Life expectancy increased for adults with inflammatory bowel disease (IBD) over recent decades, but still remained lower than life expectancy for individuals without IBD, according to data from a retrospective cohort study using Canadian health databases.

“Management of IBD has improved through increased access to specialist care, biologic therapies, and a treat-to-target approach,” wrote M. Ellen Kuenzig, PhD, of the Children’s Hospital of Eastern Ontario and colleagues. However, “Most studies evaluating mortality were conducted before the biologic era, and none evaluated life expectancy or health-adjusted life expectancy,” they said.

In a study published in the Canadian Medical Association Journal, the researchers used Canadian databases to identify a study population of 32,818 people with IBD matched to 163,284 people without IBD in 1996 that increased to 83,672 people with IBD matched to 418,360 people without IBD in 2011.

Life expectancy increases, but with caveats

Overall, life expectancy for IBD patients increased from 75.5 years to 78.4 years for women and from 72.2 years to 75.5 years for men between 1996 and 2011.

However, health-adjusted life expectancy, defined as the number of years a person is expected to live in full health, decreased by 3.9 years for men with IBD between 1996 and 2008, but did not change significantly for women with IBD, although the gap in health-adjusted life expectancy increased between women with IBD and women without IBD.

Both life expectancy and health-adjusted life expectancy remained consistently lower for individuals with IBD compared to those without IBD. Differences in life expectancy for women with and without IBD ranged from 6.6 to 8.1 years and from 5.0 to 6.1 years for men with and without IBD, depending on the year.

Differences in health-adjusted life expectancy ranged from 9.5 to 13.5 years in women with and without IBD, and from 2.6 years to 6.7 years in men with and without IBD depending on the year, the researchers said.

In addition, the researchers used the pain-attributed utility of the Health Utility Index (HUI) to calculate health-adjusted life expectancy with the effect of pain on health status. The health-adjusted life expectancy using HUI for pain was stable in women with IBD, but increased over time for women without IBD. This pattern was similar for individuals with Crohn’s disease but stable for women with and without ulcerative colitis. In men, health-adjusted life expectancy using the pain-attributed utility of the HUI was stable for those with IBD, decreased in those with Crohn’s disease, and increased among those with ulcerative colitis.

The study findings were limited by several factors including potential confounding by disease phenotype and severity, as well as lack of data on medication use for individuals younger than 65 years and limited data on confounders including smoking, ethnicity, and environmental factors, the researchers said.

In addition, “mortality may increase with disease duration, which would violate the assumption that age- and sex-specific mortality rates remain constant over a person’s lifetime that is required when using lifetables,” they said.
 

Future research should pursue effect of pain

The results support the persistence of a gap in life expectancy between individuals with and without IBD and suggest the need for improving pain management in IBD patients, given the contribution of pain to reduced health-adjusted life expectancy, they concluded. Additional research is needed to determine the effect of comorbid conditions and medication use on the difference in life expectancy for those with and without IBD, they added.

The study was supported by the Institute for Clinical Evaluative Services (Canada). Lead author Dr. Kuenzig received a Post-Doctoral Fellowship Award from the Canadian Institutes of Health Research, Canadian Association of Gastroenterology, and Crohn’s and Colitis Canada. The researchers had no financial conflicts to disclose.

SOURCE: Kuenzig ME et al. CMAJ. 2020 Nov 9. doi: 10.1503/cmaj.190976.

Life expectancy increased for adults with inflammatory bowel disease (IBD) over recent decades, but still remained lower than life expectancy for individuals without IBD, according to data from a retrospective cohort study using Canadian health databases.

“Management of IBD has improved through increased access to specialist care, biologic therapies, and a treat-to-target approach,” wrote M. Ellen Kuenzig, PhD, of the Children’s Hospital of Eastern Ontario and colleagues. However, “Most studies evaluating mortality were conducted before the biologic era, and none evaluated life expectancy or health-adjusted life expectancy,” they said.

In a study published in the Canadian Medical Association Journal, the researchers used Canadian databases to identify a study population of 32,818 people with IBD matched to 163,284 people without IBD in 1996 that increased to 83,672 people with IBD matched to 418,360 people without IBD in 2011.

Life expectancy increases, but with caveats

Overall, life expectancy for IBD patients increased from 75.5 years to 78.4 years for women and from 72.2 years to 75.5 years for men between 1996 and 2011.

However, health-adjusted life expectancy, defined as the number of years a person is expected to live in full health, decreased by 3.9 years for men with IBD between 1996 and 2008, but did not change significantly for women with IBD, although the gap in health-adjusted life expectancy increased between women with IBD and women without IBD.

Both life expectancy and health-adjusted life expectancy remained consistently lower for individuals with IBD compared to those without IBD. Differences in life expectancy for women with and without IBD ranged from 6.6 to 8.1 years and from 5.0 to 6.1 years for men with and without IBD, depending on the year.

Differences in health-adjusted life expectancy ranged from 9.5 to 13.5 years in women with and without IBD, and from 2.6 years to 6.7 years in men with and without IBD depending on the year, the researchers said.

In addition, the researchers used the pain-attributed utility of the Health Utility Index (HUI) to calculate health-adjusted life expectancy with the effect of pain on health status. The health-adjusted life expectancy using HUI for pain was stable in women with IBD, but increased over time for women without IBD. This pattern was similar for individuals with Crohn’s disease but stable for women with and without ulcerative colitis. In men, health-adjusted life expectancy using the pain-attributed utility of the HUI was stable for those with IBD, decreased in those with Crohn’s disease, and increased among those with ulcerative colitis.

The study findings were limited by several factors including potential confounding by disease phenotype and severity, as well as lack of data on medication use for individuals younger than 65 years and limited data on confounders including smoking, ethnicity, and environmental factors, the researchers said.

In addition, “mortality may increase with disease duration, which would violate the assumption that age- and sex-specific mortality rates remain constant over a person’s lifetime that is required when using lifetables,” they said.
 

Future research should pursue effect of pain

The results support the persistence of a gap in life expectancy between individuals with and without IBD and suggest the need for improving pain management in IBD patients, given the contribution of pain to reduced health-adjusted life expectancy, they concluded. Additional research is needed to determine the effect of comorbid conditions and medication use on the difference in life expectancy for those with and without IBD, they added.

The study was supported by the Institute for Clinical Evaluative Services (Canada). Lead author Dr. Kuenzig received a Post-Doctoral Fellowship Award from the Canadian Institutes of Health Research, Canadian Association of Gastroenterology, and Crohn’s and Colitis Canada. The researchers had no financial conflicts to disclose.

SOURCE: Kuenzig ME et al. CMAJ. 2020 Nov 9. doi: 10.1503/cmaj.190976.

Life expectancy increased for adults with inflammatory bowel disease (IBD) over recent decades, but still remained lower than life expectancy for individuals without IBD, according to data from a retrospective cohort study using Canadian health databases.

“Management of IBD has improved through increased access to specialist care, biologic therapies, and a treat-to-target approach,” wrote M. Ellen Kuenzig, PhD, of the Children’s Hospital of Eastern Ontario and colleagues. However, “Most studies evaluating mortality were conducted before the biologic era, and none evaluated life expectancy or health-adjusted life expectancy,” they said.

In a study published in the Canadian Medical Association Journal, the researchers used Canadian databases to identify a study population of 32,818 people with IBD matched to 163,284 people without IBD in 1996 that increased to 83,672 people with IBD matched to 418,360 people without IBD in 2011.

Life expectancy increases, but with caveats

Overall, life expectancy for IBD patients increased from 75.5 years to 78.4 years for women and from 72.2 years to 75.5 years for men between 1996 and 2011.

However, health-adjusted life expectancy, defined as the number of years a person is expected to live in full health, decreased by 3.9 years for men with IBD between 1996 and 2008, but did not change significantly for women with IBD, although the gap in health-adjusted life expectancy increased between women with IBD and women without IBD.

Both life expectancy and health-adjusted life expectancy remained consistently lower for individuals with IBD compared to those without IBD. Differences in life expectancy for women with and without IBD ranged from 6.6 to 8.1 years and from 5.0 to 6.1 years for men with and without IBD, depending on the year.

Differences in health-adjusted life expectancy ranged from 9.5 to 13.5 years in women with and without IBD, and from 2.6 years to 6.7 years in men with and without IBD depending on the year, the researchers said.

In addition, the researchers used the pain-attributed utility of the Health Utility Index (HUI) to calculate health-adjusted life expectancy with the effect of pain on health status. The health-adjusted life expectancy using HUI for pain was stable in women with IBD, but increased over time for women without IBD. This pattern was similar for individuals with Crohn’s disease but stable for women with and without ulcerative colitis. In men, health-adjusted life expectancy using the pain-attributed utility of the HUI was stable for those with IBD, decreased in those with Crohn’s disease, and increased among those with ulcerative colitis.

The study findings were limited by several factors including potential confounding by disease phenotype and severity, as well as lack of data on medication use for individuals younger than 65 years and limited data on confounders including smoking, ethnicity, and environmental factors, the researchers said.

In addition, “mortality may increase with disease duration, which would violate the assumption that age- and sex-specific mortality rates remain constant over a person’s lifetime that is required when using lifetables,” they said.
 

Future research should pursue effect of pain

The results support the persistence of a gap in life expectancy between individuals with and without IBD and suggest the need for improving pain management in IBD patients, given the contribution of pain to reduced health-adjusted life expectancy, they concluded. Additional research is needed to determine the effect of comorbid conditions and medication use on the difference in life expectancy for those with and without IBD, they added.

The study was supported by the Institute for Clinical Evaluative Services (Canada). Lead author Dr. Kuenzig received a Post-Doctoral Fellowship Award from the Canadian Institutes of Health Research, Canadian Association of Gastroenterology, and Crohn’s and Colitis Canada. The researchers had no financial conflicts to disclose.

SOURCE: Kuenzig ME et al. CMAJ. 2020 Nov 9. doi: 10.1503/cmaj.190976.

Cervical cancer screening is a routine procedure, but in rare instances, there can be medical complications. A new study finds that, compared with women who have normal results, women who are diagnosed with an invasive malignancy have an increased risk for iatrogenic injuries.

Researchers in Sweden analyzed data on more than 3 million women who had undergone cervical cancer screening. The team found that 42 iatrogenic injuries that required at least 2 days of hospitalization occurred during the diagnostic work-up of women who had an abnormal screening test.

“Although cervical cancer screening is one of the most successful cancer prevention programs ... our research indicates that women with invasive cervical cancer experienced medical complications and psychological stress during their diagnostic work-up, although at a very low level,” commented corresponding author Qing Shen, PhD, from the department of medical epidemiology and biostatistics at the Karolinska Institute in Stockholm, Sweden.

The study was published in Cancer Epidemiology, Biomarkers & Prevention.

“Injuries can occur with diagnostic evaluation for cervical cancer,” commented Kecia Gaither, MD, MPH, FACOG, director of perinatal services at Lincoln Medical and Mental Health Center, New York City Health and Hospitals System, who was not involved in the study.

“Given the fact that neovascularization occurs with cancers, a large biopsy in such a circumstance could lead to a hematoma or excessive blood loss. It rarely occurs but most certainly is possible,” said Dr. Gaither.

Also weighing in with comments, Cathy Popadiuk, MD, FRCS, an associate professor of medicine in the department of obstetrics and gynecology at Memorial University of Newfoundland, St. John’s, said the findings are reflective of the real-world and North American experience.

“There are indeed rare bad things that can happen during diagnostic work-up of abnormal pap smears, and usually this is with associated other disease, such as actual cancer or fibroids that can also bleed and may be in the cervix, etc.,” she told this news organization. “And definitely, when there is undetected cancer, this can bleed, requiring transfusion and hospital admission.”

Dr. Popadiuk pointed out that Sweden may be more liberal in admitting patients to hospital, whereas in North America, “we are trying to move away from inpatient care.” She added, “When you are getting these relatively minor procedures, you don’t expect something bad to happen in the clinic.”

Women may become anxious, and admission is the easiest way to arrange for care such as transfusions or observation for more bleeding, she noted. In addition, vaginal packing may be needed to control hemorrhage, and “with vaginal packing, women are unable to void and need a Foley catheter, and that, again, cannot be managed at home easily,” she explained. “After bleeding settles, the vaginal pack is removed, often the next day.” This may be why some women are admitted to hospital.
 

Increased risk of injury

In a previous study, Dr. Shen and colleagues found there was an increased risk for injuries during the period before and after a diagnosis of any cancer (BMJ. 2016;354:i4218). Those findings suggested the interval between first suspicion of cancer and diagnosis or initiation of treatment might be a high-risk time for injuries in cancer care.

In this latest study, they assessed whether there was a similar increase in injury risk among patients screened for cervical cancer. Using the Swedish Total Population Register, they identified 3,016,307 women who had undergone cervical screening during the period 2001-2012.

The final analysis included 1,853,510 women whose pap smear results were normal; 22,435 women who were diagnosed with cervical intraepithelial neoplasia (CIN); 20,692 women with CIN2; 36,542 women with CIN3 or adenocarcinoma in situ (AIS); and 5,189 women with invasive cervical cancer.

The team found that, among women who had an abnormal screening test, 42 iatrogenic injuries occurred that required at least 2 days of hospital admission. The highest risk was among women diagnosed with invasive cancer. The risk was also increased among women diagnosed with CIN3/AIS, but not among women with lower grades of CIN.

The most common types of iatrogenic injuries were hemorrhage or hematoma and infections. Among all groups of women, the incidence rate of injuries that were caused by medical procedures and care was greater than that of injuries caused by drugs or biological substances.

A total of 91 noniatrogenic injuries that required at least 1 day of hospitalization were identified. The risk was increased among women with invasive cervical cancer but not for women with other cervical abnormalities. The most common type of noniatrogenic injury was unintentional injuries.

The study was sponsored by the Swedish Cancer Society and the Swedish Research Council for Health, Working Life and Welfare. One author received a Karolinska Institute Senior Researcher Award and a Strategic Research Area in Epidemiology Award, and one author received a grant from the China Scholarship Council. Dr. Shen has disclosed no relevant financial relationships. Dr. Popadiuk has received personal fees and nonfinancial support as a member of the OncoSim Initiative from the Canadian Partnership Against Cancer.
 

A version of this article originally appeared on Medscape.com.

Cervical cancer screening is a routine procedure, but in rare instances, there can be medical complications. A new study finds that, compared with women who have normal results, women who are diagnosed with an invasive malignancy have an increased risk for iatrogenic injuries.

Researchers in Sweden analyzed data on more than 3 million women who had undergone cervical cancer screening. The team found that 42 iatrogenic injuries that required at least 2 days of hospitalization occurred during the diagnostic work-up of women who had an abnormal screening test.

“Although cervical cancer screening is one of the most successful cancer prevention programs ... our research indicates that women with invasive cervical cancer experienced medical complications and psychological stress during their diagnostic work-up, although at a very low level,” commented corresponding author Qing Shen, PhD, from the department of medical epidemiology and biostatistics at the Karolinska Institute in Stockholm, Sweden.

The study was published in Cancer Epidemiology, Biomarkers & Prevention.

“Injuries can occur with diagnostic evaluation for cervical cancer,” commented Kecia Gaither, MD, MPH, FACOG, director of perinatal services at Lincoln Medical and Mental Health Center, New York City Health and Hospitals System, who was not involved in the study.

“Given the fact that neovascularization occurs with cancers, a large biopsy in such a circumstance could lead to a hematoma or excessive blood loss. It rarely occurs but most certainly is possible,” said Dr. Gaither.

Also weighing in with comments, Cathy Popadiuk, MD, FRCS, an associate professor of medicine in the department of obstetrics and gynecology at Memorial University of Newfoundland, St. John’s, said the findings are reflective of the real-world and North American experience.

“There are indeed rare bad things that can happen during diagnostic work-up of abnormal pap smears, and usually this is with associated other disease, such as actual cancer or fibroids that can also bleed and may be in the cervix, etc.,” she told this news organization. “And definitely, when there is undetected cancer, this can bleed, requiring transfusion and hospital admission.”

Dr. Popadiuk pointed out that Sweden may be more liberal in admitting patients to hospital, whereas in North America, “we are trying to move away from inpatient care.” She added, “When you are getting these relatively minor procedures, you don’t expect something bad to happen in the clinic.”

