Dr. Abdel-Mannan had no relevant disclosures.
SOURCE: Abdel-Mannan O et al. CNS-ICNA 2020, Abstract PL10.
FROM CNS-ICNA 2020
Study supports halting antiseizure medications after neonatal seizures
Maintaining antiseizure medication in infants who have had acute symptomatic neonatal seizures has been standard practice, but a prospective, observational, comparative effectiveness study calls that practice into question, providing evidence that discontinuing therapy at discharge poses no harm to children and has no effect on the development of epilepsies.
“,” said Hannah C. Glass, MDCM, MAS, of the University of California, San Francisco, Benioff Children’s Hospital, co-principal investigator, who presented results of the study at the 2020 CNS-ICNA Conjoint Meeting, held virtually this year. Renee Shellhaas, MD, MS, clinical associate professor of pediatrics at C.S. Mott Children’s Hospital, University of Michigan, was the other co-principal investigator.
“Although other, smaller studies have suggested it is safe to discontinue antiseizure medication after resolution of acute symptomatic seizures, the practice of early discontinuation has been very variable and depends largely on individual provider preference,” Dr. Glass said in an interview. “In our study, two-thirds of newborns with acute symptomatic seizures were maintained on antiseizure medication at the time of hospital discharge. Thus, a change to early medication discontinuation represents a major shift.”
The study evaluated 270 infants at nine centers enrolled in the Neonatal Seizure Registry and born from July 2015 through March 2018. Inclusion criteria were acute symptomatic seizures that occurred at up to 44 weeks postmenstrual age. In this cohort, 36% of patients had antiseizure medication discontinued after a median of 6 days; the remainder stayed on antiseizure medication after discharge at a median of 4 months.
The patients were followed for 2 years. The primary outcome was functional development measured by the Warner Initial Development Evaluation of Adaptive and Functional Skills (WIDEA-FS) assessment. The secondary outcome was epilepsy defined by International League Against Epilepsy (ILAE) criteria. Follow-up consisted of phone calls and chart reviews at 12, 18, and 24 months.
“The primary outcome, functional development, was not significantly different between those children who were maintained on antiseizure medication as compared with those who were discontinued,” Dr. Glass said.
After propensity adjustment, the discontinued ASM group had an estimated WIDEA-FS score 4 points higher on average, she said. “The confidence intervals met our a priori noninferiority limit, indicating no harm to neurodevelopment for discontinuing antiseizure medication before discharge home from the neonatal seizure admission,” Dr. Glass noted.
The study also found that 13% of all participants developed epilepsy at a median of 8 months. “There was no significant difference in the frequency or timing of epilepsy between the two groups,” she said.
“We conclude there is no clear rationale for antiseizure medication maintenance,” Dr. Glass said. “There is no benefit to neurodevelopment, it prolongs the exposure to potentially harmful antiseizure medications, it does not significantly delay the onset of epilepsy, and the earliest-onset epilepsies occur in spite of antiseizure medication.”
The Patient-Centered Outcomes Research Institute (PCORI) and Pediatric Epilepsy Research Foundation funded the study. Dr. Glass has no other financial relationships to disclose.
SOURCE: Glass HC et al. CNS-ICNA 2020. Presentation PL58.
Maintaining antiseizure medication in infants who have had acute symptomatic neonatal seizures has been standard practice, but a prospective, observational, comparative effectiveness study calls that practice into question, providing evidence that discontinuing therapy at discharge poses no harm to children and has no effect on the development of epilepsies.
“,” said Hannah C. Glass, MDCM, MAS, of the University of California, San Francisco, Benioff Children’s Hospital, co-principal investigator, who presented results of the study at the 2020 CNS-ICNA Conjoint Meeting, held virtually this year. Renee Shellhaas, MD, MS, clinical associate professor of pediatrics at C.S. Mott Children’s Hospital, University of Michigan, was the other co-principal investigator.
“Although other, smaller studies have suggested it is safe to discontinue antiseizure medication after resolution of acute symptomatic seizures, the practice of early discontinuation has been very variable and depends largely on individual provider preference,” Dr. Glass said in an interview. “In our study, two-thirds of newborns with acute symptomatic seizures were maintained on antiseizure medication at the time of hospital discharge. Thus, a change to early medication discontinuation represents a major shift.”
The study evaluated 270 infants at nine centers enrolled in the Neonatal Seizure Registry and born from July 2015 through March 2018. Inclusion criteria were acute symptomatic seizures that occurred at up to 44 weeks postmenstrual age. In this cohort, 36% of patients had antiseizure medication discontinued after a median of 6 days; the remainder stayed on antiseizure medication after discharge at a median of 4 months.
The patients were followed for 2 years. The primary outcome was functional development measured by the Warner Initial Development Evaluation of Adaptive and Functional Skills (WIDEA-FS) assessment. The secondary outcome was epilepsy defined by International League Against Epilepsy (ILAE) criteria. Follow-up consisted of phone calls and chart reviews at 12, 18, and 24 months.
“The primary outcome, functional development, was not significantly different between those children who were maintained on antiseizure medication as compared with those who were discontinued,” Dr. Glass said.
After propensity adjustment, the discontinued ASM group had an estimated WIDEA-FS score 4 points higher on average, she said. “The confidence intervals met our a priori noninferiority limit, indicating no harm to neurodevelopment for discontinuing antiseizure medication before discharge home from the neonatal seizure admission,” Dr. Glass noted.
The study also found that 13% of all participants developed epilepsy at a median of 8 months. “There was no significant difference in the frequency or timing of epilepsy between the two groups,” she said.
“We conclude there is no clear rationale for antiseizure medication maintenance,” Dr. Glass said. “There is no benefit to neurodevelopment, it prolongs the exposure to potentially harmful antiseizure medications, it does not significantly delay the onset of epilepsy, and the earliest-onset epilepsies occur in spite of antiseizure medication.”
The Patient-Centered Outcomes Research Institute (PCORI) and Pediatric Epilepsy Research Foundation funded the study. Dr. Glass has no other financial relationships to disclose.
SOURCE: Glass HC et al. CNS-ICNA 2020. Presentation PL58.
Maintaining antiseizure medication in infants who have had acute symptomatic neonatal seizures has been standard practice, but a prospective, observational, comparative effectiveness study calls that practice into question, providing evidence that discontinuing therapy at discharge poses no harm to children and has no effect on the development of epilepsies.
“,” said Hannah C. Glass, MDCM, MAS, of the University of California, San Francisco, Benioff Children’s Hospital, co-principal investigator, who presented results of the study at the 2020 CNS-ICNA Conjoint Meeting, held virtually this year. Renee Shellhaas, MD, MS, clinical associate professor of pediatrics at C.S. Mott Children’s Hospital, University of Michigan, was the other co-principal investigator.
“Although other, smaller studies have suggested it is safe to discontinue antiseizure medication after resolution of acute symptomatic seizures, the practice of early discontinuation has been very variable and depends largely on individual provider preference,” Dr. Glass said in an interview. “In our study, two-thirds of newborns with acute symptomatic seizures were maintained on antiseizure medication at the time of hospital discharge. Thus, a change to early medication discontinuation represents a major shift.”
The study evaluated 270 infants at nine centers enrolled in the Neonatal Seizure Registry and born from July 2015 through March 2018. Inclusion criteria were acute symptomatic seizures that occurred at up to 44 weeks postmenstrual age. In this cohort, 36% of patients had antiseizure medication discontinued after a median of 6 days; the remainder stayed on antiseizure medication after discharge at a median of 4 months.
The patients were followed for 2 years. The primary outcome was functional development measured by the Warner Initial Development Evaluation of Adaptive and Functional Skills (WIDEA-FS) assessment. The secondary outcome was epilepsy defined by International League Against Epilepsy (ILAE) criteria. Follow-up consisted of phone calls and chart reviews at 12, 18, and 24 months.
“The primary outcome, functional development, was not significantly different between those children who were maintained on antiseizure medication as compared with those who were discontinued,” Dr. Glass said.
After propensity adjustment, the discontinued ASM group had an estimated WIDEA-FS score 4 points higher on average, she said. “The confidence intervals met our a priori noninferiority limit, indicating no harm to neurodevelopment for discontinuing antiseizure medication before discharge home from the neonatal seizure admission,” Dr. Glass noted.
The study also found that 13% of all participants developed epilepsy at a median of 8 months. “There was no significant difference in the frequency or timing of epilepsy between the two groups,” she said.
“We conclude there is no clear rationale for antiseizure medication maintenance,” Dr. Glass said. “There is no benefit to neurodevelopment, it prolongs the exposure to potentially harmful antiseizure medications, it does not significantly delay the onset of epilepsy, and the earliest-onset epilepsies occur in spite of antiseizure medication.”
The Patient-Centered Outcomes Research Institute (PCORI) and Pediatric Epilepsy Research Foundation funded the study. Dr. Glass has no other financial relationships to disclose.
SOURCE: Glass HC et al. CNS-ICNA 2020. Presentation PL58.
FROM CNS-ICNA 2020
Valvular disease and COVID-19 are a deadly mix; don’t delay intervention
Danny Dvir, MD, has a message for physicians who have patients with severe valvular heart disease who are deferring valve replacement or repair until after the COVID-19 pandemic: Urge them not to wait.
Data from the Multicenter International Valve Disease Registry vividly demonstrate that clinical outcomes are poor in patients with uncorrected valve disease who become hospitalized with COVID-19. Indeed, the mortality rate within 30 days after hospital admission in 136 such patients enrolled in the registry from centers in Europe, North America, and Israel was 42%, Dr. Dvir reported at the Transcatheter Cardiovascular Research Therapeutics virtual annual meeting.
“That’s dramatically higher than for an age-matched population infected with COVID-19 without valvular heart disease, which is 10%-15%,” he noted at the meeting sponsored by the Cardiovascular Research Foundation.
The bright spot was that, in the small subgroup of 15 registry participants who underwent transcatheter or, much less frequently, surgical treatment of their failing valve while COVID-19 infected, 30-day mortality was far lower. In fact, it was comparable with the background rate in hospitalized COVID-19 patients without valve disease, according to Dr. Dvir, an interventional cardiologist at Shaare Zedek Medical Center, Hebrew University, Jerusalem.
He personally did several of the transcatheter aortic valve replacements.
“It’s doable. I truly believe that when you get a severe aortic stenosis patient who’s infected with the coronavirus, they get very unstable, but we can treat them. We can treat them even during the infection,” Dr. Dvir said.
The majority of patients in the registry had severe aortic stenosis. In the 42 such patients aged 80 years or more who didn’t undergo transcatheter aortic valve replacement (TAVR) or surgical valve replacement, 30-day mortality was 60%. In contrast, only one of the six patients in this advanced-age category who underwent valve replacement while infected died. Similarly, 30-day mortality was 24% among those younger than age 80 who valve remained untreated, but it dropped to 11% in those who received a prosthetic valve.
“We try our best to protect our patients through social distancing, but we have a treatment that can potentially reduce their mortality risk if they get infected later on. So I say to my patients: ‘Don’t wait at home. Do not wait! If you get infected when you have severe aortic stenosis, the clinical outcome is bad.’ But it seems reasonable that if they get infected when they’ve already been treated for their aortic stenosis or mitral regurgitation, they will do better.”
Dr. Dvir noted that, although the case numbers in the registry series were small and subject to potential bias, the data suggest this treatment approach may be lifesaving.
Session comoderator Timothy D. Henry, MD, commented that this registry study contains a great take-home point: “This is really consistent with what see in a lot of the other areas of COVID, that what we know to be best clinical care, we should do it, with or without the COVID.”
He asked Dr. Dvir about any special measures he takes while doing TAVR in this extreme setting. In the United States, for example, interventionalists are increasingly using transesophageal echocardiography to guide their procedures using conscious sedation, without intubation, noted Dr. Henry, medical director of the Carl and Edyth Lindner Center for Research at the Christ Hospital, Cincinnati.
“We try to minimize the procedure time; that’s one of the important things,” Dr. Dvir replied. “And you need to be protected during the procedure in a very cautious and meticulous way. You need many fans in the room because you sweat a lot.”
Discussant Renu Virmani, MD, president of the CVPath Institute in Gaithersburg, Md., commented: “The main thing I get from this presentation is the need for patients to be educated that if you’ve got valve disease, you’re better off getting it treated before you’ve got COVID. Obviously, try to prevent getting COVID – that’s the best thing you can do – but you can’t always control that.”
Discussant Mamas Mamas, MD, professor of cardiology at Keele University, Staffordshire, England, said deferred treatment of severe valvular heart disease during the pandemic has created a looming public health crisis in the United Kingdom.
“We’ve analyzed the U.K. management of aortic stenosis, and what we’ve found is that during the COVID pandemic there have been 2,500 fewer cases of aortic stenosis that have been treated. We’ve got 2,500 patients on the waiting list, and we’ve got to work out how we’re going to treat them. We estimate with simulations that about 300 of them are going to die before we can get them treated for their aortic stenosis,” according to Dr. Mamas.
