MADRID – Oral apremilast’s beneficial effects on Behçet’s disease oral ulcer disease severity and patient quality of life were sustained through week 64 of the long-term extension phase of the pivotal RELIEF trial, Alfred Mahr, MD, PhD, reported at the annual congress of the European Academy of Dermatology and Venereology.

Bruce Jancin/MDedge News

“We now have strong evidence that apremilast is an effective and safe therapy to treat oral ulcers in patients with Behçet’s syndrome. I think this is a major advance in the field,” declared Dr. Mahr, a rheumatologist at St. Gallen (Switzerland) Cantonal Hospital.

Based largely upon the results of the 12-week, double-blind portion of the phase 3 RELIEF trial, the Food and Drug Administration approved apremilast (Otezla) for the treatment of oral ulcers in patients with Behçet’s disease in the summer of 2019.

The safety profile of the oral phosphodiesterase-4 inhibitor was as seen in other studies, including in patients with psoriatic arthritis, an FDA-approved indication for the drug since 2014. The main side effects in the long-term extension of RELIEF were diarrhea and nausea, typically mild or moderate in nature and roughly twice as frequent as in placebo-treated controls in the double-blind study phase.

“At the end of the day, at week 64, only 12% of patients treated with apremilast during the entire 64 weeks discontinued the drug due to a treatment-emergent adverse event, which I believe is a good indicator of the safety of this medication,” the rheumatologist said. “The overall feeling is that the benefit-to-risk ratio is very good and it’s a safe drug to prescribe.”

At the close of the initial 12-week, double-blind phase of RELIEF, 178 of the original 207 participants elected to enter the long-term extension, either staying on apremilast at 30 mg twice a day for an additional 52 weeks or switching to that regimen from placebo.

The focus of the long-term extension was on disease activity and quality of life outcomes. The results in patients who had switched from placebo to apremilast after 12 weeks proved to be reassuringly similar to outcomes in patients on the drug for the full duration. For example, the mean improvement on the patient-reported Behçet’s Syndrome Activity Scale was 18.6 points after 12 weeks of double-blind apremilast, 16.9 points after 64 weeks of continuous apremilast, and 16.8 points with 12 weeks of placebo followed by 52 weeks of active therapy.

After 12 weeks of double-blind apremilast, patients averaged a 3.4-point improvement on the Behçet’s Disease Quality of Life measure. After 64 weeks on the drug, the improvement over baseline was 3.6 points, while in the switch group it was 3.4 points. Similarly, on all three components of the SF-36 quality of life metric, the continuous apremilast group showed maintenance of effect from week 12 to week 64, while the placebo-to-apremilast group caught up. The same was true with regards to the Behçet’s Disease Current Activity Index, which encompasses measures of both the patient’s and clinician’s perception of disease activity.

At the outset of the RELIEF trial, participants averaged four oral ulcers. At week 64, the continuous apremilast group averaged 1.4 and the switch group 0.8, a nonsignificant difference.

Asked if apremilast had a favorable impact upon other manifestations of Behçet’s disease besides the oral ulcers, Dr. Mahr replied, “This is a very good question. People often wonder about it. We do, too. But this trial was not designed to capture less common manifestations of Behçet’s syndrome, such as genital ulcers. There have been some analyses done, but the number of patients who had genital ulcers at 12 weeks were very few. The same was true for eye manifestations. There was sort of a signal that it works, but we can’t prove it in a placebo-controlled trial.”

Dr. Mahr reported receiving research funding from and serving as a consultant to Celgene, the study sponsor.

[email protected]

MADRID – Oral apremilast’s beneficial effects on Behçet’s disease oral ulcer disease severity and patient quality of life were sustained through week 64 of the long-term extension phase of the pivotal RELIEF trial, Alfred Mahr, MD, PhD, reported at the annual congress of the European Academy of Dermatology and Venereology.

Bruce Jancin/MDedge News

“We now have strong evidence that apremilast is an effective and safe therapy to treat oral ulcers in patients with Behçet’s syndrome. I think this is a major advance in the field,” declared Dr. Mahr, a rheumatologist at St. Gallen (Switzerland) Cantonal Hospital.

Based largely upon the results of the 12-week, double-blind portion of the phase 3 RELIEF trial, the Food and Drug Administration approved apremilast (Otezla) for the treatment of oral ulcers in patients with Behçet’s disease in the summer of 2019.

The safety profile of the oral phosphodiesterase-4 inhibitor was as seen in other studies, including in patients with psoriatic arthritis, an FDA-approved indication for the drug since 2014. The main side effects in the long-term extension of RELIEF were diarrhea and nausea, typically mild or moderate in nature and roughly twice as frequent as in placebo-treated controls in the double-blind study phase.

“At the end of the day, at week 64, only 12% of patients treated with apremilast during the entire 64 weeks discontinued the drug due to a treatment-emergent adverse event, which I believe is a good indicator of the safety of this medication,” the rheumatologist said. “The overall feeling is that the benefit-to-risk ratio is very good and it’s a safe drug to prescribe.”

At the close of the initial 12-week, double-blind phase of RELIEF, 178 of the original 207 participants elected to enter the long-term extension, either staying on apremilast at 30 mg twice a day for an additional 52 weeks or switching to that regimen from placebo.

The focus of the long-term extension was on disease activity and quality of life outcomes. The results in patients who had switched from placebo to apremilast after 12 weeks proved to be reassuringly similar to outcomes in patients on the drug for the full duration. For example, the mean improvement on the patient-reported Behçet’s Syndrome Activity Scale was 18.6 points after 12 weeks of double-blind apremilast, 16.9 points after 64 weeks of continuous apremilast, and 16.8 points with 12 weeks of placebo followed by 52 weeks of active therapy.

After 12 weeks of double-blind apremilast, patients averaged a 3.4-point improvement on the Behçet’s Disease Quality of Life measure. After 64 weeks on the drug, the improvement over baseline was 3.6 points, while in the switch group it was 3.4 points. Similarly, on all three components of the SF-36 quality of life metric, the continuous apremilast group showed maintenance of effect from week 12 to week 64, while the placebo-to-apremilast group caught up. The same was true with regards to the Behçet’s Disease Current Activity Index, which encompasses measures of both the patient’s and clinician’s perception of disease activity.

At the outset of the RELIEF trial, participants averaged four oral ulcers. At week 64, the continuous apremilast group averaged 1.4 and the switch group 0.8, a nonsignificant difference.

Asked if apremilast had a favorable impact upon other manifestations of Behçet’s disease besides the oral ulcers, Dr. Mahr replied, “This is a very good question. People often wonder about it. We do, too. But this trial was not designed to capture less common manifestations of Behçet’s syndrome, such as genital ulcers. There have been some analyses done, but the number of patients who had genital ulcers at 12 weeks were very few. The same was true for eye manifestations. There was sort of a signal that it works, but we can’t prove it in a placebo-controlled trial.”

Dr. Mahr reported receiving research funding from and serving as a consultant to Celgene, the study sponsor.

[email protected]

MADRID – Oral apremilast’s beneficial effects on Behçet’s disease oral ulcer disease severity and patient quality of life were sustained through week 64 of the long-term extension phase of the pivotal RELIEF trial, Alfred Mahr, MD, PhD, reported at the annual congress of the European Academy of Dermatology and Venereology.

Bruce Jancin/MDedge News

“We now have strong evidence that apremilast is an effective and safe therapy to treat oral ulcers in patients with Behçet’s syndrome. I think this is a major advance in the field,” declared Dr. Mahr, a rheumatologist at St. Gallen (Switzerland) Cantonal Hospital.

Based largely upon the results of the 12-week, double-blind portion of the phase 3 RELIEF trial, the Food and Drug Administration approved apremilast (Otezla) for the treatment of oral ulcers in patients with Behçet’s disease in the summer of 2019.

The safety profile of the oral phosphodiesterase-4 inhibitor was as seen in other studies, including in patients with psoriatic arthritis, an FDA-approved indication for the drug since 2014. The main side effects in the long-term extension of RELIEF were diarrhea and nausea, typically mild or moderate in nature and roughly twice as frequent as in placebo-treated controls in the double-blind study phase.

“At the end of the day, at week 64, only 12% of patients treated with apremilast during the entire 64 weeks discontinued the drug due to a treatment-emergent adverse event, which I believe is a good indicator of the safety of this medication,” the rheumatologist said. “The overall feeling is that the benefit-to-risk ratio is very good and it’s a safe drug to prescribe.”

At the close of the initial 12-week, double-blind phase of RELIEF, 178 of the original 207 participants elected to enter the long-term extension, either staying on apremilast at 30 mg twice a day for an additional 52 weeks or switching to that regimen from placebo.

The focus of the long-term extension was on disease activity and quality of life outcomes. The results in patients who had switched from placebo to apremilast after 12 weeks proved to be reassuringly similar to outcomes in patients on the drug for the full duration. For example, the mean improvement on the patient-reported Behçet’s Syndrome Activity Scale was 18.6 points after 12 weeks of double-blind apremilast, 16.9 points after 64 weeks of continuous apremilast, and 16.8 points with 12 weeks of placebo followed by 52 weeks of active therapy.

After 12 weeks of double-blind apremilast, patients averaged a 3.4-point improvement on the Behçet’s Disease Quality of Life measure. After 64 weeks on the drug, the improvement over baseline was 3.6 points, while in the switch group it was 3.4 points. Similarly, on all three components of the SF-36 quality of life metric, the continuous apremilast group showed maintenance of effect from week 12 to week 64, while the placebo-to-apremilast group caught up. The same was true with regards to the Behçet’s Disease Current Activity Index, which encompasses measures of both the patient’s and clinician’s perception of disease activity.

At the outset of the RELIEF trial, participants averaged four oral ulcers. At week 64, the continuous apremilast group averaged 1.4 and the switch group 0.8, a nonsignificant difference.

Asked if apremilast had a favorable impact upon other manifestations of Behçet’s disease besides the oral ulcers, Dr. Mahr replied, “This is a very good question. People often wonder about it. We do, too. But this trial was not designed to capture less common manifestations of Behçet’s syndrome, such as genital ulcers. There have been some analyses done, but the number of patients who had genital ulcers at 12 weeks were very few. The same was true for eye manifestations. There was sort of a signal that it works, but we can’t prove it in a placebo-controlled trial.”

Dr. Mahr reported receiving research funding from and serving as a consultant to Celgene, the study sponsor.

[email protected]

ANSWER

The radiograph does not demonstrate any evidence of infiltrate or pleural effusion. However, of note is a rather large lytic lesion involving the posterior aspect of the right fourth rib. This finding is very concerning for either a primary bone neoplasm or (more likely) a metastatic one.

The patient denied any history of cancer. She was promptly referred to Hematology/Oncology for further evaluation and workup. At last update, she had undergone a bone marrow biopsy, with preliminary pathology results suggestive of a plasma cell neoplasm.

ANSWER

The radiograph does not demonstrate any evidence of infiltrate or pleural effusion. However, of note is a rather large lytic lesion involving the posterior aspect of the right fourth rib. This finding is very concerning for either a primary bone neoplasm or (more likely) a metastatic one.

The patient denied any history of cancer. She was promptly referred to Hematology/Oncology for further evaluation and workup. At last update, she had undergone a bone marrow biopsy, with preliminary pathology results suggestive of a plasma cell neoplasm.

ANSWER

The radiograph does not demonstrate any evidence of infiltrate or pleural effusion. However, of note is a rather large lytic lesion involving the posterior aspect of the right fourth rib. This finding is very concerning for either a primary bone neoplasm or (more likely) a metastatic one.

The patient denied any history of cancer. She was promptly referred to Hematology/Oncology for further evaluation and workup. At last update, she had undergone a bone marrow biopsy, with preliminary pathology results suggestive of a plasma cell neoplasm.

Cholinergic neurons in the nucleus basalis of Meynert appear more susceptible to neurofibrillary tangles and neuronal destruction in women, patients carrying the apolipoprotein E–epsilon 4 (APOE4) allele, and people with hippocampal-sparing Alzheimer’s disease, a subtype characterized by early onset and rapid cognitive decline.

Kheng guan Toh/Thinkstock

Those findings and others from a postmortem study published in JAMA Neurology also suggests that the nucleus basalis of Meynert (nbM) could be the first place that neuronal damage appears in Alzheimer’s disease (AD), according to first author Fadi S. Hanna Al-Shaikh and colleagues.

The study also confirmed the authors’ previous categorization of three AD subtypes: early-onset, rapidly declining hippocampal-sparing AD (HpSp), typical sporadic AD, and limbic predominant AD, a later-onset form with a slower rate of decline.

“We observed a wave of vulnerability in which the exacerbation of nbM neurofibrillary tangles [NFTs] in HpSp AD may leave the cortex more vulnerable to [tangle] accumulation, perhaps via a biologically accelerated process or through a mechanism of disinhibition,” wrote Mr. Al-Shaikh, of the Mayo Clinic, Jacksonville, Fla., and colleagues. “By contrast, the limbic predominant AD cases had an exacerbation of areas vulnerable early in the Braak-like pattern of NFT accumulation, perhaps via a biologically restrictive process that relatively confines pathology to limbic areas.”