Women may become anxious, and admission is the easiest way to arrange for care such as transfusions or observation for more bleeding, she noted. In addition, vaginal packing may be needed to control hemorrhage, and “with vaginal packing, women are unable to void and need a Foley catheter, and that, again, cannot be managed at home easily,” she explained. “After bleeding settles, the vaginal pack is removed, often the next day.” This may be why some women are admitted to hospital.
 

Increased risk of injury

In a previous study, Dr. Shen and colleagues found there was an increased risk for injuries during the period before and after a diagnosis of any cancer (BMJ. 2016;354:i4218). Those findings suggested the interval between first suspicion of cancer and diagnosis or initiation of treatment might be a high-risk time for injuries in cancer care.

In this latest study, they assessed whether there was a similar increase in injury risk among patients screened for cervical cancer. Using the Swedish Total Population Register, they identified 3,016,307 women who had undergone cervical screening during the period 2001-2012.

The final analysis included 1,853,510 women whose pap smear results were normal; 22,435 women who were diagnosed with cervical intraepithelial neoplasia (CIN); 20,692 women with CIN2; 36,542 women with CIN3 or adenocarcinoma in situ (AIS); and 5,189 women with invasive cervical cancer.

The team found that, among women who had an abnormal screening test, 42 iatrogenic injuries occurred that required at least 2 days of hospital admission. The highest risk was among women diagnosed with invasive cancer. The risk was also increased among women diagnosed with CIN3/AIS, but not among women with lower grades of CIN.

The most common types of iatrogenic injuries were hemorrhage or hematoma and infections. Among all groups of women, the incidence rate of injuries that were caused by medical procedures and care was greater than that of injuries caused by drugs or biological substances.

A total of 91 noniatrogenic injuries that required at least 1 day of hospitalization were identified. The risk was increased among women with invasive cervical cancer but not for women with other cervical abnormalities. The most common type of noniatrogenic injury was unintentional injuries.

The study was sponsored by the Swedish Cancer Society and the Swedish Research Council for Health, Working Life and Welfare. One author received a Karolinska Institute Senior Researcher Award and a Strategic Research Area in Epidemiology Award, and one author received a grant from the China Scholarship Council. Dr. Shen has disclosed no relevant financial relationships. Dr. Popadiuk has received personal fees and nonfinancial support as a member of the OncoSim Initiative from the Canadian Partnership Against Cancer.
 

A version of this article originally appeared on Medscape.com.

Cervical cancer screening is a routine procedure, but in rare instances, there can be medical complications. A new study finds that, compared with women who have normal results, women who are diagnosed with an invasive malignancy have an increased risk for iatrogenic injuries.

Researchers in Sweden analyzed data on more than 3 million women who had undergone cervical cancer screening. The team found that 42 iatrogenic injuries that required at least 2 days of hospitalization occurred during the diagnostic work-up of women who had an abnormal screening test.

“Although cervical cancer screening is one of the most successful cancer prevention programs ... our research indicates that women with invasive cervical cancer experienced medical complications and psychological stress during their diagnostic work-up, although at a very low level,” commented corresponding author Qing Shen, PhD, from the department of medical epidemiology and biostatistics at the Karolinska Institute in Stockholm, Sweden.

The study was published in Cancer Epidemiology, Biomarkers & Prevention.

“Injuries can occur with diagnostic evaluation for cervical cancer,” commented Kecia Gaither, MD, MPH, FACOG, director of perinatal services at Lincoln Medical and Mental Health Center, New York City Health and Hospitals System, who was not involved in the study.

“Given the fact that neovascularization occurs with cancers, a large biopsy in such a circumstance could lead to a hematoma or excessive blood loss. It rarely occurs but most certainly is possible,” said Dr. Gaither.

Also weighing in with comments, Cathy Popadiuk, MD, FRCS, an associate professor of medicine in the department of obstetrics and gynecology at Memorial University of Newfoundland, St. John’s, said the findings are reflective of the real-world and North American experience.

“There are indeed rare bad things that can happen during diagnostic work-up of abnormal pap smears, and usually this is with associated other disease, such as actual cancer or fibroids that can also bleed and may be in the cervix, etc.,” she told this news organization. “And definitely, when there is undetected cancer, this can bleed, requiring transfusion and hospital admission.”

Dr. Popadiuk pointed out that Sweden may be more liberal in admitting patients to hospital, whereas in North America, “we are trying to move away from inpatient care.” She added, “When you are getting these relatively minor procedures, you don’t expect something bad to happen in the clinic.”

Women may become anxious, and admission is the easiest way to arrange for care such as transfusions or observation for more bleeding, she noted. In addition, vaginal packing may be needed to control hemorrhage, and “with vaginal packing, women are unable to void and need a Foley catheter, and that, again, cannot be managed at home easily,” she explained. “After bleeding settles, the vaginal pack is removed, often the next day.” This may be why some women are admitted to hospital.
 

Increased risk of injury

In a previous study, Dr. Shen and colleagues found there was an increased risk for injuries during the period before and after a diagnosis of any cancer (BMJ. 2016;354:i4218). Those findings suggested the interval between first suspicion of cancer and diagnosis or initiation of treatment might be a high-risk time for injuries in cancer care.

In this latest study, they assessed whether there was a similar increase in injury risk among patients screened for cervical cancer. Using the Swedish Total Population Register, they identified 3,016,307 women who had undergone cervical screening during the period 2001-2012.

The final analysis included 1,853,510 women whose pap smear results were normal; 22,435 women who were diagnosed with cervical intraepithelial neoplasia (CIN); 20,692 women with CIN2; 36,542 women with CIN3 or adenocarcinoma in situ (AIS); and 5,189 women with invasive cervical cancer.

The team found that, among women who had an abnormal screening test, 42 iatrogenic injuries occurred that required at least 2 days of hospital admission. The highest risk was among women diagnosed with invasive cancer. The risk was also increased among women diagnosed with CIN3/AIS, but not among women with lower grades of CIN.

The most common types of iatrogenic injuries were hemorrhage or hematoma and infections. Among all groups of women, the incidence rate of injuries that were caused by medical procedures and care was greater than that of injuries caused by drugs or biological substances.

A total of 91 noniatrogenic injuries that required at least 1 day of hospitalization were identified. The risk was increased among women with invasive cervical cancer but not for women with other cervical abnormalities. The most common type of noniatrogenic injury was unintentional injuries.

The study was sponsored by the Swedish Cancer Society and the Swedish Research Council for Health, Working Life and Welfare. One author received a Karolinska Institute Senior Researcher Award and a Strategic Research Area in Epidemiology Award, and one author received a grant from the China Scholarship Council. Dr. Shen has disclosed no relevant financial relationships. Dr. Popadiuk has received personal fees and nonfinancial support as a member of the OncoSim Initiative from the Canadian Partnership Against Cancer.
 

A version of this article originally appeared on Medscape.com.

From the beginning, SHM has consciously and consistently taken a unique approach to its advocacy efforts with the federal government. The advocacy priorities of SHM most often concern issues that we feel have an impact on our patients and the broader delivery system, as opposed to a focus on issues that have direct financial benefit to our members.

This strategy has served SHM well. It has earned respect among policymakers and we have seen significant success for a young and relatively small medical society. The issues where we spend the bulk of our time and effort include advocating for issues like alternative payment models (APMs), which reward care quality as opposed to volume, as well as issues related to data integrity that APMs require. We have advocated strongly for changes to dysfunctional observation status rules, for workforce adequacy and sustainability, and for recognition of the importance of hospital medicine’s contribution to the redesign of our nations delivery system. And SHM will continue to advocate for many other issues identified as being important to hospital medicine and our patients.

This year, for the first time in the two decades that I have served on the SHM Public Policy Committee, Medicare has proposed changes that would create unprecedented financial hardship for hospital medicine groups. Each year, as a part of its advocacy agenda, SHM reviews and comments on proposed changes to the Medicare Physician Fee Schedule (PFS). Among other things, the PFS adjusts payment rates to physicians for specific services. Changes under the PFS are required to be budget neutral. In effect, budget neutrality means that whenever certain services receive an increased payment rate, CMS is required to offset these changes by making cuts to other services. This year, in an effort to correct the long-standing underfunding of primary care services, CMS has increased payment for many Evaluation and Management (E&M) codes associated with outpatient primary care services. However, due to budget neutrality requirements, many inpatient E&M care services will be receiving significant cuts.

The goal of increasing payment rates for primary care services is laudable, as many of these cognitive services have been long underfunded. However, the proposed payment increases will only apply to outpatient E&M codes and not their corresponding inpatient codes. While our outpatient Internal Medicine and Family Practice colleagues will benefit from these changes, inpatient providers, including hospitalists, stand to lose a significant amount revenue. SHM and the hospitalists we represent estimate that the proposed budget neutrality adjustment will lead to an approximate 8 percent decrease in Medicare Fee for Services (FFS) revenue. Hospitalists are among the specialties that will be most impacted from these proposed changes. If put into effect, these proposals will leave hospital medicine behind.

These changes have been proposed at a time when hospitalists, along with their colleagues in critical care and emergency medicine, have been caring for patients on the frontlines of the COVID-19 pandemic at great risk to themselves at their families. While hospitalists are working tirelessly to provide lifesaving care to COVID-positive patients throughout the country, hospitalist groups have struggled financially as a result of the pandemic. Inpatient volumes, and therefore care reimbursement, has dropped significantly. Many hospitalists have already reported pay reductions of 20% or more. Others have seen their shifts reduced, resulting in understaffing, which may compromise the quality of care. For many groups, a Medicare reimbursement cut of this magnitude add fuel to an already strained revenue stream and will not be financially sustainable.

SHM is, of course, fighting back. We are not asking CMS to completely abandon the increases in reimbursement for primary care outpatient codes, and we support properly valuing outpatient care services. However, we are asking CMS to find a solution that does not come at the expense of hospital medicine and the other specialties that care for acutely ill hospitalized patients, including patients with COVID-19. If a better solution requires holding off on the proposal for another year, CMS should do so. Furthermore, SHM is asking Congress to abandon the statutory requirement for budget neutrality in these extraordinary times as CMS and Congress work to find towards a solution that properly values both inpatient and outpatient care services.

To send a message to your representatives urging them to stop these payment cuts, please visit SHM’s Legislative Action Center at www.votervoice.net/SHM/campaigns/77226/respond. You can read our full comments on the Medicare Physician Fee Schedule Proposed Rule at www.hospitalmedicine.org/policy--advocacy/letters/2021-physician-fee-schedule-proposed-rule/.

From the beginning, SHM has consciously and consistently taken a unique approach to its advocacy efforts with the federal government. The advocacy priorities of SHM most often concern issues that we feel have an impact on our patients and the broader delivery system, as opposed to a focus on issues that have direct financial benefit to our members.

This strategy has served SHM well. It has earned respect among policymakers and we have seen significant success for a young and relatively small medical society. The issues where we spend the bulk of our time and effort include advocating for issues like alternative payment models (APMs), which reward care quality as opposed to volume, as well as issues related to data integrity that APMs require. We have advocated strongly for changes to dysfunctional observation status rules, for workforce adequacy and sustainability, and for recognition of the importance of hospital medicine’s contribution to the redesign of our nations delivery system. And SHM will continue to advocate for many other issues identified as being important to hospital medicine and our patients.

This year, for the first time in the two decades that I have served on the SHM Public Policy Committee, Medicare has proposed changes that would create unprecedented financial hardship for hospital medicine groups. Each year, as a part of its advocacy agenda, SHM reviews and comments on proposed changes to the Medicare Physician Fee Schedule (PFS). Among other things, the PFS adjusts payment rates to physicians for specific services. Changes under the PFS are required to be budget neutral. In effect, budget neutrality means that whenever certain services receive an increased payment rate, CMS is required to offset these changes by making cuts to other services. This year, in an effort to correct the long-standing underfunding of primary care services, CMS has increased payment for many Evaluation and Management (E&M) codes associated with outpatient primary care services. However, due to budget neutrality requirements, many inpatient E&M care services will be receiving significant cuts.

The goal of increasing payment rates for primary care services is laudable, as many of these cognitive services have been long underfunded. However, the proposed payment increases will only apply to outpatient E&M codes and not their corresponding inpatient codes. While our outpatient Internal Medicine and Family Practice colleagues will benefit from these changes, inpatient providers, including hospitalists, stand to lose a significant amount revenue. SHM and the hospitalists we represent estimate that the proposed budget neutrality adjustment will lead to an approximate 8 percent decrease in Medicare Fee for Services (FFS) revenue. Hospitalists are among the specialties that will be most impacted from these proposed changes. If put into effect, these proposals will leave hospital medicine behind.

These changes have been proposed at a time when hospitalists, along with their colleagues in critical care and emergency medicine, have been caring for patients on the frontlines of the COVID-19 pandemic at great risk to themselves at their families. While hospitalists are working tirelessly to provide lifesaving care to COVID-positive patients throughout the country, hospitalist groups have struggled financially as a result of the pandemic. Inpatient volumes, and therefore care reimbursement, has dropped significantly. Many hospitalists have already reported pay reductions of 20% or more. Others have seen their shifts reduced, resulting in understaffing, which may compromise the quality of care. For many groups, a Medicare reimbursement cut of this magnitude add fuel to an already strained revenue stream and will not be financially sustainable.

SHM is, of course, fighting back. We are not asking CMS to completely abandon the increases in reimbursement for primary care outpatient codes, and we support properly valuing outpatient care services. However, we are asking CMS to find a solution that does not come at the expense of hospital medicine and the other specialties that care for acutely ill hospitalized patients, including patients with COVID-19. If a better solution requires holding off on the proposal for another year, CMS should do so. Furthermore, SHM is asking Congress to abandon the statutory requirement for budget neutrality in these extraordinary times as CMS and Congress work to find towards a solution that properly values both inpatient and outpatient care services.

To send a message to your representatives urging them to stop these payment cuts, please visit SHM’s Legislative Action Center at www.votervoice.net/SHM/campaigns/77226/respond. You can read our full comments on the Medicare Physician Fee Schedule Proposed Rule at www.hospitalmedicine.org/policy--advocacy/letters/2021-physician-fee-schedule-proposed-rule/.

From the beginning, SHM has consciously and consistently taken a unique approach to its advocacy efforts with the federal government. The advocacy priorities of SHM most often concern issues that we feel have an impact on our patients and the broader delivery system, as opposed to a focus on issues that have direct financial benefit to our members.

This strategy has served SHM well. It has earned respect among policymakers and we have seen significant success for a young and relatively small medical society. The issues where we spend the bulk of our time and effort include advocating for issues like alternative payment models (APMs), which reward care quality as opposed to volume, as well as issues related to data integrity that APMs require. We have advocated strongly for changes to dysfunctional observation status rules, for workforce adequacy and sustainability, and for recognition of the importance of hospital medicine’s contribution to the redesign of our nations delivery system. And SHM will continue to advocate for many other issues identified as being important to hospital medicine and our patients.

This year, for the first time in the two decades that I have served on the SHM Public Policy Committee, Medicare has proposed changes that would create unprecedented financial hardship for hospital medicine groups. Each year, as a part of its advocacy agenda, SHM reviews and comments on proposed changes to the Medicare Physician Fee Schedule (PFS). Among other things, the PFS adjusts payment rates to physicians for specific services. Changes under the PFS are required to be budget neutral. In effect, budget neutrality means that whenever certain services receive an increased payment rate, CMS is required to offset these changes by making cuts to other services. This year, in an effort to correct the long-standing underfunding of primary care services, CMS has increased payment for many Evaluation and Management (E&M) codes associated with outpatient primary care services. However, due to budget neutrality requirements, many inpatient E&M care services will be receiving significant cuts.

The goal of increasing payment rates for primary care services is laudable, as many of these cognitive services have been long underfunded. However, the proposed payment increases will only apply to outpatient E&M codes and not their corresponding inpatient codes. While our outpatient Internal Medicine and Family Practice colleagues will benefit from these changes, inpatient providers, including hospitalists, stand to lose a significant amount revenue. SHM and the hospitalists we represent estimate that the proposed budget neutrality adjustment will lead to an approximate 8 percent decrease in Medicare Fee for Services (FFS) revenue. Hospitalists are among the specialties that will be most impacted from these proposed changes. If put into effect, these proposals will leave hospital medicine behind.