Dr. Henry commented that deferral of valve procedures is “really challenging” for a couple of reasons: Not only are patients scared to come into the hospital because they fear getting COVID, but they don’t want to be hospitalized during the pandemic because their family can’t visit them there.
“These patients are mostly over 80 years old. No one wants to come in the hospital when the family won’t be around, especially when you’re 90 years old,” the interventional cardiologist said.
Dr. Dvir reported serving as a consultant to Medtronic, Edwards Lifesciences, Abbott, and Jena.
Danny Dvir, MD, has a message for physicians who have patients with severe valvular heart disease who are deferring valve replacement or repair until after the COVID-19 pandemic: Urge them not to wait.
Data from the Multicenter International Valve Disease Registry vividly demonstrate that clinical outcomes are poor in patients with uncorrected valve disease who become hospitalized with COVID-19. Indeed, the mortality rate within 30 days after hospital admission in 136 such patients enrolled in the registry from centers in Europe, North America, and Israel was 42%, Dr. Dvir reported at the Transcatheter Cardiovascular Research Therapeutics virtual annual meeting.
“That’s dramatically higher than for an age-matched population infected with COVID-19 without valvular heart disease, which is 10%-15%,” he noted at the meeting sponsored by the Cardiovascular Research Foundation.
The bright spot was that, in the small subgroup of 15 registry participants who underwent transcatheter or, much less frequently, surgical treatment of their failing valve while COVID-19 infected, 30-day mortality was far lower. In fact, it was comparable with the background rate in hospitalized COVID-19 patients without valve disease, according to Dr. Dvir, an interventional cardiologist at Shaare Zedek Medical Center, Hebrew University, Jerusalem.
He personally did several of the transcatheter aortic valve replacements.
“It’s doable. I truly believe that when you get a severe aortic stenosis patient who’s infected with the coronavirus, they get very unstable, but we can treat them. We can treat them even during the infection,” Dr. Dvir said.
The majority of patients in the registry had severe aortic stenosis. In the 42 such patients aged 80 years or more who didn’t undergo transcatheter aortic valve replacement (TAVR) or surgical valve replacement, 30-day mortality was 60%. In contrast, only one of the six patients in this advanced-age category who underwent valve replacement while infected died. Similarly, 30-day mortality was 24% among those younger than age 80 who valve remained untreated, but it dropped to 11% in those who received a prosthetic valve.
“We try our best to protect our patients through social distancing, but we have a treatment that can potentially reduce their mortality risk if they get infected later on. So I say to my patients: ‘Don’t wait at home. Do not wait! If you get infected when you have severe aortic stenosis, the clinical outcome is bad.’ But it seems reasonable that if they get infected when they’ve already been treated for their aortic stenosis or mitral regurgitation, they will do better.”
Dr. Dvir noted that, although the case numbers in the registry series were small and subject to potential bias, the data suggest this treatment approach may be lifesaving.
Session comoderator Timothy D. Henry, MD, commented that this registry study contains a great take-home point: “This is really consistent with what see in a lot of the other areas of COVID, that what we know to be best clinical care, we should do it, with or without the COVID.”
He asked Dr. Dvir about any special measures he takes while doing TAVR in this extreme setting. In the United States, for example, interventionalists are increasingly using transesophageal echocardiography to guide their procedures using conscious sedation, without intubation, noted Dr. Henry, medical director of the Carl and Edyth Lindner Center for Research at the Christ Hospital, Cincinnati.
“We try to minimize the procedure time; that’s one of the important things,” Dr. Dvir replied. “And you need to be protected during the procedure in a very cautious and meticulous way. You need many fans in the room because you sweat a lot.”
Discussant Renu Virmani, MD, president of the CVPath Institute in Gaithersburg, Md., commented: “The main thing I get from this presentation is the need for patients to be educated that if you’ve got valve disease, you’re better off getting it treated before you’ve got COVID. Obviously, try to prevent getting COVID – that’s the best thing you can do – but you can’t always control that.”
Discussant Mamas Mamas, MD, professor of cardiology at Keele University, Staffordshire, England, said deferred treatment of severe valvular heart disease during the pandemic has created a looming public health crisis in the United Kingdom.
“We’ve analyzed the U.K. management of aortic stenosis, and what we’ve found is that during the COVID pandemic there have been 2,500 fewer cases of aortic stenosis that have been treated. We’ve got 2,500 patients on the waiting list, and we’ve got to work out how we’re going to treat them. We estimate with simulations that about 300 of them are going to die before we can get them treated for their aortic stenosis,” according to Dr. Mamas.
Dr. Henry commented that deferral of valve procedures is “really challenging” for a couple of reasons: Not only are patients scared to come into the hospital because they fear getting COVID, but they don’t want to be hospitalized during the pandemic because their family can’t visit them there.
“These patients are mostly over 80 years old. No one wants to come in the hospital when the family won’t be around, especially when you’re 90 years old,” the interventional cardiologist said.
Dr. Dvir reported serving as a consultant to Medtronic, Edwards Lifesciences, Abbott, and Jena.
Danny Dvir, MD, has a message for physicians who have patients with severe valvular heart disease who are deferring valve replacement or repair until after the COVID-19 pandemic: Urge them not to wait.
Data from the Multicenter International Valve Disease Registry vividly demonstrate that clinical outcomes are poor in patients with uncorrected valve disease who become hospitalized with COVID-19. Indeed, the mortality rate within 30 days after hospital admission in 136 such patients enrolled in the registry from centers in Europe, North America, and Israel was 42%, Dr. Dvir reported at the Transcatheter Cardiovascular Research Therapeutics virtual annual meeting.
“That’s dramatically higher than for an age-matched population infected with COVID-19 without valvular heart disease, which is 10%-15%,” he noted at the meeting sponsored by the Cardiovascular Research Foundation.
The bright spot was that, in the small subgroup of 15 registry participants who underwent transcatheter or, much less frequently, surgical treatment of their failing valve while COVID-19 infected, 30-day mortality was far lower. In fact, it was comparable with the background rate in hospitalized COVID-19 patients without valve disease, according to Dr. Dvir, an interventional cardiologist at Shaare Zedek Medical Center, Hebrew University, Jerusalem.
He personally did several of the transcatheter aortic valve replacements.
“It’s doable. I truly believe that when you get a severe aortic stenosis patient who’s infected with the coronavirus, they get very unstable, but we can treat them. We can treat them even during the infection,” Dr. Dvir said.
The majority of patients in the registry had severe aortic stenosis. In the 42 such patients aged 80 years or more who didn’t undergo transcatheter aortic valve replacement (TAVR) or surgical valve replacement, 30-day mortality was 60%. In contrast, only one of the six patients in this advanced-age category who underwent valve replacement while infected died. Similarly, 30-day mortality was 24% among those younger than age 80 who valve remained untreated, but it dropped to 11% in those who received a prosthetic valve.
“We try our best to protect our patients through social distancing, but we have a treatment that can potentially reduce their mortality risk if they get infected later on. So I say to my patients: ‘Don’t wait at home. Do not wait! If you get infected when you have severe aortic stenosis, the clinical outcome is bad.’ But it seems reasonable that if they get infected when they’ve already been treated for their aortic stenosis or mitral regurgitation, they will do better.”
Dr. Dvir noted that, although the case numbers in the registry series were small and subject to potential bias, the data suggest this treatment approach may be lifesaving.
Session comoderator Timothy D. Henry, MD, commented that this registry study contains a great take-home point: “This is really consistent with what see in a lot of the other areas of COVID, that what we know to be best clinical care, we should do it, with or without the COVID.”
He asked Dr. Dvir about any special measures he takes while doing TAVR in this extreme setting. In the United States, for example, interventionalists are increasingly using transesophageal echocardiography to guide their procedures using conscious sedation, without intubation, noted Dr. Henry, medical director of the Carl and Edyth Lindner Center for Research at the Christ Hospital, Cincinnati.
“We try to minimize the procedure time; that’s one of the important things,” Dr. Dvir replied. “And you need to be protected during the procedure in a very cautious and meticulous way. You need many fans in the room because you sweat a lot.”
Discussant Renu Virmani, MD, president of the CVPath Institute in Gaithersburg, Md., commented: “The main thing I get from this presentation is the need for patients to be educated that if you’ve got valve disease, you’re better off getting it treated before you’ve got COVID. Obviously, try to prevent getting COVID – that’s the best thing you can do – but you can’t always control that.”
Discussant Mamas Mamas, MD, professor of cardiology at Keele University, Staffordshire, England, said deferred treatment of severe valvular heart disease during the pandemic has created a looming public health crisis in the United Kingdom.
“We’ve analyzed the U.K. management of aortic stenosis, and what we’ve found is that during the COVID pandemic there have been 2,500 fewer cases of aortic stenosis that have been treated. We’ve got 2,500 patients on the waiting list, and we’ve got to work out how we’re going to treat them. We estimate with simulations that about 300 of them are going to die before we can get them treated for their aortic stenosis,” according to Dr. Mamas.
Dr. Henry commented that deferral of valve procedures is “really challenging” for a couple of reasons: Not only are patients scared to come into the hospital because they fear getting COVID, but they don’t want to be hospitalized during the pandemic because their family can’t visit them there.
“These patients are mostly over 80 years old. No one wants to come in the hospital when the family won’t be around, especially when you’re 90 years old,” the interventional cardiologist said.
Dr. Dvir reported serving as a consultant to Medtronic, Edwards Lifesciences, Abbott, and Jena.
FROM TCT 2020
Few women hospitalized for influenza have been vaccinated
Researchers analyzed data from 9,652 women ages 15-44 who were hospitalized with laboratory-confirmed influenza from October through April during the 2010-2019 influenza seasons. Data were pulled from the U.S. Influenza Hospitalization Surveillance Network (FluSurv-NET).
Of those women, 2,697 (28%) were pregnant. Median age was 28 and median gestational age was 32 weeks. Those studied included 36% who were non-Hispanic White; 29% non-Hispanic Black; and 20% Hispanic women.
Some 89% of the women, pregnant and nonpregnant, received antivirals while in the hospital but only 31% reported they had received the flu vaccine in the current season, despite guideline recommendations citing clear evidence that vaccination is safe for mother and baby.
Rachel Holstein, MPH, an epidemiology and information science fellow at the Centers for Disease Control and Prevention, who presented her team’s work as part of IDWeek 2020, explained that the mother’s vaccination can help protect the baby from flu infection for several months after birth, before the baby can be vaccinated.
She noted that pregnant women are at high risk for influenza-associated hospitalization.
“Changes in the immune system, heart, and lungs during pregnancy make pregnant women, and women up to 2 weeks post partum, more prone to severe illness from flu, including illness resulting in hospitalization,” she said in an interview
“Vaccination has been shown to reduce the risk of flu-associated acute respiratory infection in pregnant women by up to one-half,” she said. “A 2018 study showed that getting a flu shot reduced a pregnant woman’s risk of being hospitalized with flu by an average of 40%.»
FluSurv-NET data show hospitalizations were more common in the third trimester of pregnancy compared with the first and second, Holstein said. The most common underlying conditions among these women were asthma (23%) and obesity (10%), and 12% were current tobacco smokers. Overall, 5% of pregnant women with flu required ICU admission, 2% needed mechanical ventilation, and 6% developed pneumonia.
Vaccine uptake lowest in first two trimesters
Holstein said vaccine coverage was lowest among women in their first or second trimesters for all 9 seasons, and overall vaccination coverage increased significantly over time.
Uptake also differed by age. The data showed coverage was lower among women aged 15-34 years, compared with women 35 years and older (34% vs. 50%).
“It was as low as 15% among pregnant women aged 15-34 years in the 2011-12 season,” she added.
Jeanne Sheffield, MD, director of the division of maternal-fetal medicine at Johns Hopkins Medicine, Baltimore, said in an interview the low uptake of vaccine shown in this study is both familiar and frustrating.
She said education from health care providers has improved, but women are nonetheless frequently fearful. She pointed out the widespread phenomenon of vaccine hesitancy in the general population.
Coverage was 45.3% among adults in the 2018-2019 flu season, 8.2 percentage points higher than coverage during the 2017-18 season (37.1%) according to CDC estimates.
Added to that, she said, is further hesitancy when women believe vaccination could harm the unborn baby, despite “very good data that flu vaccine is safe in pregnancy, acceptable in pregnancy in all trimesters, and is optimal standard of care.”
Holstein added, “We know from past research that a range of factors – including negative attitudes and beliefs about vaccines, less knowledge about and access to vaccines, and a lack of trust in healthcare providers and vaccines – can contribute to lower vaccination rates.”
Healthcare providers play a key role in increasing flu vaccinations among pregnant women, she said.
“A provider recommendation, combined with an offer to administer a flu vaccine at the time of visit, remains one of the best ways to accomplish this,” Holstein said.
Holstein and Sheffield have disclosed no relevant financial relationships.
This article first appeared on Medscape.com.
Researchers analyzed data from 9,652 women ages 15-44 who were hospitalized with laboratory-confirmed influenza from October through April during the 2010-2019 influenza seasons. Data were pulled from the U.S. Influenza Hospitalization Surveillance Network (FluSurv-NET).