The nbM is of interest to researchers because 90% of its neurons are cholinergic with cortical penetration. “Postmortem studies of AD and more recent neuroimaging studies provide evidence that involvement of the nucleus basalis of Meynert may be critical and early in the molecular cascade of events,” the authors said. “The accumulation of NFTs in the nbM may precede entorhinal cortex and locus coeruleus involvement, making the nbM potentially one of the earliest sites where NFT accumulation occurs.”

Previously, this team had identified three AD subtypes based on patterns of corticolimbic neurofibrillary tangling. In HpSp, the hippocampus is relatively spared, while the cortex has a greater number of tangles. In limbic predominant AD, the cortex is relatively spared, and the hippocampus is severely involved. Typical AD shows the expected patterns of hippocampal and cortical tangling.

Cases in this study came from the Florida Autopsied Multi-Ethnic (FLAME) cohort, comprising 1,361 brain tissue samples from confirmed AD cases and 103 nondemented controls. The investigators sought to understand the patterns of neuronal demise in the nbM, and any associations with clinical signs, demographics, and the recently described three subtypes.

In the cohort, AD subtypes included 175 with HpSp, 1,014 with typical AD, and 172 with limbic predominant AD. Patients with HpSp were the youngest, with a median disease onset age of 65 years, compared with 71 years in typical AD and 78 in limbic predominant. There were fewer women in the HpSp group (35%), compared with the typical AD group (54%) and the limbic group (70%). More patients with HpSp had atypical presentation (38%) in comparison with typical (11%) and limbic predominant AD (2%). But patients with HpSp were less likely to be APOE4 positive (46%), whereas those with limbic predominant AD were most likely to be APOE4 positive (72%).

Cognitively, HpSp patients declined more rapidly, losing a median of 4 points per year on the Mini Mental State Exam (MMSE), compared with 2 and 1 points in those with typical and limbic predominant AD. At death, the HpSp patients had a median MMSE score of 7, versus 13 in the typical AD group and 18 in the limbic group.

Patients with HpSp had the highest concentration of tangles and the lowest neuronal density in the nbM. Limbic predominant cases had the lowest tangle burden and the highest neuronal density. Typical AD cases lay between these extremes on both measures.

A multivariate regression analysis determined the overlap of neuronal findings and AD subtypes. A younger age at symptom onset was significantly associated with higher tangle counts in the nbM regions among patients with HpSp. In women with typical AD, there were 2.5 times more tangles than in men. APOE4 carriers had 1.3 times more tangles than did noncarriers.

There were also associations with cognition. “For every 10-point decrease in final MMSE of typical AD cases, the number of nbM NFTs was expected to increase by 1.8,” the authors wrote.

Although limbic predominant AD wasn’t associated with any clinical or demographic variables in this analysis, it was associated with neuronal changes in the nbM. “For every 10 years’ younger age at onset, the number of neurons was expected to be lower by 4.6 [per mm²]. … In addition, limbic predominant cases were observed to have 4.3 [per mm²] fewer neurons for every 10-point decrease in MMSE,” the authors said.

This study was supported by the National Institute on Aging, the Florida Department of Health, the Ed and Ethel Moore Alzheimer’s Disease Research Program, a Gerstner Family Career Development Award, and the Alzheimer’s Association. Two authors reported financial relationships with industry outside the submitted work.

[email protected]

SOURCE: Al Shaikh FSH et al. JAMA Neurol. 2019 Oct 28. doi: 10.1001/jamaneurol.2019.3606.

Cholinergic neurons in the nucleus basalis of Meynert appear more susceptible to neurofibrillary tangles and neuronal destruction in women, patients carrying the apolipoprotein E–epsilon 4 (APOE4) allele, and people with hippocampal-sparing Alzheimer’s disease, a subtype characterized by early onset and rapid cognitive decline.

Kheng guan Toh/Thinkstock

Those findings and others from a postmortem study published in JAMA Neurology also suggests that the nucleus basalis of Meynert (nbM) could be the first place that neuronal damage appears in Alzheimer’s disease (AD), according to first author Fadi S. Hanna Al-Shaikh and colleagues.

The study also confirmed the authors’ previous categorization of three AD subtypes: early-onset, rapidly declining hippocampal-sparing AD (HpSp), typical sporadic AD, and limbic predominant AD, a later-onset form with a slower rate of decline.

“We observed a wave of vulnerability in which the exacerbation of nbM neurofibrillary tangles [NFTs] in HpSp AD may leave the cortex more vulnerable to [tangle] accumulation, perhaps via a biologically accelerated process or through a mechanism of disinhibition,” wrote Mr. Al-Shaikh, of the Mayo Clinic, Jacksonville, Fla., and colleagues. “By contrast, the limbic predominant AD cases had an exacerbation of areas vulnerable early in the Braak-like pattern of NFT accumulation, perhaps via a biologically restrictive process that relatively confines pathology to limbic areas.”

The nbM is of interest to researchers because 90% of its neurons are cholinergic with cortical penetration. “Postmortem studies of AD and more recent neuroimaging studies provide evidence that involvement of the nucleus basalis of Meynert may be critical and early in the molecular cascade of events,” the authors said. “The accumulation of NFTs in the nbM may precede entorhinal cortex and locus coeruleus involvement, making the nbM potentially one of the earliest sites where NFT accumulation occurs.”

Previously, this team had identified three AD subtypes based on patterns of corticolimbic neurofibrillary tangling. In HpSp, the hippocampus is relatively spared, while the cortex has a greater number of tangles. In limbic predominant AD, the cortex is relatively spared, and the hippocampus is severely involved. Typical AD shows the expected patterns of hippocampal and cortical tangling.

Cases in this study came from the Florida Autopsied Multi-Ethnic (FLAME) cohort, comprising 1,361 brain tissue samples from confirmed AD cases and 103 nondemented controls. The investigators sought to understand the patterns of neuronal demise in the nbM, and any associations with clinical signs, demographics, and the recently described three subtypes.

In the cohort, AD subtypes included 175 with HpSp, 1,014 with typical AD, and 172 with limbic predominant AD. Patients with HpSp were the youngest, with a median disease onset age of 65 years, compared with 71 years in typical AD and 78 in limbic predominant. There were fewer women in the HpSp group (35%), compared with the typical AD group (54%) and the limbic group (70%). More patients with HpSp had atypical presentation (38%) in comparison with typical (11%) and limbic predominant AD (2%). But patients with HpSp were less likely to be APOE4 positive (46%), whereas those with limbic predominant AD were most likely to be APOE4 positive (72%).

Cognitively, HpSp patients declined more rapidly, losing a median of 4 points per year on the Mini Mental State Exam (MMSE), compared with 2 and 1 points in those with typical and limbic predominant AD. At death, the HpSp patients had a median MMSE score of 7, versus 13 in the typical AD group and 18 in the limbic group.

Patients with HpSp had the highest concentration of tangles and the lowest neuronal density in the nbM. Limbic predominant cases had the lowest tangle burden and the highest neuronal density. Typical AD cases lay between these extremes on both measures.

A multivariate regression analysis determined the overlap of neuronal findings and AD subtypes. A younger age at symptom onset was significantly associated with higher tangle counts in the nbM regions among patients with HpSp. In women with typical AD, there were 2.5 times more tangles than in men. APOE4 carriers had 1.3 times more tangles than did noncarriers.

There were also associations with cognition. “For every 10-point decrease in final MMSE of typical AD cases, the number of nbM NFTs was expected to increase by 1.8,” the authors wrote.

Although limbic predominant AD wasn’t associated with any clinical or demographic variables in this analysis, it was associated with neuronal changes in the nbM. “For every 10 years’ younger age at onset, the number of neurons was expected to be lower by 4.6 [per mm²]. … In addition, limbic predominant cases were observed to have 4.3 [per mm²] fewer neurons for every 10-point decrease in MMSE,” the authors said.

This study was supported by the National Institute on Aging, the Florida Department of Health, the Ed and Ethel Moore Alzheimer’s Disease Research Program, a Gerstner Family Career Development Award, and the Alzheimer’s Association. Two authors reported financial relationships with industry outside the submitted work.

[email protected]

SOURCE: Al Shaikh FSH et al. JAMA Neurol. 2019 Oct 28. doi: 10.1001/jamaneurol.2019.3606.

Cholinergic neurons in the nucleus basalis of Meynert appear more susceptible to neurofibrillary tangles and neuronal destruction in women, patients carrying the apolipoprotein E–epsilon 4 (APOE4) allele, and people with hippocampal-sparing Alzheimer’s disease, a subtype characterized by early onset and rapid cognitive decline.

Kheng guan Toh/Thinkstock

Those findings and others from a postmortem study published in JAMA Neurology also suggests that the nucleus basalis of Meynert (nbM) could be the first place that neuronal damage appears in Alzheimer’s disease (AD), according to first author Fadi S. Hanna Al-Shaikh and colleagues.

The study also confirmed the authors’ previous categorization of three AD subtypes: early-onset, rapidly declining hippocampal-sparing AD (HpSp), typical sporadic AD, and limbic predominant AD, a later-onset form with a slower rate of decline.

“We observed a wave of vulnerability in which the exacerbation of nbM neurofibrillary tangles [NFTs] in HpSp AD may leave the cortex more vulnerable to [tangle] accumulation, perhaps via a biologically accelerated process or through a mechanism of disinhibition,” wrote Mr. Al-Shaikh, of the Mayo Clinic, Jacksonville, Fla., and colleagues. “By contrast, the limbic predominant AD cases had an exacerbation of areas vulnerable early in the Braak-like pattern of NFT accumulation, perhaps via a biologically restrictive process that relatively confines pathology to limbic areas.”

The nbM is of interest to researchers because 90% of its neurons are cholinergic with cortical penetration. “Postmortem studies of AD and more recent neuroimaging studies provide evidence that involvement of the nucleus basalis of Meynert may be critical and early in the molecular cascade of events,” the authors said. “The accumulation of NFTs in the nbM may precede entorhinal cortex and locus coeruleus involvement, making the nbM potentially one of the earliest sites where NFT accumulation occurs.”

Previously, this team had identified three AD subtypes based on patterns of corticolimbic neurofibrillary tangling. In HpSp, the hippocampus is relatively spared, while the cortex has a greater number of tangles. In limbic predominant AD, the cortex is relatively spared, and the hippocampus is severely involved. Typical AD shows the expected patterns of hippocampal and cortical tangling.

Cases in this study came from the Florida Autopsied Multi-Ethnic (FLAME) cohort, comprising 1,361 brain tissue samples from confirmed AD cases and 103 nondemented controls. The investigators sought to understand the patterns of neuronal demise in the nbM, and any associations with clinical signs, demographics, and the recently described three subtypes.

In the cohort, AD subtypes included 175 with HpSp, 1,014 with typical AD, and 172 with limbic predominant AD. Patients with HpSp were the youngest, with a median disease onset age of 65 years, compared with 71 years in typical AD and 78 in limbic predominant. There were fewer women in the HpSp group (35%), compared with the typical AD group (54%) and the limbic group (70%). More patients with HpSp had atypical presentation (38%) in comparison with typical (11%) and limbic predominant AD (2%). But patients with HpSp were less likely to be APOE4 positive (46%), whereas those with limbic predominant AD were most likely to be APOE4 positive (72%).

Cognitively, HpSp patients declined more rapidly, losing a median of 4 points per year on the Mini Mental State Exam (MMSE), compared with 2 and 1 points in those with typical and limbic predominant AD. At death, the HpSp patients had a median MMSE score of 7, versus 13 in the typical AD group and 18 in the limbic group.

Patients with HpSp had the highest concentration of tangles and the lowest neuronal density in the nbM. Limbic predominant cases had the lowest tangle burden and the highest neuronal density. Typical AD cases lay between these extremes on both measures.

A multivariate regression analysis determined the overlap of neuronal findings and AD subtypes. A younger age at symptom onset was significantly associated with higher tangle counts in the nbM regions among patients with HpSp. In women with typical AD, there were 2.5 times more tangles than in men. APOE4 carriers had 1.3 times more tangles than did noncarriers.

There were also associations with cognition. “For every 10-point decrease in final MMSE of typical AD cases, the number of nbM NFTs was expected to increase by 1.8,” the authors wrote.

Although limbic predominant AD wasn’t associated with any clinical or demographic variables in this analysis, it was associated with neuronal changes in the nbM. “For every 10 years’ younger age at onset, the number of neurons was expected to be lower by 4.6 [per mm²]. … In addition, limbic predominant cases were observed to have 4.3 [per mm²] fewer neurons for every 10-point decrease in MMSE,” the authors said.

This study was supported by the National Institute on Aging, the Florida Department of Health, the Ed and Ethel Moore Alzheimer’s Disease Research Program, a Gerstner Family Career Development Award, and the Alzheimer’s Association. Two authors reported financial relationships with industry outside the submitted work.

[email protected]

SOURCE: Al Shaikh FSH et al. JAMA Neurol. 2019 Oct 28. doi: 10.1001/jamaneurol.2019.3606.

The proportion of family physicians providing inpatient care dropped 26% over a recent 5-year span, and by 2017, only one of four FPs was practicing hospital medicine, according to the American Academy of Family Physicians.