These changes have been proposed at a time when hospitalists, along with their colleagues in critical care and emergency medicine, have been caring for patients on the frontlines of the COVID-19 pandemic at great risk to themselves at their families. While hospitalists are working tirelessly to provide lifesaving care to COVID-positive patients throughout the country, hospitalist groups have struggled financially as a result of the pandemic. Inpatient volumes, and therefore care reimbursement, has dropped significantly. Many hospitalists have already reported pay reductions of 20% or more. Others have seen their shifts reduced, resulting in understaffing, which may compromise the quality of care. For many groups, a Medicare reimbursement cut of this magnitude add fuel to an already strained revenue stream and will not be financially sustainable.

SHM is, of course, fighting back. We are not asking CMS to completely abandon the increases in reimbursement for primary care outpatient codes, and we support properly valuing outpatient care services. However, we are asking CMS to find a solution that does not come at the expense of hospital medicine and the other specialties that care for acutely ill hospitalized patients, including patients with COVID-19. If a better solution requires holding off on the proposal for another year, CMS should do so. Furthermore, SHM is asking Congress to abandon the statutory requirement for budget neutrality in these extraordinary times as CMS and Congress work to find towards a solution that properly values both inpatient and outpatient care services.

To send a message to your representatives urging them to stop these payment cuts, please visit SHM’s Legislative Action Center at www.votervoice.net/SHM/campaigns/77226/respond. You can read our full comments on the Medicare Physician Fee Schedule Proposed Rule at www.hospitalmedicine.org/policy--advocacy/letters/2021-physician-fee-schedule-proposed-rule/.

Many of the US Supreme Court Justices seem disinclined to throw out the Affordable Care Act (ACA) – at least that was the takeaway from the questions they asked during oral arguments on whether the law is unconstitutional.

The Justices conducted arguments by telephone in the case, California v Texas (previously California v US), which was brought by 18 Republican state officials and two individual plaintiffs. The Trump administration joined the plaintiffs in June, arguing that the entire law should be overturned. The ACA is being defended by Democratic state officials from 16 states and Washington, D.C.

The Republican plaintiffs have essentially argued that the ACA cannot stand without the individual mandate requirement – that it is not possible to “sever” it from the rest of the Act. In 2017, Congress set the tax penalty to $0 if an individual did not buy insurance. The mandate to buy insurance was left in place, but there were no longer any consequences. The plaintiffs said that congressional act was equivalent to severing the mandate.

But many Justices appeared to take a dim view of that argument.

“It’s a very straightforward case for severability under our precedents,” said Justice Brett Kavanaugh. “Meaning that we would excise the mandate and leave the rest of the Act in play. Congress knows how to write an inseverability clause and that is not the language that they chose here,” he said.

Justice Elena Kagan also questioned how it would jibe with legal precedent to allow the severing of one part of a law when there was no clear instruction from Congress on the issue. She also raised the concern that it would open the door to all sorts of challenges.

“It would seem a big deal to say that, if you can point to injury with respect to one provision and you can concoct some kind of inseverability argument, that allows you to challenge anything else in the statute,” she said.

“Isn’t that something that really cuts against all of our doctrine?” asked Kagan.

“I think it’s hard for you to argue that Congress intended the entire Act to fall if the mandate was struck down when the same Congress that lowered the penalty to zero did not even try to repeal the rest of the act,” said Chief Justice John Roberts.

“I think, frankly, that they wanted the Court to do that but that’s not our job,” he added.
 

Proof of harm?

To have the standing to sue, the plaintiffs have to prove they have been harmed by the ACA. Texas Solicitor General Kyle Hawkins said that individuals feel compelled to buy insurance – even without a penalty hanging over their heads.

Justice Stephen Breyer argued that many laws include what he called “precatory” language – that is, they seek to compel citizens to do something. But most don’t penalize those who fail to act – just like the ACA currently.

If, as the Texas plaintiffs argued, it’s still unconstitutional to make such a request, “I think there will be an awful lot of language in an awful lot of statutes that will suddenly be the subject of court constitutional challenge,” he said.

Hawkins disagreed. He said the ACA’s mandate “is not some suggestion, not some hortatory statement. It is the law of the United States of America today that you have to purchase health insurance and not just any health insurance, but health insurance that the federal government has decided would be best for you.”

Hawkins said that, if just one additional person signed up for Medicaid, the state of Texas and the other plaintiff states would be harmed. He said people were continuing to enroll in the program because they believed the law required them to get health insurance.

Justice Sonia Sotomayor said that defied common sense. “The problem is that your theory assumes people that people are going to pay a tax and break the law by not buying insurance, but they wouldn’t do it when the tax is zero.”
 

What’s at stake

It’s unlikely the justices will issue a decision immediately. They have until the end of the term in June to rule.

Katie Keith, JD, MPH, a principal at Keith Policy Solutions, LLC, outlined the potential outcomes in Health Affairs .

“The most likely scenario is that the Court maintains the status quo,” she wrote. They could get there by deciding Texas et al. did not have standing to bring the case. Or they could decide that either the mandate is constitutional or that it is unconstitutional but can be severed from the rest of the ACA.

The Court could alternatively find that some or all of the law’s insurance provisions – such as protections for people with pre-existing conditions – can’t be severed from the mandate. Or the justices could strike down all of the insurance consumer protections, the health insurance marketplaces, premium tax credits, and other provisions, which would force states to come up with the money to help people buy insurance. And states are unlikely to be able to do so, especially with the pandemic stretching their budgets.

Finally, the Court could find that the mandate can’t be separated, which would essentially overturn the law.

If that happens, some 15 million people could lose Medicaid coverage, 11 million who buy on health insurance exchanges could lose coverage, and 2.3 million young adults would no longer be able to stay on parents’ policies, according to the Kaiser Family Foundation. Kaiser also estimates that 54 million people under age 65 who have pre-existing conditions would no longer be guaranteed coverage.

The Urban Institute estimates that 21 million people could lose insurance – 15 million through Medicaid and the Children’s Health Insurance Program (CHIP) and 7.6 million through private nongroup coverage.
 

Medical societies weigh in

Multiple physicians’ groups, patient advocates, and hospital organizations have filed briefs with the Court in favor of keeping the law intact.

Twenty patient groups representing millions with pre-existing conditions – including the American Cancer Society, American Diabetes Association, American Heart Association, National Alliance on Mental Illness, National Organization for Rare Disorders, and the Kennedy Forum – filed a court brief in May arguing that the law has expanded access to insurance and improved patient outcomes.

“The coronavirus pandemic has only served to underscore the necessity of meaningful coverage – especially for those who are at high risk of being severely affected by the virus – including countless Americans who have pre-existing, acute or chronic conditions like heart disease, cancer, diabetes, lung diseases and multiple sclerosis,” they said in a statement.

Jacqueline W. Fincher, MD, MACP, president of the American College of Physicians, which joined a court brief in support of the law with 19 other medical organizations, said the law has worked.

“The coverage, protections and benefits provided by the ACA are critical to the well-being of millions of Americans,” she said in a statement.

“If the ACA were to be thrown out at the same time that we face the pandemic, it would cause chaos for physicians and our patients, and for the entire health care system,” said Fincher, adding that millions of Americans who have been infected could lose insurance if protections for pre-existing conditions disappeared.

“The ACA has revolutionized access to care for tens of millions of women by helping them obtain meaningful health coverage, ensuring that essential care is covered by insurers, and protecting patients from unfair insurance practices,” said Maureen G. Phipps, MD, MPH, CEO of the American College of Obstetricians and Gynecologists (ACOG), in a statement.

Overturning the ACA “would be one of the most singularly disruptive acts to be committed during this public health crisis,” she said.

American Psychiatric Association President Jeffrey Geller, MD, MPH, also warned of disruptions to care, especially for those with mental health and substance use disorders. “We urge the Supreme Court to preserve the entire Act, including the individual mandate,” he said, in a statement.

“In the midst of COVID is no time to let down the millions who we serve as our patients,” said Chip Kahn, Federation of American Health Systems president and CEO, in a statement.

“As caregivers, the goal of hospitals for our patients is to see increased access to affordable coverage for all Americans – not new obstacles,” he said, adding that the ACA “can accomplish this goal. We hope the Supreme Court will see its way clear to allow it to go forward.”
 

For the defense

Many legal analysts on social media who listened in to today’s hearing agreed that the tenor of the proceedings seemed to lean toward survival of the ACA.

“At this point I would say it is *extremely* likely that the ACA will be upheld, but the mandate struck down and severed out,” tweeted Raffi Melkonian, an appellate lawyer in Houston, Texas. “A decision on standing (throwing out the case entirely) is also possible. The chance that the ACA is struck down v. low.”

“Both Kavanaugh and Roberts have suggested this morning that they may view the individual mandate as severable from the rest of the law. If those two justices join the court’s three liberals in finding that the mandate is severable, that would be five votes to save the ACA,” tweeted the analysts at SCOTUS Blog.

Sean Marotta, a lawyer with Hogan Lovells’ Supreme Court group, agreed. “Oral argument is always an imperfect measure, but the Act’s defenders should feel good today,” he tweeted.
 

This article first appeared on Medscape.com.

Many of the US Supreme Court Justices seem disinclined to throw out the Affordable Care Act (ACA) – at least that was the takeaway from the questions they asked during oral arguments on whether the law is unconstitutional.

The Justices conducted arguments by telephone in the case, California v Texas (previously California v US), which was brought by 18 Republican state officials and two individual plaintiffs. The Trump administration joined the plaintiffs in June, arguing that the entire law should be overturned. The ACA is being defended by Democratic state officials from 16 states and Washington, D.C.

The Republican plaintiffs have essentially argued that the ACA cannot stand without the individual mandate requirement – that it is not possible to “sever” it from the rest of the Act. In 2017, Congress set the tax penalty to $0 if an individual did not buy insurance. The mandate to buy insurance was left in place, but there were no longer any consequences. The plaintiffs said that congressional act was equivalent to severing the mandate.

But many Justices appeared to take a dim view of that argument.

“It’s a very straightforward case for severability under our precedents,” said Justice Brett Kavanaugh. “Meaning that we would excise the mandate and leave the rest of the Act in play. Congress knows how to write an inseverability clause and that is not the language that they chose here,” he said.

Justice Elena Kagan also questioned how it would jibe with legal precedent to allow the severing of one part of a law when there was no clear instruction from Congress on the issue. She also raised the concern that it would open the door to all sorts of challenges.

“It would seem a big deal to say that, if you can point to injury with respect to one provision and you can concoct some kind of inseverability argument, that allows you to challenge anything else in the statute,” she said.

“Isn’t that something that really cuts against all of our doctrine?” asked Kagan.

“I think it’s hard for you to argue that Congress intended the entire Act to fall if the mandate was struck down when the same Congress that lowered the penalty to zero did not even try to repeal the rest of the act,” said Chief Justice John Roberts.

“I think, frankly, that they wanted the Court to do that but that’s not our job,” he added.
 

Proof of harm?

To have the standing to sue, the plaintiffs have to prove they have been harmed by the ACA. Texas Solicitor General Kyle Hawkins said that individuals feel compelled to buy insurance – even without a penalty hanging over their heads.

Justice Stephen Breyer argued that many laws include what he called “precatory” language – that is, they seek to compel citizens to do something. But most don’t penalize those who fail to act – just like the ACA currently.

If, as the Texas plaintiffs argued, it’s still unconstitutional to make such a request, “I think there will be an awful lot of language in an awful lot of statutes that will suddenly be the subject of court constitutional challenge,” he said.

Hawkins disagreed. He said the ACA’s mandate “is not some suggestion, not some hortatory statement. It is the law of the United States of America today that you have to purchase health insurance and not just any health insurance, but health insurance that the federal government has decided would be best for you.”

Hawkins said that, if just one additional person signed up for Medicaid, the state of Texas and the other plaintiff states would be harmed. He said people were continuing to enroll in the program because they believed the law required them to get health insurance.

Justice Sonia Sotomayor said that defied common sense. “The problem is that your theory assumes people that people are going to pay a tax and break the law by not buying insurance, but they wouldn’t do it when the tax is zero.”
 

What’s at stake

It’s unlikely the justices will issue a decision immediately. They have until the end of the term in June to rule.

Katie Keith, JD, MPH, a principal at Keith Policy Solutions, LLC, outlined the potential outcomes in Health Affairs .

“The most likely scenario is that the Court maintains the status quo,” she wrote. They could get there by deciding Texas et al. did not have standing to bring the case. Or they could decide that either the mandate is constitutional or that it is unconstitutional but can be severed from the rest of the ACA.

The Court could alternatively find that some or all of the law’s insurance provisions – such as protections for people with pre-existing conditions – can’t be severed from the mandate. Or the justices could strike down all of the insurance consumer protections, the health insurance marketplaces, premium tax credits, and other provisions, which would force states to come up with the money to help people buy insurance. And states are unlikely to be able to do so, especially with the pandemic stretching their budgets.

Finally, the Court could find that the mandate can’t be separated, which would essentially overturn the law.

If that happens, some 15 million people could lose Medicaid coverage, 11 million who buy on health insurance exchanges could lose coverage, and 2.3 million young adults would no longer be able to stay on parents’ policies, according to the Kaiser Family Foundation. Kaiser also estimates that 54 million people under age 65 who have pre-existing conditions would no longer be guaranteed coverage.

The Urban Institute estimates that 21 million people could lose insurance – 15 million through Medicaid and the Children’s Health Insurance Program (CHIP) and 7.6 million through private nongroup coverage.
 

Medical societies weigh in

Multiple physicians’ groups, patient advocates, and hospital organizations have filed briefs with the Court in favor of keeping the law intact.

Twenty patient groups representing millions with pre-existing conditions – including the American Cancer Society, American Diabetes Association, American Heart Association, National Alliance on Mental Illness, National Organization for Rare Disorders, and the Kennedy Forum – filed a court brief in May arguing that the law has expanded access to insurance and improved patient outcomes.

“The coronavirus pandemic has only served to underscore the necessity of meaningful coverage – especially for those who are at high risk of being severely affected by the virus – including countless Americans who have pre-existing, acute or chronic conditions like heart disease, cancer, diabetes, lung diseases and multiple sclerosis,” they said in a statement.

Jacqueline W. Fincher, MD, MACP, president of the American College of Physicians, which joined a court brief in support of the law with 19 other medical organizations, said the law has worked.

“The coverage, protections and benefits provided by the ACA are critical to the well-being of millions of Americans,” she said in a statement.

“If the ACA were to be thrown out at the same time that we face the pandemic, it would cause chaos for physicians and our patients, and for the entire health care system,” said Fincher, adding that millions of Americans who have been infected could lose insurance if protections for pre-existing conditions disappeared.

“The ACA has revolutionized access to care for tens of millions of women by helping them obtain meaningful health coverage, ensuring that essential care is covered by insurers, and protecting patients from unfair insurance practices,” said Maureen G. Phipps, MD, MPH, CEO of the American College of Obstetricians and Gynecologists (ACOG), in a statement.

Overturning the ACA “would be one of the most singularly disruptive acts to be committed during this public health crisis,” she said.

American Psychiatric Association President Jeffrey Geller, MD, MPH, also warned of disruptions to care, especially for those with mental health and substance use disorders. “We urge the Supreme Court to preserve the entire Act, including the individual mandate,” he said, in a statement.

“In the midst of COVID is no time to let down the millions who we serve as our patients,” said Chip Kahn, Federation of American Health Systems president and CEO, in a statement.

“As caregivers, the goal of hospitals for our patients is to see increased access to affordable coverage for all Americans – not new obstacles,” he said, adding that the ACA “can accomplish this goal. We hope the Supreme Court will see its way clear to allow it to go forward.”
 

For the defense

Many legal analysts on social media who listened in to today’s hearing agreed that the tenor of the proceedings seemed to lean toward survival of the ACA.

“At this point I would say it is *extremely* likely that the ACA will be upheld, but the mandate struck down and severed out,” tweeted Raffi Melkonian, an appellate lawyer in Houston, Texas. “A decision on standing (throwing out the case entirely) is also possible. The chance that the ACA is struck down v. low.”