Of those women, 2,697 (28%) were pregnant. Median age was 28 and median gestational age was 32 weeks. Those studied included 36% who were non-Hispanic White; 29% non-Hispanic Black; and 20% Hispanic women.
Some 89% of the women, pregnant and nonpregnant, received antivirals while in the hospital but only 31% reported they had received the flu vaccine in the current season, despite guideline recommendations citing clear evidence that vaccination is safe for mother and baby.
Rachel Holstein, MPH, an epidemiology and information science fellow at the Centers for Disease Control and Prevention, who presented her team’s work as part of IDWeek 2020, explained that the mother’s vaccination can help protect the baby from flu infection for several months after birth, before the baby can be vaccinated.
She noted that pregnant women are at high risk for influenza-associated hospitalization.
“Changes in the immune system, heart, and lungs during pregnancy make pregnant women, and women up to 2 weeks post partum, more prone to severe illness from flu, including illness resulting in hospitalization,” she said in an interview
“Vaccination has been shown to reduce the risk of flu-associated acute respiratory infection in pregnant women by up to one-half,” she said. “A 2018 study showed that getting a flu shot reduced a pregnant woman’s risk of being hospitalized with flu by an average of 40%.»
FluSurv-NET data show hospitalizations were more common in the third trimester of pregnancy compared with the first and second, Holstein said. The most common underlying conditions among these women were asthma (23%) and obesity (10%), and 12% were current tobacco smokers. Overall, 5% of pregnant women with flu required ICU admission, 2% needed mechanical ventilation, and 6% developed pneumonia.
Vaccine uptake lowest in first two trimesters
Holstein said vaccine coverage was lowest among women in their first or second trimesters for all 9 seasons, and overall vaccination coverage increased significantly over time.
Uptake also differed by age. The data showed coverage was lower among women aged 15-34 years, compared with women 35 years and older (34% vs. 50%).
“It was as low as 15% among pregnant women aged 15-34 years in the 2011-12 season,” she added.
Jeanne Sheffield, MD, director of the division of maternal-fetal medicine at Johns Hopkins Medicine, Baltimore, said in an interview the low uptake of vaccine shown in this study is both familiar and frustrating.
She said education from health care providers has improved, but women are nonetheless frequently fearful. She pointed out the widespread phenomenon of vaccine hesitancy in the general population.
Coverage was 45.3% among adults in the 2018-2019 flu season, 8.2 percentage points higher than coverage during the 2017-18 season (37.1%) according to CDC estimates.
Added to that, she said, is further hesitancy when women believe vaccination could harm the unborn baby, despite “very good data that flu vaccine is safe in pregnancy, acceptable in pregnancy in all trimesters, and is optimal standard of care.”
Holstein added, “We know from past research that a range of factors – including negative attitudes and beliefs about vaccines, less knowledge about and access to vaccines, and a lack of trust in healthcare providers and vaccines – can contribute to lower vaccination rates.”
Healthcare providers play a key role in increasing flu vaccinations among pregnant women, she said.
“A provider recommendation, combined with an offer to administer a flu vaccine at the time of visit, remains one of the best ways to accomplish this,” Holstein said.
Holstein and Sheffield have disclosed no relevant financial relationships.
This article first appeared on Medscape.com.
Researchers analyzed data from 9,652 women ages 15-44 who were hospitalized with laboratory-confirmed influenza from October through April during the 2010-2019 influenza seasons. Data were pulled from the U.S. Influenza Hospitalization Surveillance Network (FluSurv-NET).
Of those women, 2,697 (28%) were pregnant. Median age was 28 and median gestational age was 32 weeks. Those studied included 36% who were non-Hispanic White; 29% non-Hispanic Black; and 20% Hispanic women.
Some 89% of the women, pregnant and nonpregnant, received antivirals while in the hospital but only 31% reported they had received the flu vaccine in the current season, despite guideline recommendations citing clear evidence that vaccination is safe for mother and baby.
Rachel Holstein, MPH, an epidemiology and information science fellow at the Centers for Disease Control and Prevention, who presented her team’s work as part of IDWeek 2020, explained that the mother’s vaccination can help protect the baby from flu infection for several months after birth, before the baby can be vaccinated.
She noted that pregnant women are at high risk for influenza-associated hospitalization.
“Changes in the immune system, heart, and lungs during pregnancy make pregnant women, and women up to 2 weeks post partum, more prone to severe illness from flu, including illness resulting in hospitalization,” she said in an interview
“Vaccination has been shown to reduce the risk of flu-associated acute respiratory infection in pregnant women by up to one-half,” she said. “A 2018 study showed that getting a flu shot reduced a pregnant woman’s risk of being hospitalized with flu by an average of 40%.»
FluSurv-NET data show hospitalizations were more common in the third trimester of pregnancy compared with the first and second, Holstein said. The most common underlying conditions among these women were asthma (23%) and obesity (10%), and 12% were current tobacco smokers. Overall, 5% of pregnant women with flu required ICU admission, 2% needed mechanical ventilation, and 6% developed pneumonia.
Vaccine uptake lowest in first two trimesters
Holstein said vaccine coverage was lowest among women in their first or second trimesters for all 9 seasons, and overall vaccination coverage increased significantly over time.
Uptake also differed by age. The data showed coverage was lower among women aged 15-34 years, compared with women 35 years and older (34% vs. 50%).
“It was as low as 15% among pregnant women aged 15-34 years in the 2011-12 season,” she added.
Jeanne Sheffield, MD, director of the division of maternal-fetal medicine at Johns Hopkins Medicine, Baltimore, said in an interview the low uptake of vaccine shown in this study is both familiar and frustrating.
She said education from health care providers has improved, but women are nonetheless frequently fearful. She pointed out the widespread phenomenon of vaccine hesitancy in the general population.
Coverage was 45.3% among adults in the 2018-2019 flu season, 8.2 percentage points higher than coverage during the 2017-18 season (37.1%) according to CDC estimates.
Added to that, she said, is further hesitancy when women believe vaccination could harm the unborn baby, despite “very good data that flu vaccine is safe in pregnancy, acceptable in pregnancy in all trimesters, and is optimal standard of care.”
Holstein added, “We know from past research that a range of factors – including negative attitudes and beliefs about vaccines, less knowledge about and access to vaccines, and a lack of trust in healthcare providers and vaccines – can contribute to lower vaccination rates.”
Healthcare providers play a key role in increasing flu vaccinations among pregnant women, she said.
“A provider recommendation, combined with an offer to administer a flu vaccine at the time of visit, remains one of the best ways to accomplish this,” Holstein said.
Holstein and Sheffield have disclosed no relevant financial relationships.
This article first appeared on Medscape.com.
Acute HIV cases double in ED. Is COVID-19 responsible?
David Pitrak, MD, an infectious diseases specialist at the University of Chicago Medicine, and colleagues found that the incidence ratio of acute HIV infection (AHI) jumped to 14.4 this year, compared with the 6.8 average for the previous 4 years (IR, 2.14; 95% confidence interval, 1.01-4.54; P < .05).
At a press conference at IDWeek 2020, he said that this year, acute patients made up one quarter of all new diagnoses (9 of 35), “the highest percentage we have ever seen.
“Patients with acute infection, especially those with symptoms, have extremely high viral loads and progress more rapidly. Because of those high viral loads, there’s risk of transmission to others, so rapid linkage to care and ART [antiretroviral treatment] is really important,” he said.
After the IDWeek abstract was submitted in September, Dr. Pitrak said, three additional AHI cases were diagnosed in the ED, bringing the IR of AHI during the pandemic to 2.57 (95% CI, 1.29-5.11).
Should all EDs link HIV screening to COVID-19 testing?
The ED at UCM incorporated blood draws for HIV screening as part of COVID-19 evaluations early on during the pandemic, and they recommend that practice for EDs across the nation.
After a positive test result, the ID team was able to quickly link the HIV patients to care and initiation of antiretroviral treatment without adding staff or resources, Dr. Pitrak said in an interview.
Dr. Pitrak and colleagues reviewed data from 13 health care centers on the south and west sides of Chicago. At most of the centers, fourth- and fifth-generation antibody tests were available. The investigators found that the number of HIV screens that were conducted dropped significantly during the COVID-19 pandemic.
At the height of the pandemic, HIV screening at the sites decreased an average of 58%, the researchers found. As of the end of June, the number was decreased by 32%.
“This is a global problem,” he said. “HIV services have been severely impacted worldwide, with the greatest impact on the LGBTQ community.”
UCM performed 19,111 HIV screens (11,133 in the ED) between Jan. 1 and Aug. 17 this year. It performed 14,754 COVID polymerase chain reaction tests in the ED between March 17 and Aug. 17. All of the acute cases were identified in the ED.
Dr. Pitrak mentioned some possible causes of an increase in the number of patients with acute cases who present in the ED. People who do not suspect they have AHI may be coming to the ED because they think they have COVID-19, inasmuch as many of the symptoms overlap. One of the AHI patients actually did have a coinfection, Dr. Pitrak noted.
“There is also the possibility that this could be bad news,” Dr. Pitrak said in an interview. “It could be that there are more acute cases presenting because there are more community transmissions.”
He noted that follow-up visits have been canceled or converted to telehealth visits during the pandemic, and the number of patients who are initiating pre-exposure prophylaxis has declined significantly.
“I hope we’re not seeing an increase in new transmissions after so much work has been done to decrease transmissions over the past few years,” he said.
Partnership with emergency physicians
Critical to screening these patients is building a solid partnership between ID and ED physicians.
Coauthor Kimberly Stanford, MD, MPH, an assistant professor in emergency medicine at UCM, said, “You need a champion within the emergency department who can help make sure that the work flow is not disrupted, that however you implement your screening program, you’re not putting extra work on the staff.
“We can feel extremely confident that if I send a test and it comes back positive, I know someone is going to call that patient and make sure they get into care.”
Although the testing is performed in the ED at UCM, the follow-up, linkage to care, and initiation of treatment are conducted by the ID specialists.
Beverly E. Sha, MD, professor in the division of infectious diseases, department of internal medicine, Rush Medical College, Chicago, said in an interview that although she agrees that HIV screening programs in EDs “make absolute sense,” there are different ways to conduct such programs. Dr. Sha was not involved in Dr. Pitrak’s study.
At Rush’s ED, she says, HIV testing is linked with a complete blood count.
“If someone presents with fever, we would often be doing that test as well,” she said. “I think just globally increasing screening [in the ED] is what makes the most sense.”
Dr. Sha said they have not seen a similar surge in acute cases in the ED at Rush during the pandemic.
She noted, however, that UCM tested more than 11,000 people for HIV in the ED this year, whereas “we probably only did about 3500.
“The reason testing is so important, whether for HIV or COVID, is the more you test, the more you’re going to find,” she said, “especially in cities like Chicago.”
Dr. Pitrak received grant support from Gilead Sciences. His coauthors and Dr. Sha reported no relevant financial relationships.
This article first appeared on Medscape.com.
David Pitrak, MD, an infectious diseases specialist at the University of Chicago Medicine, and colleagues found that the incidence ratio of acute HIV infection (AHI) jumped to 14.4 this year, compared with the 6.8 average for the previous 4 years (IR, 2.14; 95% confidence interval, 1.01-4.54; P < .05).
At a press conference at IDWeek 2020, he said that this year, acute patients made up one quarter of all new diagnoses (9 of 35), “the highest percentage we have ever seen.
“Patients with acute infection, especially those with symptoms, have extremely high viral loads and progress more rapidly. Because of those high viral loads, there’s risk of transmission to others, so rapid linkage to care and ART [antiretroviral treatment] is really important,” he said.
After the IDWeek abstract was submitted in September, Dr. Pitrak said, three additional AHI cases were diagnosed in the ED, bringing the IR of AHI during the pandemic to 2.57 (95% CI, 1.29-5.11).
Should all EDs link HIV screening to COVID-19 testing?
The ED at UCM incorporated blood draws for HIV screening as part of COVID-19 evaluations early on during the pandemic, and they recommend that practice for EDs across the nation.
After a positive test result, the ID team was able to quickly link the HIV patients to care and initiation of antiretroviral treatment without adding staff or resources, Dr. Pitrak said in an interview.
Dr. Pitrak and colleagues reviewed data from 13 health care centers on the south and west sides of Chicago. At most of the centers, fourth- and fifth-generation antibody tests were available. The investigators found that the number of HIV screens that were conducted dropped significantly during the COVID-19 pandemic.
At the height of the pandemic, HIV screening at the sites decreased an average of 58%, the researchers found. As of the end of June, the number was decreased by 32%.
“This is a global problem,” he said. “HIV services have been severely impacted worldwide, with the greatest impact on the LGBTQ community.”
UCM performed 19,111 HIV screens (11,133 in the ED) between Jan. 1 and Aug. 17 this year. It performed 14,754 COVID polymerase chain reaction tests in the ED between March 17 and Aug. 17. All of the acute cases were identified in the ED.