The share of family physicians who provided hospital care went from 34.1% in 2013 to 25.2% in 2017, for a relative decrease of 26% that left only a quarter of FPs seeing inpatients, based on data from the annual American Board of Family Medicine certification exam application questionnaire. For the 5-year period, 46,762 individuals were included in the study sample of FPs in direct patient care.

“As observed in other domains (prenatal care, home visits, nursing home care, and obstetric care), this study adds to the evidence demonstrating contracting scope of practice among FPs,” Anuradha Jetty, MPH, of the AAFP’s Robert Graham Center in Washington, D.C., and associates said in a recent Policy Brief published in the Journal of the American Board of Family Medicine.

Much of that contraction is occurring among new family physicians who can’t “find positions that allow them to use all their expertise,” the investigators said in a separate statement. The AAFP had previously reported that about 40% of family physicians had full hospital privileges in 2018, compared with 56% in 2012.

Many new FPs now work in large multispecialty practices or hospital systems, and “[some] of these employers dictate scope of practice, limiting family physicians to coordinating outpatient care and relying on subspecialists or hospitalists to provide inpatient care,” they noted.

[email protected]

The proportion of family physicians providing inpatient care dropped 26% over a recent 5-year span, and by 2017, only one of four FPs was practicing hospital medicine, according to the American Academy of Family Physicians.

The share of family physicians who provided hospital care went from 34.1% in 2013 to 25.2% in 2017, for a relative decrease of 26% that left only a quarter of FPs seeing inpatients, based on data from the annual American Board of Family Medicine certification exam application questionnaire. For the 5-year period, 46,762 individuals were included in the study sample of FPs in direct patient care.

“As observed in other domains (prenatal care, home visits, nursing home care, and obstetric care), this study adds to the evidence demonstrating contracting scope of practice among FPs,” Anuradha Jetty, MPH, of the AAFP’s Robert Graham Center in Washington, D.C., and associates said in a recent Policy Brief published in the Journal of the American Board of Family Medicine.

Much of that contraction is occurring among new family physicians who can’t “find positions that allow them to use all their expertise,” the investigators said in a separate statement. The AAFP had previously reported that about 40% of family physicians had full hospital privileges in 2018, compared with 56% in 2012.

Many new FPs now work in large multispecialty practices or hospital systems, and “[some] of these employers dictate scope of practice, limiting family physicians to coordinating outpatient care and relying on subspecialists or hospitalists to provide inpatient care,” they noted.

[email protected]

The proportion of family physicians providing inpatient care dropped 26% over a recent 5-year span, and by 2017, only one of four FPs was practicing hospital medicine, according to the American Academy of Family Physicians.

The share of family physicians who provided hospital care went from 34.1% in 2013 to 25.2% in 2017, for a relative decrease of 26% that left only a quarter of FPs seeing inpatients, based on data from the annual American Board of Family Medicine certification exam application questionnaire. For the 5-year period, 46,762 individuals were included in the study sample of FPs in direct patient care.

“As observed in other domains (prenatal care, home visits, nursing home care, and obstetric care), this study adds to the evidence demonstrating contracting scope of practice among FPs,” Anuradha Jetty, MPH, of the AAFP’s Robert Graham Center in Washington, D.C., and associates said in a recent Policy Brief published in the Journal of the American Board of Family Medicine.

Much of that contraction is occurring among new family physicians who can’t “find positions that allow them to use all their expertise,” the investigators said in a separate statement. The AAFP had previously reported that about 40% of family physicians had full hospital privileges in 2018, compared with 56% in 2012.

Many new FPs now work in large multispecialty practices or hospital systems, and “[some] of these employers dictate scope of practice, limiting family physicians to coordinating outpatient care and relying on subspecialists or hospitalists to provide inpatient care,” they noted.

[email protected]

CHICAGO – Is your practice ready for telemedicine – and should you dive in?

Once you and your practice managers work through regulatory, legal, and technical details, having a robust telemedicine practice can boost patient and clinician satisfaction – and the bottom line, said Theresa Lee, MD, a gastroenterologist in private practice in Lone Tree, Colorado, speaking at the 2019 AGA Partners in Value meeting.

Kari Oakes/MDedge News

The general field of telehealth – in which images might be shared or patients might message their care team for medication refills – is a broad term, said Dr. Lee. She explained that telemedicine is narrowly defined for Medicare and Medicaid reimbursement purposes as “two-way, real-time interactive communication between the patient and the physician or practitioner at [a] distant site ... that includes, at a minimum, audio and video equipment.” This is the video visit that many people think of when they imagine telemedicine, she said.

There’s increasing acceptance of telehealth services, said Dr. Lee, with a recent online poll showing that two-thirds of those surveyed would be willing to use telehealth; this would translate to about 24 million Americans who would be potential telehealth patients. And a 2019 survey of internal medicine physicians showed that more than half are working in practices in which telehealth is used in some capacity. Both patients and clinicians can benefit in a telehealth relationship, said Dr. Lee. The lack of physical travel and the potential for access after normal clinic hours can be a real boon for patients; “So how does this help us? How does it improve practice and make our lives easier?” she asked. Telehealth services can lead to improved efficiency, patient satisfaction and retention, and the ability to stand out in a market, especially if a practice can initiate telehealth services now, during the rapid growth and adoption phase for this newer technology.

“You want to make sure you really understand what some of the legal issues are surrounding telehealth and telemedicine,” said Dr. Lee, to ensure compliance with state and federal laws. There can be barriers to practicing across state lines; some states require an initial in-person visit, or the signing of a consent form, before initiating telemedicine; others may limit controlled substance prescribing via telemedicine.

And the mode of communication matters, said Dr. Lee: “Why can’t we just use Facetime to call our patients? The first thing to think about is privacy, and unauthorized access to data,” so it’s critical to do your research and use fully HIPAA-compliant communications technology.

Technology – and pricing plans – can vary widely, she added. “There’s some benefit to including technology that integrates with other clinical programs;” the platform Dr. Lee’s group chose communicates with their EHR for such functions as scheduling.

Pricing models can vary; a common scheme charges a per-user monthly fee, though blanket-fee plans also exist. Some telemedicine platforms use a hybrid pricing model that charges a flat fee up to a certain number of users and then adds a per-user fee after that.

Best practices to manage liability include continuing to maintain high standards of compliance after attorney consultation and notifying your practice’s malpractice insurance carrier, said Dr. Lee.

Reimbursement is on the upswing, as insurers see the benefits of telemedicine, and employers see their patients needing less time off work for appointments, and there are fewer emergency department visits for after-hours problems. Medicaid reimbursement is fairly straightforward, but Medicare is more restrictive and requires the beneficiary to be in a rural originating site.

Coding for a telemedicine visit is strictly based on face-to-face time spent in video conference, said Dr. Lee, at levels on par with time-based coding for office visits. “But you’re not including that time you spend doing chart review and not including the time you spend coordinating care.”

Dr. Lee’s own experience with telemedicine began in late 2016, when the 22-physician general gastroenterology group looked into it as a way to increase growth.

During the first half of the next year, the gastroenterology group’s administrative leaders and an engaged physician proponent vetted a number of telemedicine companies, and the group tried the leading candidates’ technologies.

By mid-2017, the comprehensive gastroenterology group, which also employs six advanced-practice clinicians, was piloting video visits with a group of four physicians. “One of those physicians was actually one of my partners who had sustained an Achilles tendon injury, so wasn’t really coming to the office post surgery. He was starting to use this at home, to do video visits, and everything went pretty smoothly with that,” said Dr. Lee.

When this trial was successful, the group went all in, with on-boarding of clinicians accomplished by the end of the year, site visits and 1:1 training provided by the telemedicine platform providers.

The practice is seeing video visits continue to grow in popularity, among both patients and clinicians, said Dr. Lee. She shared some tips and lessons learned from her practice.

There’s currently no formal protocol that selects patients for participation in the telemedicine program at Dr. Lee’s clinic. Providers may offer video visits to patients, and triage nurses also can suggest that patients ask their provider about them; flyers in waiting rooms and exam rooms encourage patients to ask about the possibility.

The practice maintains a telehealth committee that includes the practice’s president and administrator, about three core physicians who are strong telehealth champions, and additional physicians who are high telehealth users. The committee also folds in the office and information technology managers to make sure issues of workflow, billing, and technology are addressed.

Some practical considerations can pose challenges to a successful telemedicine program, said Dr. Lee. Connectivity problems on the patient end are fairly frequent, and no-shows also can be a problem. On the clinic side, not all clinicians have embraced video visits. For these low users, telemedicine may not represent a good value proposition. However, she said, they are seeing more and more clinicians come on board with video visits as word gets out of the generally positive experiences others are having.

Dr. Lee suggested several ways to up telemedicine utilization and make it work within your practice. “Identify which patient would benefit most,” she said – this might be patients with inflammatory bowel disease who mostly need medication management, or patients with limited mobility or who live far away. Staff can also help a patient get a same-day visit by scheduling a video visit with an available clinician. By mentioning video visits as an option for uncomplicated issues or a way to get a rapid read on a new concern, clinicians can get patients thinking about telemedicine as an appealing option.

In some clinics, exam room space can limit clinician productivity, and scheduling a block of video visits when space is tight can be a great solution. Clinicians can optimize their schedules if they incorporate video visits, said Dr. Lee, citing the example of a physician assistant in her practice who stacks video visits in the evening hours, so she’s able to be with her preschool-aged children during the day. After-hours video visits have been popular among patients too, said Dr. Lee, so the scheduling flexibility may help with both patient and provider retention, and be a practice differentiator.

“There’s great potential for value through improved patient satisfaction, provider efficiency, improved health care outcomes, and cost efficiency,” she said.

Dr. Lee reported that she had no relevant disclosures.

AGA has partnered with SupportedPatientTM, a HIPAA-secure telemedicine platform. It allows you to expand your practice and connect your patients with additional specialists. Learn more at https://www.gastro.org/practice-guidance/practice-updates/supportedpatient .

[email protected]

CHICAGO – Is your practice ready for telemedicine – and should you dive in?

Once you and your practice managers work through regulatory, legal, and technical details, having a robust telemedicine practice can boost patient and clinician satisfaction – and the bottom line, said Theresa Lee, MD, a gastroenterologist in private practice in Lone Tree, Colorado, speaking at the 2019 AGA Partners in Value meeting.

Kari Oakes/MDedge News

The general field of telehealth – in which images might be shared or patients might message their care team for medication refills – is a broad term, said Dr. Lee. She explained that telemedicine is narrowly defined for Medicare and Medicaid reimbursement purposes as “two-way, real-time interactive communication between the patient and the physician or practitioner at [a] distant site ... that includes, at a minimum, audio and video equipment.” This is the video visit that many people think of when they imagine telemedicine, she said.

There’s increasing acceptance of telehealth services, said Dr. Lee, with a recent online poll showing that two-thirds of those surveyed would be willing to use telehealth; this would translate to about 24 million Americans who would be potential telehealth patients. And a 2019 survey of internal medicine physicians showed that more than half are working in practices in which telehealth is used in some capacity. Both patients and clinicians can benefit in a telehealth relationship, said Dr. Lee. The lack of physical travel and the potential for access after normal clinic hours can be a real boon for patients; “So how does this help us? How does it improve practice and make our lives easier?” she asked. Telehealth services can lead to improved efficiency, patient satisfaction and retention, and the ability to stand out in a market, especially if a practice can initiate telehealth services now, during the rapid growth and adoption phase for this newer technology.

“You want to make sure you really understand what some of the legal issues are surrounding telehealth and telemedicine,” said Dr. Lee, to ensure compliance with state and federal laws. There can be barriers to practicing across state lines; some states require an initial in-person visit, or the signing of a consent form, before initiating telemedicine; others may limit controlled substance prescribing via telemedicine.

And the mode of communication matters, said Dr. Lee: “Why can’t we just use Facetime to call our patients? The first thing to think about is privacy, and unauthorized access to data,” so it’s critical to do your research and use fully HIPAA-compliant communications technology.

Technology – and pricing plans – can vary widely, she added. “There’s some benefit to including technology that integrates with other clinical programs;” the platform Dr. Lee’s group chose communicates with their EHR for such functions as scheduling.

Pricing models can vary; a common scheme charges a per-user monthly fee, though blanket-fee plans also exist. Some telemedicine platforms use a hybrid pricing model that charges a flat fee up to a certain number of users and then adds a per-user fee after that.

Best practices to manage liability include continuing to maintain high standards of compliance after attorney consultation and notifying your practice’s malpractice insurance carrier, said Dr. Lee.

Reimbursement is on the upswing, as insurers see the benefits of telemedicine, and employers see their patients needing less time off work for appointments, and there are fewer emergency department visits for after-hours problems. Medicaid reimbursement is fairly straightforward, but Medicare is more restrictive and requires the beneficiary to be in a rural originating site.

Coding for a telemedicine visit is strictly based on face-to-face time spent in video conference, said Dr. Lee, at levels on par with time-based coding for office visits. “But you’re not including that time you spend doing chart review and not including the time you spend coordinating care.”

Dr. Lee’s own experience with telemedicine began in late 2016, when the 22-physician general gastroenterology group looked into it as a way to increase growth.

During the first half of the next year, the gastroenterology group’s administrative leaders and an engaged physician proponent vetted a number of telemedicine companies, and the group tried the leading candidates’ technologies.