“Both Kavanaugh and Roberts have suggested this morning that they may view the individual mandate as severable from the rest of the law. If those two justices join the court’s three liberals in finding that the mandate is severable, that would be five votes to save the ACA,” tweeted the analysts at SCOTUS Blog.

Sean Marotta, a lawyer with Hogan Lovells’ Supreme Court group, agreed. “Oral argument is always an imperfect measure, but the Act’s defenders should feel good today,” he tweeted.
 

This article first appeared on Medscape.com.

Many of the US Supreme Court Justices seem disinclined to throw out the Affordable Care Act (ACA) – at least that was the takeaway from the questions they asked during oral arguments on whether the law is unconstitutional.

The Justices conducted arguments by telephone in the case, California v Texas (previously California v US), which was brought by 18 Republican state officials and two individual plaintiffs. The Trump administration joined the plaintiffs in June, arguing that the entire law should be overturned. The ACA is being defended by Democratic state officials from 16 states and Washington, D.C.

The Republican plaintiffs have essentially argued that the ACA cannot stand without the individual mandate requirement – that it is not possible to “sever” it from the rest of the Act. In 2017, Congress set the tax penalty to $0 if an individual did not buy insurance. The mandate to buy insurance was left in place, but there were no longer any consequences. The plaintiffs said that congressional act was equivalent to severing the mandate.

But many Justices appeared to take a dim view of that argument.

“It’s a very straightforward case for severability under our precedents,” said Justice Brett Kavanaugh. “Meaning that we would excise the mandate and leave the rest of the Act in play. Congress knows how to write an inseverability clause and that is not the language that they chose here,” he said.

Justice Elena Kagan also questioned how it would jibe with legal precedent to allow the severing of one part of a law when there was no clear instruction from Congress on the issue. She also raised the concern that it would open the door to all sorts of challenges.

“It would seem a big deal to say that, if you can point to injury with respect to one provision and you can concoct some kind of inseverability argument, that allows you to challenge anything else in the statute,” she said.

“Isn’t that something that really cuts against all of our doctrine?” asked Kagan.

“I think it’s hard for you to argue that Congress intended the entire Act to fall if the mandate was struck down when the same Congress that lowered the penalty to zero did not even try to repeal the rest of the act,” said Chief Justice John Roberts.

“I think, frankly, that they wanted the Court to do that but that’s not our job,” he added.
 

Proof of harm?

To have the standing to sue, the plaintiffs have to prove they have been harmed by the ACA. Texas Solicitor General Kyle Hawkins said that individuals feel compelled to buy insurance – even without a penalty hanging over their heads.

Justice Stephen Breyer argued that many laws include what he called “precatory” language – that is, they seek to compel citizens to do something. But most don’t penalize those who fail to act – just like the ACA currently.

If, as the Texas plaintiffs argued, it’s still unconstitutional to make such a request, “I think there will be an awful lot of language in an awful lot of statutes that will suddenly be the subject of court constitutional challenge,” he said.

Hawkins disagreed. He said the ACA’s mandate “is not some suggestion, not some hortatory statement. It is the law of the United States of America today that you have to purchase health insurance and not just any health insurance, but health insurance that the federal government has decided would be best for you.”

Hawkins said that, if just one additional person signed up for Medicaid, the state of Texas and the other plaintiff states would be harmed. He said people were continuing to enroll in the program because they believed the law required them to get health insurance.

Justice Sonia Sotomayor said that defied common sense. “The problem is that your theory assumes people that people are going to pay a tax and break the law by not buying insurance, but they wouldn’t do it when the tax is zero.”
 

What’s at stake

It’s unlikely the justices will issue a decision immediately. They have until the end of the term in June to rule.

Katie Keith, JD, MPH, a principal at Keith Policy Solutions, LLC, outlined the potential outcomes in Health Affairs .

“The most likely scenario is that the Court maintains the status quo,” she wrote. They could get there by deciding Texas et al. did not have standing to bring the case. Or they could decide that either the mandate is constitutional or that it is unconstitutional but can be severed from the rest of the ACA.

The Court could alternatively find that some or all of the law’s insurance provisions – such as protections for people with pre-existing conditions – can’t be severed from the mandate. Or the justices could strike down all of the insurance consumer protections, the health insurance marketplaces, premium tax credits, and other provisions, which would force states to come up with the money to help people buy insurance. And states are unlikely to be able to do so, especially with the pandemic stretching their budgets.

Finally, the Court could find that the mandate can’t be separated, which would essentially overturn the law.

If that happens, some 15 million people could lose Medicaid coverage, 11 million who buy on health insurance exchanges could lose coverage, and 2.3 million young adults would no longer be able to stay on parents’ policies, according to the Kaiser Family Foundation. Kaiser also estimates that 54 million people under age 65 who have pre-existing conditions would no longer be guaranteed coverage.

The Urban Institute estimates that 21 million people could lose insurance – 15 million through Medicaid and the Children’s Health Insurance Program (CHIP) and 7.6 million through private nongroup coverage.
 

Medical societies weigh in

Multiple physicians’ groups, patient advocates, and hospital organizations have filed briefs with the Court in favor of keeping the law intact.

Twenty patient groups representing millions with pre-existing conditions – including the American Cancer Society, American Diabetes Association, American Heart Association, National Alliance on Mental Illness, National Organization for Rare Disorders, and the Kennedy Forum – filed a court brief in May arguing that the law has expanded access to insurance and improved patient outcomes.

“The coronavirus pandemic has only served to underscore the necessity of meaningful coverage – especially for those who are at high risk of being severely affected by the virus – including countless Americans who have pre-existing, acute or chronic conditions like heart disease, cancer, diabetes, lung diseases and multiple sclerosis,” they said in a statement.

Jacqueline W. Fincher, MD, MACP, president of the American College of Physicians, which joined a court brief in support of the law with 19 other medical organizations, said the law has worked.

“The coverage, protections and benefits provided by the ACA are critical to the well-being of millions of Americans,” she said in a statement.

“If the ACA were to be thrown out at the same time that we face the pandemic, it would cause chaos for physicians and our patients, and for the entire health care system,” said Fincher, adding that millions of Americans who have been infected could lose insurance if protections for pre-existing conditions disappeared.

“The ACA has revolutionized access to care for tens of millions of women by helping them obtain meaningful health coverage, ensuring that essential care is covered by insurers, and protecting patients from unfair insurance practices,” said Maureen G. Phipps, MD, MPH, CEO of the American College of Obstetricians and Gynecologists (ACOG), in a statement.

Overturning the ACA “would be one of the most singularly disruptive acts to be committed during this public health crisis,” she said.

American Psychiatric Association President Jeffrey Geller, MD, MPH, also warned of disruptions to care, especially for those with mental health and substance use disorders. “We urge the Supreme Court to preserve the entire Act, including the individual mandate,” he said, in a statement.

“In the midst of COVID is no time to let down the millions who we serve as our patients,” said Chip Kahn, Federation of American Health Systems president and CEO, in a statement.

“As caregivers, the goal of hospitals for our patients is to see increased access to affordable coverage for all Americans – not new obstacles,” he said, adding that the ACA “can accomplish this goal. We hope the Supreme Court will see its way clear to allow it to go forward.”
 

For the defense

Many legal analysts on social media who listened in to today’s hearing agreed that the tenor of the proceedings seemed to lean toward survival of the ACA.

“At this point I would say it is *extremely* likely that the ACA will be upheld, but the mandate struck down and severed out,” tweeted Raffi Melkonian, an appellate lawyer in Houston, Texas. “A decision on standing (throwing out the case entirely) is also possible. The chance that the ACA is struck down v. low.”

“Both Kavanaugh and Roberts have suggested this morning that they may view the individual mandate as severable from the rest of the law. If those two justices join the court’s three liberals in finding that the mandate is severable, that would be five votes to save the ACA,” tweeted the analysts at SCOTUS Blog.

Sean Marotta, a lawyer with Hogan Lovells’ Supreme Court group, agreed. “Oral argument is always an imperfect measure, but the Act’s defenders should feel good today,” he tweeted.
 

This article first appeared on Medscape.com.

The US Food and Drug Administration (FDA) issued an emergency use authorization (EUA) Nov. 9 for the investigational monoclonal antibody therapy bamlanivimab (Eli Lilly) to treat adults and children with mild to moderate COVID-19.

The monoclonal antibody therapy has emergency authorization for treating patients who have tested positive for SARS-CoV-2 infection and who are considered to be at high risk for progression to severe COVID-19 or hospitalization. To be eligible for treatment with bamlanivimab, patients must be at least 12 years of age and weigh at least 40 kg (approximately 88 lb). The agency notes that this includes patients aged 65 years and older or people with certain chronic conditions.

Bamlanivimab is not authorized for use in patients who are hospitalized or who require oxygen therapy because of COVID-19. The FDA’s action comes less than 2 weeks after Eli Lilly halted the ACTIV-3 study of the therapy for severe, hospitalized COVID-19 patients after evidence showed that adding the antibody therapy to standard care did not improve outcomes over standard care alone for patients with advanced COVID-19.

The government contract with Eli Lilly involves the purchase of 300,000 doses through December, with the option to procure another 650,000 doses through June 2021.

Because of Operation Warp Speed, “we have supplies to distribute now. Product distribution will begin this week,” US Health & Human Services (HHS) Secretary Alex Azar said at a news conference today.

“We talked about building the bridge to safe and effective vaccines” for COVID-19, Azar added. “With this therapeutic, the bridge is taking shape.”

Bamlanivimab 700 mg will be administered as a 1-hour infusion followed by a 1-hour observation period for detecting any infusion-related side effects. The authorized dose is 700 mg, which was on the lower end of the dose range evaluated in studies.

During the press conference, a reporter asked whether the lower dose was chosen in order that more doses of the antibody could be made available. “The lower dose is a rational choice in this situation because we don’t want to give more of a drug than you need,” said Janet Woodcock, MD, the therapeutics lead for Operation Warp Speed. “I think we could probably go lower.”

Bamlanivimab works by attaching to the virus and blocking its entry into the cells and possibly by helping the patients’ immune system clear the virus, said Woodcock, who is also director of the FDA’s Center for Drug Evaluation and Research.

“The goal is to treat high-risk people as soon as possible after they show symptoms and are diagnosed,” she added.
 

Infusions an initial challenge?

There could be some logistic challenges at first because the antibody is administered via infusion. “We expect there will initially be a challenge in administering ... these infusions and setting up infusion centers,” Woodcock said.

Outpatient intravenous infusions are normally performed at infusion centers for patients with cancer and immune disorders, she noted. “You really don’t want them mixing with people who have COVID-19 disease, so we will need to set up separate sites.”

Bamlanivimab will be provided free of cost to patients, Azar said. Patients should be aware that coinsurance may be required for the infusion.
 

“Fair and equitable” distribution planned

During phase 1 of distribution, the agent will first be allocated to hospitals and hospital-affiliated locations only, John Redd, MD, MPH, chief medical officer, Office of the Assistant Secretary for Preparedness and Response at HHS, said at the press conference.

During phase 2, “there will be expanded distribution to outpatient sites,” he said. In an effort to keep the process transparent, a new website features the latest updates on the distribution of bamlanivimab.

Allocation will be based on two factors: the number of new cases reported in a state or territory in the prior 7 days, and rates of COVID-19 hospitalization during the same period.

Asked why the government would determine distribution of the antibody on the basis of the number of hospitalized patients when the indication includes prevention of admission, Woodcock replied that hospitalization is a surrogate measure that can reflect risk factors in a particular state population, such as obesity, diabetes, or the proportion of older people.

Furthermore, the confirmed cases are a “leading indicator,” she said, that can help identify a steep rise in COVID-19 cases that could indicate more hospitalizations are likely soon. “We don’t want to miss that.”
 

Data underlying the EUA decision

A decrease in hospitalizations or emergency department visits within 28 days of treatment in preclinical studies was “the most important evidence that bamlanivimab may be effective,” the agency noted in the press release announcing the EUA. Among patients at high risk for progression, 3% required such interventions, compared with 10% of placebo-treated patients.

Potential side effects of bamlanivimab include anaphylaxis, infusion-related reactions, nausea, diarrhea, dizziness, headache, itching, and vomiting.

“As illustrated by today’s action, the FDA remains committed to expediting the development and availability of potential COVID-19 treatments and providing sick patients timely access to new therapies where appropriate,” FDA Commissioner Stephen M. Hahn, MD, said in the news release.

Healthcare providers can download a detailed FDA fact sheet on the EUA for bamlanivimab, which includes dosing instructions.
 

This article first appeared on Medscape.com.

The US Food and Drug Administration (FDA) issued an emergency use authorization (EUA) Nov. 9 for the investigational monoclonal antibody therapy bamlanivimab (Eli Lilly) to treat adults and children with mild to moderate COVID-19.

The monoclonal antibody therapy has emergency authorization for treating patients who have tested positive for SARS-CoV-2 infection and who are considered to be at high risk for progression to severe COVID-19 or hospitalization. To be eligible for treatment with bamlanivimab, patients must be at least 12 years of age and weigh at least 40 kg (approximately 88 lb). The agency notes that this includes patients aged 65 years and older or people with certain chronic conditions.

Bamlanivimab is not authorized for use in patients who are hospitalized or who require oxygen therapy because of COVID-19. The FDA’s action comes less than 2 weeks after Eli Lilly halted the ACTIV-3 study of the therapy for severe, hospitalized COVID-19 patients after evidence showed that adding the antibody therapy to standard care did not improve outcomes over standard care alone for patients with advanced COVID-19.

The government contract with Eli Lilly involves the purchase of 300,000 doses through December, with the option to procure another 650,000 doses through June 2021.

Because of Operation Warp Speed, “we have supplies to distribute now. Product distribution will begin this week,” US Health & Human Services (HHS) Secretary Alex Azar said at a news conference today.

“We talked about building the bridge to safe and effective vaccines” for COVID-19, Azar added. “With this therapeutic, the bridge is taking shape.”

Bamlanivimab 700 mg will be administered as a 1-hour infusion followed by a 1-hour observation period for detecting any infusion-related side effects. The authorized dose is 700 mg, which was on the lower end of the dose range evaluated in studies.

During the press conference, a reporter asked whether the lower dose was chosen in order that more doses of the antibody could be made available. “The lower dose is a rational choice in this situation because we don’t want to give more of a drug than you need,” said Janet Woodcock, MD, the therapeutics lead for Operation Warp Speed. “I think we could probably go lower.”

Bamlanivimab works by attaching to the virus and blocking its entry into the cells and possibly by helping the patients’ immune system clear the virus, said Woodcock, who is also director of the FDA’s Center for Drug Evaluation and Research.

“The goal is to treat high-risk people as soon as possible after they show symptoms and are diagnosed,” she added.
 

Infusions an initial challenge?

There could be some logistic challenges at first because the antibody is administered via infusion. “We expect there will initially be a challenge in administering ... these infusions and setting up infusion centers,” Woodcock said.

Outpatient intravenous infusions are normally performed at infusion centers for patients with cancer and immune disorders, she noted. “You really don’t want them mixing with people who have COVID-19 disease, so we will need to set up separate sites.”

Bamlanivimab will be provided free of cost to patients, Azar said. Patients should be aware that coinsurance may be required for the infusion.
 

“Fair and equitable” distribution planned

During phase 1 of distribution, the agent will first be allocated to hospitals and hospital-affiliated locations only, John Redd, MD, MPH, chief medical officer, Office of the Assistant Secretary for Preparedness and Response at HHS, said at the press conference.

During phase 2, “there will be expanded distribution to outpatient sites,” he said. In an effort to keep the process transparent, a new website features the latest updates on the distribution of bamlanivimab.

Allocation will be based on two factors: the number of new cases reported in a state or territory in the prior 7 days, and rates of COVID-19 hospitalization during the same period.

Asked why the government would determine distribution of the antibody on the basis of the number of hospitalized patients when the indication includes prevention of admission, Woodcock replied that hospitalization is a surrogate measure that can reflect risk factors in a particular state population, such as obesity, diabetes, or the proportion of older people.

Furthermore, the confirmed cases are a “leading indicator,” she said, that can help identify a steep rise in COVID-19 cases that could indicate more hospitalizations are likely soon. “We don’t want to miss that.”
 