Dr. Pitrak mentioned some possible causes of an increase in the number of patients with acute cases who present in the ED. People who do not suspect they have AHI may be coming to the ED because they think they have COVID-19, inasmuch as many of the symptoms overlap. One of the AHI patients actually did have a coinfection, Dr. Pitrak noted.
“There is also the possibility that this could be bad news,” Dr. Pitrak said in an interview. “It could be that there are more acute cases presenting because there are more community transmissions.”
He noted that follow-up visits have been canceled or converted to telehealth visits during the pandemic, and the number of patients who are initiating pre-exposure prophylaxis has declined significantly.
“I hope we’re not seeing an increase in new transmissions after so much work has been done to decrease transmissions over the past few years,” he said.
Partnership with emergency physicians
Critical to screening these patients is building a solid partnership between ID and ED physicians.
Coauthor Kimberly Stanford, MD, MPH, an assistant professor in emergency medicine at UCM, said, “You need a champion within the emergency department who can help make sure that the work flow is not disrupted, that however you implement your screening program, you’re not putting extra work on the staff.
“We can feel extremely confident that if I send a test and it comes back positive, I know someone is going to call that patient and make sure they get into care.”
Although the testing is performed in the ED at UCM, the follow-up, linkage to care, and initiation of treatment are conducted by the ID specialists.
Beverly E. Sha, MD, professor in the division of infectious diseases, department of internal medicine, Rush Medical College, Chicago, said in an interview that although she agrees that HIV screening programs in EDs “make absolute sense,” there are different ways to conduct such programs. Dr. Sha was not involved in Dr. Pitrak’s study.
At Rush’s ED, she says, HIV testing is linked with a complete blood count.
“If someone presents with fever, we would often be doing that test as well,” she said. “I think just globally increasing screening [in the ED] is what makes the most sense.”
Dr. Sha said they have not seen a similar surge in acute cases in the ED at Rush during the pandemic.
She noted, however, that UCM tested more than 11,000 people for HIV in the ED this year, whereas “we probably only did about 3500.
“The reason testing is so important, whether for HIV or COVID, is the more you test, the more you’re going to find,” she said, “especially in cities like Chicago.”
Dr. Pitrak received grant support from Gilead Sciences. His coauthors and Dr. Sha reported no relevant financial relationships.
This article first appeared on Medscape.com.
David Pitrak, MD, an infectious diseases specialist at the University of Chicago Medicine, and colleagues found that the incidence ratio of acute HIV infection (AHI) jumped to 14.4 this year, compared with the 6.8 average for the previous 4 years (IR, 2.14; 95% confidence interval, 1.01-4.54; P < .05).
At a press conference at IDWeek 2020, he said that this year, acute patients made up one quarter of all new diagnoses (9 of 35), “the highest percentage we have ever seen.
“Patients with acute infection, especially those with symptoms, have extremely high viral loads and progress more rapidly. Because of those high viral loads, there’s risk of transmission to others, so rapid linkage to care and ART [antiretroviral treatment] is really important,” he said.
After the IDWeek abstract was submitted in September, Dr. Pitrak said, three additional AHI cases were diagnosed in the ED, bringing the IR of AHI during the pandemic to 2.57 (95% CI, 1.29-5.11).
Should all EDs link HIV screening to COVID-19 testing?
The ED at UCM incorporated blood draws for HIV screening as part of COVID-19 evaluations early on during the pandemic, and they recommend that practice for EDs across the nation.
After a positive test result, the ID team was able to quickly link the HIV patients to care and initiation of antiretroviral treatment without adding staff or resources, Dr. Pitrak said in an interview.
Dr. Pitrak and colleagues reviewed data from 13 health care centers on the south and west sides of Chicago. At most of the centers, fourth- and fifth-generation antibody tests were available. The investigators found that the number of HIV screens that were conducted dropped significantly during the COVID-19 pandemic.
At the height of the pandemic, HIV screening at the sites decreased an average of 58%, the researchers found. As of the end of June, the number was decreased by 32%.
“This is a global problem,” he said. “HIV services have been severely impacted worldwide, with the greatest impact on the LGBTQ community.”
UCM performed 19,111 HIV screens (11,133 in the ED) between Jan. 1 and Aug. 17 this year. It performed 14,754 COVID polymerase chain reaction tests in the ED between March 17 and Aug. 17. All of the acute cases were identified in the ED.
Dr. Pitrak mentioned some possible causes of an increase in the number of patients with acute cases who present in the ED. People who do not suspect they have AHI may be coming to the ED because they think they have COVID-19, inasmuch as many of the symptoms overlap. One of the AHI patients actually did have a coinfection, Dr. Pitrak noted.
“There is also the possibility that this could be bad news,” Dr. Pitrak said in an interview. “It could be that there are more acute cases presenting because there are more community transmissions.”
He noted that follow-up visits have been canceled or converted to telehealth visits during the pandemic, and the number of patients who are initiating pre-exposure prophylaxis has declined significantly.
“I hope we’re not seeing an increase in new transmissions after so much work has been done to decrease transmissions over the past few years,” he said.
Partnership with emergency physicians
Critical to screening these patients is building a solid partnership between ID and ED physicians.
Coauthor Kimberly Stanford, MD, MPH, an assistant professor in emergency medicine at UCM, said, “You need a champion within the emergency department who can help make sure that the work flow is not disrupted, that however you implement your screening program, you’re not putting extra work on the staff.
“We can feel extremely confident that if I send a test and it comes back positive, I know someone is going to call that patient and make sure they get into care.”
Although the testing is performed in the ED at UCM, the follow-up, linkage to care, and initiation of treatment are conducted by the ID specialists.
Beverly E. Sha, MD, professor in the division of infectious diseases, department of internal medicine, Rush Medical College, Chicago, said in an interview that although she agrees that HIV screening programs in EDs “make absolute sense,” there are different ways to conduct such programs. Dr. Sha was not involved in Dr. Pitrak’s study.
At Rush’s ED, she says, HIV testing is linked with a complete blood count.
“If someone presents with fever, we would often be doing that test as well,” she said. “I think just globally increasing screening [in the ED] is what makes the most sense.”
Dr. Sha said they have not seen a similar surge in acute cases in the ED at Rush during the pandemic.
She noted, however, that UCM tested more than 11,000 people for HIV in the ED this year, whereas “we probably only did about 3500.
“The reason testing is so important, whether for HIV or COVID, is the more you test, the more you’re going to find,” she said, “especially in cities like Chicago.”
Dr. Pitrak received grant support from Gilead Sciences. His coauthors and Dr. Sha reported no relevant financial relationships.
This article first appeared on Medscape.com.
Tofacitinib retreatment effective for ulcerative colitis
Retreatment with tofacitinib after a period of treatment interruption was well tolerated and effective in patients with ulcerative colitis who had shown a previous response to tofacitinib induction, according to an analysis of data from the OCTAVE extension trial.
“Clinical response was recaptured in most patients by month 2, and about half of patients by month 36, irrespective of prior anti–[tumor necrosis factor] status,” said lead researcher Edward V. Loftus Jr, MD, from the Mayo Medical School, Rochester, Minn.
A temporary suspension of treatment with the oral, small-molecule Janus kinase (JAK) inhibitor might be necessary for a number of reasons, such as if a patient has to undergo surgery, experiences adverse events, or becomes pregnant.
For their study, Dr. Loftus and colleagues set out to assess the safety and efficacy of retreatment after a period of interruption.
“The population we’re interested in are patients who received tofacitinib during induction and placebo during maintenance” in the original OCTAVE trials, said Dr. Loftus. “They then either completed the trial or flared and rolled over to the open-label extension.”
The researchers looked at the 100 patients who had achieved a clinical response after 8 weeks of treatment with tofacitinib 10 mg twice-daily in the OCTAVE Induction 1 and OCTAVE Induction 2 trials and then received placebo in the OCTAVE Sustain trial and experienced treatment failure between week 8 and week 52. These patients went on to receive tofacitinib 10 mg twice daily as part of the ongoing, open-label, long-term extension OCTAVE Open trial.
Treatment failure was defined as an increase of at least 3 points from the baseline total Mayo score achieved in OCTAVE Sustain, plus an increase of at least 1 point in rectal bleeding and endoscopic subscores and an absolute endoscopic subscore of at least 2 points after at least 8 weeks of treatment. Efficacy was evaluated for up to 36 months in the open-label extension; adverse events were assessed throughout the study period.
The median time to treatment failure was 135 days, Dr. Loftus reported during his award-winning presentation at the virtual annual meeting of the American College of Gastroenterology.
On last observation carried forward (LOCF) analysis, or observed data, 85.2% of the patients had recaptured clinical response by month 2. That rate fell to 74.3% when the analysis was modified for nonresponder imputation (NRI).
“The truth lies somewhere in between,” Dr. Loftus said.
Of interest, a clinical response to tofacitinib retreatment at month 2 was achieved by 92.5% (observed data) and 80.4% (NRI-LOCF) of patients who experienced treatment failure after tumor necrosis factor inhibitor therapy.
“Many patients were able to regain response with tofacitinib and then maintain that over time,” said Dr. Loftus.
Study supports retreatment, which is good news for patients
Incidence rates of adverse events were comparable in the retreatment population and in the overall extension cohort. “There are no signals jumping out, saying that safety events were higher or more frequent in this retreatment population, which is reassuring,” Dr. Loftus added.
Findings such as these are to be expected given the mechanism of action and pharmacologic features of tofacitinib, said Gionata Fiorino, MD, from Humanitas University in Milan, who was not involved in the study.
“I think this is important for patients who need to stop therapy for several reasons – pregnancy, adverse events that do not require permanent withdrawal of the drug, or surgical interventions – and experience a flare after drug withdrawal,” he said in an interview.
“There are several other therapeutic options for these patients, but I have experienced many patients who do not respond to other mechanisms of action apart from JAK [inhibitors],” he added. “And, in the case of a patient who has stopped the drug after having achieved remission, this study clearly supports retreatment, which is good news, especially for patients.”
This study was funded by Pfizer. Dr. Loftus reported financial relationships with AbbVie, Allergan, Amgen, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Celltrion, Eli Lilly, Exact Sciences, Genentech, Gilead, Janssen, Pfizer, Robarts Clinical Trials, Takeda, and UCB. Dr. Fiorino reports financial relationships with MSD, Takeda, AbbVie, Janssen, Pfizer, Celltrion, Sandoz, AlfaSigma, Samsung, Amgen, Roche, and Ferring.
A version of this article originally appeared on Medscape.com.
Retreatment with tofacitinib after a period of treatment interruption was well tolerated and effective in patients with ulcerative colitis who had shown a previous response to tofacitinib induction, according to an analysis of data from the OCTAVE extension trial.
“Clinical response was recaptured in most patients by month 2, and about half of patients by month 36, irrespective of prior anti–[tumor necrosis factor] status,” said lead researcher Edward V. Loftus Jr, MD, from the Mayo Medical School, Rochester, Minn.
A temporary suspension of treatment with the oral, small-molecule Janus kinase (JAK) inhibitor might be necessary for a number of reasons, such as if a patient has to undergo surgery, experiences adverse events, or becomes pregnant.
For their study, Dr. Loftus and colleagues set out to assess the safety and efficacy of retreatment after a period of interruption.
“The population we’re interested in are patients who received tofacitinib during induction and placebo during maintenance” in the original OCTAVE trials, said Dr. Loftus. “They then either completed the trial or flared and rolled over to the open-label extension.”
The researchers looked at the 100 patients who had achieved a clinical response after 8 weeks of treatment with tofacitinib 10 mg twice-daily in the OCTAVE Induction 1 and OCTAVE Induction 2 trials and then received placebo in the OCTAVE Sustain trial and experienced treatment failure between week 8 and week 52. These patients went on to receive tofacitinib 10 mg twice daily as part of the ongoing, open-label, long-term extension OCTAVE Open trial.
Treatment failure was defined as an increase of at least 3 points from the baseline total Mayo score achieved in OCTAVE Sustain, plus an increase of at least 1 point in rectal bleeding and endoscopic subscores and an absolute endoscopic subscore of at least 2 points after at least 8 weeks of treatment. Efficacy was evaluated for up to 36 months in the open-label extension; adverse events were assessed throughout the study period.
The median time to treatment failure was 135 days, Dr. Loftus reported during his award-winning presentation at the virtual annual meeting of the American College of Gastroenterology.
On last observation carried forward (LOCF) analysis, or observed data, 85.2% of the patients had recaptured clinical response by month 2. That rate fell to 74.3% when the analysis was modified for nonresponder imputation (NRI).
“The truth lies somewhere in between,” Dr. Loftus said.
Of interest, a clinical response to tofacitinib retreatment at month 2 was achieved by 92.5% (observed data) and 80.4% (NRI-LOCF) of patients who experienced treatment failure after tumor necrosis factor inhibitor therapy.
“Many patients were able to regain response with tofacitinib and then maintain that over time,” said Dr. Loftus.
Study supports retreatment, which is good news for patients
Incidence rates of adverse events were comparable in the retreatment population and in the overall extension cohort. “There are no signals jumping out, saying that safety events were higher or more frequent in this retreatment population, which is reassuring,” Dr. Loftus added.