By mid-2017, the comprehensive gastroenterology group, which also employs six advanced-practice clinicians, was piloting video visits with a group of four physicians. “One of those physicians was actually one of my partners who had sustained an Achilles tendon injury, so wasn’t really coming to the office post surgery. He was starting to use this at home, to do video visits, and everything went pretty smoothly with that,” said Dr. Lee.

When this trial was successful, the group went all in, with on-boarding of clinicians accomplished by the end of the year, site visits and 1:1 training provided by the telemedicine platform providers.

The practice is seeing video visits continue to grow in popularity, among both patients and clinicians, said Dr. Lee. She shared some tips and lessons learned from her practice.

There’s currently no formal protocol that selects patients for participation in the telemedicine program at Dr. Lee’s clinic. Providers may offer video visits to patients, and triage nurses also can suggest that patients ask their provider about them; flyers in waiting rooms and exam rooms encourage patients to ask about the possibility.

The practice maintains a telehealth committee that includes the practice’s president and administrator, about three core physicians who are strong telehealth champions, and additional physicians who are high telehealth users. The committee also folds in the office and information technology managers to make sure issues of workflow, billing, and technology are addressed.

Some practical considerations can pose challenges to a successful telemedicine program, said Dr. Lee. Connectivity problems on the patient end are fairly frequent, and no-shows also can be a problem. On the clinic side, not all clinicians have embraced video visits. For these low users, telemedicine may not represent a good value proposition. However, she said, they are seeing more and more clinicians come on board with video visits as word gets out of the generally positive experiences others are having.

Dr. Lee suggested several ways to up telemedicine utilization and make it work within your practice. “Identify which patient would benefit most,” she said – this might be patients with inflammatory bowel disease who mostly need medication management, or patients with limited mobility or who live far away. Staff can also help a patient get a same-day visit by scheduling a video visit with an available clinician. By mentioning video visits as an option for uncomplicated issues or a way to get a rapid read on a new concern, clinicians can get patients thinking about telemedicine as an appealing option.

In some clinics, exam room space can limit clinician productivity, and scheduling a block of video visits when space is tight can be a great solution. Clinicians can optimize their schedules if they incorporate video visits, said Dr. Lee, citing the example of a physician assistant in her practice who stacks video visits in the evening hours, so she’s able to be with her preschool-aged children during the day. After-hours video visits have been popular among patients too, said Dr. Lee, so the scheduling flexibility may help with both patient and provider retention, and be a practice differentiator.

“There’s great potential for value through improved patient satisfaction, provider efficiency, improved health care outcomes, and cost efficiency,” she said.

Dr. Lee reported that she had no relevant disclosures.

AGA has partnered with SupportedPatientTM, a HIPAA-secure telemedicine platform. It allows you to expand your practice and connect your patients with additional specialists. Learn more at https://www.gastro.org/practice-guidance/practice-updates/supportedpatient .

[email protected]

CHICAGO – Is your practice ready for telemedicine – and should you dive in?

Once you and your practice managers work through regulatory, legal, and technical details, having a robust telemedicine practice can boost patient and clinician satisfaction – and the bottom line, said Theresa Lee, MD, a gastroenterologist in private practice in Lone Tree, Colorado, speaking at the 2019 AGA Partners in Value meeting.

Kari Oakes/MDedge News

The general field of telehealth – in which images might be shared or patients might message their care team for medication refills – is a broad term, said Dr. Lee. She explained that telemedicine is narrowly defined for Medicare and Medicaid reimbursement purposes as “two-way, real-time interactive communication between the patient and the physician or practitioner at [a] distant site ... that includes, at a minimum, audio and video equipment.” This is the video visit that many people think of when they imagine telemedicine, she said.

There’s increasing acceptance of telehealth services, said Dr. Lee, with a recent online poll showing that two-thirds of those surveyed would be willing to use telehealth; this would translate to about 24 million Americans who would be potential telehealth patients. And a 2019 survey of internal medicine physicians showed that more than half are working in practices in which telehealth is used in some capacity. Both patients and clinicians can benefit in a telehealth relationship, said Dr. Lee. The lack of physical travel and the potential for access after normal clinic hours can be a real boon for patients; “So how does this help us? How does it improve practice and make our lives easier?” she asked. Telehealth services can lead to improved efficiency, patient satisfaction and retention, and the ability to stand out in a market, especially if a practice can initiate telehealth services now, during the rapid growth and adoption phase for this newer technology.

“You want to make sure you really understand what some of the legal issues are surrounding telehealth and telemedicine,” said Dr. Lee, to ensure compliance with state and federal laws. There can be barriers to practicing across state lines; some states require an initial in-person visit, or the signing of a consent form, before initiating telemedicine; others may limit controlled substance prescribing via telemedicine.

And the mode of communication matters, said Dr. Lee: “Why can’t we just use Facetime to call our patients? The first thing to think about is privacy, and unauthorized access to data,” so it’s critical to do your research and use fully HIPAA-compliant communications technology.

Technology – and pricing plans – can vary widely, she added. “There’s some benefit to including technology that integrates with other clinical programs;” the platform Dr. Lee’s group chose communicates with their EHR for such functions as scheduling.

Pricing models can vary; a common scheme charges a per-user monthly fee, though blanket-fee plans also exist. Some telemedicine platforms use a hybrid pricing model that charges a flat fee up to a certain number of users and then adds a per-user fee after that.

Best practices to manage liability include continuing to maintain high standards of compliance after attorney consultation and notifying your practice’s malpractice insurance carrier, said Dr. Lee.

Reimbursement is on the upswing, as insurers see the benefits of telemedicine, and employers see their patients needing less time off work for appointments, and there are fewer emergency department visits for after-hours problems. Medicaid reimbursement is fairly straightforward, but Medicare is more restrictive and requires the beneficiary to be in a rural originating site.

Coding for a telemedicine visit is strictly based on face-to-face time spent in video conference, said Dr. Lee, at levels on par with time-based coding for office visits. “But you’re not including that time you spend doing chart review and not including the time you spend coordinating care.”

Dr. Lee’s own experience with telemedicine began in late 2016, when the 22-physician general gastroenterology group looked into it as a way to increase growth.

During the first half of the next year, the gastroenterology group’s administrative leaders and an engaged physician proponent vetted a number of telemedicine companies, and the group tried the leading candidates’ technologies.

By mid-2017, the comprehensive gastroenterology group, which also employs six advanced-practice clinicians, was piloting video visits with a group of four physicians. “One of those physicians was actually one of my partners who had sustained an Achilles tendon injury, so wasn’t really coming to the office post surgery. He was starting to use this at home, to do video visits, and everything went pretty smoothly with that,” said Dr. Lee.

When this trial was successful, the group went all in, with on-boarding of clinicians accomplished by the end of the year, site visits and 1:1 training provided by the telemedicine platform providers.

The practice is seeing video visits continue to grow in popularity, among both patients and clinicians, said Dr. Lee. She shared some tips and lessons learned from her practice.

There’s currently no formal protocol that selects patients for participation in the telemedicine program at Dr. Lee’s clinic. Providers may offer video visits to patients, and triage nurses also can suggest that patients ask their provider about them; flyers in waiting rooms and exam rooms encourage patients to ask about the possibility.

The practice maintains a telehealth committee that includes the practice’s president and administrator, about three core physicians who are strong telehealth champions, and additional physicians who are high telehealth users. The committee also folds in the office and information technology managers to make sure issues of workflow, billing, and technology are addressed.

Some practical considerations can pose challenges to a successful telemedicine program, said Dr. Lee. Connectivity problems on the patient end are fairly frequent, and no-shows also can be a problem. On the clinic side, not all clinicians have embraced video visits. For these low users, telemedicine may not represent a good value proposition. However, she said, they are seeing more and more clinicians come on board with video visits as word gets out of the generally positive experiences others are having.

Dr. Lee suggested several ways to up telemedicine utilization and make it work within your practice. “Identify which patient would benefit most,” she said – this might be patients with inflammatory bowel disease who mostly need medication management, or patients with limited mobility or who live far away. Staff can also help a patient get a same-day visit by scheduling a video visit with an available clinician. By mentioning video visits as an option for uncomplicated issues or a way to get a rapid read on a new concern, clinicians can get patients thinking about telemedicine as an appealing option.

In some clinics, exam room space can limit clinician productivity, and scheduling a block of video visits when space is tight can be a great solution. Clinicians can optimize their schedules if they incorporate video visits, said Dr. Lee, citing the example of a physician assistant in her practice who stacks video visits in the evening hours, so she’s able to be with her preschool-aged children during the day. After-hours video visits have been popular among patients too, said Dr. Lee, so the scheduling flexibility may help with both patient and provider retention, and be a practice differentiator.

“There’s great potential for value through improved patient satisfaction, provider efficiency, improved health care outcomes, and cost efficiency,” she said.

Dr. Lee reported that she had no relevant disclosures.

AGA has partnered with SupportedPatientTM, a HIPAA-secure telemedicine platform. It allows you to expand your practice and connect your patients with additional specialists. Learn more at https://www.gastro.org/practice-guidance/practice-updates/supportedpatient .

[email protected]

NATIONAL HARBOR, MD. – New research has shown increased immune infiltration in patients with TP53-mutated acute myeloid leukemia (AML).

Jennifer Smith/MDedge News

Patients with TP53-mutated AML had higher levels of T-cell infiltration, immune checkpoint molecules, and interferon (IFN)–gamma signaling than patients with wild-type TP53.

These findings may indicate that patients with TP53-mutated AML will respond to T-cell targeting immunotherapies, but more investigation is needed, according to Sergio Rutella, MD, PhD, of Nottingham (England) Trent University.

Dr. Rutella described the findings at the annual meeting of the Society for Immunotherapy of Cancer.

He and his colleagues recently identified subgroups of AML, called “immune infiltrated” and “immune depleted,” that can predict chemotherapy resistance and response to flotetuzumab (ASH 2019, Abstract 460). However, the team has not determined the genetic drivers of immune infiltration in AML.*

With the current study, Dr. Rutella and his colleagues wanted to determine if TP53 mutations are associated with the AML immune milieu and see if TP53-mutated patients might benefit from immunotherapy.

Discovery cohort

The researchers first analyzed 147 patients with non-promyelocytic AML from the Cancer Genome Atlas. In total, 9% of these patients (n = 13) had TP53-mutated AML. The researchers assessed how 45 immune gene and biological activity signatures correlated with prognostic molecular lesions (TP53 mutations, FLT3-ITD, etc.) and clinical outcomes in this cohort.

The data showed that immune subtypes were associated with overall survival (OS). The median OS was 11.8 months in patients with immune-infiltrated AML, 16.4 months in patients with intermediate AML, and 25.8 months in patients with immune-depleted AML.

The inflammatory chemokine score (P = .011), IDO1 score (P = .027), IFN-gamma score (P = .036), and B7H3 score (P = .045) were all significantly associated with OS. In fact, these factors were all better predictors of OS than cytogenetic risk score (P = .049).

The IFN-gamma score, inflammatory chemokine score, and lymphoid score were all significantly higher in TP53-mutated patients than in patients with RUNX1 mutations, NPM1 mutations, FLT3-ITD (with or without NPM1 mutations), and TET2/DNMT3A/ASXL1 mutations (P values ranging from less than .0001 to .05).

Likewise, the tumor inflammation signature score was significantly higher among TP53-mutated patients than among patients with NPM1 mutations, FLT3-ITD (with or without NPM1 mutations), and TET2/DNMT3A/ASXL1 mutations (P values ranging from less than .0001 to .01).

Validation cohort and bone marrow samples

The researchers also looked at data from a validation cohort, which consisted of 140 patients with non-promyelocytic AML in the Beat AML Master Trial. Twelve percent of these patients (n = 17) had TP53 mutations.

Data in this cohort showed that CD3G messenger RNA (mRNA) was significantly higher in TP53-mutated AML than in TP53-wild-type AML (P = .04). The same was true for CD8A mRNA (P = .0002) and GZMB mRNA (P = .0005).

Likewise, IFN-gamma mRNA (P = .0052), IFIT2 mRNA (P = .0064), and IFIT3 mRNA (P = .003) were all significantly higher in patients with TP53-mutated AML.

Lastly, the researchers analyzed gene expression profiles of bone marrow samples from patients with AML, 36 with mutated TP53 and 24 with wild-type TP53.

The team found that IFN-gamma–induced genes (IFNG and IRF1), markers of T-cell infiltration (CD8A and CD3G) and senescence (EOMES, KLRD1, and HRAS), immune checkpoint molecules (IDO1, LAG3, PDL1, and VISTA), effector function molecules (GZMB, GZMK, and GZMM), and proinflammatory cytokines (IL17A and TNF) were all significantly overexpressed in TP53-mutated AML.

Among the top overexpressed genes in TP53-mutated AML were genes associated with IFN signaling and inflammation pathways – IL-33, IL-6, IFN-gamma, OASL, RIPK2, TNFAIP3, CSF1, and PTGER4. The IL-17 and TNF signaling pathways were the most enriched pathways in TP53-mutated AML.

“Our analysis of primary bone marrow samples showed that TP53-mutated samples are enriched in IL-17, TNF, and IFN signaling molecules, and show higher levels of T-cell infiltrations and immune checkpoints relative to their wild-type counterparts,” Dr. Rutella said.