Data underlying the EUA decision

A decrease in hospitalizations or emergency department visits within 28 days of treatment in preclinical studies was “the most important evidence that bamlanivimab may be effective,” the agency noted in the press release announcing the EUA. Among patients at high risk for progression, 3% required such interventions, compared with 10% of placebo-treated patients.

Potential side effects of bamlanivimab include anaphylaxis, infusion-related reactions, nausea, diarrhea, dizziness, headache, itching, and vomiting.

“As illustrated by today’s action, the FDA remains committed to expediting the development and availability of potential COVID-19 treatments and providing sick patients timely access to new therapies where appropriate,” FDA Commissioner Stephen M. Hahn, MD, said in the news release.

Healthcare providers can download a detailed FDA fact sheet on the EUA for bamlanivimab, which includes dosing instructions.
 

This article first appeared on Medscape.com.

The US Food and Drug Administration (FDA) issued an emergency use authorization (EUA) Nov. 9 for the investigational monoclonal antibody therapy bamlanivimab (Eli Lilly) to treat adults and children with mild to moderate COVID-19.

The monoclonal antibody therapy has emergency authorization for treating patients who have tested positive for SARS-CoV-2 infection and who are considered to be at high risk for progression to severe COVID-19 or hospitalization. To be eligible for treatment with bamlanivimab, patients must be at least 12 years of age and weigh at least 40 kg (approximately 88 lb). The agency notes that this includes patients aged 65 years and older or people with certain chronic conditions.

Bamlanivimab is not authorized for use in patients who are hospitalized or who require oxygen therapy because of COVID-19. The FDA’s action comes less than 2 weeks after Eli Lilly halted the ACTIV-3 study of the therapy for severe, hospitalized COVID-19 patients after evidence showed that adding the antibody therapy to standard care did not improve outcomes over standard care alone for patients with advanced COVID-19.

The government contract with Eli Lilly involves the purchase of 300,000 doses through December, with the option to procure another 650,000 doses through June 2021.

Because of Operation Warp Speed, “we have supplies to distribute now. Product distribution will begin this week,” US Health & Human Services (HHS) Secretary Alex Azar said at a news conference today.

“We talked about building the bridge to safe and effective vaccines” for COVID-19, Azar added. “With this therapeutic, the bridge is taking shape.”

Bamlanivimab 700 mg will be administered as a 1-hour infusion followed by a 1-hour observation period for detecting any infusion-related side effects. The authorized dose is 700 mg, which was on the lower end of the dose range evaluated in studies.

During the press conference, a reporter asked whether the lower dose was chosen in order that more doses of the antibody could be made available. “The lower dose is a rational choice in this situation because we don’t want to give more of a drug than you need,” said Janet Woodcock, MD, the therapeutics lead for Operation Warp Speed. “I think we could probably go lower.”

Bamlanivimab works by attaching to the virus and blocking its entry into the cells and possibly by helping the patients’ immune system clear the virus, said Woodcock, who is also director of the FDA’s Center for Drug Evaluation and Research.

“The goal is to treat high-risk people as soon as possible after they show symptoms and are diagnosed,” she added.
 

Infusions an initial challenge?

There could be some logistic challenges at first because the antibody is administered via infusion. “We expect there will initially be a challenge in administering ... these infusions and setting up infusion centers,” Woodcock said.

Outpatient intravenous infusions are normally performed at infusion centers for patients with cancer and immune disorders, she noted. “You really don’t want them mixing with people who have COVID-19 disease, so we will need to set up separate sites.”

Bamlanivimab will be provided free of cost to patients, Azar said. Patients should be aware that coinsurance may be required for the infusion.
 

“Fair and equitable” distribution planned

During phase 1 of distribution, the agent will first be allocated to hospitals and hospital-affiliated locations only, John Redd, MD, MPH, chief medical officer, Office of the Assistant Secretary for Preparedness and Response at HHS, said at the press conference.

During phase 2, “there will be expanded distribution to outpatient sites,” he said. In an effort to keep the process transparent, a new website features the latest updates on the distribution of bamlanivimab.

Allocation will be based on two factors: the number of new cases reported in a state or territory in the prior 7 days, and rates of COVID-19 hospitalization during the same period.

Asked why the government would determine distribution of the antibody on the basis of the number of hospitalized patients when the indication includes prevention of admission, Woodcock replied that hospitalization is a surrogate measure that can reflect risk factors in a particular state population, such as obesity, diabetes, or the proportion of older people.

Furthermore, the confirmed cases are a “leading indicator,” she said, that can help identify a steep rise in COVID-19 cases that could indicate more hospitalizations are likely soon. “We don’t want to miss that.”
 

Data underlying the EUA decision

A decrease in hospitalizations or emergency department visits within 28 days of treatment in preclinical studies was “the most important evidence that bamlanivimab may be effective,” the agency noted in the press release announcing the EUA. Among patients at high risk for progression, 3% required such interventions, compared with 10% of placebo-treated patients.

Potential side effects of bamlanivimab include anaphylaxis, infusion-related reactions, nausea, diarrhea, dizziness, headache, itching, and vomiting.

“As illustrated by today’s action, the FDA remains committed to expediting the development and availability of potential COVID-19 treatments and providing sick patients timely access to new therapies where appropriate,” FDA Commissioner Stephen M. Hahn, MD, said in the news release.

Healthcare providers can download a detailed FDA fact sheet on the EUA for bamlanivimab, which includes dosing instructions.
 

This article first appeared on Medscape.com.

Febuxostat (Uloric) emerged as noninferior to allopurinol regarding risk of cardiovascular death among people 60 years and older with gout and at least one additional cardiovascular risk factor, results of the Febuxostat versus Allopurinol Streamlined Trial (FAST) suggest.

This primary outcome of the FAST trial stands in contrast to results of the CARES trial in 2018. The CARES researchers previously reported a 4.3% increased risk of cardiovascular death associated with febuxostat, compared with a 3.2% rate with allopurinol, a statistically significant 34% increase in the relative risk.

“In contrast to previous studies, there was no evidence of increased mortality with febuxostat, and we believe the regulators should review febuxostat licensing restrictions,” senior author Thomas MacDonald, MD, of the University of Dundee (Scotland), said during a late-breaking abstract session at the virtual annual meeting of the American College of Rheumatology.

The results of the FAST trial were simultaneously published online in The Lancet.

Both febuxostat and allopurinol treat gout by lowering urate levels. Concerns about the cardiovascular safety of febuxostat led to two post-licensing studies: the Cardiovascular Safety of Febuxostat and Allopurinol in Participants with Gout and Cardiovascular Comorbidities (CARES) study, mandated by the U.S. Food and Drug Administration, and FAST, requested by the European Medicines Agency. In February 2019, the FDA added a warning about elevated cardiovascular death and death risk associated with febuxostat.

“When CARES was published, it was somewhat of a threat to our study,” Dr. MacDonald said. “After hearing from our data-monitoring committee, we were told we could continue the trial.”
 

Some switched from allopurinol to febuxostat

So Dr. MacDonald, lead author Isla Mackenzie, MBChB, and their colleagues enrolled 6,128 people with gout in the United Kingdom, Sweden, and Denmark between December 2011 and January 2018. They followed patients for a median of 4 years. Participants had a mean age of 71 years, 85% were men, and 33% had a history of cardiovascular disease. The investigators excluded anyone with a stroke or myocardial infarction in the previous 6 months.

All participants were being treated with allopurinol. The investigators titrated those not at target up to an ideal dose that achieved a serum urate concentration of less than 0.357 mmol/L (< 6 mg/dL). Next, they randomly assigned 3,065 people to continue allopurinol and another 3,063 to switch to 80-120 mg of febuxostat.

The primary outcome of the multicenter, prospective, randomized, open-label FAST trial was a composite of hospitalization for nonfatal MI or biomarker positive for acute coronary syndrome, nonfatal stroke, or cardiovascular death.
 

Key findings

“There was definitely a noninferior primary outcome,” Dr. MacDonald said. In the on-treatment analysis, 172 patients in the febuxostat group reached the composite endpoint versus 241 patients in the allopurinol group. There were 1.72 events per 100 patient-years in the febuxostat group versus 2.05 events in the allopurinol group (adjusted hazard ratio, 0.85; 95% confidence interval, 0.70-1.03). An intent-to-treat analysis also found that febuxostat was noninferior to allopurinol on this measure.

Urate levels were approximately 80 micromoles lower in the febuxostat group versus the allopurinol group each year of the study, Dr. MacDonald said.

At least one gout flare was experienced by 1,017 patients in the febuxostat group and by 1,044 participants in the allopurinol group. “However, there was no placebo group, so we don’t know the effectiveness of either of these agents at preventing flares” based on this research, he said.

Both the on-treatment and intention-to-treat (ITT) secondary analyses demonstrated the noninferiority of febuxostat, compared with allopurinol, for all-cause death, each individual component of the composite primary outcome – cardiovascular death, hospitalization for heart failure, and hospitalization for new, unstable, or worsening angina.

In contrast, the ITT analysis revealed a “nominally significant increase” in hospitalization for arrhythmia with no evidence of ischemia in the febuxostat group. The 0.583 events per 100 patient-years in this group versus 0.385 events in the allopurinol cohort generated an adjusted HR of 1.51 (95% CI, 1.05-2.17).

In terms of all-cause mortality, 222 participants (7.2%) in the febuxostat group died, compared with 263 people (8.6%) in the allopurinol group.

Adverse events and withdrawals

A total 1,720 participants (57.3%) in the febuxostat group experienced at least one serious adverse event, as did 1,812 participants (59.4%) in the allopurinol group. Less than 1% of serious adverse events in each group were considered treatment-related.

Dr. MacDonald said that 6.2% of the febuxostat patients and 5.5% of the allopurinol group withdrew from the study. “We had pretty good follow-up [94%],” Dr. MacDonald said. “I don’t want to criticize CARES, but 47% did drop out of that study, and they could not follow them anymore.”

Limitations of FAST include its open-label design and lack of a placebo group, although Dr. MacDonald pointed out that a placebo group would have been unethical. Strengths included its large randomized trial design and good external validity, he added. “This is what will happen in clinical practice if you switch people from allopurinol to febuxostat.”

When asked how he would treat people with gout now given the FAST findings, Dr. MacDonald said, “I’m not a rheumatologist, I’m a cardiovascular physician. But I would say from the evidence from the FAST trial, it appears to be safe to give patients febuxostat whether or not they have cardiovascular risk factors or prior cardiovascular disease.”

“The FAST study indicates that febuxostat is similar to allopurinol in terms of cardiovascular events during the treatment period. The strengths of this study are its large sample size, excellent follow-up rate, and the relatively long follow-up time,” session moderator Shervin Assassi, MD, said when asked for comment. Dr. Assassi, director of the division of rheumatology at the University of Texas Health Science Center at Houston, was not involved in the research.

Menarini, Ipsen, and Teijin Pharma funded the study. The University of Dundee receives research funds from Menarini. Dr. MacDonald disclosed that he received speaker or consultant fees from Menarini. Dr. Assassi had no relevant disclosures.

SOURCE: MacDonald T et al. Arthritis Rheumatol. 2020;72(suppl 10). ACR 2020, Abstract L08.

Febuxostat (Uloric) emerged as noninferior to allopurinol regarding risk of cardiovascular death among people 60 years and older with gout and at least one additional cardiovascular risk factor, results of the Febuxostat versus Allopurinol Streamlined Trial (FAST) suggest.

This primary outcome of the FAST trial stands in contrast to results of the CARES trial in 2018. The CARES researchers previously reported a 4.3% increased risk of cardiovascular death associated with febuxostat, compared with a 3.2% rate with allopurinol, a statistically significant 34% increase in the relative risk.

“In contrast to previous studies, there was no evidence of increased mortality with febuxostat, and we believe the regulators should review febuxostat licensing restrictions,” senior author Thomas MacDonald, MD, of the University of Dundee (Scotland), said during a late-breaking abstract session at the virtual annual meeting of the American College of Rheumatology.

The results of the FAST trial were simultaneously published online in The Lancet.

Both febuxostat and allopurinol treat gout by lowering urate levels. Concerns about the cardiovascular safety of febuxostat led to two post-licensing studies: the Cardiovascular Safety of Febuxostat and Allopurinol in Participants with Gout and Cardiovascular Comorbidities (CARES) study, mandated by the U.S. Food and Drug Administration, and FAST, requested by the European Medicines Agency. In February 2019, the FDA added a warning about elevated cardiovascular death and death risk associated with febuxostat.

“When CARES was published, it was somewhat of a threat to our study,” Dr. MacDonald said. “After hearing from our data-monitoring committee, we were told we could continue the trial.”
 

Some switched from allopurinol to febuxostat

So Dr. MacDonald, lead author Isla Mackenzie, MBChB, and their colleagues enrolled 6,128 people with gout in the United Kingdom, Sweden, and Denmark between December 2011 and January 2018. They followed patients for a median of 4 years. Participants had a mean age of 71 years, 85% were men, and 33% had a history of cardiovascular disease. The investigators excluded anyone with a stroke or myocardial infarction in the previous 6 months.

All participants were being treated with allopurinol. The investigators titrated those not at target up to an ideal dose that achieved a serum urate concentration of less than 0.357 mmol/L (< 6 mg/dL). Next, they randomly assigned 3,065 people to continue allopurinol and another 3,063 to switch to 80-120 mg of febuxostat.

The primary outcome of the multicenter, prospective, randomized, open-label FAST trial was a composite of hospitalization for nonfatal MI or biomarker positive for acute coronary syndrome, nonfatal stroke, or cardiovascular death.
 

Key findings

“There was definitely a noninferior primary outcome,” Dr. MacDonald said. In the on-treatment analysis, 172 patients in the febuxostat group reached the composite endpoint versus 241 patients in the allopurinol group. There were 1.72 events per 100 patient-years in the febuxostat group versus 2.05 events in the allopurinol group (adjusted hazard ratio, 0.85; 95% confidence interval, 0.70-1.03). An intent-to-treat analysis also found that febuxostat was noninferior to allopurinol on this measure.

Urate levels were approximately 80 micromoles lower in the febuxostat group versus the allopurinol group each year of the study, Dr. MacDonald said.

At least one gout flare was experienced by 1,017 patients in the febuxostat group and by 1,044 participants in the allopurinol group. “However, there was no placebo group, so we don’t know the effectiveness of either of these agents at preventing flares” based on this research, he said.

Both the on-treatment and intention-to-treat (ITT) secondary analyses demonstrated the noninferiority of febuxostat, compared with allopurinol, for all-cause death, each individual component of the composite primary outcome – cardiovascular death, hospitalization for heart failure, and hospitalization for new, unstable, or worsening angina.

In contrast, the ITT analysis revealed a “nominally significant increase” in hospitalization for arrhythmia with no evidence of ischemia in the febuxostat group. The 0.583 events per 100 patient-years in this group versus 0.385 events in the allopurinol cohort generated an adjusted HR of 1.51 (95% CI, 1.05-2.17).

In terms of all-cause mortality, 222 participants (7.2%) in the febuxostat group died, compared with 263 people (8.6%) in the allopurinol group.

Adverse events and withdrawals

A total 1,720 participants (57.3%) in the febuxostat group experienced at least one serious adverse event, as did 1,812 participants (59.4%) in the allopurinol group. Less than 1% of serious adverse events in each group were considered treatment-related.

Dr. MacDonald said that 6.2% of the febuxostat patients and 5.5% of the allopurinol group withdrew from the study. “We had pretty good follow-up [94%],” Dr. MacDonald said. “I don’t want to criticize CARES, but 47% did drop out of that study, and they could not follow them anymore.”

Limitations of FAST include its open-label design and lack of a placebo group, although Dr. MacDonald pointed out that a placebo group would have been unethical. Strengths included its large randomized trial design and good external validity, he added. “This is what will happen in clinical practice if you switch people from allopurinol to febuxostat.”

When asked how he would treat people with gout now given the FAST findings, Dr. MacDonald said, “I’m not a rheumatologist, I’m a cardiovascular physician. But I would say from the evidence from the FAST trial, it appears to be safe to give patients febuxostat whether or not they have cardiovascular risk factors or prior cardiovascular disease.”