Findings such as these are to be expected given the mechanism of action and pharmacologic features of tofacitinib, said Gionata Fiorino, MD, from Humanitas University in Milan, who was not involved in the study.
“I think this is important for patients who need to stop therapy for several reasons – pregnancy, adverse events that do not require permanent withdrawal of the drug, or surgical interventions – and experience a flare after drug withdrawal,” he said in an interview.
“There are several other therapeutic options for these patients, but I have experienced many patients who do not respond to other mechanisms of action apart from JAK [inhibitors],” he added. “And, in the case of a patient who has stopped the drug after having achieved remission, this study clearly supports retreatment, which is good news, especially for patients.”
This study was funded by Pfizer. Dr. Loftus reported financial relationships with AbbVie, Allergan, Amgen, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Celltrion, Eli Lilly, Exact Sciences, Genentech, Gilead, Janssen, Pfizer, Robarts Clinical Trials, Takeda, and UCB. Dr. Fiorino reports financial relationships with MSD, Takeda, AbbVie, Janssen, Pfizer, Celltrion, Sandoz, AlfaSigma, Samsung, Amgen, Roche, and Ferring.
A version of this article originally appeared on Medscape.com.
Retreatment with tofacitinib after a period of treatment interruption was well tolerated and effective in patients with ulcerative colitis who had shown a previous response to tofacitinib induction, according to an analysis of data from the OCTAVE extension trial.
“Clinical response was recaptured in most patients by month 2, and about half of patients by month 36, irrespective of prior anti–[tumor necrosis factor] status,” said lead researcher Edward V. Loftus Jr, MD, from the Mayo Medical School, Rochester, Minn.
A temporary suspension of treatment with the oral, small-molecule Janus kinase (JAK) inhibitor might be necessary for a number of reasons, such as if a patient has to undergo surgery, experiences adverse events, or becomes pregnant.
For their study, Dr. Loftus and colleagues set out to assess the safety and efficacy of retreatment after a period of interruption.
“The population we’re interested in are patients who received tofacitinib during induction and placebo during maintenance” in the original OCTAVE trials, said Dr. Loftus. “They then either completed the trial or flared and rolled over to the open-label extension.”
The researchers looked at the 100 patients who had achieved a clinical response after 8 weeks of treatment with tofacitinib 10 mg twice-daily in the OCTAVE Induction 1 and OCTAVE Induction 2 trials and then received placebo in the OCTAVE Sustain trial and experienced treatment failure between week 8 and week 52. These patients went on to receive tofacitinib 10 mg twice daily as part of the ongoing, open-label, long-term extension OCTAVE Open trial.
Treatment failure was defined as an increase of at least 3 points from the baseline total Mayo score achieved in OCTAVE Sustain, plus an increase of at least 1 point in rectal bleeding and endoscopic subscores and an absolute endoscopic subscore of at least 2 points after at least 8 weeks of treatment. Efficacy was evaluated for up to 36 months in the open-label extension; adverse events were assessed throughout the study period.
The median time to treatment failure was 135 days, Dr. Loftus reported during his award-winning presentation at the virtual annual meeting of the American College of Gastroenterology.
On last observation carried forward (LOCF) analysis, or observed data, 85.2% of the patients had recaptured clinical response by month 2. That rate fell to 74.3% when the analysis was modified for nonresponder imputation (NRI).
“The truth lies somewhere in between,” Dr. Loftus said.
Of interest, a clinical response to tofacitinib retreatment at month 2 was achieved by 92.5% (observed data) and 80.4% (NRI-LOCF) of patients who experienced treatment failure after tumor necrosis factor inhibitor therapy.
“Many patients were able to regain response with tofacitinib and then maintain that over time,” said Dr. Loftus.
Study supports retreatment, which is good news for patients
Incidence rates of adverse events were comparable in the retreatment population and in the overall extension cohort. “There are no signals jumping out, saying that safety events were higher or more frequent in this retreatment population, which is reassuring,” Dr. Loftus added.
Findings such as these are to be expected given the mechanism of action and pharmacologic features of tofacitinib, said Gionata Fiorino, MD, from Humanitas University in Milan, who was not involved in the study.
“I think this is important for patients who need to stop therapy for several reasons – pregnancy, adverse events that do not require permanent withdrawal of the drug, or surgical interventions – and experience a flare after drug withdrawal,” he said in an interview.
“There are several other therapeutic options for these patients, but I have experienced many patients who do not respond to other mechanisms of action apart from JAK [inhibitors],” he added. “And, in the case of a patient who has stopped the drug after having achieved remission, this study clearly supports retreatment, which is good news, especially for patients.”
This study was funded by Pfizer. Dr. Loftus reported financial relationships with AbbVie, Allergan, Amgen, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Celltrion, Eli Lilly, Exact Sciences, Genentech, Gilead, Janssen, Pfizer, Robarts Clinical Trials, Takeda, and UCB. Dr. Fiorino reports financial relationships with MSD, Takeda, AbbVie, Janssen, Pfizer, Celltrion, Sandoz, AlfaSigma, Samsung, Amgen, Roche, and Ferring.
A version of this article originally appeared on Medscape.com.
Cannabis may improve liver function in patients with obesity
Cannabis use is associated with a decrease in the prevalence of steatohepatitis and a slowing of its progression in patients with obesity, results from a retrospective cohort study show.
This suggests “that the anti-inflammatory effects of cannabis may be leading to reduced prevalence of steatohepatitis in cannabis users,” said Ikechukwu Achebe, MD, from the John H. Stroger, Jr. Hospital of Cook County in Chicago.
Liver injuries such as nonalcoholic steatohepatitis are characterized by hepatocellular injury and inflammation, which combine to contribute to an increase in the risk for liver failure, cirrhosis, and hepatocellular carcinoma.
“This is where cannabis comes in,” said Dr. Achebe, who presented the study results at the virtual annual meeting of the American College of Gastroenterology. “It is the most commonly used psychoactive substance worldwide and has been shown to reduce hepatic myofibroblast and stellate cell injury. Studies using mouse models have demonstrated reduced liver fibrosis and cirrhosis as a consequence of cannabis exposure.”
Given this possible connection, Dr. Achebe and colleagues set out to determine whether cannabis use affects the prevalence and progression of nonalcoholic fatty liver disease (NAFLD) in obese patients.
To do so, they analyzed the discharge records of 879,952 obese adults in the 2016 Healthcare Cost and Utilization Project National Inpatient Sample. The primary outcome was the prevalence of the four presentations of NAFLD: steatosis, steatohepatitis, cirrhosis, and hepatocellular carcinoma.
The researchers compared disease stages in cannabis users and nonusers. In the study cohort of 14,236 patients, 1.6% used cannabis. Steatohepatitis was less common among cannabis users than among nonusers (0.4% vs. 0.7%; P < .001), as was cirrhosis (1.1% vs. 1.5%; P < .001).
After propensity matching, the association between cannabis use and lower rates of steatohepatitis remained significant (0.4% vs. 0.5%; P = .035), but the association between cannabis use and the prevalence of nonalcoholic fatty liver, cirrhosis, and hepatocellular carcinoma did not.
These results might be partly explained by the protective effect of cannabis on hepatocytes regulated by the endocannabinoid system, the researchers concluded.
More studies are needed to explore this relation, said Dr. Achebe.
The challenge of self-reported use
The study is “incredibly interesting,” said Nancy S. Reau, MD, from Rush Medical College, Chicago. However, the association between cannabis and nonalcoholic fatty liver needs to be further investigated before clinicians can counsel their patients to use the agent to prevent progression.
It is difficult in a study such as this to tease out other lifestyle factors that might be linked to cannabis use, she explained. For example, “is it possible that the cannabis users exercise more, drink more coffee, or eat differently?”
And “self-reported use is challenging,” Dr. Reau said in an interview. “This cannot differentiate someone who occasionally uses from someone who is a heavy daily user. There must be some minimum level of exposure needed for it to have protective effects, if they exist.”
This study was honored at the meeting as an ACG Newsworthy Abstract and an ACG Outstanding Poster Presenter.
Dr. Achebe disclosed no relevant financial relationships. Dr. Reau reported receiving research support from Genfit and having a consultant relationship with Intercept Pharmaceuticals.
A version of this article originally appeared on Medscape.com.
Cannabis use is associated with a decrease in the prevalence of steatohepatitis and a slowing of its progression in patients with obesity, results from a retrospective cohort study show.
This suggests “that the anti-inflammatory effects of cannabis may be leading to reduced prevalence of steatohepatitis in cannabis users,” said Ikechukwu Achebe, MD, from the John H. Stroger, Jr. Hospital of Cook County in Chicago.
Liver injuries such as nonalcoholic steatohepatitis are characterized by hepatocellular injury and inflammation, which combine to contribute to an increase in the risk for liver failure, cirrhosis, and hepatocellular carcinoma.
“This is where cannabis comes in,” said Dr. Achebe, who presented the study results at the virtual annual meeting of the American College of Gastroenterology. “It is the most commonly used psychoactive substance worldwide and has been shown to reduce hepatic myofibroblast and stellate cell injury. Studies using mouse models have demonstrated reduced liver fibrosis and cirrhosis as a consequence of cannabis exposure.”
Given this possible connection, Dr. Achebe and colleagues set out to determine whether cannabis use affects the prevalence and progression of nonalcoholic fatty liver disease (NAFLD) in obese patients.
To do so, they analyzed the discharge records of 879,952 obese adults in the 2016 Healthcare Cost and Utilization Project National Inpatient Sample. The primary outcome was the prevalence of the four presentations of NAFLD: steatosis, steatohepatitis, cirrhosis, and hepatocellular carcinoma.
The researchers compared disease stages in cannabis users and nonusers. In the study cohort of 14,236 patients, 1.6% used cannabis. Steatohepatitis was less common among cannabis users than among nonusers (0.4% vs. 0.7%; P < .001), as was cirrhosis (1.1% vs. 1.5%; P < .001).
After propensity matching, the association between cannabis use and lower rates of steatohepatitis remained significant (0.4% vs. 0.5%; P = .035), but the association between cannabis use and the prevalence of nonalcoholic fatty liver, cirrhosis, and hepatocellular carcinoma did not.
These results might be partly explained by the protective effect of cannabis on hepatocytes regulated by the endocannabinoid system, the researchers concluded.
More studies are needed to explore this relation, said Dr. Achebe.
The challenge of self-reported use
The study is “incredibly interesting,” said Nancy S. Reau, MD, from Rush Medical College, Chicago. However, the association between cannabis and nonalcoholic fatty liver needs to be further investigated before clinicians can counsel their patients to use the agent to prevent progression.
It is difficult in a study such as this to tease out other lifestyle factors that might be linked to cannabis use, she explained. For example, “is it possible that the cannabis users exercise more, drink more coffee, or eat differently?”
And “self-reported use is challenging,” Dr. Reau said in an interview. “This cannot differentiate someone who occasionally uses from someone who is a heavy daily user. There must be some minimum level of exposure needed for it to have protective effects, if they exist.”
This study was honored at the meeting as an ACG Newsworthy Abstract and an ACG Outstanding Poster Presenter.
Dr. Achebe disclosed no relevant financial relationships. Dr. Reau reported receiving research support from Genfit and having a consultant relationship with Intercept Pharmaceuticals.
A version of this article originally appeared on Medscape.com.
Cannabis use is associated with a decrease in the prevalence of steatohepatitis and a slowing of its progression in patients with obesity, results from a retrospective cohort study show.
This suggests “that the anti-inflammatory effects of cannabis may be leading to reduced prevalence of steatohepatitis in cannabis users,” said Ikechukwu Achebe, MD, from the John H. Stroger, Jr. Hospital of Cook County in Chicago.
Liver injuries such as nonalcoholic steatohepatitis are characterized by hepatocellular injury and inflammation, which combine to contribute to an increase in the risk for liver failure, cirrhosis, and hepatocellular carcinoma.
“This is where cannabis comes in,” said Dr. Achebe, who presented the study results at the virtual annual meeting of the American College of Gastroenterology. “It is the most commonly used psychoactive substance worldwide and has been shown to reduce hepatic myofibroblast and stellate cell injury. Studies using mouse models have demonstrated reduced liver fibrosis and cirrhosis as a consequence of cannabis exposure.”
Given this possible connection, Dr. Achebe and colleagues set out to determine whether cannabis use affects the prevalence and progression of nonalcoholic fatty liver disease (NAFLD) in obese patients.
To do so, they analyzed the discharge records of 879,952 obese adults in the 2016 Healthcare Cost and Utilization Project National Inpatient Sample. The primary outcome was the prevalence of the four presentations of NAFLD: steatosis, steatohepatitis, cirrhosis, and hepatocellular carcinoma.
The researchers compared disease stages in cannabis users and nonusers. In the study cohort of 14,236 patients, 1.6% used cannabis. Steatohepatitis was less common among cannabis users than among nonusers (0.4% vs. 0.7%; P < .001), as was cirrhosis (1.1% vs. 1.5%; P < .001).