“The in silico analysis indicated that TP53-mutated cases will show higher levels of T-cell infiltration, immune checkpoints, and IFN-gamma signaling, compared with AML subgroups without risk-defining molecular lesions,” he added. “This is speculative. Whether TP53-mutated AML can be amenable to respond to T-cell targeting immunotherapies is still to be determined.”

Dr. Rutella reported research support from NanoString Technologies, MacroGenics, and Kura Oncology.

[email protected]

SOURCE: Rutella S et al. SITC 2019. Abstract O3.

*This article was updated on 11/19/2019.

NATIONAL HARBOR, MD. – New research has shown increased immune infiltration in patients with TP53-mutated acute myeloid leukemia (AML).

Jennifer Smith/MDedge News

Patients with TP53-mutated AML had higher levels of T-cell infiltration, immune checkpoint molecules, and interferon (IFN)–gamma signaling than patients with wild-type TP53.

These findings may indicate that patients with TP53-mutated AML will respond to T-cell targeting immunotherapies, but more investigation is needed, according to Sergio Rutella, MD, PhD, of Nottingham (England) Trent University.

Dr. Rutella described the findings at the annual meeting of the Society for Immunotherapy of Cancer.

He and his colleagues recently identified subgroups of AML, called “immune infiltrated” and “immune depleted,” that can predict chemotherapy resistance and response to flotetuzumab (ASH 2019, Abstract 460). However, the team has not determined the genetic drivers of immune infiltration in AML.*

With the current study, Dr. Rutella and his colleagues wanted to determine if TP53 mutations are associated with the AML immune milieu and see if TP53-mutated patients might benefit from immunotherapy.

Discovery cohort

The researchers first analyzed 147 patients with non-promyelocytic AML from the Cancer Genome Atlas. In total, 9% of these patients (n = 13) had TP53-mutated AML. The researchers assessed how 45 immune gene and biological activity signatures correlated with prognostic molecular lesions (TP53 mutations, FLT3-ITD, etc.) and clinical outcomes in this cohort.

The data showed that immune subtypes were associated with overall survival (OS). The median OS was 11.8 months in patients with immune-infiltrated AML, 16.4 months in patients with intermediate AML, and 25.8 months in patients with immune-depleted AML.

The inflammatory chemokine score (P = .011), IDO1 score (P = .027), IFN-gamma score (P = .036), and B7H3 score (P = .045) were all significantly associated with OS. In fact, these factors were all better predictors of OS than cytogenetic risk score (P = .049).

The IFN-gamma score, inflammatory chemokine score, and lymphoid score were all significantly higher in TP53-mutated patients than in patients with RUNX1 mutations, NPM1 mutations, FLT3-ITD (with or without NPM1 mutations), and TET2/DNMT3A/ASXL1 mutations (P values ranging from less than .0001 to .05).

Likewise, the tumor inflammation signature score was significantly higher among TP53-mutated patients than among patients with NPM1 mutations, FLT3-ITD (with or without NPM1 mutations), and TET2/DNMT3A/ASXL1 mutations (P values ranging from less than .0001 to .01).

Validation cohort and bone marrow samples

The researchers also looked at data from a validation cohort, which consisted of 140 patients with non-promyelocytic AML in the Beat AML Master Trial. Twelve percent of these patients (n = 17) had TP53 mutations.

Data in this cohort showed that CD3G messenger RNA (mRNA) was significantly higher in TP53-mutated AML than in TP53-wild-type AML (P = .04). The same was true for CD8A mRNA (P = .0002) and GZMB mRNA (P = .0005).

Likewise, IFN-gamma mRNA (P = .0052), IFIT2 mRNA (P = .0064), and IFIT3 mRNA (P = .003) were all significantly higher in patients with TP53-mutated AML.

Lastly, the researchers analyzed gene expression profiles of bone marrow samples from patients with AML, 36 with mutated TP53 and 24 with wild-type TP53.

The team found that IFN-gamma–induced genes (IFNG and IRF1), markers of T-cell infiltration (CD8A and CD3G) and senescence (EOMES, KLRD1, and HRAS), immune checkpoint molecules (IDO1, LAG3, PDL1, and VISTA), effector function molecules (GZMB, GZMK, and GZMM), and proinflammatory cytokines (IL17A and TNF) were all significantly overexpressed in TP53-mutated AML.

Among the top overexpressed genes in TP53-mutated AML were genes associated with IFN signaling and inflammation pathways – IL-33, IL-6, IFN-gamma, OASL, RIPK2, TNFAIP3, CSF1, and PTGER4. The IL-17 and TNF signaling pathways were the most enriched pathways in TP53-mutated AML.

“Our analysis of primary bone marrow samples showed that TP53-mutated samples are enriched in IL-17, TNF, and IFN signaling molecules, and show higher levels of T-cell infiltrations and immune checkpoints relative to their wild-type counterparts,” Dr. Rutella said.

“The in silico analysis indicated that TP53-mutated cases will show higher levels of T-cell infiltration, immune checkpoints, and IFN-gamma signaling, compared with AML subgroups without risk-defining molecular lesions,” he added. “This is speculative. Whether TP53-mutated AML can be amenable to respond to T-cell targeting immunotherapies is still to be determined.”

Dr. Rutella reported research support from NanoString Technologies, MacroGenics, and Kura Oncology.

[email protected]

SOURCE: Rutella S et al. SITC 2019. Abstract O3.

*This article was updated on 11/19/2019.

NATIONAL HARBOR, MD. – New research has shown increased immune infiltration in patients with TP53-mutated acute myeloid leukemia (AML).

Jennifer Smith/MDedge News

Patients with TP53-mutated AML had higher levels of T-cell infiltration, immune checkpoint molecules, and interferon (IFN)–gamma signaling than patients with wild-type TP53.

These findings may indicate that patients with TP53-mutated AML will respond to T-cell targeting immunotherapies, but more investigation is needed, according to Sergio Rutella, MD, PhD, of Nottingham (England) Trent University.

Dr. Rutella described the findings at the annual meeting of the Society for Immunotherapy of Cancer.

He and his colleagues recently identified subgroups of AML, called “immune infiltrated” and “immune depleted,” that can predict chemotherapy resistance and response to flotetuzumab (ASH 2019, Abstract 460). However, the team has not determined the genetic drivers of immune infiltration in AML.*

With the current study, Dr. Rutella and his colleagues wanted to determine if TP53 mutations are associated with the AML immune milieu and see if TP53-mutated patients might benefit from immunotherapy.

Discovery cohort

The researchers first analyzed 147 patients with non-promyelocytic AML from the Cancer Genome Atlas. In total, 9% of these patients (n = 13) had TP53-mutated AML. The researchers assessed how 45 immune gene and biological activity signatures correlated with prognostic molecular lesions (TP53 mutations, FLT3-ITD, etc.) and clinical outcomes in this cohort.

The data showed that immune subtypes were associated with overall survival (OS). The median OS was 11.8 months in patients with immune-infiltrated AML, 16.4 months in patients with intermediate AML, and 25.8 months in patients with immune-depleted AML.

The inflammatory chemokine score (P = .011), IDO1 score (P = .027), IFN-gamma score (P = .036), and B7H3 score (P = .045) were all significantly associated with OS. In fact, these factors were all better predictors of OS than cytogenetic risk score (P = .049).

The IFN-gamma score, inflammatory chemokine score, and lymphoid score were all significantly higher in TP53-mutated patients than in patients with RUNX1 mutations, NPM1 mutations, FLT3-ITD (with or without NPM1 mutations), and TET2/DNMT3A/ASXL1 mutations (P values ranging from less than .0001 to .05).

Likewise, the tumor inflammation signature score was significantly higher among TP53-mutated patients than among patients with NPM1 mutations, FLT3-ITD (with or without NPM1 mutations), and TET2/DNMT3A/ASXL1 mutations (P values ranging from less than .0001 to .01).

Validation cohort and bone marrow samples

The researchers also looked at data from a validation cohort, which consisted of 140 patients with non-promyelocytic AML in the Beat AML Master Trial. Twelve percent of these patients (n = 17) had TP53 mutations.

Data in this cohort showed that CD3G messenger RNA (mRNA) was significantly higher in TP53-mutated AML than in TP53-wild-type AML (P = .04). The same was true for CD8A mRNA (P = .0002) and GZMB mRNA (P = .0005).

Likewise, IFN-gamma mRNA (P = .0052), IFIT2 mRNA (P = .0064), and IFIT3 mRNA (P = .003) were all significantly higher in patients with TP53-mutated AML.

Lastly, the researchers analyzed gene expression profiles of bone marrow samples from patients with AML, 36 with mutated TP53 and 24 with wild-type TP53.

The team found that IFN-gamma–induced genes (IFNG and IRF1), markers of T-cell infiltration (CD8A and CD3G) and senescence (EOMES, KLRD1, and HRAS), immune checkpoint molecules (IDO1, LAG3, PDL1, and VISTA), effector function molecules (GZMB, GZMK, and GZMM), and proinflammatory cytokines (IL17A and TNF) were all significantly overexpressed in TP53-mutated AML.

Among the top overexpressed genes in TP53-mutated AML were genes associated with IFN signaling and inflammation pathways – IL-33, IL-6, IFN-gamma, OASL, RIPK2, TNFAIP3, CSF1, and PTGER4. The IL-17 and TNF signaling pathways were the most enriched pathways in TP53-mutated AML.

“Our analysis of primary bone marrow samples showed that TP53-mutated samples are enriched in IL-17, TNF, and IFN signaling molecules, and show higher levels of T-cell infiltrations and immune checkpoints relative to their wild-type counterparts,” Dr. Rutella said.

“The in silico analysis indicated that TP53-mutated cases will show higher levels of T-cell infiltration, immune checkpoints, and IFN-gamma signaling, compared with AML subgroups without risk-defining molecular lesions,” he added. “This is speculative. Whether TP53-mutated AML can be amenable to respond to T-cell targeting immunotherapies is still to be determined.”

Dr. Rutella reported research support from NanoString Technologies, MacroGenics, and Kura Oncology.

[email protected]

SOURCE: Rutella S et al. SITC 2019. Abstract O3.

*This article was updated on 11/19/2019.

A chimeric antigen receptor (CAR) T-cell “cocktail” targeting both CD19 and CD22 could improve outcomes for patients with refractory or relapsed B-cell malignancies, according to investigators.

This dual approach, which appeared safe and effective, may be able to overcome antigen escape relapse, reported Na Wang, MD, of Huazhong University of Science and Technology in China, and colleagues.

The investigators tested this method in an open-label, single-arm pilot study involving 89 patients with refractory/relapsed B cell malignancies. Of these, 51 patients had B-cell acute lymphoblastic leukemia (B-ALL), while the remaining 38 had non-Hodgkin lymphoma (NHL). All patients had dual expression of CD19 and CD22 on malignant B cells, good performance status, and “essentially” normal organ function, the investigators reported in Blood.

Following lymphodepletion, patients were infused with CAR19 and CAR22 T cells, then evaluated for responses with imaging or bone marrow aspiration on a monthly basis for 6 months, then every 3 months thereafter.

After 30 days, most patients with ALL (96%) achieved a minimal residual disease-negative complete response or complete response with incomplete count recovery. After a median follow-up of 16.7 months, almost half of these responders relapsed (49%), median progression-free survival was 13.6 months, and overall survival was 31 months.

With a minimum follow-up of 3 months, half of the patients with NHL (50%) achieved complete responses, with the caveat that two patients who died of septic shock and severe cytokine release syndrome were excluded from this efficacy analysis. After a median follow-up of 14.4 months, in the NHL group, median progression-free survival was 9.9 months and overall survival was 18 months.

Across disease types, almost all patients (95.5%) experienced cytokine release syndrome, with more than three-quarters (77.6%) categorized as grade 1 or 2. CAR T cell-related encephalopathy syndrome (CRES) occurred in 13.5% of patients; most were low grade, apart from one case that was grade 4. In total, 12 patients died due to adverse events.

“The severe [adverse events] were mostly cytopenias and the most frequent fatal [adverse event] was lung infection, which was attributable in part to the high disease burden and heavy pretreatment of the enrolled patients,” the investigators wrote. “Nearly all the high-grade CRS and CRES were reversible and occurred in similar incidences as previously reported. Thus, the sequential infusion of CAR19/22 T-cell “cocktail” was an efficient and well-tolerated approach to circumvent antigen loss of CD19 or CD22.”

The investigators reported having no conflicts of interest.

SOURCE: Wang N et al. 2019 Oct 29. doi: 10.1182/blood.2019000017.

A chimeric antigen receptor (CAR) T-cell “cocktail” targeting both CD19 and CD22 could improve outcomes for patients with refractory or relapsed B-cell malignancies, according to investigators.

This dual approach, which appeared safe and effective, may be able to overcome antigen escape relapse, reported Na Wang, MD, of Huazhong University of Science and Technology in China, and colleagues.

The investigators tested this method in an open-label, single-arm pilot study involving 89 patients with refractory/relapsed B cell malignancies. Of these, 51 patients had B-cell acute lymphoblastic leukemia (B-ALL), while the remaining 38 had non-Hodgkin lymphoma (NHL). All patients had dual expression of CD19 and CD22 on malignant B cells, good performance status, and “essentially” normal organ function, the investigators reported in Blood.