“The FAST study indicates that febuxostat is similar to allopurinol in terms of cardiovascular events during the treatment period. The strengths of this study are its large sample size, excellent follow-up rate, and the relatively long follow-up time,” session moderator Shervin Assassi, MD, said when asked for comment. Dr. Assassi, director of the division of rheumatology at the University of Texas Health Science Center at Houston, was not involved in the research.

Menarini, Ipsen, and Teijin Pharma funded the study. The University of Dundee receives research funds from Menarini. Dr. MacDonald disclosed that he received speaker or consultant fees from Menarini. Dr. Assassi had no relevant disclosures.

SOURCE: MacDonald T et al. Arthritis Rheumatol. 2020;72(suppl 10). ACR 2020, Abstract L08.

Febuxostat (Uloric) emerged as noninferior to allopurinol regarding risk of cardiovascular death among people 60 years and older with gout and at least one additional cardiovascular risk factor, results of the Febuxostat versus Allopurinol Streamlined Trial (FAST) suggest.

This primary outcome of the FAST trial stands in contrast to results of the CARES trial in 2018. The CARES researchers previously reported a 4.3% increased risk of cardiovascular death associated with febuxostat, compared with a 3.2% rate with allopurinol, a statistically significant 34% increase in the relative risk.

“In contrast to previous studies, there was no evidence of increased mortality with febuxostat, and we believe the regulators should review febuxostat licensing restrictions,” senior author Thomas MacDonald, MD, of the University of Dundee (Scotland), said during a late-breaking abstract session at the virtual annual meeting of the American College of Rheumatology.

The results of the FAST trial were simultaneously published online in The Lancet.

Both febuxostat and allopurinol treat gout by lowering urate levels. Concerns about the cardiovascular safety of febuxostat led to two post-licensing studies: the Cardiovascular Safety of Febuxostat and Allopurinol in Participants with Gout and Cardiovascular Comorbidities (CARES) study, mandated by the U.S. Food and Drug Administration, and FAST, requested by the European Medicines Agency. In February 2019, the FDA added a warning about elevated cardiovascular death and death risk associated with febuxostat.

“When CARES was published, it was somewhat of a threat to our study,” Dr. MacDonald said. “After hearing from our data-monitoring committee, we were told we could continue the trial.”
 

Some switched from allopurinol to febuxostat

So Dr. MacDonald, lead author Isla Mackenzie, MBChB, and their colleagues enrolled 6,128 people with gout in the United Kingdom, Sweden, and Denmark between December 2011 and January 2018. They followed patients for a median of 4 years. Participants had a mean age of 71 years, 85% were men, and 33% had a history of cardiovascular disease. The investigators excluded anyone with a stroke or myocardial infarction in the previous 6 months.

All participants were being treated with allopurinol. The investigators titrated those not at target up to an ideal dose that achieved a serum urate concentration of less than 0.357 mmol/L (< 6 mg/dL). Next, they randomly assigned 3,065 people to continue allopurinol and another 3,063 to switch to 80-120 mg of febuxostat.

The primary outcome of the multicenter, prospective, randomized, open-label FAST trial was a composite of hospitalization for nonfatal MI or biomarker positive for acute coronary syndrome, nonfatal stroke, or cardiovascular death.
 

Key findings

“There was definitely a noninferior primary outcome,” Dr. MacDonald said. In the on-treatment analysis, 172 patients in the febuxostat group reached the composite endpoint versus 241 patients in the allopurinol group. There were 1.72 events per 100 patient-years in the febuxostat group versus 2.05 events in the allopurinol group (adjusted hazard ratio, 0.85; 95% confidence interval, 0.70-1.03). An intent-to-treat analysis also found that febuxostat was noninferior to allopurinol on this measure.

Urate levels were approximately 80 micromoles lower in the febuxostat group versus the allopurinol group each year of the study, Dr. MacDonald said.

At least one gout flare was experienced by 1,017 patients in the febuxostat group and by 1,044 participants in the allopurinol group. “However, there was no placebo group, so we don’t know the effectiveness of either of these agents at preventing flares” based on this research, he said.

Both the on-treatment and intention-to-treat (ITT) secondary analyses demonstrated the noninferiority of febuxostat, compared with allopurinol, for all-cause death, each individual component of the composite primary outcome – cardiovascular death, hospitalization for heart failure, and hospitalization for new, unstable, or worsening angina.

In contrast, the ITT analysis revealed a “nominally significant increase” in hospitalization for arrhythmia with no evidence of ischemia in the febuxostat group. The 0.583 events per 100 patient-years in this group versus 0.385 events in the allopurinol cohort generated an adjusted HR of 1.51 (95% CI, 1.05-2.17).

In terms of all-cause mortality, 222 participants (7.2%) in the febuxostat group died, compared with 263 people (8.6%) in the allopurinol group.

Adverse events and withdrawals

A total 1,720 participants (57.3%) in the febuxostat group experienced at least one serious adverse event, as did 1,812 participants (59.4%) in the allopurinol group. Less than 1% of serious adverse events in each group were considered treatment-related.

Dr. MacDonald said that 6.2% of the febuxostat patients and 5.5% of the allopurinol group withdrew from the study. “We had pretty good follow-up [94%],” Dr. MacDonald said. “I don’t want to criticize CARES, but 47% did drop out of that study, and they could not follow them anymore.”

Limitations of FAST include its open-label design and lack of a placebo group, although Dr. MacDonald pointed out that a placebo group would have been unethical. Strengths included its large randomized trial design and good external validity, he added. “This is what will happen in clinical practice if you switch people from allopurinol to febuxostat.”

When asked how he would treat people with gout now given the FAST findings, Dr. MacDonald said, “I’m not a rheumatologist, I’m a cardiovascular physician. But I would say from the evidence from the FAST trial, it appears to be safe to give patients febuxostat whether or not they have cardiovascular risk factors or prior cardiovascular disease.”

“The FAST study indicates that febuxostat is similar to allopurinol in terms of cardiovascular events during the treatment period. The strengths of this study are its large sample size, excellent follow-up rate, and the relatively long follow-up time,” session moderator Shervin Assassi, MD, said when asked for comment. Dr. Assassi, director of the division of rheumatology at the University of Texas Health Science Center at Houston, was not involved in the research.

Menarini, Ipsen, and Teijin Pharma funded the study. The University of Dundee receives research funds from Menarini. Dr. MacDonald disclosed that he received speaker or consultant fees from Menarini. Dr. Assassi had no relevant disclosures.

SOURCE: MacDonald T et al. Arthritis Rheumatol. 2020;72(suppl 10). ACR 2020, Abstract L08.

Severe constipation affected 34% of adults with gastroparesis symptoms and showed a significant positive correlation with symptom severity in a multicenter prospective study.

Henry P. Parkman, MD, of Temple University in Philadelphia and his associates used a modified GI symptoms questionnaire, gastric-emptying scintigraphy, and wireless motility capsule studies of 338 participants in the National Institutes of Health Gastroparesis Registry, which enrolls individuals with gastroparesis symptoms (whether or not they have delayed gastric emptying). In the multivariable analysis, severe constipation (a score of 4 or 5 on a 5-point scale) correlated significantly with a higher score on the Gastroparesis Cardinal Symptoms Index (GCSI), with an odds ratio of 1.85 (95% confidence interval, 1.30-2.67). In addition, patients with gastroparesis symptoms were significantly more likely to report pain in the lower abdomen (OR, 1.34; 95% CI, 1.06-1.69) and to use medications to manage constipation (OR, 5.09; 95% CI, 2.75-9.41). The findings were published online in Clinical Gastroenterology and Hepatology.

Constipation was not significantly linked with the use of individual drug classes, including opiates, tricyclic antidepressants, 5HT3 receptor antagonists, or cannabinoids. However, many patients were taking combinations of medications, and it is unclear if these induced constipation or if patients had primary disorders, such as abnormal colonic motility or anorectal dysfunction, said Adil E. Bharucha, MBBS, MD, a professor of medicine in the gastroenterology and hepatology division and a medical director in the office of clinical trials at Mayo Clinic, Rochester, Minn., who was not involved in the study. For patients with gastroparesis and constipation, clinicians should consider withdrawing constipating medications, performing anorectal testing, and referring patients for pelvic floor biofeedback therapy if anorectal tests are positive, he said while acknowledging the need for more data on these approaches. For patients without evidence of anorectal disorders, he recommended “simple laxatives or, if necessary, prescription medications, some of which may also benefit upper gastrointestinal symptoms.”

In this study, constipation also did not correlate with gastric emptying, which suggests that “motility disturbances in the foregut are separable from those in the hindgut,” said David Levinthal, MD, PhD, director of the neurogastroenterology and motility center at the University of Pittsburgh Medical Center, who also was not involved in the work. Constipation was only marginally linked with colonic transit time (OR, 1.04; 95% CI, 1.00-1.07), and delayed gastric emptying did not predict the severity of dyspepsia, he noted. “These observations highlight that sensory mechanisms are very important factors that are not interrogated by physiological motility tests, but that nonetheless may have an outsized impact on how patients feel.”

Despite “fairly good phenotyping of patients [based on] physiological measures, medication use, and detailed symptom questionnaires,” the study’s method of grouping patients based on continuous variables could mask relevant clinical nuances, Dr. Levinthal said. He emphasized that individual physiological tests do not reliably predict the presence or severity of GI symptoms: “What would you make of a 50-hour colonic transit time [CTT]? Or a 60-hour CTT? One could have either no constipation or severe constipation with those values. In clinical practice, it is less certain how useful it is to know a specific CTT result [when] formulating a treatment plan.”

Therefore, future studies of patients with gastroparesis and constipation should forgo grouping patients based on GI motor patterns and instead validate patient-reported symptom measures by using novel sensory tests with stimuli such as eating, drinking, and balloon distension, Dr. Levinthal said. He also recommended studying cognitive and emotional functioning in this patients, given that conditions such as depression and anxiety are known to affect GI sensation.

The National Institute of Diabetes and Digestive and Kidney Diseases provided funding. The investigators reported having no conflicts of interest. Dr. Bharucha reported having filed patents for anorectal devices jointly with Minnesota Medical Technologies, Medspira, and Medtronic and receiving royalties from Medspira. Dr. Levinthal reported having served on advisory boards for Takeda Pharmaceuticals and Alexza Pharmaceuticals.

SOURCE: Parkman HP et al. Clin Gastroenterol Hepatol. 2020 Oct 28. doi: 10.1016/j.cgh.2020.10.045.
 

Severe constipation affected 34% of adults with gastroparesis symptoms and showed a significant positive correlation with symptom severity in a multicenter prospective study.

Henry P. Parkman, MD, of Temple University in Philadelphia and his associates used a modified GI symptoms questionnaire, gastric-emptying scintigraphy, and wireless motility capsule studies of 338 participants in the National Institutes of Health Gastroparesis Registry, which enrolls individuals with gastroparesis symptoms (whether or not they have delayed gastric emptying). In the multivariable analysis, severe constipation (a score of 4 or 5 on a 5-point scale) correlated significantly with a higher score on the Gastroparesis Cardinal Symptoms Index (GCSI), with an odds ratio of 1.85 (95% confidence interval, 1.30-2.67). In addition, patients with gastroparesis symptoms were significantly more likely to report pain in the lower abdomen (OR, 1.34; 95% CI, 1.06-1.69) and to use medications to manage constipation (OR, 5.09; 95% CI, 2.75-9.41). The findings were published online in Clinical Gastroenterology and Hepatology.

Constipation was not significantly linked with the use of individual drug classes, including opiates, tricyclic antidepressants, 5HT3 receptor antagonists, or cannabinoids. However, many patients were taking combinations of medications, and it is unclear if these induced constipation or if patients had primary disorders, such as abnormal colonic motility or anorectal dysfunction, said Adil E. Bharucha, MBBS, MD, a professor of medicine in the gastroenterology and hepatology division and a medical director in the office of clinical trials at Mayo Clinic, Rochester, Minn., who was not involved in the study. For patients with gastroparesis and constipation, clinicians should consider withdrawing constipating medications, performing anorectal testing, and referring patients for pelvic floor biofeedback therapy if anorectal tests are positive, he said while acknowledging the need for more data on these approaches. For patients without evidence of anorectal disorders, he recommended “simple laxatives or, if necessary, prescription medications, some of which may also benefit upper gastrointestinal symptoms.”

In this study, constipation also did not correlate with gastric emptying, which suggests that “motility disturbances in the foregut are separable from those in the hindgut,” said David Levinthal, MD, PhD, director of the neurogastroenterology and motility center at the University of Pittsburgh Medical Center, who also was not involved in the work. Constipation was only marginally linked with colonic transit time (OR, 1.04; 95% CI, 1.00-1.07), and delayed gastric emptying did not predict the severity of dyspepsia, he noted. “These observations highlight that sensory mechanisms are very important factors that are not interrogated by physiological motility tests, but that nonetheless may have an outsized impact on how patients feel.”

Despite “fairly good phenotyping of patients [based on] physiological measures, medication use, and detailed symptom questionnaires,” the study’s method of grouping patients based on continuous variables could mask relevant clinical nuances, Dr. Levinthal said. He emphasized that individual physiological tests do not reliably predict the presence or severity of GI symptoms: “What would you make of a 50-hour colonic transit time [CTT]? Or a 60-hour CTT? One could have either no constipation or severe constipation with those values. In clinical practice, it is less certain how useful it is to know a specific CTT result [when] formulating a treatment plan.”

Therefore, future studies of patients with gastroparesis and constipation should forgo grouping patients based on GI motor patterns and instead validate patient-reported symptom measures by using novel sensory tests with stimuli such as eating, drinking, and balloon distension, Dr. Levinthal said. He also recommended studying cognitive and emotional functioning in this patients, given that conditions such as depression and anxiety are known to affect GI sensation.

The National Institute of Diabetes and Digestive and Kidney Diseases provided funding. The investigators reported having no conflicts of interest. Dr. Bharucha reported having filed patents for anorectal devices jointly with Minnesota Medical Technologies, Medspira, and Medtronic and receiving royalties from Medspira. Dr. Levinthal reported having served on advisory boards for Takeda Pharmaceuticals and Alexza Pharmaceuticals.

SOURCE: Parkman HP et al. Clin Gastroenterol Hepatol. 2020 Oct 28. doi: 10.1016/j.cgh.2020.10.045.
 

Severe constipation affected 34% of adults with gastroparesis symptoms and showed a significant positive correlation with symptom severity in a multicenter prospective study.

Henry P. Parkman, MD, of Temple University in Philadelphia and his associates used a modified GI symptoms questionnaire, gastric-emptying scintigraphy, and wireless motility capsule studies of 338 participants in the National Institutes of Health Gastroparesis Registry, which enrolls individuals with gastroparesis symptoms (whether or not they have delayed gastric emptying). In the multivariable analysis, severe constipation (a score of 4 or 5 on a 5-point scale) correlated significantly with a higher score on the Gastroparesis Cardinal Symptoms Index (GCSI), with an odds ratio of 1.85 (95% confidence interval, 1.30-2.67). In addition, patients with gastroparesis symptoms were significantly more likely to report pain in the lower abdomen (OR, 1.34; 95% CI, 1.06-1.69) and to use medications to manage constipation (OR, 5.09; 95% CI, 2.75-9.41). The findings were published online in Clinical Gastroenterology and Hepatology.

Constipation was not significantly linked with the use of individual drug classes, including opiates, tricyclic antidepressants, 5HT3 receptor antagonists, or cannabinoids. However, many patients were taking combinations of medications, and it is unclear if these induced constipation or if patients had primary disorders, such as abnormal colonic motility or anorectal dysfunction, said Adil E. Bharucha, MBBS, MD, a professor of medicine in the gastroenterology and hepatology division and a medical director in the office of clinical trials at Mayo Clinic, Rochester, Minn., who was not involved in the study. For patients with gastroparesis and constipation, clinicians should consider withdrawing constipating medications, performing anorectal testing, and referring patients for pelvic floor biofeedback therapy if anorectal tests are positive, he said while acknowledging the need for more data on these approaches. For patients without evidence of anorectal disorders, he recommended “simple laxatives or, if necessary, prescription medications, some of which may also benefit upper gastrointestinal symptoms.”