After propensity matching, the association between cannabis use and lower rates of steatohepatitis remained significant (0.4% vs. 0.5%; P = .035), but the association between cannabis use and the prevalence of nonalcoholic fatty liver, cirrhosis, and hepatocellular carcinoma did not.
These results might be partly explained by the protective effect of cannabis on hepatocytes regulated by the endocannabinoid system, the researchers concluded.
More studies are needed to explore this relation, said Dr. Achebe.
The challenge of self-reported use
The study is “incredibly interesting,” said Nancy S. Reau, MD, from Rush Medical College, Chicago. However, the association between cannabis and nonalcoholic fatty liver needs to be further investigated before clinicians can counsel their patients to use the agent to prevent progression.
It is difficult in a study such as this to tease out other lifestyle factors that might be linked to cannabis use, she explained. For example, “is it possible that the cannabis users exercise more, drink more coffee, or eat differently?”
And “self-reported use is challenging,” Dr. Reau said in an interview. “This cannot differentiate someone who occasionally uses from someone who is a heavy daily user. There must be some minimum level of exposure needed for it to have protective effects, if they exist.”
This study was honored at the meeting as an ACG Newsworthy Abstract and an ACG Outstanding Poster Presenter.
Dr. Achebe disclosed no relevant financial relationships. Dr. Reau reported receiving research support from Genfit and having a consultant relationship with Intercept Pharmaceuticals.
A version of this article originally appeared on Medscape.com.
FROM ACG 2020
Novel treatments under study for chronic graft-versus-host disease in allo-HCT
Physicians are gaining a greater understanding of the pathophysiology of chronic graft-versus-host disease (cGVHD) in allo-hematopoietic cell transplantation (allo-HCT), a hematologist/oncologist told colleagues, and novel treatments are being tested.
However, options remain limited. There’s only one Food and Drug Administration–approved therapy for cGVHD that’s failed one or more treatments, and clinical trials remain a crucial option in some cases, said Mary E.D. Flowers, MD, professor of medicine at the University of Washington’s Fred Hutchinson Cancer Research Center, Seattle, in a presentation at the virtual Acute Leukemia Forum of Hemedicus.
According to Dr. Flowers, cGVHD – a product of a graft’s “immunological assault” against the person receiving a transplant – occurs in 40% of patients within a year after allo-HCT. The disorder “is associated with a poor quality of life, disability, and increased mortality after allo-transplantation,” she said. “It’s a syndrome that can be inflammatory and fibrotic. It involves several organs – the skin, the mouth, the eyes, the lungs, the GI tract.”
The median length of treatment after peripheral blood stem cell transplant is 3.5 years, Dr. Flowers said. Seven years after treatment, 10% of those who are alive – and have avoided relapse – will still need treatment. “Corticosteroids remain the first-line [treatment], at 0.5-1.0 [mg/kg], but they do not control at least 40% of the patients with cGVHD.”
In regard to pathophysiology, she highlighted a 2017 report that presented findings about the pathophysiology of cGVHD. The findings, the report authors wrote, “have yielded a raft of potential new therapeutics, centered on naive T-cell depletion, interleukin-17/21 inhibition, kinase inhibition, regulatory T-cell restoration, and CSF-1 inhibition.”
For now, no agents other than corticosteroids have shown benefit in cGVHD as initial therapy, Dr. Flowers said. In fact, several trials closed early from lack of benefit. But trials continue, she said: Results are pending for a completed phase 3 trial of ibrutinib, a Bruton tyrosine kinase inhibitor, plus steroids for initial treatment of cGVHD. Nearly 500 patients were enrolled, she said. And there’s an ongoing phase 2/3 trial of itacitinib, a Janus kinase 1 inhibitor plus steroids as initial treatment.
Dr. Flowers highlighted the case of a patient with moderate cGVHD. The patient was treated with infection prophylaxis, supportive care for oral and eyes manifestations, and prednisone 0.5 mg/kg (at a lower dose because of diabetes) plus a substitution of tacrolimus with sirolimus, a calcineurin inhibitor.
Why sirolimus? At this early point in progression, she said, the patient didn’t necessarily need systemwide chemo-suppression, and calcineurin inhibitors can be “quite effective” in management of inflammation in the liver. “It would be a completely different story once the patient develops severe cGVHR.” In that case, she said, calcineurin inhibitors wouldn’t be appropriate.
The patient’s status deteriorated to severe cGVHD, and sirolimus was replaced with ibrutinib. Other drugs were added to prevent infection and treat bronchiolitis obliterans syndrome.
In general, “the goal of the treatment is get adequate control of clinical manifestations and prevent more severe disease from developing,” Dr. Flowers said.
In response to a question about polypharmacy in patient with advanced disease – “we tend not to peel those drugs off” – Dr. Flowers said she does see new patients who appear to be taking too many medications. “They are on five drugs, and I say, ‘What are we doing?’ ”
Quite often, Dr. Flowers said, she doesn’t add therapies to existing ones but instead looks for substitutes. “A clinical lesson that I feel that I learned over time is: Ask your questions first. What would you like to see in 3 months? Or 6 months? Before you just add another therapy, do you really know what the trajectory of a disease might be?”
Dr. Flowers discloses research support (Pharmacyclics, Incyte), speaker honorarium (Janssen, Johnson & Johnson, Astellas, Mallinckrodt), and consulting relationships (Pharmacyclics, CSL Behring, Fresenius Kabi).
The Acute Leukemia Forum is held by Hemedicus, which is owned by the same company as this news organization.
Physicians are gaining a greater understanding of the pathophysiology of chronic graft-versus-host disease (cGVHD) in allo-hematopoietic cell transplantation (allo-HCT), a hematologist/oncologist told colleagues, and novel treatments are being tested.
However, options remain limited. There’s only one Food and Drug Administration–approved therapy for cGVHD that’s failed one or more treatments, and clinical trials remain a crucial option in some cases, said Mary E.D. Flowers, MD, professor of medicine at the University of Washington’s Fred Hutchinson Cancer Research Center, Seattle, in a presentation at the virtual Acute Leukemia Forum of Hemedicus.
According to Dr. Flowers, cGVHD – a product of a graft’s “immunological assault” against the person receiving a transplant – occurs in 40% of patients within a year after allo-HCT. The disorder “is associated with a poor quality of life, disability, and increased mortality after allo-transplantation,” she said. “It’s a syndrome that can be inflammatory and fibrotic. It involves several organs – the skin, the mouth, the eyes, the lungs, the GI tract.”
The median length of treatment after peripheral blood stem cell transplant is 3.5 years, Dr. Flowers said. Seven years after treatment, 10% of those who are alive – and have avoided relapse – will still need treatment. “Corticosteroids remain the first-line [treatment], at 0.5-1.0 [mg/kg], but they do not control at least 40% of the patients with cGVHD.”
In regard to pathophysiology, she highlighted a 2017 report that presented findings about the pathophysiology of cGVHD. The findings, the report authors wrote, “have yielded a raft of potential new therapeutics, centered on naive T-cell depletion, interleukin-17/21 inhibition, kinase inhibition, regulatory T-cell restoration, and CSF-1 inhibition.”
For now, no agents other than corticosteroids have shown benefit in cGVHD as initial therapy, Dr. Flowers said. In fact, several trials closed early from lack of benefit. But trials continue, she said: Results are pending for a completed phase 3 trial of ibrutinib, a Bruton tyrosine kinase inhibitor, plus steroids for initial treatment of cGVHD. Nearly 500 patients were enrolled, she said. And there’s an ongoing phase 2/3 trial of itacitinib, a Janus kinase 1 inhibitor plus steroids as initial treatment.
Dr. Flowers highlighted the case of a patient with moderate cGVHD. The patient was treated with infection prophylaxis, supportive care for oral and eyes manifestations, and prednisone 0.5 mg/kg (at a lower dose because of diabetes) plus a substitution of tacrolimus with sirolimus, a calcineurin inhibitor.
Why sirolimus? At this early point in progression, she said, the patient didn’t necessarily need systemwide chemo-suppression, and calcineurin inhibitors can be “quite effective” in management of inflammation in the liver. “It would be a completely different story once the patient develops severe cGVHR.” In that case, she said, calcineurin inhibitors wouldn’t be appropriate.
The patient’s status deteriorated to severe cGVHD, and sirolimus was replaced with ibrutinib. Other drugs were added to prevent infection and treat bronchiolitis obliterans syndrome.
In general, “the goal of the treatment is get adequate control of clinical manifestations and prevent more severe disease from developing,” Dr. Flowers said.
In response to a question about polypharmacy in patient with advanced disease – “we tend not to peel those drugs off” – Dr. Flowers said she does see new patients who appear to be taking too many medications. “They are on five drugs, and I say, ‘What are we doing?’ ”
Quite often, Dr. Flowers said, she doesn’t add therapies to existing ones but instead looks for substitutes. “A clinical lesson that I feel that I learned over time is: Ask your questions first. What would you like to see in 3 months? Or 6 months? Before you just add another therapy, do you really know what the trajectory of a disease might be?”
Dr. Flowers discloses research support (Pharmacyclics, Incyte), speaker honorarium (Janssen, Johnson & Johnson, Astellas, Mallinckrodt), and consulting relationships (Pharmacyclics, CSL Behring, Fresenius Kabi).
The Acute Leukemia Forum is held by Hemedicus, which is owned by the same company as this news organization.
Physicians are gaining a greater understanding of the pathophysiology of chronic graft-versus-host disease (cGVHD) in allo-hematopoietic cell transplantation (allo-HCT), a hematologist/oncologist told colleagues, and novel treatments are being tested.
However, options remain limited. There’s only one Food and Drug Administration–approved therapy for cGVHD that’s failed one or more treatments, and clinical trials remain a crucial option in some cases, said Mary E.D. Flowers, MD, professor of medicine at the University of Washington’s Fred Hutchinson Cancer Research Center, Seattle, in a presentation at the virtual Acute Leukemia Forum of Hemedicus.
According to Dr. Flowers, cGVHD – a product of a graft’s “immunological assault” against the person receiving a transplant – occurs in 40% of patients within a year after allo-HCT. The disorder “is associated with a poor quality of life, disability, and increased mortality after allo-transplantation,” she said. “It’s a syndrome that can be inflammatory and fibrotic. It involves several organs – the skin, the mouth, the eyes, the lungs, the GI tract.”
The median length of treatment after peripheral blood stem cell transplant is 3.5 years, Dr. Flowers said. Seven years after treatment, 10% of those who are alive – and have avoided relapse – will still need treatment. “Corticosteroids remain the first-line [treatment], at 0.5-1.0 [mg/kg], but they do not control at least 40% of the patients with cGVHD.”
In regard to pathophysiology, she highlighted a 2017 report that presented findings about the pathophysiology of cGVHD. The findings, the report authors wrote, “have yielded a raft of potential new therapeutics, centered on naive T-cell depletion, interleukin-17/21 inhibition, kinase inhibition, regulatory T-cell restoration, and CSF-1 inhibition.”
For now, no agents other than corticosteroids have shown benefit in cGVHD as initial therapy, Dr. Flowers said. In fact, several trials closed early from lack of benefit. But trials continue, she said: Results are pending for a completed phase 3 trial of ibrutinib, a Bruton tyrosine kinase inhibitor, plus steroids for initial treatment of cGVHD. Nearly 500 patients were enrolled, she said. And there’s an ongoing phase 2/3 trial of itacitinib, a Janus kinase 1 inhibitor plus steroids as initial treatment.
Dr. Flowers highlighted the case of a patient with moderate cGVHD. The patient was treated with infection prophylaxis, supportive care for oral and eyes manifestations, and prednisone 0.5 mg/kg (at a lower dose because of diabetes) plus a substitution of tacrolimus with sirolimus, a calcineurin inhibitor.
Why sirolimus? At this early point in progression, she said, the patient didn’t necessarily need systemwide chemo-suppression, and calcineurin inhibitors can be “quite effective” in management of inflammation in the liver. “It would be a completely different story once the patient develops severe cGVHR.” In that case, she said, calcineurin inhibitors wouldn’t be appropriate.
The patient’s status deteriorated to severe cGVHD, and sirolimus was replaced with ibrutinib. Other drugs were added to prevent infection and treat bronchiolitis obliterans syndrome.
In general, “the goal of the treatment is get adequate control of clinical manifestations and prevent more severe disease from developing,” Dr. Flowers said.
In response to a question about polypharmacy in patient with advanced disease – “we tend not to peel those drugs off” – Dr. Flowers said she does see new patients who appear to be taking too many medications. “They are on five drugs, and I say, ‘What are we doing?’ ”
Quite often, Dr. Flowers said, she doesn’t add therapies to existing ones but instead looks for substitutes. “A clinical lesson that I feel that I learned over time is: Ask your questions first. What would you like to see in 3 months? Or 6 months? Before you just add another therapy, do you really know what the trajectory of a disease might be?”