Following lymphodepletion, patients were infused with CAR19 and CAR22 T cells, then evaluated for responses with imaging or bone marrow aspiration on a monthly basis for 6 months, then every 3 months thereafter.

After 30 days, most patients with ALL (96%) achieved a minimal residual disease-negative complete response or complete response with incomplete count recovery. After a median follow-up of 16.7 months, almost half of these responders relapsed (49%), median progression-free survival was 13.6 months, and overall survival was 31 months.

With a minimum follow-up of 3 months, half of the patients with NHL (50%) achieved complete responses, with the caveat that two patients who died of septic shock and severe cytokine release syndrome were excluded from this efficacy analysis. After a median follow-up of 14.4 months, in the NHL group, median progression-free survival was 9.9 months and overall survival was 18 months.

Across disease types, almost all patients (95.5%) experienced cytokine release syndrome, with more than three-quarters (77.6%) categorized as grade 1 or 2. CAR T cell-related encephalopathy syndrome (CRES) occurred in 13.5% of patients; most were low grade, apart from one case that was grade 4. In total, 12 patients died due to adverse events.

“The severe [adverse events] were mostly cytopenias and the most frequent fatal [adverse event] was lung infection, which was attributable in part to the high disease burden and heavy pretreatment of the enrolled patients,” the investigators wrote. “Nearly all the high-grade CRS and CRES were reversible and occurred in similar incidences as previously reported. Thus, the sequential infusion of CAR19/22 T-cell “cocktail” was an efficient and well-tolerated approach to circumvent antigen loss of CD19 or CD22.”

The investigators reported having no conflicts of interest.

SOURCE: Wang N et al. 2019 Oct 29. doi: 10.1182/blood.2019000017.

A chimeric antigen receptor (CAR) T-cell “cocktail” targeting both CD19 and CD22 could improve outcomes for patients with refractory or relapsed B-cell malignancies, according to investigators.

This dual approach, which appeared safe and effective, may be able to overcome antigen escape relapse, reported Na Wang, MD, of Huazhong University of Science and Technology in China, and colleagues.

The investigators tested this method in an open-label, single-arm pilot study involving 89 patients with refractory/relapsed B cell malignancies. Of these, 51 patients had B-cell acute lymphoblastic leukemia (B-ALL), while the remaining 38 had non-Hodgkin lymphoma (NHL). All patients had dual expression of CD19 and CD22 on malignant B cells, good performance status, and “essentially” normal organ function, the investigators reported in Blood.

Following lymphodepletion, patients were infused with CAR19 and CAR22 T cells, then evaluated for responses with imaging or bone marrow aspiration on a monthly basis for 6 months, then every 3 months thereafter.

After 30 days, most patients with ALL (96%) achieved a minimal residual disease-negative complete response or complete response with incomplete count recovery. After a median follow-up of 16.7 months, almost half of these responders relapsed (49%), median progression-free survival was 13.6 months, and overall survival was 31 months.

With a minimum follow-up of 3 months, half of the patients with NHL (50%) achieved complete responses, with the caveat that two patients who died of septic shock and severe cytokine release syndrome were excluded from this efficacy analysis. After a median follow-up of 14.4 months, in the NHL group, median progression-free survival was 9.9 months and overall survival was 18 months.

Across disease types, almost all patients (95.5%) experienced cytokine release syndrome, with more than three-quarters (77.6%) categorized as grade 1 or 2. CAR T cell-related encephalopathy syndrome (CRES) occurred in 13.5% of patients; most were low grade, apart from one case that was grade 4. In total, 12 patients died due to adverse events.

“The severe [adverse events] were mostly cytopenias and the most frequent fatal [adverse event] was lung infection, which was attributable in part to the high disease burden and heavy pretreatment of the enrolled patients,” the investigators wrote. “Nearly all the high-grade CRS and CRES were reversible and occurred in similar incidences as previously reported. Thus, the sequential infusion of CAR19/22 T-cell “cocktail” was an efficient and well-tolerated approach to circumvent antigen loss of CD19 or CD22.”

The investigators reported having no conflicts of interest.

SOURCE: Wang N et al. 2019 Oct 29. doi: 10.1182/blood.2019000017.

Each year, CHEST honors physicians and others who are making significant or meritorious contributions to chest medicine. All honorees are recognized for advancing work in specific areas of chest medicine, mentorship, and training, furthering the work of CHEST, and more.

If you believe you have a colleague who should be recognized for their distinguished work, please submit a nomination. Those selected for an annual award and honor lecture will be featured at CHEST 2020 in Chicago.

Deadline: Monday, January 6, 2020

Questions? Please contact Emily Petraglia, Manager, Volunteer Engagement ([email protected]).


The following awards are now open for nominations:

 Annual Awards

College Medalist Award

Distinguished Service AwardMaster FCCP

Honor and Memorial Lectures

Edward C. Rosenow III, MD, Master FCCP/Master Teacher Endowed Honor Lecture.

Roger C. Bone Memorial Lecture in Critical CareMurray Kornfeld Memorial Founders Award

Distinguished Scientist Honor Lecture in Cardiopulmonary PhysiologyPasquale Ciaglia Memorial Lecture in Interventional MedicineMargaret Pfrommer Endowed Memorial Lecture in Home-Based Mechanical VentilationThomas L. Petty, MD, Master FCCP Endowed Memorial Lecture

Educator Awards

Early Career Clinician Educator

Master Clinician Educator
 

Each year, CHEST honors physicians and others who are making significant or meritorious contributions to chest medicine. All honorees are recognized for advancing work in specific areas of chest medicine, mentorship, and training, furthering the work of CHEST, and more.

If you believe you have a colleague who should be recognized for their distinguished work, please submit a nomination. Those selected for an annual award and honor lecture will be featured at CHEST 2020 in Chicago.

Deadline: Monday, January 6, 2020

Questions? Please contact Emily Petraglia, Manager, Volunteer Engagement ([email protected]).


The following awards are now open for nominations:

 Annual Awards

College Medalist Award

Distinguished Service AwardMaster FCCP

Honor and Memorial Lectures

Edward C. Rosenow III, MD, Master FCCP/Master Teacher Endowed Honor Lecture.

Roger C. Bone Memorial Lecture in Critical CareMurray Kornfeld Memorial Founders Award

Distinguished Scientist Honor Lecture in Cardiopulmonary PhysiologyPasquale Ciaglia Memorial Lecture in Interventional MedicineMargaret Pfrommer Endowed Memorial Lecture in Home-Based Mechanical VentilationThomas L. Petty, MD, Master FCCP Endowed Memorial Lecture

Educator Awards

Early Career Clinician Educator

Master Clinician Educator
 

Each year, CHEST honors physicians and others who are making significant or meritorious contributions to chest medicine. All honorees are recognized for advancing work in specific areas of chest medicine, mentorship, and training, furthering the work of CHEST, and more.

If you believe you have a colleague who should be recognized for their distinguished work, please submit a nomination. Those selected for an annual award and honor lecture will be featured at CHEST 2020 in Chicago.

Deadline: Monday, January 6, 2020

Questions? Please contact Emily Petraglia, Manager, Volunteer Engagement ([email protected]).


The following awards are now open for nominations:

 Annual Awards

College Medalist Award

Distinguished Service AwardMaster FCCP

Honor and Memorial Lectures

Edward C. Rosenow III, MD, Master FCCP/Master Teacher Endowed Honor Lecture.

Roger C. Bone Memorial Lecture in Critical CareMurray Kornfeld Memorial Founders Award

Distinguished Scientist Honor Lecture in Cardiopulmonary PhysiologyPasquale Ciaglia Memorial Lecture in Interventional MedicineMargaret Pfrommer Endowed Memorial Lecture in Home-Based Mechanical VentilationThomas L. Petty, MD, Master FCCP Endowed Memorial Lecture

Educator Awards

Early Career Clinician Educator

Master Clinician Educator
 

PHILADELPHIA – Downshifting to ticagrelor monotherapy after just 3 months of dual antiplatelet therapy is a winning strategy in high-risk patients who’ve undergone PCI for non-ST-elevation acute coronary syndrome, Usman Baber, MD, reported at the American Heart Association scientific sessions.

Bruce Jancin/MDedge News

He presented a prespecified subgroup analysis of the previously reported TWILIGHT study that was restricted to the 4,614 participants with non-ST-elevation ACS who underwent PCI, completed 3 months of dual antiplatelet therapy (DAPT) with ticagrelor and aspirin, and were then randomized double-blind to an additional 12 months on the same regimen or to ticagrelor plus placebo.

The key finding: After a year on ticagrelor monotherapy, the risk of clinically significant or major bleeding was reduced by 53%, compared with the DAPT group, and with no increased risk of ischemic major adverse cardiovascular events, said Dr. Baber, a cardiologist at the Icahn School of Medicine at Mount Sinai, New York.

This secondary analysis of the TWILIGHT study was carried out because none of the several prior studies of short-term DAPT followed by an aspirin-free strategy after PCI was double-blind. Nor did any include patients with non-ST-elevation ACS, he explained.

The TWILIGHT substudy included 2,494 participants with unstable angina and 2,120 with non-ST-elevation MI. Roughly two-thirds had four or more high-risk clinical or angiographic features, such as diabetes, chronic kidney disease, multivessel CAD, or left main lesions.

The primary study endpoint at month 15 – the rate of Bleeding Academic Research Consortium (BARC) type 2, 3, or 5 bleeding events – was 7.6% with ticagrelor plus aspirin, compared with 3.6% with ticagrelor plus placebo, for a highly significant 53% relative risk reduction in favor of ticagrelor monotherapy. The key secondary endpoint, a composite of all-cause mortality, MI, or stroke, occurred in roughly 4.4% of patients in each study arm.

Of note, ticagrelor monotherapy after 3 months of DAPT was associated with a similar 50%-60% reduction in the risk of BARC 2, 3, or 5 bleeding regardless of whether patients had 1-3, 4 or 5, or 6-9 prespecified high-risk clinical and angiographic features. Nor was the impact of ticagrelor monotherapy on ischemic events impacted by risk factor burden.

Discussant Michelle L. O’Donoghue, MD, observed that while the current practice of most cardiologists in patients undergoing stenting in the setting of ACS is 12 months of DAPT followed by discontinuation of the P2Y₁₂ inhibitor and indefinite continuation of aspirin, mounting evidence suggests there’s a better approach.

Bruce Jancin/MDedge News

Indeed, the new TWILIGHT findings in patients with non-ST-elevation ACS dovetail nicely with the results of three other recent studies of discontinuing aspirin after 1-3 months versus continuing DAPT with ticagrelor or another P2Y₁₂ inhibitor plus aspirin. These studies, GLOBAL LEADERS (Lancet. 2018 Sep 15;392[10151]:940-9); SMART CHOICE (JAMA. 2019 Jun 25;321[24]:2428-37); and STOPDAPT-2 (JAMA. 2019 Jun 25;321[24]:2414-27) included patients undergoing PCI either for stable coronary disease or for ST-elevation MI, but not for non-ST-elevation ACS.

Dr. O’Donoghue, a cardiologist at Brigham and Women’s Hospital and Harvard Medical School, Boston, conducted a meta-analysis including the TWILIGHT ACS trial and the other three studies. In a total population of 29,205 patients, a strategy of dropping aspirin while continuing a P2Y₁₂ inhibitor after 1-3 months of DAPT was associated with a 40% relative risk reduction in major bleeding events when compared with continued DAPT, with no indication of an increased risk of major adverse cardiovascular events. When she looked specifically at the nearly 14,000 post-ACS patients in the studies, the same consistency with respect to outcomes held true: an overall 51% reduction in bleeding, and – if anything – a favorable trend involving an 11% reduction in the risk of major adverse cardiovascular events, although this difference didn’t reach statistical significance.

“I believe that discontinuation of aspirin markedly reduces bleeding when stopped 1-3 months post PCI for patients initially started on DAPT,” Dr. O’Donoghue declared. “The evidence to date does not indicate that stopping aspirin leads to any increase in the risk of major adverse cardiovascular events. And these findings now extend to patients with ACS, including those with high-risk clinical and angiographic features.”

The important remaining questions, she added, include the best-choice P2Y₁₂ inhibitor for early monotherapy post-PCI, whether the medication should be continued indefinitely past the 12-month mark, and whether aspirin might be safely discontinued even earlier than at 1-3 months.

“If you are thinking about establishing a clopidogrel monotherapy, you need to keep in mind that there exists significant interpatient variability in terms of pharmacodynamic response,” she noted, adding that platelet function testing or genotyping to identify clopidogrel resistance is worth considering in such patients.

The primary results of the full TWILIGHT study, which included 7,119 randomized patients, have been published (N Engl J Med. 2019 Sep 26. doi: 10.1056/NEJMoa1908419).

The TWILIGHT study was sponsored by AstraZeneca. Dr. Baber reported receiving honoraria from that company as well as Boston Scientific.

Dr. O’Donoghue reported receiving institutional research support from a handful of pharmaceutical companies.

[email protected]

SOURCE: Baber U. AHA late breaker.