In this study, constipation also did not correlate with gastric emptying, which suggests that “motility disturbances in the foregut are separable from those in the hindgut,” said David Levinthal, MD, PhD, director of the neurogastroenterology and motility center at the University of Pittsburgh Medical Center, who also was not involved in the work. Constipation was only marginally linked with colonic transit time (OR, 1.04; 95% CI, 1.00-1.07), and delayed gastric emptying did not predict the severity of dyspepsia, he noted. “These observations highlight that sensory mechanisms are very important factors that are not interrogated by physiological motility tests, but that nonetheless may have an outsized impact on how patients feel.”

Despite “fairly good phenotyping of patients [based on] physiological measures, medication use, and detailed symptom questionnaires,” the study’s method of grouping patients based on continuous variables could mask relevant clinical nuances, Dr. Levinthal said. He emphasized that individual physiological tests do not reliably predict the presence or severity of GI symptoms: “What would you make of a 50-hour colonic transit time [CTT]? Or a 60-hour CTT? One could have either no constipation or severe constipation with those values. In clinical practice, it is less certain how useful it is to know a specific CTT result [when] formulating a treatment plan.”

Therefore, future studies of patients with gastroparesis and constipation should forgo grouping patients based on GI motor patterns and instead validate patient-reported symptom measures by using novel sensory tests with stimuli such as eating, drinking, and balloon distension, Dr. Levinthal said. He also recommended studying cognitive and emotional functioning in this patients, given that conditions such as depression and anxiety are known to affect GI sensation.

The National Institute of Diabetes and Digestive and Kidney Diseases provided funding. The investigators reported having no conflicts of interest. Dr. Bharucha reported having filed patents for anorectal devices jointly with Minnesota Medical Technologies, Medspira, and Medtronic and receiving royalties from Medspira. Dr. Levinthal reported having served on advisory boards for Takeda Pharmaceuticals and Alexza Pharmaceuticals.

SOURCE: Parkman HP et al. Clin Gastroenterol Hepatol. 2020 Oct 28. doi: 10.1016/j.cgh.2020.10.045.
 

Ibrutinib showed significant impact on circulating malignant and nonmalignant immune cells and was found to restore healthy T-cell function in patients with chronic lymphocytic leukemia (CLL), according to the results of a comparative study of CLL patients and healthy controls.

Researchers compared circulating counts of 21 immune blood cell subsets throughout the first year of treatment in 55 patients with relapsed/refractory (R/R) CLL from the RESONATE trial and 50 previously untreated CLL patients from the RESONATE-2 trial with 20 untreated age-matched healthy donors, according to a report published online in Leukemia Research.

In addition, T-cell function was assessed in response to T-cell–receptor stimulation in 21 patients with R/R CLL, compared with 18 age-matched healthy donors, according to Isabelle G. Solman, MS, an employee of Translational Medicine, Pharmacyclics, Sunnyvale, Calif. and colleagues.
 

Positive indicators

Ibrutinib significantly decreased pathologically high circulating B cells, regulatory T cells, effector/memory CD4+ and CD8+ T cells (including exhausted and chronically activated T cells), natural killer (NK) T cells, and myeloid-derived suppressor cells; preserved naive T cells and NK cells; and increased circulating classical monocytes, according to the researchers.

Ibrutinib also significantly restored T-cell proliferative ability, degranulation, and cytokine secretion. Over the same period, ofatumumab or chlorambucil did not confer the same spectrum of normalization as ibrutinib in multiple immune subsets that were examined, they added.

“These results establish that ibrutinib has a significant and likely positive impact on circulating malignant and nonmalignant immune cells and restores healthy T-cell function,” the researchers indicated.

“Ibrutinib has a significant, progressively positive impact on both malignant and nonmalignant immune cells in CLL. These positive effects on circulating nonmalignant immune cells may contribute to long-term CLL disease control, overall health status, and decreased susceptibility to infection,” they concluded.

The study was funded by Pharmacyclics, an AbbVie Company. Ms. Solman is an employee of Translational Medicine, Pharmacyclics, Sunnyvale, Calif. as were several other authors.

[email protected]

SOURCE: Solman IG et al. Leuk Res. 2020;97. doi: 10.1016/j.leukres.2020.106432.

Ibrutinib showed significant impact on circulating malignant and nonmalignant immune cells and was found to restore healthy T-cell function in patients with chronic lymphocytic leukemia (CLL), according to the results of a comparative study of CLL patients and healthy controls.

Researchers compared circulating counts of 21 immune blood cell subsets throughout the first year of treatment in 55 patients with relapsed/refractory (R/R) CLL from the RESONATE trial and 50 previously untreated CLL patients from the RESONATE-2 trial with 20 untreated age-matched healthy donors, according to a report published online in Leukemia Research.

In addition, T-cell function was assessed in response to T-cell–receptor stimulation in 21 patients with R/R CLL, compared with 18 age-matched healthy donors, according to Isabelle G. Solman, MS, an employee of Translational Medicine, Pharmacyclics, Sunnyvale, Calif. and colleagues.
 

Positive indicators

Ibrutinib significantly decreased pathologically high circulating B cells, regulatory T cells, effector/memory CD4+ and CD8+ T cells (including exhausted and chronically activated T cells), natural killer (NK) T cells, and myeloid-derived suppressor cells; preserved naive T cells and NK cells; and increased circulating classical monocytes, according to the researchers.

Ibrutinib also significantly restored T-cell proliferative ability, degranulation, and cytokine secretion. Over the same period, ofatumumab or chlorambucil did not confer the same spectrum of normalization as ibrutinib in multiple immune subsets that were examined, they added.

“These results establish that ibrutinib has a significant and likely positive impact on circulating malignant and nonmalignant immune cells and restores healthy T-cell function,” the researchers indicated.

“Ibrutinib has a significant, progressively positive impact on both malignant and nonmalignant immune cells in CLL. These positive effects on circulating nonmalignant immune cells may contribute to long-term CLL disease control, overall health status, and decreased susceptibility to infection,” they concluded.

The study was funded by Pharmacyclics, an AbbVie Company. Ms. Solman is an employee of Translational Medicine, Pharmacyclics, Sunnyvale, Calif. as were several other authors.

[email protected]

SOURCE: Solman IG et al. Leuk Res. 2020;97. doi: 10.1016/j.leukres.2020.106432.

Ibrutinib showed significant impact on circulating malignant and nonmalignant immune cells and was found to restore healthy T-cell function in patients with chronic lymphocytic leukemia (CLL), according to the results of a comparative study of CLL patients and healthy controls.

Researchers compared circulating counts of 21 immune blood cell subsets throughout the first year of treatment in 55 patients with relapsed/refractory (R/R) CLL from the RESONATE trial and 50 previously untreated CLL patients from the RESONATE-2 trial with 20 untreated age-matched healthy donors, according to a report published online in Leukemia Research.

In addition, T-cell function was assessed in response to T-cell–receptor stimulation in 21 patients with R/R CLL, compared with 18 age-matched healthy donors, according to Isabelle G. Solman, MS, an employee of Translational Medicine, Pharmacyclics, Sunnyvale, Calif. and colleagues.
 

Positive indicators

Ibrutinib significantly decreased pathologically high circulating B cells, regulatory T cells, effector/memory CD4+ and CD8+ T cells (including exhausted and chronically activated T cells), natural killer (NK) T cells, and myeloid-derived suppressor cells; preserved naive T cells and NK cells; and increased circulating classical monocytes, according to the researchers.

Ibrutinib also significantly restored T-cell proliferative ability, degranulation, and cytokine secretion. Over the same period, ofatumumab or chlorambucil did not confer the same spectrum of normalization as ibrutinib in multiple immune subsets that were examined, they added.

“These results establish that ibrutinib has a significant and likely positive impact on circulating malignant and nonmalignant immune cells and restores healthy T-cell function,” the researchers indicated.

“Ibrutinib has a significant, progressively positive impact on both malignant and nonmalignant immune cells in CLL. These positive effects on circulating nonmalignant immune cells may contribute to long-term CLL disease control, overall health status, and decreased susceptibility to infection,” they concluded.

The study was funded by Pharmacyclics, an AbbVie Company. Ms. Solman is an employee of Translational Medicine, Pharmacyclics, Sunnyvale, Calif. as were several other authors.

[email protected]

SOURCE: Solman IG et al. Leuk Res. 2020;97. doi: 10.1016/j.leukres.2020.106432.

Precision medicine therapy proved feasible and superior to standard-of-care (SOC) chemotherapy in patients with acute myeloid leukemia in the Beat AML Master Clinical Trial.

The 30-day mortality rates were 3.7% versus 20.4% in 224 patients who enrolled in the Beat AML trial precision medicine substudies within 7 days of prospective genomic profiling and 103 who elected SOC chemotherapy, respectively, Amy Burd, PhD, vice president of research strategy for the Leukemia & Lymphoma Society, Rye Brook, N.Y. and her colleagues reported online in Nature Medicine.

Overall survival (OS) at a median of 7.1 months was also significantly longer with precision medicine than with SOC chemotherapy (median, 12.8 vs. 3.9 months), the investigators found.

In an additional 28 patients who selected an investigational therapy rather than a precision medicine strategy or SOC chemotherapy, median OS was not reached, and in 38 who chose palliative care, median OS was 0.6 months, they noted. Care type was unknown in two patients.

The results were similar after controlling for demographic, clinical, and molecular variables and did not change when patients with adverse events of special interest were excluded from the analysis or when only those with survival greater than 2 weeks were included in the analysis.

AML confers an adverse outcome in older adults and therefore is typically treated rapidly after diagnosis. This has precluded consideration of patients’ mutational profile for treatment decisions.

Beat AML, however, sought to prospectively assess the feasibility of quickly ascertaining cytogenetic and mutational data for the purpose of improving outcomes through targeted treatment.

“The study shows that delaying treatment up to 7 days is feasible and safe, and that patients who opted for the precision medicine approach experienced a lower early death rate and superior overall survival, compared with patients who opted for standard of care,” lead study author John C. Byrd, MD, the D. Warren Brown Chair of Leukemia Research of the Ohio State University, Columbus, noted in a press statement from the Leukemia & Lymphoma Society, which conducted the trial. “This patient-centric study shows that we can move away from chemotherapy treatment for patients who won’t respond or can’t withstand the harsh effects of the same chemotherapies we’ve been using for 40 years and match them with a treatment better suited for their individual cases.”

The ongoing Beat AML trial was launched by LLS in 2016 to assess various novel targeted therapies in newly diagnosed AML patients aged 60 years and older. Participants underwent next-generation genomic sequencing, were matched to the appropriate targeted therapy, and were given the option of enrolling on the relevant substudy or selecting an alternate treatment strategy. There are currently 11 substudies assessing novel therapies that have emerged in the wake of “significant progress in understanding the molecular pathogenesis of AML.”

The current findings represent outcomes in patients enrolled between Nov. 2016 and Jan. 2018. The patients had a mean age of 72 years, and those selecting precision medicine vs. SOC had similar demographic and genetic features, the authors noted.

LLS president and chief executive officer Louis J. DeGennaro, PhD, said the findings are practice changing and provide a template for studying precision medicine in other cancers.

“The study is changing significantly the way we look at treating patients with AML, showing that precision medicine ... can improve short- and long-term outcomes for patients with this deadly blood cancer,” he said in the LLS statement. “Further, BEAT AML has proven to be a viable model for other cancer clinical trials to emulate.”

In fact, the model has been applied to the recently launched Beat COVID trial, which looks at acalabrutinib in patients with hematologic cancers and COVID-19 infection, and other trials, including the LLS PedAL global precision medicine trial for children with relapsed acute leukemia, are planned.

“This study sets the path to establish the safety of precision medicine in AML and sets the stage to extend this same approach to younger patients with this disease and other cancers that are urgently treated as a single disease despite recognition of multiple subtypes, the authors concluded.

Dr. Burd is an employee of LLS, which received funding from AbbVie, Agios Pharmaceuticals, Alexion Pharmaceuticals, and a variety of other pharmaceutical and biotechnology companies. Dr. Byrd has received research support from Acerta Pharma, Genentech, Janssen Pharmaceutica, and Pharmacyclics and has served on the advisory board of Syndax Pharmaceuticals.

[email protected]

SOURCE: Burd A et al. Nature Medicine 2020 Oct 26. doi: 10.1038/s41591-020-1089-8.

Precision medicine therapy proved feasible and superior to standard-of-care (SOC) chemotherapy in patients with acute myeloid leukemia in the Beat AML Master Clinical Trial.

The 30-day mortality rates were 3.7% versus 20.4% in 224 patients who enrolled in the Beat AML trial precision medicine substudies within 7 days of prospective genomic profiling and 103 who elected SOC chemotherapy, respectively, Amy Burd, PhD, vice president of research strategy for the Leukemia & Lymphoma Society, Rye Brook, N.Y. and her colleagues reported online in Nature Medicine.

Overall survival (OS) at a median of 7.1 months was also significantly longer with precision medicine than with SOC chemotherapy (median, 12.8 vs. 3.9 months), the investigators found.

In an additional 28 patients who selected an investigational therapy rather than a precision medicine strategy or SOC chemotherapy, median OS was not reached, and in 38 who chose palliative care, median OS was 0.6 months, they noted. Care type was unknown in two patients.

The results were similar after controlling for demographic, clinical, and molecular variables and did not change when patients with adverse events of special interest were excluded from the analysis or when only those with survival greater than 2 weeks were included in the analysis.

AML confers an adverse outcome in older adults and therefore is typically treated rapidly after diagnosis. This has precluded consideration of patients’ mutational profile for treatment decisions.

Beat AML, however, sought to prospectively assess the feasibility of quickly ascertaining cytogenetic and mutational data for the purpose of improving outcomes through targeted treatment.

“The study shows that delaying treatment up to 7 days is feasible and safe, and that patients who opted for the precision medicine approach experienced a lower early death rate and superior overall survival, compared with patients who opted for standard of care,” lead study author John C. Byrd, MD, the D. Warren Brown Chair of Leukemia Research of the Ohio State University, Columbus, noted in a press statement from the Leukemia & Lymphoma Society, which conducted the trial. “This patient-centric study shows that we can move away from chemotherapy treatment for patients who won’t respond or can’t withstand the harsh effects of the same chemotherapies we’ve been using for 40 years and match them with a treatment better suited for their individual cases.”

The ongoing Beat AML trial was launched by LLS in 2016 to assess various novel targeted therapies in newly diagnosed AML patients aged 60 years and older. Participants underwent next-generation genomic sequencing, were matched to the appropriate targeted therapy, and were given the option of enrolling on the relevant substudy or selecting an alternate treatment strategy. There are currently 11 substudies assessing novel therapies that have emerged in the wake of “significant progress in understanding the molecular pathogenesis of AML.”

The current findings represent outcomes in patients enrolled between Nov. 2016 and Jan. 2018. The patients had a mean age of 72 years, and those selecting precision medicine vs. SOC had similar demographic and genetic features, the authors noted.

LLS president and chief executive officer Louis J. DeGennaro, PhD, said the findings are practice changing and provide a template for studying precision medicine in other cancers.

“The study is changing significantly the way we look at treating patients with AML, showing that precision medicine ... can improve short- and long-term outcomes for patients with this deadly blood cancer,” he said in the LLS statement. “Further, BEAT AML has proven to be a viable model for other cancer clinical trials to emulate.”

In fact, the model has been applied to the recently launched Beat COVID trial, which looks at acalabrutinib in patients with hematologic cancers and COVID-19 infection, and other trials, including the LLS PedAL global precision medicine trial for children with relapsed acute leukemia, are planned.

“This study sets the path to establish the safety of precision medicine in AML and sets the stage to extend this same approach to younger patients with this disease and other cancers that are urgently treated as a single disease despite recognition of multiple subtypes, the authors concluded.

Dr. Burd is an employee of LLS, which received funding from AbbVie, Agios Pharmaceuticals, Alexion Pharmaceuticals, and a variety of other pharmaceutical and biotechnology companies. Dr. Byrd has received research support from Acerta Pharma, Genentech, Janssen Pharmaceutica, and Pharmacyclics and has served on the advisory board of Syndax Pharmaceuticals.