Dr. Flowers discloses research support (Pharmacyclics, Incyte), speaker honorarium (Janssen, Johnson & Johnson, Astellas, Mallinckrodt), and consulting relationships (Pharmacyclics, CSL Behring, Fresenius Kabi).
The Acute Leukemia Forum is held by Hemedicus, which is owned by the same company as this news organization.
FROM ALF 2020
Lower BP and better tumor control with drug combo?
It’s not ready for the clinic, but new research suggests that angiotensin receptor II blockers (ARBs) widely used to treat hypertension may improve responses to cancer immunotherapy agents targeted against the programmed death-1/ligand-1 (PD-1/PD-L1) pathway.
That conclusion comes from an observational study of 597 patients with more than 3 dozen different cancer types treated in clinical trials at the US National Institutes of Health. Investigators found that both objective response rates and 3-year overall survival (OS) rates were significantly higher for patients treated with a PD-1/PD-L1 inhibitor who were on ARBs, compared with patients who weren’t taking the antihypertensive agents.
An association was also seen between higher ORR and OS rates for patients taking ACE inhibitors, but it was not statistically significant, reported Julius Strauss, MD, from the Center for Cancer Research at the National Cancer Institute in Bethesda, Md.
All study patients received PD-1/PD-L1 inhibitors, and the ORR for patients treated with ARBs was 33.8%, compared with 19.5% for those treated with ACE inhibitors, and 17% for those who took neither drug. The respective complete response (CR) rates were 11.3%, 3.7%, and 3.1%.
Strauss discussed the data during an online briefing prior to his presentation of the findings during the 32nd EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics, which is taking place virtually.
Several early studies have suggested that angiotensin II, in addition to its effect on blood pressure, can also affect cancer growth by leading to downstream production of two proteins: vascular endothelial growth factor (VEGF) and transforming growth factor–beta (TGF-beta), he explained.
“Both of these [proteins] have been linked to cancer growth and cancer resistance to immune system attack,” Strauss observed.
He also discussed the mechanics of possible effects. Angiotensin II increases VEGF and TGF-beta through binding to the AT1 receptor, but has the opposite effect when it binds to the AT2 receptor, resulting in a decrease in both of the growth factors, he added.
ACE inhibitors prevent the conversion of angiotensin I to angiotensin II, with the result being that the drugs indirectly block both the AT1 and AT2 receptors.
In contrast, ARBs block only the AT1 receptor and leave the AT2 counter-regulatory receptor alone, said Strauss.
More data, including on overall survival
Strauss and colleagues examined whether ACE inhibitors and/or ARBs could have an effect on the response to PD-1/PD-L1 immune checkpoint inhibitors delivered with or without other immunotherapies, such as anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) checkpoint inhibitors, or targeted agents such as tyrosine kinase inhibitors (TKIs).
They pooled data on 597 patients receiving PD-1/PD-L1 inhibitors in clinical trials for various cancers, including 71 receiving concomitant ARBs, 82 receiving an ACE inhibitor, and 444 who were not receiving either class of antihypertensives.
The above-mentioned improvement in ORR with ARBs compared with patients not receiving the drug was statistically significant (P = .001), as was the improvement in CR rates (P = .002). In contrast, neither ORR nor CR were significantly better with patients on ACE inhibitors compared with patients not taking these drugs.
In multiple regression analysis controlling for age, gender, body mass index (BMI), tumor type, and additional therapies given, the superior ORR and CR rates with ARBs remained (P = .039 and .002, respectively), while there continued to be no significant additional benefit with ACE inhibitors.
The median overall survival was 35.2 months for patients on ARBs, 26.2 months for those on ACE inhibitors, and 18.8 months for patients on neither drug. The respective 3-year OS rates were 48.1%, 37.2%, and 31.5%, with the difference between the ARB and no-drug groups being significant (P = .0078).
In regression analysis controlling for the factors mentioned before, the OS advantage with ARBs but not ACE inhibitors remained significant (P = .006 for ARBs, and .078 for ACE inhibitors).
Strauss emphasized that further study is needed to determine if AT1 blockade can improve outcomes when combined anti-PD-1/PD-L1-based therapy.
It might be reasonable for patients who are taking ACE inhibitors to control blood pressure and are also receiving immunotherapy with a PD-1/PD-L1 inhibitor to be switched to an ARB if it is deemed safe and if further research bears it out, said Strauss in response to a question from Medscape Medical News.
Hypothesis-generating study
Meeting cochair Emiliano Calvo, MD, PhD, from Hospital de Madrid Norte Sanchinarro in Madrid, who attended the media briefing but was not involved in the study, commented that hypothesis-generating research using drugs already on the market for other indications adds important value to cancer therapy.
James Gulley, MD, PhD, from the Center for Cancer Research at the NCI, also a meeting cochair, agreed with Calvo.
“Thinking about utilizing the data that already exists to really get hypothesis-generating questions, it also opens up the possibility for real-world data, real-world evidence from these big datasets from [electronic medical records] that we could really interrogate and understand what we might see and get these hypothesis-generating findings that we could then prospectively evaluate,” Gulley said.
The research was funded by the National Cancer Institute. Strauss and Gulley are National Cancer Institute employees. Calvo disclosed no relevant financial relationships.
This article first appeared on Medscape.com.
It’s not ready for the clinic, but new research suggests that angiotensin receptor II blockers (ARBs) widely used to treat hypertension may improve responses to cancer immunotherapy agents targeted against the programmed death-1/ligand-1 (PD-1/PD-L1) pathway.
That conclusion comes from an observational study of 597 patients with more than 3 dozen different cancer types treated in clinical trials at the US National Institutes of Health. Investigators found that both objective response rates and 3-year overall survival (OS) rates were significantly higher for patients treated with a PD-1/PD-L1 inhibitor who were on ARBs, compared with patients who weren’t taking the antihypertensive agents.
An association was also seen between higher ORR and OS rates for patients taking ACE inhibitors, but it was not statistically significant, reported Julius Strauss, MD, from the Center for Cancer Research at the National Cancer Institute in Bethesda, Md.
All study patients received PD-1/PD-L1 inhibitors, and the ORR for patients treated with ARBs was 33.8%, compared with 19.5% for those treated with ACE inhibitors, and 17% for those who took neither drug. The respective complete response (CR) rates were 11.3%, 3.7%, and 3.1%.
Strauss discussed the data during an online briefing prior to his presentation of the findings during the 32nd EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics, which is taking place virtually.
Several early studies have suggested that angiotensin II, in addition to its effect on blood pressure, can also affect cancer growth by leading to downstream production of two proteins: vascular endothelial growth factor (VEGF) and transforming growth factor–beta (TGF-beta), he explained.
“Both of these [proteins] have been linked to cancer growth and cancer resistance to immune system attack,” Strauss observed.
He also discussed the mechanics of possible effects. Angiotensin II increases VEGF and TGF-beta through binding to the AT1 receptor, but has the opposite effect when it binds to the AT2 receptor, resulting in a decrease in both of the growth factors, he added.
ACE inhibitors prevent the conversion of angiotensin I to angiotensin II, with the result being that the drugs indirectly block both the AT1 and AT2 receptors.
In contrast, ARBs block only the AT1 receptor and leave the AT2 counter-regulatory receptor alone, said Strauss.
More data, including on overall survival
Strauss and colleagues examined whether ACE inhibitors and/or ARBs could have an effect on the response to PD-1/PD-L1 immune checkpoint inhibitors delivered with or without other immunotherapies, such as anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) checkpoint inhibitors, or targeted agents such as tyrosine kinase inhibitors (TKIs).
They pooled data on 597 patients receiving PD-1/PD-L1 inhibitors in clinical trials for various cancers, including 71 receiving concomitant ARBs, 82 receiving an ACE inhibitor, and 444 who were not receiving either class of antihypertensives.
The above-mentioned improvement in ORR with ARBs compared with patients not receiving the drug was statistically significant (P = .001), as was the improvement in CR rates (P = .002). In contrast, neither ORR nor CR were significantly better with patients on ACE inhibitors compared with patients not taking these drugs.
In multiple regression analysis controlling for age, gender, body mass index (BMI), tumor type, and additional therapies given, the superior ORR and CR rates with ARBs remained (P = .039 and .002, respectively), while there continued to be no significant additional benefit with ACE inhibitors.
The median overall survival was 35.2 months for patients on ARBs, 26.2 months for those on ACE inhibitors, and 18.8 months for patients on neither drug. The respective 3-year OS rates were 48.1%, 37.2%, and 31.5%, with the difference between the ARB and no-drug groups being significant (P = .0078).
In regression analysis controlling for the factors mentioned before, the OS advantage with ARBs but not ACE inhibitors remained significant (P = .006 for ARBs, and .078 for ACE inhibitors).
Strauss emphasized that further study is needed to determine if AT1 blockade can improve outcomes when combined anti-PD-1/PD-L1-based therapy.
It might be reasonable for patients who are taking ACE inhibitors to control blood pressure and are also receiving immunotherapy with a PD-1/PD-L1 inhibitor to be switched to an ARB if it is deemed safe and if further research bears it out, said Strauss in response to a question from Medscape Medical News.
Hypothesis-generating study
Meeting cochair Emiliano Calvo, MD, PhD, from Hospital de Madrid Norte Sanchinarro in Madrid, who attended the media briefing but was not involved in the study, commented that hypothesis-generating research using drugs already on the market for other indications adds important value to cancer therapy.
James Gulley, MD, PhD, from the Center for Cancer Research at the NCI, also a meeting cochair, agreed with Calvo.
“Thinking about utilizing the data that already exists to really get hypothesis-generating questions, it also opens up the possibility for real-world data, real-world evidence from these big datasets from [electronic medical records] that we could really interrogate and understand what we might see and get these hypothesis-generating findings that we could then prospectively evaluate,” Gulley said.
The research was funded by the National Cancer Institute. Strauss and Gulley are National Cancer Institute employees. Calvo disclosed no relevant financial relationships.
This article first appeared on Medscape.com.
It’s not ready for the clinic, but new research suggests that angiotensin receptor II blockers (ARBs) widely used to treat hypertension may improve responses to cancer immunotherapy agents targeted against the programmed death-1/ligand-1 (PD-1/PD-L1) pathway.
That conclusion comes from an observational study of 597 patients with more than 3 dozen different cancer types treated in clinical trials at the US National Institutes of Health. Investigators found that both objective response rates and 3-year overall survival (OS) rates were significantly higher for patients treated with a PD-1/PD-L1 inhibitor who were on ARBs, compared with patients who weren’t taking the antihypertensive agents.
An association was also seen between higher ORR and OS rates for patients taking ACE inhibitors, but it was not statistically significant, reported Julius Strauss, MD, from the Center for Cancer Research at the National Cancer Institute in Bethesda, Md.
All study patients received PD-1/PD-L1 inhibitors, and the ORR for patients treated with ARBs was 33.8%, compared with 19.5% for those treated with ACE inhibitors, and 17% for those who took neither drug. The respective complete response (CR) rates were 11.3%, 3.7%, and 3.1%.
Strauss discussed the data during an online briefing prior to his presentation of the findings during the 32nd EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics, which is taking place virtually.
Several early studies have suggested that angiotensin II, in addition to its effect on blood pressure, can also affect cancer growth by leading to downstream production of two proteins: vascular endothelial growth factor (VEGF) and transforming growth factor–beta (TGF-beta), he explained.
“Both of these [proteins] have been linked to cancer growth and cancer resistance to immune system attack,” Strauss observed.
He also discussed the mechanics of possible effects. Angiotensin II increases VEGF and TGF-beta through binding to the AT1 receptor, but has the opposite effect when it binds to the AT2 receptor, resulting in a decrease in both of the growth factors, he added.
ACE inhibitors prevent the conversion of angiotensin I to angiotensin II, with the result being that the drugs indirectly block both the AT1 and AT2 receptors.
In contrast, ARBs block only the AT1 receptor and leave the AT2 counter-regulatory receptor alone, said Strauss.
More data, including on overall survival
Strauss and colleagues examined whether ACE inhibitors and/or ARBs could have an effect on the response to PD-1/PD-L1 immune checkpoint inhibitors delivered with or without other immunotherapies, such as anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) checkpoint inhibitors, or targeted agents such as tyrosine kinase inhibitors (TKIs).
They pooled data on 597 patients receiving PD-1/PD-L1 inhibitors in clinical trials for various cancers, including 71 receiving concomitant ARBs, 82 receiving an ACE inhibitor, and 444 who were not receiving either class of antihypertensives.
The above-mentioned improvement in ORR with ARBs compared with patients not receiving the drug was statistically significant (P = .001), as was the improvement in CR rates (P = .002). In contrast, neither ORR nor CR were significantly better with patients on ACE inhibitors compared with patients not taking these drugs.
In multiple regression analysis controlling for age, gender, body mass index (BMI), tumor type, and additional therapies given, the superior ORR and CR rates with ARBs remained (P = .039 and .002, respectively), while there continued to be no significant additional benefit with ACE inhibitors.
The median overall survival was 35.2 months for patients on ARBs, 26.2 months for those on ACE inhibitors, and 18.8 months for patients on neither drug. The respective 3-year OS rates were 48.1%, 37.2%, and 31.5%, with the difference between the ARB and no-drug groups being significant (P = .0078).