PHILADELPHIA – Downshifting to ticagrelor monotherapy after just 3 months of dual antiplatelet therapy is a winning strategy in high-risk patients who’ve undergone PCI for non-ST-elevation acute coronary syndrome, Usman Baber, MD, reported at the American Heart Association scientific sessions.

Bruce Jancin/MDedge News

He presented a prespecified subgroup analysis of the previously reported TWILIGHT study that was restricted to the 4,614 participants with non-ST-elevation ACS who underwent PCI, completed 3 months of dual antiplatelet therapy (DAPT) with ticagrelor and aspirin, and were then randomized double-blind to an additional 12 months on the same regimen or to ticagrelor plus placebo.

The key finding: After a year on ticagrelor monotherapy, the risk of clinically significant or major bleeding was reduced by 53%, compared with the DAPT group, and with no increased risk of ischemic major adverse cardiovascular events, said Dr. Baber, a cardiologist at the Icahn School of Medicine at Mount Sinai, New York.

This secondary analysis of the TWILIGHT study was carried out because none of the several prior studies of short-term DAPT followed by an aspirin-free strategy after PCI was double-blind. Nor did any include patients with non-ST-elevation ACS, he explained.

The TWILIGHT substudy included 2,494 participants with unstable angina and 2,120 with non-ST-elevation MI. Roughly two-thirds had four or more high-risk clinical or angiographic features, such as diabetes, chronic kidney disease, multivessel CAD, or left main lesions.

The primary study endpoint at month 15 – the rate of Bleeding Academic Research Consortium (BARC) type 2, 3, or 5 bleeding events – was 7.6% with ticagrelor plus aspirin, compared with 3.6% with ticagrelor plus placebo, for a highly significant 53% relative risk reduction in favor of ticagrelor monotherapy. The key secondary endpoint, a composite of all-cause mortality, MI, or stroke, occurred in roughly 4.4% of patients in each study arm.

Of note, ticagrelor monotherapy after 3 months of DAPT was associated with a similar 50%-60% reduction in the risk of BARC 2, 3, or 5 bleeding regardless of whether patients had 1-3, 4 or 5, or 6-9 prespecified high-risk clinical and angiographic features. Nor was the impact of ticagrelor monotherapy on ischemic events impacted by risk factor burden.

Discussant Michelle L. O’Donoghue, MD, observed that while the current practice of most cardiologists in patients undergoing stenting in the setting of ACS is 12 months of DAPT followed by discontinuation of the P2Y₁₂ inhibitor and indefinite continuation of aspirin, mounting evidence suggests there’s a better approach.

Bruce Jancin/MDedge News

Indeed, the new TWILIGHT findings in patients with non-ST-elevation ACS dovetail nicely with the results of three other recent studies of discontinuing aspirin after 1-3 months versus continuing DAPT with ticagrelor or another P2Y₁₂ inhibitor plus aspirin. These studies, GLOBAL LEADERS (Lancet. 2018 Sep 15;392[10151]:940-9); SMART CHOICE (JAMA. 2019 Jun 25;321[24]:2428-37); and STOPDAPT-2 (JAMA. 2019 Jun 25;321[24]:2414-27) included patients undergoing PCI either for stable coronary disease or for ST-elevation MI, but not for non-ST-elevation ACS.

Dr. O’Donoghue, a cardiologist at Brigham and Women’s Hospital and Harvard Medical School, Boston, conducted a meta-analysis including the TWILIGHT ACS trial and the other three studies. In a total population of 29,205 patients, a strategy of dropping aspirin while continuing a P2Y₁₂ inhibitor after 1-3 months of DAPT was associated with a 40% relative risk reduction in major bleeding events when compared with continued DAPT, with no indication of an increased risk of major adverse cardiovascular events. When she looked specifically at the nearly 14,000 post-ACS patients in the studies, the same consistency with respect to outcomes held true: an overall 51% reduction in bleeding, and – if anything – a favorable trend involving an 11% reduction in the risk of major adverse cardiovascular events, although this difference didn’t reach statistical significance.

“I believe that discontinuation of aspirin markedly reduces bleeding when stopped 1-3 months post PCI for patients initially started on DAPT,” Dr. O’Donoghue declared. “The evidence to date does not indicate that stopping aspirin leads to any increase in the risk of major adverse cardiovascular events. And these findings now extend to patients with ACS, including those with high-risk clinical and angiographic features.”

The important remaining questions, she added, include the best-choice P2Y₁₂ inhibitor for early monotherapy post-PCI, whether the medication should be continued indefinitely past the 12-month mark, and whether aspirin might be safely discontinued even earlier than at 1-3 months.

“If you are thinking about establishing a clopidogrel monotherapy, you need to keep in mind that there exists significant interpatient variability in terms of pharmacodynamic response,” she noted, adding that platelet function testing or genotyping to identify clopidogrel resistance is worth considering in such patients.

The primary results of the full TWILIGHT study, which included 7,119 randomized patients, have been published (N Engl J Med. 2019 Sep 26. doi: 10.1056/NEJMoa1908419).

The TWILIGHT study was sponsored by AstraZeneca. Dr. Baber reported receiving honoraria from that company as well as Boston Scientific.

Dr. O’Donoghue reported receiving institutional research support from a handful of pharmaceutical companies.

[email protected]

SOURCE: Baber U. AHA late breaker.

PHILADELPHIA – Downshifting to ticagrelor monotherapy after just 3 months of dual antiplatelet therapy is a winning strategy in high-risk patients who’ve undergone PCI for non-ST-elevation acute coronary syndrome, Usman Baber, MD, reported at the American Heart Association scientific sessions.

Bruce Jancin/MDedge News

He presented a prespecified subgroup analysis of the previously reported TWILIGHT study that was restricted to the 4,614 participants with non-ST-elevation ACS who underwent PCI, completed 3 months of dual antiplatelet therapy (DAPT) with ticagrelor and aspirin, and were then randomized double-blind to an additional 12 months on the same regimen or to ticagrelor plus placebo.

The key finding: After a year on ticagrelor monotherapy, the risk of clinically significant or major bleeding was reduced by 53%, compared with the DAPT group, and with no increased risk of ischemic major adverse cardiovascular events, said Dr. Baber, a cardiologist at the Icahn School of Medicine at Mount Sinai, New York.

This secondary analysis of the TWILIGHT study was carried out because none of the several prior studies of short-term DAPT followed by an aspirin-free strategy after PCI was double-blind. Nor did any include patients with non-ST-elevation ACS, he explained.

The TWILIGHT substudy included 2,494 participants with unstable angina and 2,120 with non-ST-elevation MI. Roughly two-thirds had four or more high-risk clinical or angiographic features, such as diabetes, chronic kidney disease, multivessel CAD, or left main lesions.

The primary study endpoint at month 15 – the rate of Bleeding Academic Research Consortium (BARC) type 2, 3, or 5 bleeding events – was 7.6% with ticagrelor plus aspirin, compared with 3.6% with ticagrelor plus placebo, for a highly significant 53% relative risk reduction in favor of ticagrelor monotherapy. The key secondary endpoint, a composite of all-cause mortality, MI, or stroke, occurred in roughly 4.4% of patients in each study arm.

Of note, ticagrelor monotherapy after 3 months of DAPT was associated with a similar 50%-60% reduction in the risk of BARC 2, 3, or 5 bleeding regardless of whether patients had 1-3, 4 or 5, or 6-9 prespecified high-risk clinical and angiographic features. Nor was the impact of ticagrelor monotherapy on ischemic events impacted by risk factor burden.

Discussant Michelle L. O’Donoghue, MD, observed that while the current practice of most cardiologists in patients undergoing stenting in the setting of ACS is 12 months of DAPT followed by discontinuation of the P2Y₁₂ inhibitor and indefinite continuation of aspirin, mounting evidence suggests there’s a better approach.

Bruce Jancin/MDedge News

Indeed, the new TWILIGHT findings in patients with non-ST-elevation ACS dovetail nicely with the results of three other recent studies of discontinuing aspirin after 1-3 months versus continuing DAPT with ticagrelor or another P2Y₁₂ inhibitor plus aspirin. These studies, GLOBAL LEADERS (Lancet. 2018 Sep 15;392[10151]:940-9); SMART CHOICE (JAMA. 2019 Jun 25;321[24]:2428-37); and STOPDAPT-2 (JAMA. 2019 Jun 25;321[24]:2414-27) included patients undergoing PCI either for stable coronary disease or for ST-elevation MI, but not for non-ST-elevation ACS.

Dr. O’Donoghue, a cardiologist at Brigham and Women’s Hospital and Harvard Medical School, Boston, conducted a meta-analysis including the TWILIGHT ACS trial and the other three studies. In a total population of 29,205 patients, a strategy of dropping aspirin while continuing a P2Y₁₂ inhibitor after 1-3 months of DAPT was associated with a 40% relative risk reduction in major bleeding events when compared with continued DAPT, with no indication of an increased risk of major adverse cardiovascular events. When she looked specifically at the nearly 14,000 post-ACS patients in the studies, the same consistency with respect to outcomes held true: an overall 51% reduction in bleeding, and – if anything – a favorable trend involving an 11% reduction in the risk of major adverse cardiovascular events, although this difference didn’t reach statistical significance.

“I believe that discontinuation of aspirin markedly reduces bleeding when stopped 1-3 months post PCI for patients initially started on DAPT,” Dr. O’Donoghue declared. “The evidence to date does not indicate that stopping aspirin leads to any increase in the risk of major adverse cardiovascular events. And these findings now extend to patients with ACS, including those with high-risk clinical and angiographic features.”

The important remaining questions, she added, include the best-choice P2Y₁₂ inhibitor for early monotherapy post-PCI, whether the medication should be continued indefinitely past the 12-month mark, and whether aspirin might be safely discontinued even earlier than at 1-3 months.

“If you are thinking about establishing a clopidogrel monotherapy, you need to keep in mind that there exists significant interpatient variability in terms of pharmacodynamic response,” she noted, adding that platelet function testing or genotyping to identify clopidogrel resistance is worth considering in such patients.

The primary results of the full TWILIGHT study, which included 7,119 randomized patients, have been published (N Engl J Med. 2019 Sep 26. doi: 10.1056/NEJMoa1908419).

The TWILIGHT study was sponsored by AstraZeneca. Dr. Baber reported receiving honoraria from that company as well as Boston Scientific.

Dr. O’Donoghue reported receiving institutional research support from a handful of pharmaceutical companies.

[email protected]

SOURCE: Baber U. AHA late breaker.

Allowing people aged 50-64 to buy into Medicare might result in higher premiums for people who purchase their health insurance on the individual market, a finding that runs counter to many people’s expectations, said the authors of a newly released report.

In the report, Christine Eibner, PhD, of the RAND Corporation and colleagues estimated that the premium for so-called bronze market plans might increase by 2%-10%, depending on the design of a Medicare buy-in program. (The bronze plans are ones with fewer benefits sold on exchanges created through the implementation of the Affordable Care Act of 2010 [ACA].)

A perception has been that younger adults have been in effect subsidizing the cost of older ones in the marketplace plans. Instead, it appears that younger adults who enroll in the individual market tend to be relatively unhealthy and thus expensive to cover.

“When older adults leave the market, insurers are left with a smaller pool of younger, less healthy, and relatively expensive people given their age, leading to higher premiums,” Dr. Eibner and colleagues said in the report.

This result was unexpected, as there has been discussion of using a Medicare buy-in to reduce the cost of premiums for others in the marketplace, Dr. Eibner and colleagues said. But this result is consistent with other recent findings, including research presented by the consulting firm Milliman at a Society of Actuaries meeting in June. The Blue Cross Blue Shield Association estimates that losing a large group of customers could raise premiums by about 10% for the remaining pool of insured people, the New York Times has reported.

A buy-in would be less expensive than most ACA plans and would not have the kinds of limits on spending used in private insurance. That might make it attractive to middle-aged Americans. Dr. Eibner and colleagues estimated the annual premium for a Medicare buy-in at $9,747 in 2022. For a 50-year-old, a bronze-level ACA plan would cost $9,208 and a gold-level one, $12,277. For a 60-year-old, the annual premium for a bronze-level plan might be $13,512 and $18,016 for a gold-level plan.

Total out-of-pocket health spending, including premiums, would fall, on average, by 16%-35% for those who moved from ACA-compliant individual market coverage to a buy-in. The lower spending reflects that buy-in enrollees would have access to Medicare payment rates, which are substantially lower than private rates, and lower administrative costs.

There may be growing interest in allowing people aged 50-64 to buy into Medicare if enthusiasm wanes for bids to create a giant national health program, Dr. Eibner said in an interview.

“If there is concern that Medicare for all is going too far, I think this option is something that could become more prominent,” she said.

Many Democratic lawmakers already are focused on a Medicare buy-in approach. Sen. Debbie Stabenow (D-Mich.) has 20 Democratic cosponsors for her bill, which would allow for a Medicare buy-in at age 50. Sen. Bernie Sanders (I-Vt.) has 14 Democratic cosponsors for the current version of his well-known “Medicare-for-all” bill. That’s two fewer than he had for the Medicare-for-all bill he offered in the 115th session of Congress (Jan. 3, 2017–Jan. 3, 2019).