[email protected]

SOURCE: Burd A et al. Nature Medicine 2020 Oct 26. doi: 10.1038/s41591-020-1089-8.

Precision medicine therapy proved feasible and superior to standard-of-care (SOC) chemotherapy in patients with acute myeloid leukemia in the Beat AML Master Clinical Trial.

The 30-day mortality rates were 3.7% versus 20.4% in 224 patients who enrolled in the Beat AML trial precision medicine substudies within 7 days of prospective genomic profiling and 103 who elected SOC chemotherapy, respectively, Amy Burd, PhD, vice president of research strategy for the Leukemia & Lymphoma Society, Rye Brook, N.Y. and her colleagues reported online in Nature Medicine.

Overall survival (OS) at a median of 7.1 months was also significantly longer with precision medicine than with SOC chemotherapy (median, 12.8 vs. 3.9 months), the investigators found.

In an additional 28 patients who selected an investigational therapy rather than a precision medicine strategy or SOC chemotherapy, median OS was not reached, and in 38 who chose palliative care, median OS was 0.6 months, they noted. Care type was unknown in two patients.

The results were similar after controlling for demographic, clinical, and molecular variables and did not change when patients with adverse events of special interest were excluded from the analysis or when only those with survival greater than 2 weeks were included in the analysis.

AML confers an adverse outcome in older adults and therefore is typically treated rapidly after diagnosis. This has precluded consideration of patients’ mutational profile for treatment decisions.

Beat AML, however, sought to prospectively assess the feasibility of quickly ascertaining cytogenetic and mutational data for the purpose of improving outcomes through targeted treatment.

“The study shows that delaying treatment up to 7 days is feasible and safe, and that patients who opted for the precision medicine approach experienced a lower early death rate and superior overall survival, compared with patients who opted for standard of care,” lead study author John C. Byrd, MD, the D. Warren Brown Chair of Leukemia Research of the Ohio State University, Columbus, noted in a press statement from the Leukemia & Lymphoma Society, which conducted the trial. “This patient-centric study shows that we can move away from chemotherapy treatment for patients who won’t respond or can’t withstand the harsh effects of the same chemotherapies we’ve been using for 40 years and match them with a treatment better suited for their individual cases.”

The ongoing Beat AML trial was launched by LLS in 2016 to assess various novel targeted therapies in newly diagnosed AML patients aged 60 years and older. Participants underwent next-generation genomic sequencing, were matched to the appropriate targeted therapy, and were given the option of enrolling on the relevant substudy or selecting an alternate treatment strategy. There are currently 11 substudies assessing novel therapies that have emerged in the wake of “significant progress in understanding the molecular pathogenesis of AML.”

The current findings represent outcomes in patients enrolled between Nov. 2016 and Jan. 2018. The patients had a mean age of 72 years, and those selecting precision medicine vs. SOC had similar demographic and genetic features, the authors noted.

LLS president and chief executive officer Louis J. DeGennaro, PhD, said the findings are practice changing and provide a template for studying precision medicine in other cancers.

“The study is changing significantly the way we look at treating patients with AML, showing that precision medicine ... can improve short- and long-term outcomes for patients with this deadly blood cancer,” he said in the LLS statement. “Further, BEAT AML has proven to be a viable model for other cancer clinical trials to emulate.”

In fact, the model has been applied to the recently launched Beat COVID trial, which looks at acalabrutinib in patients with hematologic cancers and COVID-19 infection, and other trials, including the LLS PedAL global precision medicine trial for children with relapsed acute leukemia, are planned.

“This study sets the path to establish the safety of precision medicine in AML and sets the stage to extend this same approach to younger patients with this disease and other cancers that are urgently treated as a single disease despite recognition of multiple subtypes, the authors concluded.

Dr. Burd is an employee of LLS, which received funding from AbbVie, Agios Pharmaceuticals, Alexion Pharmaceuticals, and a variety of other pharmaceutical and biotechnology companies. Dr. Byrd has received research support from Acerta Pharma, Genentech, Janssen Pharmaceutica, and Pharmacyclics and has served on the advisory board of Syndax Pharmaceuticals.

[email protected]

SOURCE: Burd A et al. Nature Medicine 2020 Oct 26. doi: 10.1038/s41591-020-1089-8.

Inflammatory bowel disease (IBD) is rapidly increasing among racial and ethnic minorities, which makes it important to consider for patients with compatible symptoms, experts wrote in Gastroenterology.

Crohn’s disease and ulcerative colitis are “chronic diseases with intermittent periods of flare and remission, so access to specialists, appropriate therapies, and frequent follow-up visits are vital to good outcomes,” wrote Edward L. Barnes, MD, MPH, of University of North Carolina at Chapel Hill, with his associates. However, Blacks with IBD tend to be diagnosed later than Whites, are less likely to receive recommended biologics and immunomodulators, and are more likely to receive care at an emergency department, to experience delays in colectomy, and to miss regular visits to IBD specialists because of financial and transportation barriers, they added.

These disparities are known to worsen outcomes. Compared with Whites, for example, Black patients with Crohn’s disease have higher rates of stricture and penetrating lesions and are at greater risk for postsurgical complications and death, even after potential confounders such age, sex, smoking status, time to operation, and obesity are controlled for. To help close these gaps, Dr. Barnes and his associates recommended enhanced recovery after surgery (ERAS) protocols, which “streamline [the] multidisciplinary management of patients with IBD before surgery, incorporating evidence-based practices focused on nutrition, prevention of postoperative ileus, and use of nonopioid analgesia and goal-directed fluid therapy.”

Similar approaches also might improve nonsurgical outcomes in minorities with IBD, the experts said. In the Sinai-Helmsley Alliance for Research Excellence (SHARE) study, Black patients had more complicated IBD at baseline but similar clinical outcomes and patterns of medication use as Whites when they were treated at academic IBD centers. In other studies, race and ethnicity did not affect patterns of medication use, surgery, or surgical outcomes if patients had similar access to care. Such findings “indicate that when patients of minority races and ethnicities have access to appropriate specialty care and IBD-related therapy, many previously identified disparities are resolved or reduced,” the experts said.

However, race and ethnicity do affect some aspects of IBD disease activity, genetics, and treatment safety and efficacy. Since White patients have made up the vast majority of research participants, studies of racial and ethnic minorities are needed to improve their IBD diagnosis, prevention, and treatment. Such research is particularly vital because IBD incidence is rising three times faster rates in racial and ethnic minorities than Whites, said Aline Charabaty, MD, AGAF, clinical director of the gastroenterology division at Johns Hopkins University in Baltimore, and director of the IBD Center at Sibley Memorial Hospital in Washington.

She explained that, when immigrants from countries where IBD is rare adopt the United States’ sedentary lifestyle and Western diet (low in fruits and vegetables; high in proinflammatory saturated fats, sugars, and processed foods), their gut microbiome shifts and their IBD risk increases markedly. Studies in other countries have produced similar findings, said Dr. Charabaty, who did not help author the review article.

She also noted that patients from communities with a historically low prevalence of IBD may not understand its chronicity or the need for long-term treatment. However, treatment adherence is a common issue for patients of all backgrounds with IBD, she said. “What is unique is barriers to continuity of care – not being able to get to the treatment center, not being able to afford treatment or take time off work if you live paycheck to paycheck, not being able to pay someone to care for your kids while you see the doctor.”

Other potential barriers to seeking IBD treatment include cultural taboos against discussing lower GI symptoms or concerns that chronic disease will harm marriage prospects, Dr. Charabaty said. Such challenges only heighten the need to ascertain IBD symptoms: “Studies show that minorities have less follow-up care and their symptoms tend to be minimized. There is a lot of unconscious bias among providers that factors into this. The barriers are multiple, and it is important to define them and find strategies to overcome them at the level of the patient, the clinician, and the health system.”

The Crohn’s and Colitis Foundation supported the work. Dr. Barnes disclosed ties to AbbVie, Gilead, Takeda, and Target Pharmasolutions. Two coauthors also disclosed relevant ties to pharmaceutical companies. Dr. Charabaty disclosed relationships with AbbVie, Takeda, Pfizer, Janssen, and UCB.

SOURCE: Barnes EL et al. Gastroenterology. 2020 Oct 20. doi: 10.1053/j.gastro.2020.08.064.
 

Inflammatory bowel disease (IBD) is rapidly increasing among racial and ethnic minorities, which makes it important to consider for patients with compatible symptoms, experts wrote in Gastroenterology.

Crohn’s disease and ulcerative colitis are “chronic diseases with intermittent periods of flare and remission, so access to specialists, appropriate therapies, and frequent follow-up visits are vital to good outcomes,” wrote Edward L. Barnes, MD, MPH, of University of North Carolina at Chapel Hill, with his associates. However, Blacks with IBD tend to be diagnosed later than Whites, are less likely to receive recommended biologics and immunomodulators, and are more likely to receive care at an emergency department, to experience delays in colectomy, and to miss regular visits to IBD specialists because of financial and transportation barriers, they added.

These disparities are known to worsen outcomes. Compared with Whites, for example, Black patients with Crohn’s disease have higher rates of stricture and penetrating lesions and are at greater risk for postsurgical complications and death, even after potential confounders such age, sex, smoking status, time to operation, and obesity are controlled for. To help close these gaps, Dr. Barnes and his associates recommended enhanced recovery after surgery (ERAS) protocols, which “streamline [the] multidisciplinary management of patients with IBD before surgery, incorporating evidence-based practices focused on nutrition, prevention of postoperative ileus, and use of nonopioid analgesia and goal-directed fluid therapy.”

Similar approaches also might improve nonsurgical outcomes in minorities with IBD, the experts said. In the Sinai-Helmsley Alliance for Research Excellence (SHARE) study, Black patients had more complicated IBD at baseline but similar clinical outcomes and patterns of medication use as Whites when they were treated at academic IBD centers. In other studies, race and ethnicity did not affect patterns of medication use, surgery, or surgical outcomes if patients had similar access to care. Such findings “indicate that when patients of minority races and ethnicities have access to appropriate specialty care and IBD-related therapy, many previously identified disparities are resolved or reduced,” the experts said.

However, race and ethnicity do affect some aspects of IBD disease activity, genetics, and treatment safety and efficacy. Since White patients have made up the vast majority of research participants, studies of racial and ethnic minorities are needed to improve their IBD diagnosis, prevention, and treatment. Such research is particularly vital because IBD incidence is rising three times faster rates in racial and ethnic minorities than Whites, said Aline Charabaty, MD, AGAF, clinical director of the gastroenterology division at Johns Hopkins University in Baltimore, and director of the IBD Center at Sibley Memorial Hospital in Washington.

She explained that, when immigrants from countries where IBD is rare adopt the United States’ sedentary lifestyle and Western diet (low in fruits and vegetables; high in proinflammatory saturated fats, sugars, and processed foods), their gut microbiome shifts and their IBD risk increases markedly. Studies in other countries have produced similar findings, said Dr. Charabaty, who did not help author the review article.

She also noted that patients from communities with a historically low prevalence of IBD may not understand its chronicity or the need for long-term treatment. However, treatment adherence is a common issue for patients of all backgrounds with IBD, she said. “What is unique is barriers to continuity of care – not being able to get to the treatment center, not being able to afford treatment or take time off work if you live paycheck to paycheck, not being able to pay someone to care for your kids while you see the doctor.”

Other potential barriers to seeking IBD treatment include cultural taboos against discussing lower GI symptoms or concerns that chronic disease will harm marriage prospects, Dr. Charabaty said. Such challenges only heighten the need to ascertain IBD symptoms: “Studies show that minorities have less follow-up care and their symptoms tend to be minimized. There is a lot of unconscious bias among providers that factors into this. The barriers are multiple, and it is important to define them and find strategies to overcome them at the level of the patient, the clinician, and the health system.”

The Crohn’s and Colitis Foundation supported the work. Dr. Barnes disclosed ties to AbbVie, Gilead, Takeda, and Target Pharmasolutions. Two coauthors also disclosed relevant ties to pharmaceutical companies. Dr. Charabaty disclosed relationships with AbbVie, Takeda, Pfizer, Janssen, and UCB.

SOURCE: Barnes EL et al. Gastroenterology. 2020 Oct 20. doi: 10.1053/j.gastro.2020.08.064.
 

Inflammatory bowel disease (IBD) is rapidly increasing among racial and ethnic minorities, which makes it important to consider for patients with compatible symptoms, experts wrote in Gastroenterology.

Crohn’s disease and ulcerative colitis are “chronic diseases with intermittent periods of flare and remission, so access to specialists, appropriate therapies, and frequent follow-up visits are vital to good outcomes,” wrote Edward L. Barnes, MD, MPH, of University of North Carolina at Chapel Hill, with his associates. However, Blacks with IBD tend to be diagnosed later than Whites, are less likely to receive recommended biologics and immunomodulators, and are more likely to receive care at an emergency department, to experience delays in colectomy, and to miss regular visits to IBD specialists because of financial and transportation barriers, they added.

These disparities are known to worsen outcomes. Compared with Whites, for example, Black patients with Crohn’s disease have higher rates of stricture and penetrating lesions and are at greater risk for postsurgical complications and death, even after potential confounders such age, sex, smoking status, time to operation, and obesity are controlled for. To help close these gaps, Dr. Barnes and his associates recommended enhanced recovery after surgery (ERAS) protocols, which “streamline [the] multidisciplinary management of patients with IBD before surgery, incorporating evidence-based practices focused on nutrition, prevention of postoperative ileus, and use of nonopioid analgesia and goal-directed fluid therapy.”

Similar approaches also might improve nonsurgical outcomes in minorities with IBD, the experts said. In the Sinai-Helmsley Alliance for Research Excellence (SHARE) study, Black patients had more complicated IBD at baseline but similar clinical outcomes and patterns of medication use as Whites when they were treated at academic IBD centers. In other studies, race and ethnicity did not affect patterns of medication use, surgery, or surgical outcomes if patients had similar access to care. Such findings “indicate that when patients of minority races and ethnicities have access to appropriate specialty care and IBD-related therapy, many previously identified disparities are resolved or reduced,” the experts said.

However, race and ethnicity do affect some aspects of IBD disease activity, genetics, and treatment safety and efficacy. Since White patients have made up the vast majority of research participants, studies of racial and ethnic minorities are needed to improve their IBD diagnosis, prevention, and treatment. Such research is particularly vital because IBD incidence is rising three times faster rates in racial and ethnic minorities than Whites, said Aline Charabaty, MD, AGAF, clinical director of the gastroenterology division at Johns Hopkins University in Baltimore, and director of the IBD Center at Sibley Memorial Hospital in Washington.

She explained that, when immigrants from countries where IBD is rare adopt the United States’ sedentary lifestyle and Western diet (low in fruits and vegetables; high in proinflammatory saturated fats, sugars, and processed foods), their gut microbiome shifts and their IBD risk increases markedly. Studies in other countries have produced similar findings, said Dr. Charabaty, who did not help author the review article.

She also noted that patients from communities with a historically low prevalence of IBD may not understand its chronicity or the need for long-term treatment. However, treatment adherence is a common issue for patients of all backgrounds with IBD, she said. “What is unique is barriers to continuity of care – not being able to get to the treatment center, not being able to afford treatment or take time off work if you live paycheck to paycheck, not being able to pay someone to care for your kids while you see the doctor.”

Other potential barriers to seeking IBD treatment include cultural taboos against discussing lower GI symptoms or concerns that chronic disease will harm marriage prospects, Dr. Charabaty said. Such challenges only heighten the need to ascertain IBD symptoms: “Studies show that minorities have less follow-up care and their symptoms tend to be minimized. There is a lot of unconscious bias among providers that factors into this. The barriers are multiple, and it is important to define them and find strategies to overcome them at the level of the patient, the clinician, and the health system.”

The Crohn’s and Colitis Foundation supported the work. Dr. Barnes disclosed ties to AbbVie, Gilead, Takeda, and Target Pharmasolutions. Two coauthors also disclosed relevant ties to pharmaceutical companies. Dr. Charabaty disclosed relationships with AbbVie, Takeda, Pfizer, Janssen, and UCB.

SOURCE: Barnes EL et al. Gastroenterology. 2020 Oct 20. doi: 10.1053/j.gastro.2020.08.064.