In regression analysis controlling for the factors mentioned before, the OS advantage with ARBs but not ACE inhibitors remained significant (P = .006 for ARBs, and .078 for ACE inhibitors).
Strauss emphasized that further study is needed to determine if AT1 blockade can improve outcomes when combined anti-PD-1/PD-L1-based therapy.
It might be reasonable for patients who are taking ACE inhibitors to control blood pressure and are also receiving immunotherapy with a PD-1/PD-L1 inhibitor to be switched to an ARB if it is deemed safe and if further research bears it out, said Strauss in response to a question from Medscape Medical News.
Hypothesis-generating study
Meeting cochair Emiliano Calvo, MD, PhD, from Hospital de Madrid Norte Sanchinarro in Madrid, who attended the media briefing but was not involved in the study, commented that hypothesis-generating research using drugs already on the market for other indications adds important value to cancer therapy.
James Gulley, MD, PhD, from the Center for Cancer Research at the NCI, also a meeting cochair, agreed with Calvo.
“Thinking about utilizing the data that already exists to really get hypothesis-generating questions, it also opens up the possibility for real-world data, real-world evidence from these big datasets from [electronic medical records] that we could really interrogate and understand what we might see and get these hypothesis-generating findings that we could then prospectively evaluate,” Gulley said.
The research was funded by the National Cancer Institute. Strauss and Gulley are National Cancer Institute employees. Calvo disclosed no relevant financial relationships.
This article first appeared on Medscape.com.
OSA diagnoses not carried forward to the inpatient setting
Obstructive sleep apnea diagnoses may not be carried over to the inpatient setting, with potentially negative consequences for clinical outcomes, quality of life, and health care costs, an investigator said at the virtual meeting of the American College of Chest Physicians.
In a retrospective, single-center study, nearly 40% of patients with obstructive sleep apnea (OSA) diagnosed in the outpatient setting did not have a corresponding diagnosis during hospitalization, according to researcher Nitasa Sahu, MD.*
The missed OSA diagnoses could have especially negative implications for patients who don’t continue on positive airway pressure (PAP) therapy during the hospital stay, said Dr. Sahu, a fellow in pulmonary/critical care at St. Luke’s University Health Network in Bethlehem, Pa.
The finding indicates a large-magnitude opportunity to improve health care through better communication and optimized care, according to the researcher.
“Obstructive sleep apnea is underrecognized, it’s underdiagnosed, and it has a lot of implications for a patient’s hospitalization,” she said in interview
Clinical pathways should be set up to ensure that patients with OSA are properly identified and use their prescribed treatment, according to Dr. Sahu.
“I think that should, and would, reduce overall health care costs, with better outcomes as well,” she said.
Pulmonologist Saadia A. Faiz, MD, FCCP, said she hoped this study, presented at a late-breaking abstract at the virtual meeting, would highlight the importance of OSA screening and call attention to barriers to screening that may be in place in the inpatient setting.
That’s especially important because, after admission, the focus is often on the cause of admission rather than underlying comorbidities such as OSA, said Dr. Faiz, professor in the department of pulmonary medicine at the University of Texas MD Anderson Cancer Center in Houston.
“Working in a cancer hospital, the focus is always on the cancer, so sometimes even the patient will dismiss issues with their sleep,” Dr. Faiz said of her own experience in an interview.
“Often with sleep apnea, for people in the general population, the reason they seek medical attention is because their spouse notices that they’re snoring, so it is something that is not as emphasized,” added Dr. Faiz, who was not involved in the study.
In their study, Dr. Sahu and coauthors reviewed electronic health record data for adults hospitalized on the general internal medicine service at Penn State Hershey Medical Center from January 2017 through 2018. They restricted their search to first admissions.
The researchers looked for ICD-9 codes indicating an OSA diagnosis during their inpatient admission. They looked for the same codes in the preceding 5 years to see if the patients had a prior outpatient OSA diagnosis.
The inpatient cohort included 13,067 patients, of whom 53% were male, 87% were White, and 77% were over 50 years of age. Comorbidities included hypertension in 42%, atrial fibrillation in 21%, type 2 diabetes mellitus in 14%, congestive heart failure in 15%, and prior stroke in 0.5%.
A total of 991 individuals in the inpatient cohort had a prior outpatient OSA diagnosis. Of that group, 376 patients (38%) did not have an inpatient OSA diagnosis on inpatient record, according to the reported study data.
That large proportion of discordant diagnoses suggests a lot of missed opportunities to provide OSA therapy in the inpatient setting and to reinforce chronic disease state management, according to Dr. Sahu and colleagues.
How those discordant OSA diagnoses impact length of stay, cost of care, and readmissions are unanswered questions that deserve further study, Dr. Sahu said.
Among patients who did not have outpatient OSA diagnoses, another 804 patients, or about 6%, ended up with an inpatient diagnosis during their hospitalization, the researchers also reported.
While a number of those inpatient OSA diagnoses could have been coded in error, it’s also possible that they were indeed cases of OSA that went unrecognized until the individuals were hospitalized, Dr. Sahu said.
Dr. Sahu had no relevant relationships to report related to the study. One of four study coauthors reported relationships with Boehringer-Ingelheim, Nitto Denko, and Galapagos.
SOURCE: Sahu N. CHEST 2020. Abstract.
*Correction, 11/3/20: An earlier version of this article misstated the name of Nitasa Sahu, MD.
Obstructive sleep apnea diagnoses may not be carried over to the inpatient setting, with potentially negative consequences for clinical outcomes, quality of life, and health care costs, an investigator said at the virtual meeting of the American College of Chest Physicians.
In a retrospective, single-center study, nearly 40% of patients with obstructive sleep apnea (OSA) diagnosed in the outpatient setting did not have a corresponding diagnosis during hospitalization, according to researcher Nitasa Sahu, MD.*
The missed OSA diagnoses could have especially negative implications for patients who don’t continue on positive airway pressure (PAP) therapy during the hospital stay, said Dr. Sahu, a fellow in pulmonary/critical care at St. Luke’s University Health Network in Bethlehem, Pa.
The finding indicates a large-magnitude opportunity to improve health care through better communication and optimized care, according to the researcher.
“Obstructive sleep apnea is underrecognized, it’s underdiagnosed, and it has a lot of implications for a patient’s hospitalization,” she said in interview
Clinical pathways should be set up to ensure that patients with OSA are properly identified and use their prescribed treatment, according to Dr. Sahu.
“I think that should, and would, reduce overall health care costs, with better outcomes as well,” she said.
Pulmonologist Saadia A. Faiz, MD, FCCP, said she hoped this study, presented at a late-breaking abstract at the virtual meeting, would highlight the importance of OSA screening and call attention to barriers to screening that may be in place in the inpatient setting.
That’s especially important because, after admission, the focus is often on the cause of admission rather than underlying comorbidities such as OSA, said Dr. Faiz, professor in the department of pulmonary medicine at the University of Texas MD Anderson Cancer Center in Houston.
“Working in a cancer hospital, the focus is always on the cancer, so sometimes even the patient will dismiss issues with their sleep,” Dr. Faiz said of her own experience in an interview.
“Often with sleep apnea, for people in the general population, the reason they seek medical attention is because their spouse notices that they’re snoring, so it is something that is not as emphasized,” added Dr. Faiz, who was not involved in the study.
In their study, Dr. Sahu and coauthors reviewed electronic health record data for adults hospitalized on the general internal medicine service at Penn State Hershey Medical Center from January 2017 through 2018. They restricted their search to first admissions.
The researchers looked for ICD-9 codes indicating an OSA diagnosis during their inpatient admission. They looked for the same codes in the preceding 5 years to see if the patients had a prior outpatient OSA diagnosis.
The inpatient cohort included 13,067 patients, of whom 53% were male, 87% were White, and 77% were over 50 years of age. Comorbidities included hypertension in 42%, atrial fibrillation in 21%, type 2 diabetes mellitus in 14%, congestive heart failure in 15%, and prior stroke in 0.5%.
A total of 991 individuals in the inpatient cohort had a prior outpatient OSA diagnosis. Of that group, 376 patients (38%) did not have an inpatient OSA diagnosis on inpatient record, according to the reported study data.
That large proportion of discordant diagnoses suggests a lot of missed opportunities to provide OSA therapy in the inpatient setting and to reinforce chronic disease state management, according to Dr. Sahu and colleagues.
How those discordant OSA diagnoses impact length of stay, cost of care, and readmissions are unanswered questions that deserve further study, Dr. Sahu said.
Among patients who did not have outpatient OSA diagnoses, another 804 patients, or about 6%, ended up with an inpatient diagnosis during their hospitalization, the researchers also reported.
While a number of those inpatient OSA diagnoses could have been coded in error, it’s also possible that they were indeed cases of OSA that went unrecognized until the individuals were hospitalized, Dr. Sahu said.
Dr. Sahu had no relevant relationships to report related to the study. One of four study coauthors reported relationships with Boehringer-Ingelheim, Nitto Denko, and Galapagos.
SOURCE: Sahu N. CHEST 2020. Abstract.
*Correction, 11/3/20: An earlier version of this article misstated the name of Nitasa Sahu, MD.
Obstructive sleep apnea diagnoses may not be carried over to the inpatient setting, with potentially negative consequences for clinical outcomes, quality of life, and health care costs, an investigator said at the virtual meeting of the American College of Chest Physicians.
In a retrospective, single-center study, nearly 40% of patients with obstructive sleep apnea (OSA) diagnosed in the outpatient setting did not have a corresponding diagnosis during hospitalization, according to researcher Nitasa Sahu, MD.*
The missed OSA diagnoses could have especially negative implications for patients who don’t continue on positive airway pressure (PAP) therapy during the hospital stay, said Dr. Sahu, a fellow in pulmonary/critical care at St. Luke’s University Health Network in Bethlehem, Pa.
The finding indicates a large-magnitude opportunity to improve health care through better communication and optimized care, according to the researcher.
“Obstructive sleep apnea is underrecognized, it’s underdiagnosed, and it has a lot of implications for a patient’s hospitalization,” she said in interview
Clinical pathways should be set up to ensure that patients with OSA are properly identified and use their prescribed treatment, according to Dr. Sahu.
“I think that should, and would, reduce overall health care costs, with better outcomes as well,” she said.
Pulmonologist Saadia A. Faiz, MD, FCCP, said she hoped this study, presented at a late-breaking abstract at the virtual meeting, would highlight the importance of OSA screening and call attention to barriers to screening that may be in place in the inpatient setting.
That’s especially important because, after admission, the focus is often on the cause of admission rather than underlying comorbidities such as OSA, said Dr. Faiz, professor in the department of pulmonary medicine at the University of Texas MD Anderson Cancer Center in Houston.
“Working in a cancer hospital, the focus is always on the cancer, so sometimes even the patient will dismiss issues with their sleep,” Dr. Faiz said of her own experience in an interview.
“Often with sleep apnea, for people in the general population, the reason they seek medical attention is because their spouse notices that they’re snoring, so it is something that is not as emphasized,” added Dr. Faiz, who was not involved in the study.
In their study, Dr. Sahu and coauthors reviewed electronic health record data for adults hospitalized on the general internal medicine service at Penn State Hershey Medical Center from January 2017 through 2018. They restricted their search to first admissions.
The researchers looked for ICD-9 codes indicating an OSA diagnosis during their inpatient admission. They looked for the same codes in the preceding 5 years to see if the patients had a prior outpatient OSA diagnosis.
The inpatient cohort included 13,067 patients, of whom 53% were male, 87% were White, and 77% were over 50 years of age. Comorbidities included hypertension in 42%, atrial fibrillation in 21%, type 2 diabetes mellitus in 14%, congestive heart failure in 15%, and prior stroke in 0.5%.
A total of 991 individuals in the inpatient cohort had a prior outpatient OSA diagnosis. Of that group, 376 patients (38%) did not have an inpatient OSA diagnosis on inpatient record, according to the reported study data.
That large proportion of discordant diagnoses suggests a lot of missed opportunities to provide OSA therapy in the inpatient setting and to reinforce chronic disease state management, according to Dr. Sahu and colleagues.
How those discordant OSA diagnoses impact length of stay, cost of care, and readmissions are unanswered questions that deserve further study, Dr. Sahu said.
Among patients who did not have outpatient OSA diagnoses, another 804 patients, or about 6%, ended up with an inpatient diagnosis during their hospitalization, the researchers also reported.
While a number of those inpatient OSA diagnoses could have been coded in error, it’s also possible that they were indeed cases of OSA that went unrecognized until the individuals were hospitalized, Dr. Sahu said.
Dr. Sahu had no relevant relationships to report related to the study. One of four study coauthors reported relationships with Boehringer-Ingelheim, Nitto Denko, and Galapagos.
SOURCE: Sahu N. CHEST 2020. Abstract.
*Correction, 11/3/20: An earlier version of this article misstated the name of Nitasa Sahu, MD.
FROM CHEST 2020