Among the supporters of Sen. Stabenow’s bill are several 2020 presidential contenders: Sen. Cory Booker (D-N.J.), Sen. Amy Klobuchar (D-Minn.), and Sen. Kamala Harris (D-Calif). As of Saturday, Sen. Elizabeth Warren (D-Mass.) backed Sanders’ bill, but not Stabenow’s. But Sen. Warren also has spoken recently of a Medicare expansion for people at age 50 as a step on the path toward universal coverage. Former Vice President Joseph R. Biden and Mayor Pete Buttigieg of South Bend, Ind., have said they would like to offer Americans the option to buy into Medicare or a public plan.

The idea of lowering the Medicare age has been considered for many years by Democrats. It was seen as a way to help older Americans afford medical care before the enactment of the ACA. Before that law took effect, consumers were not guaranteed access to a health plan, causing many older Americans to go without coverage.

But Dr. Eibner and colleagues found that a Medicare buy-in would have little to no effect on total health insurance enrollment. A Medicare buy-in might increase enrollment by 400,000 to 1.6 million for those over age 50, while decreasing enrollment by 100,000 to 800,000 for those under age 50 because of rising premiums.

“It’s not doing a lot to get people covered,” Dr. Eibner said in the interview.

In the report, Dr. Eibner and colleagues estimated that between 2.8 million and 7.0 million people would choose to enroll, depending on the approach used to design a Medicare buy-in. They considered numerous potential options for the design of a Medicare expansion, including various levels of federal subsidy for people using the buy-in. Dr. Eibner and colleagues also considered whether insurers would respond by trying to selectively market to healthier individuals, increasing their chance of enrolling.

The envisioned Medicare buy-in would have no effect on the Medicare Trust Fund, which pools money available through previously collected dedicated taxes, Dr. Eibner and colleagues said. In creating their model, they drew upon data from the Survey of Income and Program Participation, the Medical Expenditure Panel Survey, and the Kaiser Family Foundation and Health Research and Educational Trust Employer Health Benefits Survey.

Dr. Eibner and colleagues noted “several important limitations” for their work. It does not look at how the buy-in might affect clinicians and hospitals. Lower Medicare payment rates might cause some physicians to turn away patients covered by a Medicare buy-in.

“On the other hand, even if some providers decided not to participate in the buy-in, the buy-in might offer enrollees a broader network than what is available on the individual market,” Dr. Eibner and colleagues wrote. “Furthermore, it is not clear that providers would be legally allowed to opt out of the buy-in while still accepting payment for current Medicare beneficiaries.”

The Rand report was developed with the support of funding by the AARP.

SOURCE: Eibner C et al. RAND Corporation. Research Report. 2019. doi: 10.7249/RR4246.

Allowing people aged 50-64 to buy into Medicare might result in higher premiums for people who purchase their health insurance on the individual market, a finding that runs counter to many people’s expectations, said the authors of a newly released report.

In the report, Christine Eibner, PhD, of the RAND Corporation and colleagues estimated that the premium for so-called bronze market plans might increase by 2%-10%, depending on the design of a Medicare buy-in program. (The bronze plans are ones with fewer benefits sold on exchanges created through the implementation of the Affordable Care Act of 2010 [ACA].)

A perception has been that younger adults have been in effect subsidizing the cost of older ones in the marketplace plans. Instead, it appears that younger adults who enroll in the individual market tend to be relatively unhealthy and thus expensive to cover.

“When older adults leave the market, insurers are left with a smaller pool of younger, less healthy, and relatively expensive people given their age, leading to higher premiums,” Dr. Eibner and colleagues said in the report.

This result was unexpected, as there has been discussion of using a Medicare buy-in to reduce the cost of premiums for others in the marketplace, Dr. Eibner and colleagues said. But this result is consistent with other recent findings, including research presented by the consulting firm Milliman at a Society of Actuaries meeting in June. The Blue Cross Blue Shield Association estimates that losing a large group of customers could raise premiums by about 10% for the remaining pool of insured people, the New York Times has reported.

A buy-in would be less expensive than most ACA plans and would not have the kinds of limits on spending used in private insurance. That might make it attractive to middle-aged Americans. Dr. Eibner and colleagues estimated the annual premium for a Medicare buy-in at $9,747 in 2022. For a 50-year-old, a bronze-level ACA plan would cost $9,208 and a gold-level one, $12,277. For a 60-year-old, the annual premium for a bronze-level plan might be $13,512 and $18,016 for a gold-level plan.

Total out-of-pocket health spending, including premiums, would fall, on average, by 16%-35% for those who moved from ACA-compliant individual market coverage to a buy-in. The lower spending reflects that buy-in enrollees would have access to Medicare payment rates, which are substantially lower than private rates, and lower administrative costs.

There may be growing interest in allowing people aged 50-64 to buy into Medicare if enthusiasm wanes for bids to create a giant national health program, Dr. Eibner said in an interview.

“If there is concern that Medicare for all is going too far, I think this option is something that could become more prominent,” she said.

Many Democratic lawmakers already are focused on a Medicare buy-in approach. Sen. Debbie Stabenow (D-Mich.) has 20 Democratic cosponsors for her bill, which would allow for a Medicare buy-in at age 50. Sen. Bernie Sanders (I-Vt.) has 14 Democratic cosponsors for the current version of his well-known “Medicare-for-all” bill. That’s two fewer than he had for the Medicare-for-all bill he offered in the 115th session of Congress (Jan. 3, 2017–Jan. 3, 2019).

Among the supporters of Sen. Stabenow’s bill are several 2020 presidential contenders: Sen. Cory Booker (D-N.J.), Sen. Amy Klobuchar (D-Minn.), and Sen. Kamala Harris (D-Calif). As of Saturday, Sen. Elizabeth Warren (D-Mass.) backed Sanders’ bill, but not Stabenow’s. But Sen. Warren also has spoken recently of a Medicare expansion for people at age 50 as a step on the path toward universal coverage. Former Vice President Joseph R. Biden and Mayor Pete Buttigieg of South Bend, Ind., have said they would like to offer Americans the option to buy into Medicare or a public plan.

The idea of lowering the Medicare age has been considered for many years by Democrats. It was seen as a way to help older Americans afford medical care before the enactment of the ACA. Before that law took effect, consumers were not guaranteed access to a health plan, causing many older Americans to go without coverage.

But Dr. Eibner and colleagues found that a Medicare buy-in would have little to no effect on total health insurance enrollment. A Medicare buy-in might increase enrollment by 400,000 to 1.6 million for those over age 50, while decreasing enrollment by 100,000 to 800,000 for those under age 50 because of rising premiums.

“It’s not doing a lot to get people covered,” Dr. Eibner said in the interview.

In the report, Dr. Eibner and colleagues estimated that between 2.8 million and 7.0 million people would choose to enroll, depending on the approach used to design a Medicare buy-in. They considered numerous potential options for the design of a Medicare expansion, including various levels of federal subsidy for people using the buy-in. Dr. Eibner and colleagues also considered whether insurers would respond by trying to selectively market to healthier individuals, increasing their chance of enrolling.

The envisioned Medicare buy-in would have no effect on the Medicare Trust Fund, which pools money available through previously collected dedicated taxes, Dr. Eibner and colleagues said. In creating their model, they drew upon data from the Survey of Income and Program Participation, the Medical Expenditure Panel Survey, and the Kaiser Family Foundation and Health Research and Educational Trust Employer Health Benefits Survey.

Dr. Eibner and colleagues noted “several important limitations” for their work. It does not look at how the buy-in might affect clinicians and hospitals. Lower Medicare payment rates might cause some physicians to turn away patients covered by a Medicare buy-in.

“On the other hand, even if some providers decided not to participate in the buy-in, the buy-in might offer enrollees a broader network than what is available on the individual market,” Dr. Eibner and colleagues wrote. “Furthermore, it is not clear that providers would be legally allowed to opt out of the buy-in while still accepting payment for current Medicare beneficiaries.”

The Rand report was developed with the support of funding by the AARP.

SOURCE: Eibner C et al. RAND Corporation. Research Report. 2019. doi: 10.7249/RR4246.

Allowing people aged 50-64 to buy into Medicare might result in higher premiums for people who purchase their health insurance on the individual market, a finding that runs counter to many people’s expectations, said the authors of a newly released report.

In the report, Christine Eibner, PhD, of the RAND Corporation and colleagues estimated that the premium for so-called bronze market plans might increase by 2%-10%, depending on the design of a Medicare buy-in program. (The bronze plans are ones with fewer benefits sold on exchanges created through the implementation of the Affordable Care Act of 2010 [ACA].)

A perception has been that younger adults have been in effect subsidizing the cost of older ones in the marketplace plans. Instead, it appears that younger adults who enroll in the individual market tend to be relatively unhealthy and thus expensive to cover.

“When older adults leave the market, insurers are left with a smaller pool of younger, less healthy, and relatively expensive people given their age, leading to higher premiums,” Dr. Eibner and colleagues said in the report.

This result was unexpected, as there has been discussion of using a Medicare buy-in to reduce the cost of premiums for others in the marketplace, Dr. Eibner and colleagues said. But this result is consistent with other recent findings, including research presented by the consulting firm Milliman at a Society of Actuaries meeting in June. The Blue Cross Blue Shield Association estimates that losing a large group of customers could raise premiums by about 10% for the remaining pool of insured people, the New York Times has reported.

A buy-in would be less expensive than most ACA plans and would not have the kinds of limits on spending used in private insurance. That might make it attractive to middle-aged Americans. Dr. Eibner and colleagues estimated the annual premium for a Medicare buy-in at $9,747 in 2022. For a 50-year-old, a bronze-level ACA plan would cost $9,208 and a gold-level one, $12,277. For a 60-year-old, the annual premium for a bronze-level plan might be $13,512 and $18,016 for a gold-level plan.

Total out-of-pocket health spending, including premiums, would fall, on average, by 16%-35% for those who moved from ACA-compliant individual market coverage to a buy-in. The lower spending reflects that buy-in enrollees would have access to Medicare payment rates, which are substantially lower than private rates, and lower administrative costs.

There may be growing interest in allowing people aged 50-64 to buy into Medicare if enthusiasm wanes for bids to create a giant national health program, Dr. Eibner said in an interview.

“If there is concern that Medicare for all is going too far, I think this option is something that could become more prominent,” she said.

Many Democratic lawmakers already are focused on a Medicare buy-in approach. Sen. Debbie Stabenow (D-Mich.) has 20 Democratic cosponsors for her bill, which would allow for a Medicare buy-in at age 50. Sen. Bernie Sanders (I-Vt.) has 14 Democratic cosponsors for the current version of his well-known “Medicare-for-all” bill. That’s two fewer than he had for the Medicare-for-all bill he offered in the 115th session of Congress (Jan. 3, 2017–Jan. 3, 2019).

Among the supporters of Sen. Stabenow’s bill are several 2020 presidential contenders: Sen. Cory Booker (D-N.J.), Sen. Amy Klobuchar (D-Minn.), and Sen. Kamala Harris (D-Calif). As of Saturday, Sen. Elizabeth Warren (D-Mass.) backed Sanders’ bill, but not Stabenow’s. But Sen. Warren also has spoken recently of a Medicare expansion for people at age 50 as a step on the path toward universal coverage. Former Vice President Joseph R. Biden and Mayor Pete Buttigieg of South Bend, Ind., have said they would like to offer Americans the option to buy into Medicare or a public plan.

The idea of lowering the Medicare age has been considered for many years by Democrats. It was seen as a way to help older Americans afford medical care before the enactment of the ACA. Before that law took effect, consumers were not guaranteed access to a health plan, causing many older Americans to go without coverage.

But Dr. Eibner and colleagues found that a Medicare buy-in would have little to no effect on total health insurance enrollment. A Medicare buy-in might increase enrollment by 400,000 to 1.6 million for those over age 50, while decreasing enrollment by 100,000 to 800,000 for those under age 50 because of rising premiums.

“It’s not doing a lot to get people covered,” Dr. Eibner said in the interview.

In the report, Dr. Eibner and colleagues estimated that between 2.8 million and 7.0 million people would choose to enroll, depending on the approach used to design a Medicare buy-in. They considered numerous potential options for the design of a Medicare expansion, including various levels of federal subsidy for people using the buy-in. Dr. Eibner and colleagues also considered whether insurers would respond by trying to selectively market to healthier individuals, increasing their chance of enrolling.

The envisioned Medicare buy-in would have no effect on the Medicare Trust Fund, which pools money available through previously collected dedicated taxes, Dr. Eibner and colleagues said. In creating their model, they drew upon data from the Survey of Income and Program Participation, the Medical Expenditure Panel Survey, and the Kaiser Family Foundation and Health Research and Educational Trust Employer Health Benefits Survey.

Dr. Eibner and colleagues noted “several important limitations” for their work. It does not look at how the buy-in might affect clinicians and hospitals. Lower Medicare payment rates might cause some physicians to turn away patients covered by a Medicare buy-in.

“On the other hand, even if some providers decided not to participate in the buy-in, the buy-in might offer enrollees a broader network than what is available on the individual market,” Dr. Eibner and colleagues wrote. “Furthermore, it is not clear that providers would be legally allowed to opt out of the buy-in while still accepting payment for current Medicare beneficiaries.”

The Rand report was developed with the support of funding by the AARP.

SOURCE: Eibner C et al. RAND Corporation. Research Report. 2019. doi: 10.7249/RR4246.